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H3K4me3 polyclonal antibody (sample size)

CUT&Tag grade Abs

ChIP-seq grade Abs

ChIP grade Abs

Negative IgG control

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Antibodies

Catalog Number

Format

Price

C15410003-10
(pAb-003-010)

10 µg

$115.00
Bulk order

Other format

C15410003

50 µg

Polyclonal antibody raised in rabbit against the region of histone H3 containing the trimethylated lysine 4 (H3K4me3), using a KLH-conjugated synthetic peptide.

Lot	A8034D
Concentration	1.3 µg/µl
Species reactivity	Human, mouse, pig, zebrafish, trout, Daphnia, Arabidopsis, rice, tomato, maize, poplar, silena latifolia, wide range expected.
Type	Polyclonal, ChIP grade, ChIP-seq grade
Purity	Affinity purified polyclonal antibody.
Host	Rabbit
Storage Conditions	Store at -20°C; for long storage, store at -80°C. Avoid multiple freeze-thaw cycles.
Storage Buffer	PBS containing 0.05% azide and 0.05% ProClin 300.
Precautions	This product is for research use only. Not for use in diagnostic or therapeutic procedures.

Applications	Suggested dilution	References
ChIP/ChIP-seq^*	0.5 - 1 µg	Fig 1, 2
CUT&Tag	0.5 µg	Fig 3
ELISA	1:2,000	Fig 4
Dot Blotting	1:1000	Fig 5
Western Blotting	1:1,000	Fig 6
Immunofluorescence	1:200	Fig 7

^* Please note that the optimal antibody amount per IP should be determined by the end-user. We recommend testing 0.5-5 µg per IP.

Validation Data

Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3
ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 µg of antibody per ChIP experiment was analyzed. IgG (1 µg/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).

A.B.C.D.

Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3
ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 µg of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.

A.

B.

Figure 3. Cut&Tag results obtained with the Diagenode antibody directed against H3K4me3
CUT&TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 µg of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).

Figure 4. Determination of the antibody titer
To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.

Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3
To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.

Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3
Western blot was performed on whole cell extracts (40 µg, lane 1) from HeLa cells, and on 1 µg of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.

Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3
HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20’ and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.
Target Description
お客様の声
I have used Diagenode's antibodies for my ChIP–qPCR experiments in HK-2 cells. The antibodies performed very well in our experiments with specific signal, and good signal to noise ratio in the promoter of the gapdh gene.

Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3 ChIP assays were performed using human HK-2 cells, the Diagenode antibody against H3K4me3 (Cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with standard fixation and sonication protocol, using sheared chromatin from 4 million cells. A total amount of 4 ug of antibody were used per ChIP experiment, normal mouse IgG (4 μg/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). These results are in accordance with the observation that trimethylation of K4 at histone H3 is associated with the promoters of active genes.
Claudio Cappelli PhD. Post-Doc. Investigator, Laboratory of Molecular Pathology, Institute of Biochemestry and Microbiology, University Austral of Chile, about H3K4me3 polyclonal antibody Premium, 50 μl size.

In life sciences, epigenetics is nowadays the most rapid developing field with new astonishing discoveries made every day. To keep pace with this field, we are in need of reliable tools to foster our research - tools Diagenode provides us with. From antibodies to automated solutions - all from one source and with robust support. Antibodies used in our lab: H3K27me3 polyclonal antibody – Premium, H3K4me3 polyclonal antibody – Premium, H3K9me3 polyclonal antibody – Premium, H3K4me1 polyclonal antibody – Premium, CTCF polyclonal antibody – Classic, Rabbit IgG.
Dr. Florian Uhle, Dept. of Anesthesiology, Heidelberg University Hospital, Germany

We use the Bioruptor sonication device and the antibody against the histone modification H3K4me3 in our lab. The Bioruptor device is used for the shearing of chromatin in ChIP-Seq experiments and for generation of protein lysates (whole cell extracts). Thanks to the Bioruptor device we achieve excellent and reproducible results in both applications. The H3K4me3 antibody is used in our ChIP-Seq experiments as well as Western Blotting. With this antibody we are able to generate highly enriched ChIP-Seq samples with extremely low background. In Western Blot we can detect one specific, strong band with the H3K4me3 antibody.

Diagenode provides not only very good products for research but also an excellent customer support.
Dr Lora Dimitrova, Charité-Universitätsmedizin Berlin, Germany

I work with Diagenode’s Plant ChIP-seq kit and shear the DNA on the Bioruptor Pico for the last year and I have to say that these two products saved my PhD project! Some time ago, our well-established ChIP protocol suddenly stopped to work and after long time of figuring out the reason, we invested into Bioruptor Pico. I am very satisfied from the way it works, plus it’s super quiet! Combining the sonicator with the Plant ChIP-seq kit we finally got things working. I have also decided to try the Microplex Library Prep kit, which is amazing. I have been working with other kits and I find this one efficient and very easy to use. Recently, I have tested one of the epigenetics antibody (H3K4me3) and it works very well on the plant tissue, together with the ChIP-seq kit and Bioruptor.

Thanks Diagenode for saving my PhD!
Kamila Kwasniewska, Plant Developmental Genetics, Smurfit Institute, Trinity College, Dublin

I am working with the True MicroChIP & Microplex Library Preparation Kits and several histone modification antibodies like H3K27ac, H3K4me3, H3K36me3, and H3K27me3. I got always very good and reproducible results for my ChIP-seq experiments.
Andrea Thiesen, ZMB, Developmental Biology, Prof. Dr. Andrea Vortkamp´s lab, University Duisburg-Essen, Germany

実験手法

ELISA
Enzyme-linked immunosorbent assay. Read more

DB
Dot blotting Read more

WB
Western blot : The quality of antibodies used in this technique is crucial for correct and specific protein identification. Diagenode offers huge selection of highly sensitive and specific western blot-validated antibodies. Learn more about: Load... Read more

IF
Immunofluorescence: Diagenode offers huge selection of highly sensitive antibodies validated in IF. Immunofluorescence using the Diagenode monoclonal antibody directed against CRISPR/Cas9 HeLa cells transfected with a Cas9 expression vector (... Read more

Peptide array
Peptide array Read more

ChIP-seq (ab)
Read more

ChIP-qPCR (ab)
Read more

CUT&Tag
CUT＆Tagアッセイを成功させるための重要な要素の1つは使用される抗体の品質です。特異性高い抗体は、目的のタンパク質のみをターゲットとした確実な結果を可能にします。 CUT＆Tagで検証済みの抗体のセレクションはこちらからご覧ください。 Read more: Products for CUT&Tag assay Performance of Diagenode's antibodies in CUT&Tag Read more

出版物

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Zhang P. et al.
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Local euchromatin enrichment in lamina-associated domains anticipatestheir repositioning in the adipogenic lineage.
Madsen-Østerbye J. et al.
BACKGROUND: Interactions of chromatin with the nuclear lamina via lamina-associated domains (LADs) confer structural stability to the genome. The dynamics of positioning of LADs during differentiation, and how LADs impinge on developmental gene expression, remains, however, elusive. RESULTS: We examined changes in t...

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Comprehensive characterization of the epigenetic landscape in Multiple Myeloma
Alaterre, Elina and Ovejero, Sara and Herviou, Laurie and de Boussac, Hugues and Papadopoulos, Giorgio and Kulis, Marta and Boireau, Stéphanie and Robert, Nicolas and Requirand, Guilhem and Bruyer, Angélique and Cartron, Guillaume and Vincent, Laure and M
Background: Human multiple myeloma (MM) cell lines (HMCLs) have been widely used to understand the molecular processes that drive MM biology. Epigenetic modifications are involved in MM development, progression, and drug resistance. A comprehensive characterization of the epigenetic landscape of MM would advance our...

Loss of KMT2C reprograms the epigenomic landscape in hPSCsresulting in NODAL overexpression and a failure of hemogenic endotheliumspecification.
Maurya Shailendra et al.
Germline or somatic variation in the family of KMT2 lysine methyltransferases have been associated with a variety of congenital disorders and cancers. Notably, -fusions are prevalent in 70\% of infant leukaemias but fail to phenocopy short latency leukaemogenesis in mammalian models, suggesting additional factors ar...

The long noncoding RNA H19 regulates tumor plasticity inneuroendocrine prostate cancer
Singh N. et al.
Neuroendocrine (NE) prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (PCa) arising either de novo or from transdifferentiated prostate adenocarcinoma following androgen deprivation therapy (ADT). Extensive computational analysis has identified a high degree of association between th...

Epromoters function as a hub to recruit key transcription factorsrequired for the inflammatory response
Santiago-Algarra D. et al.
Gene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. Our previous results demonstrated that a subset of gene promoters, termed Epromoters, work as bona fide enhancers and regulate distal gene expression. Here, we hypothesized that Epromoters play a...

Comparing the epigenetic landscape in myonuclei purified with a PCM1antibody from a fast/glycolytic and a slow/oxidative muscle.
Bengtsen Mads et al.
Muscle cells have different phenotypes adapted to different usage, and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of the epigenetic landscape by ChIP-Seq in two muscle extremes, the fast/...

Rhesus macaques self-curing from a schistosome infection can displaycomplete immunity to challenge
Amaral MS et al.
The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict \>200 million people worldwide. By monitoring bloodstream levels of parasite-gut-derived antigen, we show that from week 10 onwards an established infection with Schistosoma mansoni is cleared in an exponential man...

p300 suppresses the transition of myelodysplastic syndromes to acutemyeloid leukemia
Man Na et al.
Myelodysplastic syndromes (MDS) are hematopoietic stem and progenitor cell (HSPC) malignancies characterized by ineffective hematopoiesis and an increased risk of leukemia transformation. Epigenetic regulators are recurrently mutated in MDS, directly implicating epigenetic dysregulation in MDS pathogenesis. Here, we...

Differential contribution to gene expression prediction of histonemodifications at enhancers or promoters.
González-Ramírez M. et al.
The ChIP-seq signal of histone modifications at promoters is a good predictor of gene expression in different cellular contexts, but whether this is also true at enhancers is not clear. To address this issue, we develop quantitative models to characterize the relationship of gene expression with histone modification...

DOT1L O-GlcNAcylation promotes its protein stability andMLL-fusion leukemia cell proliferation.
Song Tanjing et al.
Histone lysine methylation functions at the interface of the extracellular environment and intracellular gene expression. DOT1L is a versatile histone H3K79 methyltransferase with a prominent role in MLL-fusion leukemia, yet little is known about how DOT1L responds to extracellular stimuli. Here, we report that DOT1...

INTS11 regulates hematopoiesis by promoting PRC2 function.
Zhang Peng et al.
INTS11, the catalytic subunit of the Integrator (INT) complex, is crucial for the biogenesis of small nuclear RNAs and enhancer RNAs. However, the role of INTS11 in hematopoietic stem and progenitor cell (HSPC) biology is unknown. Here, we report that INTS11 is required for normal hematopoiesis and hematopoietic-spe...

Enhanced targeted DNA methylation of the CMV and endogenous promoterswith dCas9-DNMT3A3L entails distinct subsequent histonemodification changes in CHO cells.
Marx Nicolas et al.
With the emergence of new CRISPR/dCas9 tools that enable site specific modulation of DNA methylation and histone modifications, more detailed investigations of the contribution of epigenetic regulation to the precise phenotype of cells in culture, including recombinant production subclones, is now possible. These al...

ChIP-seq protocol for sperm cells and embryos to assess environmentalimpacts and epigenetic inheritance
Lismer, Ariane and Lambrot, Romain and Lafleur, Christine and Dumeaux,Vanessa and Kimmins, Sarah
In the field of epigenetic inheritance, delineating molecular mechanisms implicated in the transfer of paternal environmental conditions to descendants has been elusive. This protocol details how to track sperm chromatin intergenerationally. We describe mouse model design to probe chromatin states in single mouse sp...

E2F6 initiates stable epigenetic silencing of germline genes duringembryonic development
Dahlet T. et al.
In mouse development, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes; however, the molecular mechanisms of this specificity remain unclear. Here, we demonstrate that the transcription factor E2F6, a member of the polycomb repressive complex 1.6 (PRC1.6), is critical to t...

Lasp1 regulates adherens junction dynamics and fibroblast transformationin destructive arthritis
Beckmann D. et al.
The LIM and SH3 domain protein 1 (Lasp1) was originally cloned from metastatic breast cancer and characterised as an adaptor molecule associated with tumourigenesis and cancer cell invasion. However, the regulation of Lasp1 and its function in the aggressive transformation of cells is unclear. Here we use integrativ...

Placental uptake and metabolism of 25(OH)Vitamin D determines itsactivity within the fetoplacental unit
Ashley, B. et al.
Pregnancy 25-hydroxyvitamin D (25(OH)D) concentrations are associated with maternal and fetal health outcomes, but the underlying mechanisms have not been elucidated. Using physiological human placental perfusion approaches and intact villous explants we demonstrate a role for the placenta in regulating the relation...

Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.
Pettinato, Anthony M. et al.
Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization by unclear mechanisms. To study this process, we engineer a human cardiomyocyte model to track replication and polyploidization using fluorescently tagged cyclin B1 and cardiac troponin T. Using time-lapse i...

The SAM domain-containing protein 1 (SAMD1) acts as a repressivechromatin regulator at unmethylated CpG islands
Stielow B. et al.
CpG islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here, we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 has an atypical winged-helix domain that direct...

Simplification of culture conditions and feeder-free expansion of bovineembryonic stem cells
Soto D. A. et al.
Bovine embryonic stem cells (bESCs) extend the lifespan of the transient pluripotent bovine inner cell mass in vitro. After years of research, derivation of stable bESCs was only recently reported. Although successful, bESC culture relies on complex culture conditions that require a custom-made base medium and mouse...

The anti-inflammatory cytokine interleukin-37 is an inhibitor of trainedimmunity.
Cavalli, Giulio and Tengesdal, Isak W and Gresnigt, Mark and Nemkov, Travisand Arts, Rob J W and Domínguez-Andrés, Jorge and Molteni, Raffaella andStefanoni, Davide and Cantoni, Eleonora and Cassina, Laura and Giugliano,Silvia and Schraa, Kiki and Mill
Trained immunity (TI) is a de facto innate immune memory program induced in monocytes/macrophages by exposure to pathogens or vaccines, which evolved as protection against infections. TI is characterized by immunometabolic changes and histone post-translational modifications, which enhance production of pro-inflamma...

Comparative analysis of histone H3K4me3 modifications between blastocystsand somatic tissues in cattle.
Ishibashi, Mao et al.
Epigenetic changes induced in the early developmental stages by the surrounding environment can have not only short-term but also long-term consequences throughout life. This concept constitutes the "Developmental Origins of Health and Disease" (DOHaD) hypothesis and encompasses the possibility of controlling livest...

Genetic perturbation of PU.1 binding and chromatin looping at neutrophilenhancers associates with autoimmune disease.
Watt, Stephen et al.
Neutrophils play fundamental roles in innate immune response, shape adaptive immunity, and are a potentially causal cell type underpinning genetic associations with immune system traits and diseases. Here, we profile the binding of myeloid master regulator PU.1 in primary neutrophils across nearly a hundred voluntee...

Loss of SETD1B results in the redistribution of genomic H3K4me3 in theoocyte
Hanna, C. W. et al.
Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransferases SETD1B and MLL2 are essential for oogenesis. We investigated cha...

Epigenomic tensor predicts disease subtypes and reveals constrained tumorevolution.
Leistico, Jacob R et al.
Understanding the epigenomic evolution and specificity of disease subtypes from complex patient data remains a major biomedical problem. We here present DeCET (decomposition and classification of epigenomic tensors), an integrative computational approach for simultaneously analyzing hierarchical heterogeneous data, ...

Functional annotations of three domestic animal genomes provide vitalresources for comparative and agricultural research.
Kern C. et al.
Gene regulatory elements are central drivers of phenotypic variation and thus of critical importance towards understanding the genetics of complex traits. The Functional Annotation of Animal Genomes consortium was formed to collaboratively annotate the functional elements in animal genomes, starting with domesticate...

The histone modification H3K4me3 is altered at the locus in Alzheimer'sdisease brain.
Smith, Adam et al.
Several epigenome-wide association studies of DNA methylation have highlighted altered DNA methylation in the gene in Alzheimer's disease (AD) brain samples. However, no study has specifically examined histone modifications in the disease. We use chromatin immunoprecipitation-qPCR to quantify tri-methylation at hist...

The G2-phase enriched lncRNA SNHG26 is necessary for proper cell cycleprogression and proliferation
Samdal, H. et al.
Long noncoding RNAs (lncRNAs) are involved in the regulation of cell cycle, although only a few have been functionally characterized. By combining RNA sequencing and ChIP sequencing of cell cycle synchronized HaCaT cells we have previously identified lncRNAs highly enriched for cell cycle functions. Based on a cycli...

The epigenetic landscape in purified myonuclei from fast and slow muscles
Bengtsen, M. et al.
Muscle cells have different phenotypes adapted to different usage and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of chromatin environment by ChIP-Seq in two muscle extremes, the almost co...

WAPL maintains a cohesin loading cycle to preserve cell-type-specificdistal gene regulation.
Liu N. Q.et al.
The cohesin complex has an essential role in maintaining genome organization. However, its role in gene regulation remains largely unresolved. Here we report that the cohesin release factor WAPL creates a pool of free cohesin, in a process known as cohesin turnover, which reloads it to cell-type-specific binding sit...

Dissecting Herpes Simplex Virus 1-Induced Host Shutoff at the RNA Level.
Friedel, Caroline C and Whisnant, Adam W and Djakovic, Lara and Rutkowski,Andrzej J and Friedl, Marie-Sophie and Kluge, Michael and Williamson, JamesC and Sai, Somesh and Vidal, Ramon Oliveira and Sauer, Sascha and Hennig,Thomas and Grothey, Arnhild an
Herpes simplex virus 1 (HSV-1) induces a profound host shut-off during lytic infection. The virion host shut-off () protein plays a key role in this process by efficiently cleaving host and viral mRNAs. Furthermore, the onset of viral DNA replication is accompanied by a rapid decline in host transcriptional activity...

Increased H3K4me3 methylation and decreased miR-7113-5p expression lead toenhanced Wnt/β-catenin signaling in immune cells from PTSD patientsleading to inflammatory phenotype.
Bam, Marpe and Yang, Xiaoming and Busbee, Brandon P and Aiello, Allison Eand Uddin, Monica and Ginsberg, Jay P and Galea, Sandro and Nagarkatti,Prakash S and Nagarkatti, Mitzi
BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric disorder accompanied by chronic peripheral inflammation. What triggers inflammation in PTSD is currently unclear. In the present study, we identified potential defects in signaling pathways in peripheral blood mononuclear cells (PBMCs) from individual...

BCG Vaccination Induces Long-Term Functional Reprogramming of HumanNeutrophils.
Moorlag, Simone J C F M and Rodriguez-Rosales, Yessica Alina and Gillard,Joshua and Fanucchi, Stephanie and Theunissen, Kate and Novakovic, Borisand de Bont, Cynthia M and Negishi, Yutaka and Fok, Ezio T and Kalafati,Lydia and Verginis, Panayotis and M
The tuberculosis vaccine bacillus Calmette-Guérin (BCG) protects against some heterologous infections, probably via induction of non-specific innate immune memory in monocytes and natural killer (NK) cells, a process known as trained immunity. Recent studies have revealed that the induction of trained immunit...

ZNF354C is a transcriptional repressor that inhibits endothelialangiogenic sprouting.
Oo, James A and Irmer, Barnabas and Günther, Stefan and Warwick, Timothyand Pálfi, Katalin and Izquierdo Ponce, Judit and Teichmann, Tom andPflüger-Müller, Beatrice and Gilsbach, Ralf and Brandes, Ralf P andLeisegang, Matthias S
Zinc finger proteins (ZNF) are a large group of transcription factors with diverse functions. We recently discovered that endothelial cells harbour a specific mechanism to limit the action of ZNF354C, whose function in endothelial cells is unknown. Given that ZNF354C has so far only been studied in bone and tum...

Derivation of Intermediate Pluripotent Stem Cells Amenable to PrimordialGerm Cell Specification.
Yu L. et al.
Dynamic pluripotent stem cell (PSC) states are in vitro adaptations of pluripotency continuum in vivo. Previous studies have generated a number of PSCs with distinct properties. To date, however, no known PSCs have demonstrated dual competency for chimera formation and direct responsiveness to primordial g...

The epigenetic regulator RINF (CXXC5) maintains SMAD7 expression in human immature erythroid cells and sustains red blood cellsexpansion.
Astori A. et al.
The gene CXXC5, encoding a Retinoid-Inducible Nuclear Factor (RINF), is located within a region at 5q31.2 commonly deleted in myelodysplastic syndrome (MDS) and adult acute myeloid leukemia (AML). RINF may act as an epigenetic regulator and has been proposed as a tumor suppressor in hematopoietic malignancies. Howev...

StE(z)2, a Polycomb group methyltransferase and deposition of H3K27me3 andH3K4me3 regulate the expression of tuberization genes in potato.
Kumar, Amit and Kondhare, Kirtikumar R and Malankar, Nilam N and Banerjee,Anjan K
Polycomb Repressive Complex (PRC) group proteins regulate various developmental processes in plants by repressing the target genes via H3K27 trimethylation, whereas their function is antagonized by Trithorax group proteins-mediated H3K4 trimethylation. Tuberization in potato is widely studied, but the role of histon...

Priming for enhanced ARGONAUTE2 activation accompanies induced resistanceto cucumber mosaic virus in Arabidopsis thaliana.
Ando, Sugihiro and Jaskiewicz, Michal and Mochizuki, Sei and Koseki, Saekoand Miyashita, Shuhei and Takahashi, Hideki and Conrath, Uwe
Systemic acquired resistance (SAR) is a broad-spectrum disease resistance response that can be induced upon infection from pathogens or by chemical treatment, such as with benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH). SAR involves priming for more robust activation of defence genes upon pathogen...

Digging Deeper into Breast Cancer Epigenetics: Insights from ChemicalInhibition of Histone Acetyltransferase TIP60 .
Idrissou, Mouhamed and Lebert, Andre and Boisnier, Tiphanie and Sanchez,Anna and Houfaf Khoufaf, Fatma Zohra and Penault-Llorca, Frédérique andBignon, Yves-Jean and Bernard-Gallon, Dominique
Breast cancer is often sporadic due to several factors. Among them, the deregulation of epigenetic proteins may be involved. TIP60 or KAT5 is an acetyltransferase that regulates gene transcription through the chromatin structure. This pleiotropic protein acts in several cellular pathways by acetylating proteins. RNA...

NSD1-deposited H3K36me2 directs de novo methylation in the mouse malegermline and counteracts Polycomb-associated silencing.
Shirane, Kenjiro and Miura, Fumihito and Ito, Takashi and Lorincz, MatthewC
De novo DNA methylation (DNAme) in mammalian germ cells is dependent on DNMT3A and DNMT3L. However, oocytes and spermatozoa show distinct patterns of DNAme. In mouse oocytes, de novo DNAme requires the lysine methyltransferase (KMTase) SETD2, which deposits H3K36me3. We show here that SETD2 is dispensable for de nov...

Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth andPotentiates Checkpoint Inhibition.
Priem, Bram and van Leent, Mandy M T and Teunissen, Abraham J P and Sofias,Alexandros Marios and Mourits, Vera P and Willemsen, Lisa and Klein, Emma Dand Oosterwijk, Roderick S and Meerwaldt, Anu E and Munitz, Jazz andPrévot, Geoffrey and Vera Verschuu
Trained immunity, a functional state of myeloid cells, has been proposed as a compelling immune-oncological target. Its efficient induction requires direct engagement of myeloid progenitors in the bone marrow. For this purpose, we developed a bone marrow-avid nanobiologic platform designed specifically to induce tra...

Formation of the CenH3-Deficient Holocentromere in Lepidoptera AvoidsActive Chromatin.
Senaratne, Aruni P and Muller, Héloïse and Fryer, Kelsey A and Kawamoto,Munetaka and Katsuma, Susumu and Drinnenberg, Ines A
Despite the essentiality for faithful chromosome segregation, centromere architectures are diverse among eukaryotes and embody two main configurations: mono- and holocentromeres, referring, respectively, to localized or unrestricted distribution of centromeric activity. Of the two, some holocentromeres offer the cur...

Epigenetic regulation of the lineage specificity of primary human dermallymphatic and blood vascular endothelial cells.
Tacconi, Carlotta and He, Yuliang and Ducoli, Luca and Detmar, Michael
Lymphatic and blood vascular endothelial cells (ECs) share several molecular and developmental features. However, these two cell types possess distinct phenotypic signatures, reflecting their different biological functions. Despite significant advances in elucidating how the specification of lymphatic and blood vasc...

OxLDL-mediated immunologic memory in endothelial cells.
Sohrabi Y, Lagache SMM, Voges VC, Semo D, Sonntag G, Hanemann I, Kahles F, Waltenberger J, Findeisen HM
Trained innate immunity describes the metabolic reprogramming and long-term proinflammatory activation of innate immune cells in response to different pathogen or damage associated molecular patterns, such as oxidized low-density lipoprotein (oxLDL). Here, we have investigated whether the regulatory networks of trai...

The Human Integrator Complex Facilitates Transcriptional Elongation by Endonucleolytic Cleavage of Nascent Transcripts.
Beckedorff F, Blumenthal E, daSilva LF, Aoi Y, Cingaram PR, Yue J, Zhang A, Dokaneheifard S, Valencia MG, Gaidosh G, Shilatifard A, Shiekhattar R
Transcription by RNA polymerase II (RNAPII) is pervasive in the human genome. However, the mechanisms controlling transcription at promoters and enhancers remain enigmatic. Here, we demonstrate that Integrator subunit 11 (INTS11), the catalytic subunit of the Integrator complex, regulates transcription at these loci...

Prostate cancer reactivates developmental epigenomic programs during metastatic progression.
Pomerantz MM, Qiu X, Zhu Y, Takeda DY, Pan W, Baca SC, Gusev A, Korthauer KD, Severson TM, Ha G, Viswanathan SR, Seo JH, Nguyen HM, Zhang B, Pasaniuc B, Giambartolomei C, Alaiwi SA, Bell CA, O'Connor EP, Chabot MS, Stillman DR, Lis R, Font-Tello A, Li L,
Epigenetic processes govern prostate cancer (PCa) biology, as evidenced by the dependency of PCa cells on the androgen receptor (AR), a prostate master transcription factor. We generated 268 epigenomic datasets spanning two state transitions-from normal prostate epithelium to localized PCa to metastases-in specimens...

The hypomethylation of imprinted genes in IVF/ICSI placenta samples is associated with concomitant changes in histone modifications.
Choux C, Petazzi P, Sanchez-Delgado M, Hernandez Mora JR, Monteagudo A, Sagot P, Monk D, Fauque P
Although more and more children are born by Assisted Reproductive Technologies (ART), ART safety has not fully been demonstrated. Notably, ART could disturb the delicate step of implantation, and trigger placenta-related adverse outcomes with potential long-term effects, through disrupted epigenetic regulation. We h...

Epigenetic priming by Dppa2 and 4 in pluripotency facilitates multi-lineage commitment.
Eckersley-Maslin MA, Parry A, Blotenburg M, Krueger C, Ito Y, Franklin VNR, Narita M, D'Santos CS, Reik W
How the epigenetic landscape is established in development is still being elucidated. Here, we uncover developmental pluripotency associated 2 and 4 (DPPA2/4) as epigenetic priming factors that establish a permissive epigenetic landscape at a subset of developmentally important bivalent promoters characterized by lo...

Genomic deregulation of PRMT5 supports growth and stress tolerance in chronic lymphocytic leukemia.
Schnormeier AK, Pommerenke C, Kaufmann M, Drexler HG, Koeppel M
Patients suffering from chronic lymphocytic leukemia (CLL) display highly diverse clinical courses ranging from indolent cases to aggressive disease, with genetic and epigenetic features resembling this diversity. Here, we developed a comprehensive approach combining a variety of molecular and clinical data to pinpo...

The hypomethylation of imprinted genes in IVF/ICSI placenta samplesis associated with concomitant changes in histone modifications.
Choux C. et al.
Although more and more children are born by Assisted Reproductive Technologies (ART), ART safety has not fully been demonstrated. Notably, ART could disturb the delicate step of implantation, and trigger placenta-related adverse outcomes with potential long-term effects, through disrupted epigenetic regulation. We h...

Measuring Histone Modifications in the Human Parasite Schistosoma mansoni
de Carvalho Augusto R, Roquis D, Al Picard M, Chaparro C, Cosseau C, Grunau C.
DNA-binding proteins play critical roles in many major processes such as development and sexual biology of Schistosoma mansoni and are important for the pathogenesis of schistosomiasis. Chromatin immunoprecipitation (ChIP) experiments followed by sequencing (ChIP-seq) are useful to characterize the association of ge...

Histone post-translational modifications in Silene latifolia X and Y chromosomes suggest a mammal-like dosage compensation system
Luis Rodríguez Lorenzo José, Hubinský Marcel, Vyskot Boris, Hobza Roman
Silene latifolia is a model organism to study evolutionary young heteromorphic sex chromosome evolution in plants. Previous research indicates a Y-allele gene degeneration and a dosage compensation system already operating. Here, we propose an epigenetic approach based on analysis of several histone post-translation...

TET3 controls the expression of the H3K27me3 demethylase Kdm6b during neural commitment.
Montibus B, Cercy J, Bouschet T, Charras A, Maupetit-Méhouas S, Nury D, Gonthier-Guéret C, Chauveau S, Allegre N, Chariau C, Hong CC, Vaillant I, Marques CJ, Court F, Arnaud P
The acquisition of cell identity is associated with developmentally regulated changes in the cellular histone methylation signatures. For instance, commitment to neural differentiation relies on the tightly controlled gain or loss of H3K27me3, a hallmark of polycomb-mediated transcriptional gene silencing, at specif...

In vitro capture and characterization of embryonic rosette-stage pluripotency between naive and primed states.
Neagu A, van Genderen E, Escudero I, Verwegen L, Kurek D, Lehmann J, Stel J, Dirks RAM, van Mierlo G, Maas A, Eleveld C, Ge Y, den Dekker AT, Brouwer RWW, van IJcken WFJ, Modic M, Drukker M, Jansen JH, Rivron NC, Baart EB, Marks H, Ten Berge D
Following implantation, the naive pluripotent epiblast of the mouse blastocyst generates a rosette, undergoes lumenogenesis and forms the primed pluripotent egg cylinder, which is able to generate the embryonic tissues. How pluripotency progression and morphogenesis are linked and whether intermediate pluripotent st...

The TGF-β profibrotic cascade targets ecto-5'-nucleotidase gene in proximal tubule epithelial cells and is a traceable marker of progressive diabetic kidney disease.
Cappelli C, Tellez A, Jara C, Alarcón S, Torres A, Mendoza P, Podestá L, Flores C, Quezada C, Oyarzún C, Martín RS
Progressive diabetic nephropathy (DN) and loss of renal function correlate with kidney fibrosis. Crosstalk between TGF-β and adenosinergic signaling contributes to the phenotypic transition of cells and to renal fibrosis in DN models. We evaluated the role of TGF-β on NT5E gene expression coding for the ec...

LXR Activation Induces a Proinflammatory Trained Innate Immunity-Phenotype in Human Monocytes
Sohrabi Yahya, Sonntag Glenn V. H., Braun Laura C., Lagache Sina M. M., Liebmann Marie, Klotz Luisa, Godfrey Rinesh, Kahles Florian, Waltenberger Johannes, Findeisen Hannes M.
The concept of trained innate immunity describes a long-term proinflammatory memory in innate immune cells. Trained innate immunity is regulated through reprogramming of cellular metabolic pathways including cholesterol and fatty acid synthesis. Here, we have analyzed the role of Liver X Receptor (LXR), a key regula...

A MORC-driven transcriptional switch controls Toxoplasma developmental trajectories and sexual commitment.
Farhat DC, Swale C, Dard C, Cannella D, Ortet P, Barakat M, Sindikubwabo F, Belmudes L, De Bock PJ, Couté Y, Bougdour A, Hakimi MA
Toxoplasma gondii has a complex life cycle that is typified by asexual development that takes place in vertebrates, and sexual reproduction, which occurs exclusively in felids and is therefore less studied. The developmental transitions rely on changes in the patterns of gene expression, and recent studies have assi...

Recombination may occur in the absence of transcription in the immunoglobulin heavy chain recombination centre.
Oudinet C, Braikia FZ, Dauba A, Khamlichi AA
Developing B cells undergo V(D)J recombination to generate a vast repertoire of Ig molecules. V(D)J recombination is initiated by the RAG1/RAG2 complex in recombination centres (RCs), where gene segments become accessible to the complex. Whether transcription is the causal factor of accessibility or whether it is a ...

Inhibition of methyltransferase activity of enhancer of zeste 2 leads to enhanced lipid accumulation and altered chromatin status in zebrafish.
den Broeder MJ, Ballangby J, Kamminga LM, Aleström P, Legler J, Lindeman LC, Kamstra JH
BACKGROUND: Recent studies indicate that exposure to environmental chemicals may increase susceptibility to developing metabolic diseases. This susceptibility may in part be caused by changes to the epigenetic landscape which consequently affect gene expression and lead to changes in lipid metabolism. The epigenetic...

Targeting Macrophage Histone H3 Modification as a Leishmania Strategy to Dampen the NF-κB/NLRP3-Mediated Inflammatory Response.
Lecoeur H, Prina E, Rosazza T, Kokou K, N'Diaye P, Aulner N, Varet H, Bussotti G, Xing Y, Milon G, Weil R, Meng G, Späth GF
Aberrant macrophage activation during intracellular infection generates immunopathologies that can cause severe human morbidity. A better understanding of immune subversion strategies and macrophage phenotypic and functional responses is necessary to design host-directed intervention strategies. Here, we uncover a f...

Replicational Dilution of H3K27me3 in Mammalian Cells and the Role of Poised Promoters.
Jadhav U, Manieri E, Nalapareddy K, Madha S, Chakrabarti S, Wucherpfennig K, Barefoot M, Shivdasani RA
Polycomb repressive complex 2 (PRC2) places H3K27me3 at developmental genes and is causally implicated in keeping bivalent genes silent. It is unclear if that silence requires minimum H3K27me3 levels and how the mark transmits faithfully across mammalian somatic cell generations. Mouse intestinal cells lacking EZH2 ...

A comprehensive epigenomic analysis of phenotypically distinguishable, genetically identical female and male Daphnia pulex.
Kvist J, Athanàsio CG, Pfrender ME, Brown JB, Colbourne JK, Mirbahai L
BACKGROUND: Daphnia species reproduce by cyclic parthenogenesis involving both sexual and asexual reproduction. The sex of the offspring is environmentally determined and mediated via endocrine signalling by the mother. Interestingly, male and female Daphnia can be genetically identical, yet display large difference...

Analysis of Histone Modifications in Rodent Pancreatic Islets by Native Chromatin Immunoprecipitation.
Sandovici I, Nicholas LM, O'Neill LP
The islets of Langerhans are clusters of cells dispersed throughout the pancreas that produce several hormones essential for controlling a variety of metabolic processes, including glucose homeostasis and lipid metabolism. Studying the transcriptional control of pancreatic islet cells has important implications for ...

Changes in H3K27ac at Gene Regulatory Regions in Porcine AlveolarMacrophages Following LPS or PolyIC Exposure.
Herrera-Uribe, Juber and Liu, Haibo and Byrne, Kristen A and Bond, Zahra Fand Loving, Crystal L and Tuggle, Christopher K
Changes in chromatin structure, especially in histone modifications (HMs), linked with chromatin accessibility for transcription machinery, are considered to play significant roles in transcriptional regulation. Alveolar macrophages (AM) are important immune cells for protection against pulmonary pathogens, and must...

Functionally Annotating Regulatory Elements in the Equine Genome Using Histone Mark ChIP-Seq.
Kingsley NB, Kern C, Creppe C, Hales EN, Zhou H, Kalbfleisch TS, MacLeod JN, Petersen JL, Finno CJ, Bellone RR
One of the primary aims of the Functional Annotation of ANimal Genomes (FAANG) initiative is to characterize tissue-specific regulation within animal genomes. To this end, we used chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to map four histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me...

H3K4me1 Supports Memory-like NK Cells Induced by Systemic Inflammation.
Rasid O, Chevalier C, Camarasa TM, Fitting C, Cavaillon JM, Hamon MA
Natural killer (NK) cells are unique players in innate immunity and, as such, an attractive target for immunotherapy. NK cells display immune memory properties in certain models, but the long-term status of NK cells following systemic inflammation is unknown. Here we show that following LPS-induced endotoxemia in mi...

Trained immunity modulates inflammation-induced fibrosis.
Jeljeli M, Riccio LGC, Doridot L, Chêne C, Nicco C, Chouzenoux S, Deletang Q, Allanore Y, Kavian N, Batteux F
Chronic inflammation and fibrosis can result from inappropriately activated immune responses that are mediated by macrophages. Macrophages can acquire memory-like characteristics in response to antigen exposure. Here, we show the effect of BCG or low-dose LPS stimulation on macrophage phenotype, cytokine production,...

MicroRNA-708 is a novel regulator of the Hoxa9 program in myeloid cells.
Schneider E, Pochert N, Ruess C, MacPhee L, Escano L, Miller C, Krowiorz K, Delsing Malmberg E, Heravi-Moussavi A, Lorzadeh A, Ashouri A, Grasedieck S, Sperb N, Kumar Kopparapu P, Iben S, Staffas A, Xiang P, Rösler R, Kanduri M, Larsson E, Fogelstrand L,
MicroRNAs (miRNAs) are commonly deregulated in acute myeloid leukemia (AML), affecting critical genes not only through direct targeting, but also through modulation of downstream effectors. Homeobox (Hox) genes balance self-renewal, proliferation, cell death, and differentiation in many tissues and aberrant Hox gene...

Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.
Aloia L, McKie MA, Vernaz G, Cordero-Espinoza L, Aleksieva N, van den Ameele J, Antonica F, Font-Cunill B, Raven A, Aiese Cigliano R, Belenguer G, Mort RL, Brand AH, Zernicka-Goetz M, Forbes SJ, Miska EA, Huch M
Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal ...

Transcriptional alterations in glioma result primarily from DNA methylation-independent mechanisms.
Court F, Le Boiteux E, Fogli A, Müller-Barthélémy M, Vaurs-Barrière C, Chautard E, Pereira B, Biau J, Kemeny JL, Khalil T, Karayan-Tapon L, Verrelle P, Arnaud P
In cancer cells, aberrant DNA methylation is commonly associated with transcriptional alterations, including silencing of tumor suppressor genes. However, multiple epigenetic mechanisms, including polycomb repressive marks, contribute to gene deregulation in cancer. To dissect the relative contribution of DNA methyl...

Functional analyses of a low-penetrance risk variant rs6702619/1p21.2 associating with colorectal cancer in Polish population.
Statkiewicz M, Maryan N, Kulecka M, Kuklinska U, Ostrowski J, Mikula M
Several studies employed the genome-wide association (GWA) analysis of single-nucleotide polymorphisms (SNPs) to identify susceptibility regions in colorectal cancer (CRC). However, the functional studies exploring the role of associating SNPs with cancer biology are limited. Herein, using chromatin immunoprecipitat...

β-Glucan-Induced Trained Immunity Protects against Leishmania braziliensis Infection: a Crucial Role for IL-32.
Dos Santos JC, Barroso de Figueiredo AM, Teodoro Silva MV, Cirovic B, de Bree LCJ, Damen MSMA, Moorlag SJCFM, Gomes RS, Helsen MM, Oosting M, Keating ST, Schlitzer A, Netea MG, Ribeiro-Dias F, Joosten LAB
American tegumentary leishmaniasis is a vector-borne parasitic disease caused by Leishmania protozoans. Innate immune cells undergo long-term functional reprogramming in response to infection or Bacillus Calmette-Guérin (BCG) vaccination via a process called trained immunity, conferring non-specific protectio...

Reactivation of super-enhancers by KLF4 in human Head and Neck Squamous Cell Carcinoma.
Tsompana M, Gluck C, Sethi I, Joshi I, Bard J, Nowak NJ, Sinha S, Buck MJ
Head and neck squamous cell carcinoma (HNSCC) is a disease of significant morbidity and mortality and rarely diagnosed in early stages. Despite extensive genetic and genomic characterization, targeted therapeutics and diagnostic markers of HNSCC are lacking due to the inherent heterogeneity and complexity of the dis...

Nucleome Dynamics during Retinal Development.
Norrie JL, Lupo MS, Xu B, Al Diri I, Valentine M, Putnam D, Griffiths L, Zhang J, Johnson D, Easton J, Shao Y, Honnell V, Frase S, Miller S, Stewart V, Zhou X, Chen X, Dyer MA
More than 8,000 genes are turned on or off as progenitor cells produce the 7 classes of retinal cell types during development. Thousands of enhancers are also active in the developing retinae, many having features of cell- and developmental stage-specific activity. We studied dynamic changes in the 3D chromatin land...

Development and epigenetic plasticity of murine Müller glia.
Dvoriantchikova G, Seemungal RJ, Ivanov D
The ability to regenerate the entire retina and restore lost sight after injury is found in some species and relies mostly on the epigenetic plasticity of Müller glia. To understand the role of mammalian Müller glia as a source of progenitors for retinal regeneration, we investigated changes in gene expres...

The alarmin S100A9 hampers osteoclast differentiation from human circulating precursors by reducing the expression of RANK.
Di Ceglie I, Blom AB, Davar R, Logie C, Martens JHA, Habibi E, Böttcher LM, Roth J, Vogl T, Goodyear CS, van der Kraan PM, van Lent PL, van den Bosch MH
The alarmin S100A8/A9 is implicated in sterile inflammation-induced bone resorption and has been shown to increase the bone-resorptive capacity of mature osteoclasts. Here, we investigated the effects of S100A9 on osteoclast differentiation from human CD14 circulating precursors. Hereto, human CD14 monocytes were is...

Probing the Tumor Suppressor Function of BAP1 in CRISPR-Engineered Human Liver Organoids.
Artegiani B, van Voorthuijsen L, Lindeboom RGH, Seinstra D, Heo I, Tapia P, López-Iglesias C, Postrach D, Dayton T, Oka R, Hu H, van Boxtel R, van Es JH, Offerhaus J, Peters PJ, van Rheenen J, Vermeulen M, Clevers H
The deubiquitinating enzyme BAP1 is a tumor suppressor, among others involved in cholangiocarcinoma. BAP1 has many proposed molecular targets, while its Drosophila homolog is known to deubiquitinate histone H2AK119. We introduce BAP1 loss-of-function by CRISPR/Cas9 in normal human cholangiocyte organoids. We find th...

Complementary Activity of ETV5, RBPJ, and TCF3 Drives Formative Transition from Naive Pluripotency.
Kalkan T, Bornelöv S, Mulas C, Diamanti E, Lohoff T, Ralser M, Middelkamp S, Lombard P, Nichols J, Smith A
The gene regulatory network (GRN) of naive mouse embryonic stem cells (ESCs) must be reconfigured to enable lineage commitment. TCF3 sanctions rewiring by suppressing components of the ESC transcription factor circuitry. However, TCF3 depletion only delays and does not prevent transition to formative pluripotency. H...

PML modulates H3.3 targeting to telomeric and centromeric repeats in mouse fibroblasts.
Spirkoski J, Shah A, Reiner AH, Collas P, Delbarre E
Targeted deposition of histone variant H3.3 into chromatin is paramount for proper regulation of chromatin integrity, particularly in heterochromatic regions including repeats. We have recently shown that the promyelocytic leukemia (PML) protein prevents H3.3 from being deposited in large heterochromatic PML-associa...

Long intergenic non-coding RNAs regulate human lung fibroblast function: Implications for idiopathic pulmonary fibrosis.
Hadjicharalambous MR, Roux BT, Csomor E, Feghali-Bostwick CA, Murray LA, Clarke DL, Lindsay MA
Phenotypic changes in lung fibroblasts are believed to contribute to the development of Idiopathic Pulmonary Fibrosis (IPF), a progressive and fatal lung disease. Long intergenic non-coding RNAs (lincRNAs) have been identified as novel regulators of gene expression and protein activity. In non-stimulated cells, we o...

Identification of ADGRE5 as discriminating MYC target between Burkitt lymphoma and diffuse large B-cell lymphoma.
Kleo K, Dimitrova L, Oker E, Tomaszewski N, Berg E, Taruttis F, Engelmann JC, Schwarzfischer P, Reinders J, Spang R, Gronwald W, Oefner PJ, Hummel M
BACKGROUND: MYC is a heterogeneously expressed transcription factor that plays a multifunctional role in many biological processes such as cell proliferation and differentiation. It is also associated with many types of cancer including the malignant lymphomas. There are two types of aggressive B-cell lymphoma, name...

Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis.
Mallaney C, Ostrander EL, Celik H, Kramer AC, Martens A, Kothari A, Koh WK, Haussler E, Iwamori N, Gontarz P, Zhang B, Challen GA
The histone demethylase KDM6B (JMJD3) is upregulated in blood disorders, suggesting that it may have important pathogenic functions. Here we examined the function of Kdm6b in hematopoietic stem cells (HSC) to evaluate its potential as a therapeutic target. Loss of Kdm6b lead to depletion of phenotypic and functional...

A critical regulator of Bcl2 revealed by systematic transcript discovery of lncRNAs associated with T-cell differentiation.
Saadi W, Kermezli Y, Dao LTM, Mathieu E, Santiago-Algarra D, Manosalva I, Torres M, Belhocine M, Pradel L, Loriod B, Aribi M, Puthier D, Spicuglia S
Normal T-cell differentiation requires a complex regulatory network which supports a series of maturation steps, including lineage commitment, T-cell receptor (TCR) gene rearrangement, and thymic positive and negative selection. However, the underlying molecular mechanisms are difficult to assess due to limited T-ce...

The role of TCF3 as potential master regulator in blastemal Wilms tumors.
Kehl T, Schneider L, Kattler K, Stöckel D, Wegert J, Gerstner N, Ludwig N, Distler U, Tenzer S, Gessler M, Walter J, Keller A, Graf N, Meese E, Lenhof HP
Wilms tumors are the most common type of pediatric kidney tumors. While the overall prognosis for patients is favorable, especially tumors that exhibit a blastemal subtype after preoperative chemotherapy have a poor prognosis. For an improved risk assessment and therapy stratification, it is essential to identify th...

Extensive Recovery of Embryonic Enhancer and Gene Memory Stored in Hypomethylated Enhancer DNA.
Jadhav U, Cavazza A, Banerjee KK, Xie H, O'Neill NK, Saenz-Vash V, Herbert Z, Madha S, Orkin SH, Zhai H, Shivdasani RA
Developing and adult tissues use different cis-regulatory elements. Although DNA at some decommissioned embryonic enhancers is hypomethylated in adult cells, it is unknown whether this putative epigenetic memory is complete and recoverable. We find that, in adult mouse cells, hypomethylated CpG dinucleotides preserv...

The epigenetic basis for the impaired ability of adult murine retinal pigment epithelium cells to regenerate retinal tissue.
Dvoriantchikova G, Seemungal RJ, Ivanov D
The epigenetic plasticity of amphibian retinal pigment epithelium (RPE) allows them to regenerate the entire retina, a trait known to be absent in mammals. In this study, we investigated the epigenetic plasticity of adult murine RPE to identify possible mechanisms that prevent mammalian RPE from regenerating retinal...

Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes.
Yi G, Wierenga ATJ, Petraglia F, Narang P, Janssen-Megens EM, Mandoli A, Merkel A, Berentsen K, Kim B, Matarese F, Singh AA, Habibi E, Prange KHM, Mulder AB, Jansen JH, Clarke L, Heath S, van der Reijden BA, Flicek P, Yaspo ML, Gut I, Bock C, Schuringa JJ
Global investigation of histone marks in acute myeloid leukemia (AML) remains limited. Analyses of 38 AML samples through integrated transcriptional and chromatin mark analysis exposes 2 major subtypes. One subtype is dominated by patients with NPM1 mutations or MLL-fusion genes, shows activation of the regulat...

Comprehensive Analysis of Chromatin States in Atypical Teratoid/Rhabdoid Tumor Identifies Diverging Roles for SWI/SNF and Polycomb in Gene Regulation.
Erkek S, Johann PD, Finetti MA, Drosos Y, Chou HC, Zapatka M, Sturm D, Jones DTW, Korshunov A, Rhyzova M, Wolf S, Mallm JP, Beck K, Witt O, Kulozik AE, Frühwald MC, Northcott PA, Korbel JO, Lichter P, Eils R, Gajjar A, Roberts CWM, Williamson D, Hasselbla
Biallelic inactivation of SMARCB1, encoding a member of the SWI/SNF chromatin remodeling complex, is the hallmark genetic aberration of atypical teratoid rhabdoid tumors (ATRT). Here, we report how loss of SMARCB1 affects the epigenome in these tumors. Using chromatin immunoprecipitation sequencing (ChIP-seq) on pri...

The Wnt-Driven Mll1 Epigenome Regulates Salivary Gland and Head and Neck Cancer.
Zhu Q, Fang L, Heuberger J, Kranz A, Schipper J, Scheckenbach K, Vidal RO, Sunaga-Franze DY, Müller M, Wulf-Goldenberg A, Sauer S, Birchmeier W
We identified a regulatory system that acts downstream of Wnt/β-catenin signaling in salivary gland and head and neck carcinomas. We show in a mouse tumor model of K14-Cre-induced Wnt/β-catenin gain-of-function and Bmpr1a loss-of-function mutations that tumor-propagating cells exhibit increased Mll1 activi...

Gamma radiation induces locus specific changes to histone modification enrichment in zebrafish and Atlantic salmon.
Lindeman LC, Kamstra JH, Ballangby J, Hurem S, Martín LM, Brede DA, Teien HC, Oughton DH, Salbu B, Lyche JL, Aleström P
Ionizing radiation is a recognized genotoxic agent, however, little is known about the role of the functional form of DNA in these processes. Post translational modifications on histone proteins control the organization of chromatin and hence control transcriptional responses that ultimately affect the phenotype. Th...

Mutant p63 Affects Epidermal Cell Identity through Rewiring the Enhancer Landscape.
Qu J, Tanis SEJ, Smits JPH, Kouwenhoven EN, Oti M, van den Bogaard EH, Logie C, Stunnenberg HG, van Bokhoven H, Mulder KW, Zhou H
Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Mutations in the p63 DNA-binding domain are associated with ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome. However, the underlying molecular mechanism of these mutations remains unclear....

Promoter bivalency favors an open chromatin architecture in embryonic stem cells.
Mas G, Blanco E, Ballaré C, Sansó M, Spill YG, Hu D, Aoi Y, Le Dily F, Shilatifard A, Marti-Renom MA, Di Croce L
In embryonic stem cells (ESCs), developmental gene promoters are characterized by their bivalent chromatin state, with simultaneous modification by MLL2 and Polycomb complexes. Although essential for embryogenesis, bivalency is functionally not well understood. Here, we show that MLL2 plays a central role in ESC gen...

PRC2 targeting is a therapeutic strategy for EZ score defined high-risk multiple myeloma patients and overcome resistance to IMiDs.
Herviou L, Kassambara A, Boireau S, Robert N, Requirand G, Müller-Tidow C, Vincent L, Seckinger A, Goldschmidt H, Cartron G, Hose D, Cavalli G, Moreaux J
BACKGROUND: Multiple myeloma (MM) is a malignant plasma cell disease with a poor survival, characterized by the accumulation of myeloma cells (MMCs) within the bone marrow. Epigenetic modifications in MM are associated not only with cancer development and progression, but also with drug resistance. METHODS: We ident...

The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity
Domínguez-Andrés Jorge, Novakovic Boris, Li Yang, Scicluna Brendon P., Gresnigt Mark S., Arts Rob J.W., Oosting Marije, Moorlag Simone J.C.F.M., Groh Laszlo A., Zwaag Jelle, Koch Rebecca M., ter Horst Rob, Joosten Leo A.B., Wijmenga Cisca, Michelucci Ales
Sepsis involves simultaneous hyperactivation of the immune system and immune paralysis, leading to both organ dysfunction and increased susceptibility to secondary infections. Acute activation of myeloid cells induced itaconate synthesis, which subsequently mediated innate immune tolerance in human monocytes. In con...

Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes.
Ferguson GB, Van Handel B, Bay M, Fiziev P, Org T, Lee S, Shkhyan R, Banks NW, Scheinberg M, Wu L, Saitta B, Elphingstone J, Larson AN, Riester SM, Pyle AD, Bernthal NM, Mikkola HK, Ernst J, van Wijnen AJ, Bonaguidi M, Evseenko D
Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application of cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differen...

RNA Sequencing and Pathway Analysis Identify Important Pathways Involved in Hypertrichosis and Intellectual Disability in Patients with Wiedemann-Steiner Syndrome.
Mietton L, Lebrun N, Giurgea I, Goldenberg A, Saintpierre B, Hamroune J, Afenjar A, Billuart P, Bienvenu T
A growing number of histone modifiers are involved in human neurodevelopmental disorders, suggesting that proper regulation of chromatin state is essential for the development of the central nervous system. Among them, heterozygous de novo variants in KMT2A, a gene coding for histone methyltransferase, have been ass...

Atopic asthma after rhinovirus-induced wheezing is associated with DNA methylation change in the SMAD3 gene promoter.
Lund RJ, Osmala M, Malonzo M, Lukkarinen M, Leino A, Salmi J, Vuorikoski S, Turunen R, Vuorinen T, Akdis C, Lähdesmäki H, Lahesmaa R, Jartti T
Children with rhinovirus-induced severe early wheezing have an increased risk of developing asthma later in life. The exact molecular mechanisms for this association are still mostly unknown. To identify potential changes in the transcriptional and epigenetic regulation in rhinovirus-associated atopic or nonatopic a...

Integrative multi-omics analysis of intestinal organoid differentiation
Rik GH Lindeboom, Lisa van Voorthuijsen1, Koen C Oost, Maria J Rodríguez-Colman, Maria V Luna-Velez, Cristina Furlan, Floriane Baraille, Pascal WTC Jansen, Agnès Ribeiro, Boudewijn MT Burgering, Hugo J Snippert, & Michiel Vermeulen
Intestinal organoids accurately recapitulate epithelial homeostasis in vivo, thereby representing a powerful in vitro system to investigate lineage specification and cellular differentiation. Here, we applied a multi-omics framework on stem cell-enriched and stem cell-depleted mouse intestinal organoids to obtain a ...

The Polycomb-Dependent Epigenome Controls β Cell Dysfunction, Dedifferentiation, and Diabetes.
Lu TT, Heyne S, Dror E, Casas E, Leonhardt L, Boenke T, Yang CH, Sagar , Arrigoni L, Dalgaard K, Teperino R, Enders L, Selvaraj M, Ruf M, Raja SJ, Xie H, Boenisch U, Orkin SH, Lynn FC, Hoffman BG, Grün D, Vavouri T, Lempradl AM, Pospisilik JA
To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single-cell transcriptomics to mine for evidence of chromatin dysregulation in type 2 diabetes. We find two chromatin-state signat...

The reference epigenome and regulatory chromatin landscape of chronic lymphocytic leukemia
Beekman R. et al.
Chronic lymphocytic leukemia (CLL) is a frequent hematological neoplasm in which underlying epigenetic alterations are only partially understood. Here, we analyze the reference epigenome of seven primary CLLs and the regulatory chromatin landscape of 107 primary cases in the context of normal B cell differentiation....

Increased H3K9 methylation and impaired expression of Protocadherins are associated with the cognitive dysfunctions of the Kleefstra syndrome.
Iacono G, Dubos A, Méziane H, Benevento M, Habibi E, Mandoli A, Riet F, Selloum M, Feil R, Zhou H, Kleefstra T, Kasri NN, van Bokhoven H, Herault Y, Stunnenberg HG
Kleefstra syndrome, a disease with intellectual disability, autism spectrum disorders and other developmental defects is caused in humans by haploinsufficiency of EHMT1. Although EHMT1 and its paralog EHMT2 were shown to be histone methyltransferases responsible for deposition of the di-methylated H3K9 (H3K9me2), th...

Pro-inflammatory cytokines activate hypoxia-inducible factor 3α via epigenetic changes in mesenchymal stromal/stem cells.
Cuomo F, Coppola A, Botti C, Maione C, Forte A, Scisciola L, Liguori G, Caiafa I, Ursini MV, Galderisi U, Cipollaro M, Altucci L, Cobellis G
Human mesenchymal stromal/stem cells (hMSCs) emerged as a promising therapeutic tool for ischemic disorders, due to their ability to regenerate damaged tissues, promote angiogenesis and reduce inflammation, leading to encouraging, but still limited results. The outcomes in clinical trials exploring hMSC therapy are ...

Epigenetic modifiers promote mitochondrial biogenesis and oxidative metabolism leading to enhanced differentiation of neuroprogenitor cells.
Martine Uittenbogaard, Christine A. Brantner, Anne Chiaramello1
During neural development, epigenetic modulation of chromatin acetylation is part of a dynamic, sequential and critical process to steer the fate of multipotent neural progenitors toward a specific lineage. Pan-HDAC inhibitors (HDCis) trigger neuronal differentiation by generating an "acetylation" signature and prom...

Micro-ribonucleic acid-155 is a direct target of Meis1, but not a driver in acute myeloid leukemia
Schneider E. et al.
Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute ...

Metabolic Induction of Trained Immunity through the Mevalonate Pathway.
Bekkering S, Arts RJW, Novakovic B, Kourtzelis I, van der Heijden CDCC, Li Y, Popa CD, Ter Horst R, van Tuijl J, Netea-Maier RT, van de Veerdonk FL, Chavakis T, Joosten LAB, van der Meer JWM, Stunnenberg H, Riksen NP, Netea MG
Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that activation of the cholesterol synthesis pathway, but not the synthesis of...

BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity.
Arts RJW, Moorlag SJCFM, Novakovic B, Li Y, Wang SY, Oosting M, Kumar V, Xavier RJ, Wijmenga C, Joosten LAB, Reusken CBEM, Benn CS, Aaby P, Koopmans MP, Stunnenberg HG, van Crevel R, Netea MG
The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide epigenetic repr...

Senescence-associated reprogramming promotes cancer stemness.
Milanovic M, Fan DNY, Belenki D, Däbritz JHM, Zhao Z, Yu Y, Dörr JR, Dimitrova L, Lenze D, Monteiro Barbosa IA, Mendoza-Parra MA, Kanashova T, Metzner M, Pardon K, Reimann M, Trumpp A, Dörken B, Zuber J, Gronemeyer H, Hummel M, Dittmar G, Lee S, Schmitt C
Cellular senescence is a stress-responsive cell-cycle arrest program that terminates the further expansion of (pre-)malignant cells. Key signalling components of the senescence machinery, such as p16, p21 and p53, as well as trimethylation of lysine 9 at histone H3 (H3K9me3), also operate as critical regulators of s...

MLL2 conveys transcription-independent H3K4 trimethylation in oocytes
Hanna C.W. et al.
Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyte provides an attractive system to investigate these mechanisms, becau...

The histone code reader Spin1 controls skeletal muscle development
Greschik H. et al.
While several studies correlated increased expression of the histone code reader Spin1 with tumor formation or growth, little is known about physiological functions of the protein. We generated Spin1M5 mice with ablation of Spin1 in myoblast precursors using the Myf5-Cre deleter strain. Most Spin1M5 mice die shortly...

In Situ Fixation Redefines Quiescence and Early Activation of Skeletal Muscle Stem Cells
Machado L. et al.
Summary State of the art techniques have been developed to isolate and analyze cells from various tissues, aiming to capture their in vivo state. However, the majority of cell isolation protocols involve lengthy mechanical and enzymatic dissociation steps followed by flow cytometry, exposing cells to stres...

GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency
Krendl C. et al.
To elucidate the molecular basis of BMP4-induced differentiation of human pluripotent stem cells (PSCs) toward progeny with trophectoderm characteristics, we produced transcriptome, epigenome H3K4me3, H3K27me3, and CpG methylation maps of trophoblast progenitors, purified using the surface marker APA. We combined th...

The mixed lineage leukemia 4 (MLL4) methyltransferase complex is involved in transforming growth factor beta (TGF-β)-activated gene transcription.
Baas R. et al.
Sma and Mad related (SMAD)-mediated Transforming Growth Factor β (TGF-β) and Bone Morphogenetic Protein (BMP) signaling is required for various cellular processes. The activated heterotrimeric SMAD protein complexes associate with nuclear proteins such as the histone acetyltransferases p300, PCAF and the M...

Predicting stimulation-dependent enhancer-promoter interactions from ChIP-Seq time course data
Dzida T. et al.
We have developed a machine learning approach to predict stimulation-dependent enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ERα), RNA polymerase (Pol II) and histone marks H2AZ and H3K4me3 were measured over time us...

Genetic Predisposition to Multiple Myeloma at 5q15 Is Mediated by an ELL2 Enhancer Polymorphism
Li N. et al.
Multiple myeloma (MM) is a malignancy of plasma cells. Genome-wide association studies have shown that variation at 5q15 influences MM risk. Here, we have sought to decipher the causal variant at 5q15 and the mechanism by which it influences tumorigenesis. We show that rs6877329 G > C resides in a predicted ...

Chromosome contacts in activated T cells identify autoimmune disease candidate genes
Burren OS et al.
BACKGROUND: Autoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4+ T cells. Linking such regulatory regions to gene promoters in disease-relevant cell contexts facilitates identification of candidate disease genes. RESULTS: Within 4 h, act...

A lncRNA fine tunes the dynamics of a cell state transition involving Lin28, let-7 and de novo DNA methylation
Li M.A. et al.
Execution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific ...

Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation
Pünzeler S. et al.
Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine the comprehensive interactome of H2A.Z and identify PWWP2A as a novel...

Mouse models of 17q21.31 microdeletion and microduplication syndromes highlight the importance of Kansl1 for cognition
Arbogast T. et al.
Koolen-de Vries syndrome (KdVS) is a multi-system disorder characterized by intellectual disability, friendly behavior, and congenital malformations. The syndrome is caused either by microdeletions in the 17q21.31 chromosomal region or by variants in the KANSL1 gene. The reciprocal 17q21.31 microduplication syndrome...

Platelet function is modified by common sequence variation in megakaryocyte super enhancers
Petersen R. et al.
Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quantitative traits usi...

Chromatin Immunoprecipitation (ChIP) in Mouse T-cell Lines
Giaimo B.D. et al.
Signaling pathways regulate gene expression programs via the modulation of the chromatin structure at different levels, such as by post-translational modifications (PTMs) of histone tails, the exchange of canonical histones with histone variants, and nucleosome eviction. Such regulation requires the binding of signa...

DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats
Brocks D. et al.
Several mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known about their genome-wide transcriptional and epigenomic consequences. By mapping global transcription start site (TSS) an...

Evolutionary re-wiring of p63 and the epigenomic regulatory landscape in keratinocytes and its potential implications on species-specific gene expression and phenotypes
Sethi I. et al.
Although epidermal keratinocyte development and differentiation proceeds in similar fashion between humans and mice, evolutionary pressures have also wrought significant species-specific physiological differences. These differences between species could arise in part, by the rewiring of regulatory network due to cha...

RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA(+) and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells.
Lund R.J. et al.
POLR3G is expressed at high levels in human pluripotent stem cells (hPSCs) and is required for maintenance of stem cell state through mechanisms not known in detail. To explore how POLR3G regulates stem cell state, we carried out deep-sequencing analysis of polyA+ and smallRNA transcriptomes present in hPSCs an...

The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis.
Aldiri I. et al.
In the developing retina, multipotent neural progenitors undergo unidirectional differentiation in a precise spatiotemporal order. Here we profile the epigenetic and transcriptional changes that occur during retinogenesis in mice and humans. Although some progenitor genes and cell cycle genes were epigenetically sil...

Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions
Frank-Bertoncelj M, Trenkmann M, Klein K, Karouzakis E, Rehrauer H, Bratus A, Kolling C, Armaka M, Filer A, Michel BA, Gay RE, Buckley CD, Kollias G, Gay S, Ospelt C
A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synov...

Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells
Tumber A. et al.
Methylation of lysine residues on histone tail is a dynamic epigenetic modification that plays a key role in chromatin structure and gene regulation. Members of the KDM5 (also known as JARID1) sub-family are 2-oxoglutarate (2-OG) and Fe2+-dependent oxygenases acting as histone 3 lysine 4 trimethyl (H3K4me3) demethyl...

Decoupling of DNA methylation and activity of intergenic LINE-1 promoters in colorectal cancer
Vafadar-Isfahani N. et al.
Hypomethylation of LINE-1 repeats in cancer has been proposed as the main mechanism behind their activation; this assumption, however, was based on findings from early studies that were biased toward young and transpositionally active elements. Here, we investigate the relationship between methylation of 2 intergeni...

Assessing histone demethylase inhibitors in cells: lessons learned
Hatch S.B. et al.
Background Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The first KDM inhibitors for KDM1 have entered clinical trials, and efforts are ongoing to develop...

RNF40 regulates gene expression in an epigenetic context-dependent manner
Xie W. et al.
BACKGROUND: Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlat...

Menin regulates Inhbb expression through an Akt/Ezh2-mediated H3K27 histone modification
Gherardi S. et al.
Although Men1 is a well-known tumour suppressor gene, little is known about the functions of Menin, the protein it encodes for. Since few years, numerous publications support a major role of Menin in the control of epigenetics gene regulation. While Menin interaction with MLL complex favours transcriptional activati...

A novel DLX3-PKC integrated signaling network drives keratinocyte differentiation
Palazzo E. et al.
Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regul...

Muscle catabolic capacities and global hepatic epigenome are modified in juvenile rainbow trout fed different vitamin levels at first feeding
Panserat S. et al.
Based on the concept of nutritional programming in mammals, we tested whether a short term hyper or hypo vitamin stimulus during first-feeding could induce long-lasting changes in nutrient metabolism in rainbow trout. Trout alevins received during the 4 first weeks of exogenous feeding a diet either without suppleme...

DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma
Sheffield N.C. et al.
Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genetically homogeneous cancers. We performed genome-scale DNA methylation ...

MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct enhancer repertoire and target the RUNX1 program in 11q23 acute myeloid leukemia.
Prange KH et al.
In 11q23 leukemias, the N-terminal part of the mixed lineage leukemia (MLL) gene is fused to >60 different partner genes. In order to define a core set of MLL rearranged targets, we investigated the genome-wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and associated epigenetic signatures in acute myeloi...

Arabidopsis SWI/SNF chromatin remodeling complex binds both promoters and terminators to regulate gene expression
Archacki R. et al.
ATP-dependent chromatin remodeling complexes are important regulators of gene expression in Eukaryotes. In plants, SWI/SNF-type complexes have been shown critical for transcriptional control of key developmental processes, growth and stress responses. To gain insight into mechanisms underlying these roles, we perfor...

Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals
Schwörer S. et al.
The functionality of stem cells declines during ageing, and this decline contributes to ageing-associated impairments in tissue regeneration and function. Alterations in developmental pathways have been associated with declines in stem-cell function during ageing, but the nature of this process remains poorly unders...

Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity
Arts R.J. et al.
Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol s...

Immunometabolic Pathways in BCG-Induced Trained Immunity
Arts R.J. et al.
The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity. Here, we show that BC...

TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells
de la Rica L. et al.
BACKGROUND: Ten-eleven translocation (TET) enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable elements (TEs), which make up nearly half of the mouse and human genomes....

β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance
Novakovic B. et al.
Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as lipopolysaccharide (LPS). We apply an integrated epigenomic approach to characterize the molecular events involved in LPS-induced to...

EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells
Beringer M. et al.
The cellular plasticity of pluripotent stem cells is thought to be sustained by genomic regions that display both active and repressive chromatin properties. These regions exhibit low levels of gene expression, yet the mechanisms controlling these levels remain unknown. Here, we describe Elongin BC as a binding fact...

The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs
Mandoli A. et al.
The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels of histone acetyl...

Iterative Fragmentation Improves the Detection of ChIP-seq Peaks for Inactive Histone Marks
Laczik M. et al.
As chromatin immunoprecipitation (ChIP) sequencing is becoming the dominant technique for studying chromatin modifications, new protocols surface to improve the method. Bioinformatics is also essential to analyze and understand the results, and precise analysis helps us to identify the effects of protocol optimizati...

Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition
Sciacovelli M et al.
Mutations of the tricarboxylic acid cycle enzyme fumarate hydratase cause hereditary leiomyomatosis and renal cell cancer1. Fumarate hydratase-deficient renal cancers are highly aggressive and metastasize even when small, leading to a very poor clinical outcome2. Fumarate, a small molecule metabolite that accumulate...

reChIP-seq reveals widespread bivalency of H3K4me3 and H3K27me3 in CD4(+) memory T cells
Kinkley S et al.
The combinatorial action of co-localizing chromatin modifications and regulators determines chromatin structure and function. However, identifying co-localizing chromatin features in a high-throughput manner remains a technical challenge. Here we describe a novel reChIP-seq approach and tailored bioinformatic analys...

Phenotypic Plasticity through Transcriptional Regulation of the Evolutionary Hotspot Gene tan in Drosophila melanogaster
Gibert JM et al.
Phenotypic plasticity is the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions. Phenotypic plasticity can be adaptive. Furthermore, it is thought to facilitate evolution. Although phenotypic plasticity is a widespread phenomenon, its molecular mechanisms are...

MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis
Wang W et al.
DNA double strand break (DSB) repair is critical for generation of B-cell receptors, which are pre-requisite for B-cell progenitor survival. However, the transcription factors that promote DSB repair in B cells are not known. Here we show that MEF2C enhances the expression of DNA repair and recombination factors in ...

Toxoplasma gondii TgIST co-opts host chromatin repressors dampening STAT1-dependent gene regulation and IFN-γ-mediated host defenses
Gay G et al.
An early hallmark of Toxoplasma gondii infection is the rapid control of the parasite population by a potent multifaceted innate immune response that engages resident and homing immune cells along with pro- and counter-inflammatory cytokines. In this context, IFN-γ activates a variety of T. gondii-targeting ac...

Epigenetic dynamics of monocyte-to-macrophage differentiation
Wallner S et al.
BACKGROUND: Monocyte-to-macrophage differentiation involves major biochemical and structural changes. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete transcriptome and epigenome of human monocytes that were differentiated in...

Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis
Rinaldi L et al.
The genome-wide localization and function of endogenous Dnmt3a and Dnmt3b in adult stem cells are unknown. Here, we show that in human epidermal stem cells, the two proteins bind in a histone H3K36me3-dependent manner to the most active enhancers and are required to produce their associated enhancer RNAs. Both prote...

PAFAH1B1 and the lncRNA NONHSAT073641 maintain an angiogenic phenotype in human endothelial cells
Josipovic I at al.
AIM: Platelet-activating factor acetyl hydrolase 1B1 (PAFAH1B1, also known as Lis1) is a protein essentially involved in neurogenesis and mostly studied in the nervous system. As we observed a significant expression of PAFAH1B1 in the vascular system, we hypothesized that PAFAH1B1 is important during angiogenesis o...

Chromatin immunoprecipitation from fixed clinical tissues reveals tumor-specific enhancer profiles.
Cejas P et al.
Extensive cross-linking introduced during routine tissue fixation of clinical pathology specimens severely hampers chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) analysis from archived tissue samples. This limits the ability to study the epigenomes of valuable, clinically annotated t...

Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time
Feichtinger J, Hernández I, Fischer C, Hanscho M, Auer N, Hackl M, Jadhav V, Baumann M, Krempl PM, Schmidl C, Farlik M, Schuster M, Merkel A, Sommer A, Heath S, Rico D, Bock C, Thallinger GG, Borth N
The most striking characteristic of CHO cells is their adaptability, which enables efficient production of proteins as well as growth under a variety of culture conditions, but also results in genomic and phenotypic instability. To investigate the relative contribution of genomic and epigenetic modifications towards...

GATA-1 Inhibits PU.1 Gene via DNA and Histone H3K9 Methylation of Its Distal Enhancer in Erythroleukemia
Burda P, Vargova J, Curik N, Salek C, Papadopoulos GL, Strouboulis J, Stopka T
GATA-1 and PU.1 are two important hematopoietic transcription factors that mutually inhibit each other in progenitor cells to guide entrance into the erythroid or myeloid lineage, respectively. PU.1 controls its own expression during myelopoiesis by binding to the distal URE enhancer, whose deletion leads to acute m...

Role of Annexin gene and its regulation during zebrafish caudal fin regeneration
Saxena S, Purushothaman S, Meghah V, Bhatti B, Poruri A, Meena Lakshmi MG, Sarath Babu N, Murthy CL, Mandal KK, Kumar A, Idris MM
The molecular mechanism of epimorphic regeneration is elusive due to its complexity and limitation in mammals. Epigenetic regulatory mechanisms play a crucial role in development and regeneration. This investigation attempted to reveal the role of epigenetic regulatory mechanisms, such as histone H3 and H4 lysine ac...

Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis
Weigel C. et al.
Radiotherapy is a fundamental part of cancer treatment but its use is limited by the onset of late adverse effects in the normal tissue, especially radiation-induced fibrosis. Since the molecular causes for fibrosis are largely unknown, we analyse if epigenetic regulation might explain inter-individual differences i...

Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development.
Yuan S et al.
Although it is believed that mammalian sperm carry small noncoding RNAs (sncRNAs) into oocytes during fertilization, it remains unknown whether these sperm-borne sncRNAs truly have any function during fertilization and preimplantation embryonic development. Germline-specific Dicer and Drosha conditional knockout (cK...

MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199
Benito JM et al.
Targeted therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of current research. Mixed Lineage Leukemia (MLL) mutations such as the t(4;11) translocation cause aggressive leukemias that are refractory to conventional treatment. The t(4;11) translocation produces an M...

Standardizing chromatin research: a simple and universal method for ChIP-seq
Laura Arrigoni, Andreas S. Richter, Emily Betancourt, Kerstin Bruder, Sarah Diehl, Thomas Manke and Ulrike Bönisch
Here we demonstrate that harmonization of ChIP-seq workflows across cell types and conditions is possible when obtaining chromatin from properly isolated nuclei. We established an ultrasound-based nuclei extraction method (Nuclei Extraction by Sonication) that is highly effective across various organisms, cell ...

Dynamic changes in histone modifications precede de novo DNA methylation in oocytes
Stewart KR et al.
Erasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation establishment remain poorly understood, but a number of post-translational modifications of histones are implicated in...

Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma
Aldiri I et al.
Retinal development requires precise temporal and spatial coordination of cell cycle exit, cell fate specification, cell migration and differentiation. When this process is disrupted, retinoblastoma, a developmental tumor of the retina, can form. Epigenetic modulators are central to precisely coordinating developmen...

Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization
Kuznetsova T et al.
BACKGROUND: The impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from remodeling of higher order chromatin architecture by activated transcrip...

Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells
Rønningen T, Shah A, Reiner AH, Collas P, Moskaug JØ
Cellular metabolism confers wide-spread epigenetic modifications required for regulation of transcriptional networks that determine cellular states. Mesenchymal stromal cells are responsive to metabolic cues including circulating glucose levels and modulate inflammatory responses. We show here that long term exposur...

The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth
Palazzo E et al.
Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epidermal hyperplasia and squamous tumorigenesis. By integrating genetic and t...

VEGF-mediated cell survival in non-small-cell lung cancer: implications for epigenetic targeting of VEGF receptors as a therapeutic approach
Barr MP et al.
AIMS: To evaluate the potential therapeutic utility of histone deacetylase inhibitors (HDACi) in targeting VEGF receptors in non-small-cell lung cancer. MATERIALS & METHODS: Non-small-cell lung cancer cells were screened for the VEGF receptors at the mRNA and protein levels, while cellular responses to vari...

Chromatin assembly factor CAF-1 represses priming of plant defence response genes
Mozgova I et al.
Plants have evolved efficient defence systems against pathogens that often rely on specific transcriptional responses. Priming is part of the defence syndrome, by establishing a hypersensitive state of defence genes such as after a first encounter with a pathogen. Because activation of defence responses has a fitnes...

Spatiotemporal control of estrogen-responsive transcription in ERα-positive breast cancer cells.
P-Y Hsu, H-K Hsu, T-H Hsiao, Z Ye, E Wang, A L Profit, I Jatoi, Y Chen, N B Kirma, V X Jin, Z D Sharp and T H-M Huang
Recruitment of transcription machinery to target promoters for aberrant gene expression has been well studied, but underlying control directed by distant-acting enhancers remains unclear in cancer development. Our previous study demonstrated that distant estrogen response elements (DEREs) located on chromosome 20q13...

Non-coding recurrent mutations in chronic lymphocytic leukaemia.
Xose S. Puente, Silvia Beà, Rafael Valdés-Mas, Neus Villamor, Jesús Gutiérrez-Abril et al.
Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder....

Allele-specific binding of ZFP57 in the epigenetic regulation of imprinted and non-imprinted monoallelic expression
Strogantsev R, Krueger F, Yamazawa K, Shi H, Gould P, Goldman-Roberts M, McEwen K, Sun B, Pedersen R, Ferguson-Smith AC
BACKGROUND: Selective maintenance of genomic epigenetic imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary for maintaining the DNA methylation memory at multiple imprinting contr...

Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency.
Chen H, Aksoy I, Gonnot F, Osteil P, Aubry M, Hamela C, Rognard C, Hochard A, Voisin S, Fontaine E, Mure M, Afanassieff M, Cleroux E, Guibert S, Chen J, Vallot C, Acloque H, Genthon C, Donnadieu C, De Vos J, Sanlaville D, Guérin JF, Weber M, Stanton LW, R
Leukemia inhibitory factor (LIF)/STAT3 signalling is a hallmark of naive pluripotency in rodent pluripotent stem cells (PSCs), whereas fibroblast growth factor (FGF)-2 and activin/nodal signalling is required to sustain self-renewal of human PSCs in a condition referred to as the primed state. It is unknown why LIF/...

Opposite expression of CYP51A1 and its natural antisense transcript AluCYP51A1 in adenovirus type 37 infected retinal pigmented epithelial cells.
Pickl JM, Kamel W, Ciftci S, Punga T, Akusjärvi G
Cytochrome P450 family member CYP51A1 is a key enzyme in cholesterol biosynthesis whose deregulation is implicated in numerous diseases, including retinal degeneration. Here we describe that HAdV-37 infection leads to downregulation of CYP51A1 expression and overexpression of its antisense non-coding Alu element (Al...

A cohesin-OCT4 complex mediates Sox enhancers to prime an early embryonic lineage.
Abboud N, Moore-Morris T, Hiriart E, Yang H, Bezerra H, Gualazzi MG, Stefanovic S, Guénantin AC, Evans SM, Pucéat M
Short- and long-scales intra- and inter-chromosomal interactions are linked to gene transcription, but the molecular events underlying these structures and how they affect cell fate decision during embryonic development are poorly understood. One of the first embryonic cell fate decisions (that is, mesendoderm deter...

Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1.
Tomazou EM, Sheffield NC, Schmidl C, Schuster M, Schönegger A, Datlinger P, Kubicek S, Bock C, Kovar H
Transcription factor fusion proteins can transform cells by inducing global changes of the transcriptome, often creating a state of oncogene addiction. Here, we investigate the role of epigenetic mechanisms in this process, focusing on Ewing sarcoma cells that are dependent on the EWS-FLI1 fusion protein. We establi...

Embryonic stem cell differentiation requires full length Chd1.
Piatti P, Lim CY, Nat R, Villunger A, Geley S, Shue YT, Soratroi C, Moser M, Lusser A
The modulation of chromatin dynamics by ATP-dependent chromatin remodeling factors has been recognized as an important mechanism to regulate the balancing of self-renewal and pluripotency in embryonic stem cells (ESCs). Here we have studied the effects of a partial deletion of the gene encoding the chromatin remodel...

A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus.
Lazorthes S, Vallot C, Briois S, Aguirrebengoa M, Thuret JY, Laurent GS, Rougeulle C, Kapranov P, Mann C, Trouche D, Nicolas E
Non-coding RNAs (ncRNAs) play major roles in proper chromatin organization and function. Senescence, a strong anti-proliferative process and a major anticancer barrier, is associated with dramatic chromatin reorganization in heterochromatin foci. Here we analyze strand-specific transcriptome changes during oncogene-...

Cryosectioning the intestinal crypt-villus axis: an ex vivo method to study the dynamics of epigenetic modifications from stem cells to differentiated cells
Vincent A, Kazmierczak C, Duchêne B, Jonckheere N, Leteurtre E, Van Seuningen I
The intestinal epithelium is a particularly attractive biological adult model to study epigenetic mechanisms driving adult stem cell renewal and cell differentiation. Since epigenetic modifications are dynamic, we have developed an original ex vivo approach to study the expression and epigenetic profiles of key gene...

Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs.
Adoue V, Schiavi A, Light N, Almlöf JC, Lundmark P, Ge B, Kwan T, Caron M, Rönnblom L, Wang C, Chen SH, Goodall AH, Cambien F, Deloukas P, Ouwehand WH, Syvänen AC, Pastinen T
Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-...

Obesity increases histone H3 lysine 9 and 18 acetylation at Tnfa and Ccl2 genes in mouse liver
Mikula M, Majewska A, Ledwon JK, Dzwonek A, Ostrowski J
Obesity contributes to the development of non‑alcoholic fatty liver disease (NAFLD), which is characterized by the upregulated expression of two key inflammatory mediators: tumor necrosis factor (Tnfa) and monocyte chemotactic protein 1 (Mcp1; also known as Ccl2). However, the chromatin make-up at these genes in the...

The specific alteration of histone methylation profiles by DZNep during early zebrafish development.
Ostrup O, Reiner AH, Aleström P, Collas P
Early embryo development constitutes a unique opportunity to study acquisition of epigenetic marks, including histone methylation. This study investigates the in vivo function and specificity of 3-deazaneplanocin A (DZNep), a promising anti-cancer drug that targets polycomb complex genes. One- to two-cell stage embr...

Interrogation of allelic chromatin states in human cells by high-density ChIP-genotyping.
Light N, Adoue V, Ge B, Chen SH, Kwan T, Pastinen T
Allele-specific (AS) assessment of chromatin has the potential to elucidate specific cis-regulatory mechanisms, which are predicted to underlie the majority of the known genetic associations to complex disease. However, development of chromatin landscapes at allelic resolution has been challenging since sites of var...

Differences among brain tumor stem cell types and fetal neural stem cells in focal regions of histone modifications and DNA methylation, broad regions of modifications, and bivalent promoters.
Yoo S, Bieda MC
BACKGROUND: Aberrational epigenetic marks are believed to play a major role in establishing the abnormal features of cancer cells. Rational use and development of drugs aimed at epigenetic processes requires an understanding of the range, extent, and roles of epigenetic reprogramming in cancer cells. Using ChIP-chip...

Long Noncoding RNA TARID Directs Demethylation and Activation of the Tumor Suppressor TCF21 via GADD45A.
Arab K, Park YJ, Lindroth AM, Schäfer A, Oakes C, Weichenhan D, Lukanova A, Lundin E, Risch A, Meister M, Dienemann H, Dyckhoff G, Herold-Mende C, Grummt I, Niehrs C, Plass C
DNA methylation is a dynamic and reversible process that governs gene expression during development and disease. Several examples of active DNA demethylation have been documented, involving genome-wide and gene-specific DNA demethylation. How demethylating enzymes are targeted to specific genomic loci remains largel...

Identification of a large protein network involved in epigenetic transmission in replicating DNA of embryonic stem cells.
Aranda S, Rutishauser D, Ernfors P
Pluripotency of embryonic stem cells (ESCs) is maintained by transcriptional activities and chromatin modifying complexes highly organized within the chromatin. Although much effort has been focused on identifying genome-binding sites, little is known on their dynamic association with chromatin across cell divisions...

Seminoma and embryonal carcinoma footprints identified by analysis of integrated genome-wide epigenetic and expression profiles of germ cell cancer cell lines.
van der Zwan YG, Rijlaarsdam MA, Rossello FJ, Notini AJ, de Boer S, Watkins DN, Gillis AJ, Dorssers LC, White SJ, Looijenga LH
BACKGROUND: Originating from Primordial Germ Cells/gonocytes and developing via a precursor lesion called Carcinoma In Situ (CIS), Germ Cell Cancers (GCC) are the most common cancer in young men, subdivided in seminoma (SE) and non-seminoma (NS). During physiological germ cell formation/maturation, epigenetic proces...

Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer
Zecchini V, Madhu B, Russell R, Pértega-Gomes N, Warren A, Gaude E, Borlido J, Stark R, Ireland-Zecchini H, Rao R, Scott H, Boren J, Massie C, Asim M, Brindle K, Griffiths J, Frezza C, Neal DE, Mills IG
Tumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. Hypoxia-inducible factor 1A (HIF1A) is a major regulator of this process, but its activation under normoxic con...

Stage-specific control of early B cell development by the transcription factor Ikaros.
Schwickert TA, Tagoh H, Gültekin S, Dakic A, Axelsson E, Minnich M, Ebert A, Werner B, Roth M, Cimmino L, Dickins RA, Zuber J, Jaritz M, Busslinger M
The transcription factor Ikaros is an essential regulator of lymphopoiesis. Here we studied its B cell-specific function by conditional inactivation of the gene encoding Ikaros (Ikzf1) in pro-B cells. B cell development was arrested at an aberrant 'pro-B cell' stage characterized by increased cell adhesion and loss ...

A novel microscopy-based high-throughput screening method to identify proteins that regulate global histone modification levels.
Baas R, Lelieveld D, van Teeffelen H, Lijnzaad P, Castelijns B, van Schaik FM, Vermeulen M, Egan DA, Timmers HT, de Graaf P
Posttranslational modifications of histones play an important role in the regulation of gene expression and chromatin structure in eukaryotes. The balance between chromatin factors depositing (writers) and removing (erasers) histone marks regulates the steady-state levels of chromatin modifications. Here we describe...

Pan-histone demethylase inhibitors simultaneously targeting Jumonji C and lysine-specific demethylases display high anticancer activities.
Rotili D, Tomassi S, Conte M, Benedetti R, Tortorici M, Ciossani G, Valente S, Marrocco B, Labella D, Novellino E, Mattevi A, Altucci L, Tumber A, Yapp C, King ON, Hopkinson RJ, Kawamura A, Schofield CJ, Mai A
In prostate cancer, two different types of histone lysine demethylases (KDM), LSD1/KDM1 and JMJD2/KDM4, are coexpressed and colocalize with the androgen receptor. We designed and synthesized hybrid LSD1/JmjC or "pan-KDM" inhibitors 1-6 by coupling the skeleton of tranylcypromine 7, a known LSD1 inhibitor, with 4-car...

Interplay between active chromatin marks and RNA-directed DNA methylation in Arabidopsis thaliana.
Greenberg MV, Deleris A, Hale CJ, Liu A, Feng S, Jacobsen SE
DNA methylation is an epigenetic mark that is associated with transcriptional repression of transposable elements and protein-coding genes. Conversely, transcriptionally active regulatory regions are strongly correlated with histone 3 lysine 4 di- and trimethylation (H3K4m2/m3). We previously showed that Arabidopsis...

A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis.
Kollmann K, Heller G, Schneckenleithner C, Warsch W, Scheicher R, Ott RG, Schäfer M, Fajmann S, Schlederer M, Schiefer AI, Reichart U, Mayerhofer M, Hoeller C, Zöchbauer-Müller S, Kerjaschki D, Bock C, Kenner L, Hoefler G, Freissmuth M, Green AR, Moriggl
In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185(BCR-ABL+) B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16(INK4a) and the pro-angiogenic f...

Disease-Related Growth Factor and Embryonic Signaling Pathways Modulate an Enhancer of TCF21 Expression at the 6q23.2 Coronary Heart Disease Locus.
Miller CL, Anderson DR, Kundu RK, Raiesdana A, Nürnberg ST, Diaz R, Cheng K, Leeper NJ, Chen CH, Chang IS, Schadt EE, Hsiung CA, Assimes TL, Quertermous T
Coronary heart disease (CHD) is the leading cause of mortality in both developed and developing countries worldwide. Genome-wide association studies (GWAS) have now identified 46 independent susceptibility loci for CHD, however, the biological and disease-relevant mechanisms for these associations remain elusive. Th...

Bivalent chromatin marks developmental regulatory genes in the mouse embryonic germline in vivo.
Sachs M, Onodera C, Blaschke K, Ebata KT, Song JS, Ramalho-Santos M
Developmental regulatory genes have both activating (H3K4me3) and repressive (H3K27me3) histone modifications in embryonic stem cells (ESCs). This bivalent configuration is thought to maintain lineage commitment programs in a poised state. However, establishing physiological relevance has been complicated by the hig...

Integrative analysis of deep sequencing data identifies estrogen receptor early response genes and links ATAD3B to poor survival in breast cancer.
Ovaska K, Matarese F, Grote K, Charapitsa I, Cervera A, Liu C, Reid G, Seifert M, Stunnenberg HG, Hautaniemi S
Identification of responsive genes to an extra-cellular cue enables characterization of pathophysiologically crucial biological processes. Deep sequencing technologies provide a powerful means to identify responsive genes, which creates a need for computational methods able to analyze dynamic and multi-level deep se...

Expression of a large LINE-1-driven antisense RNA is linked to epigenetic silencing of the metastasis suppressor gene TFPI-2 in cancer.
Cruickshanks HA, Vafadar-Isfahani N, Dunican DS, Lee A, Sproul D, Lund JN, Meehan RR, Tufarelli C
LINE-1 retrotransposons are abundant repetitive elements of viral origin, which in normal cells are kept quiescent through epigenetic mechanisms. Activation of LINE-1 occurs frequently in cancer and can enable LINE-1 mobilization but also has retrotransposition-independent consequences. We previously reported that i...

The developmental epigenomics toolbox: ChIP-seq and MethylCap-seq profiling of early zebrafish embryos.
Bogdanović O, Fernández-Miñán A, Tena JJ, de la Calle-Mustienes E, Gómez-Skarmeta JL
Genome-wide profiling of DNA methylation and histone modifications answered many questions as to how the genes are regulated on a global scale and what their epigenetic makeup is. Yet, little is known about the function of these marks during early vertebrate embryogenesis. Here we provide detailed protocols for ChIP...

Genome-wide analysis of LXRα activation reveals new transcriptional networks in human atherosclerotic foam cells.
Feldmann R, Fischer C, Kodelja V, Behrens S, Haas S, Vingron M, Timmermann B, Geikowski A, Sauer S
Increased physiological levels of oxysterols are major risk factors for developing atherosclerosis and cardiovascular disease. Lipid-loaded macrophages, termed foam cells, are important during the early development of atherosclerotic plaques. To pursue the hypothesis that ligand-based modulation of the nuclear recep...

Regulation of transcription through acetylation of H3K122 on the lateral surface of the histone octamer.
Tropberger P, Pott S, Keller C, Kamieniarz-Gdula K, Caron M, Richter F, Li G, Mittler G, Liu ET, Bühler M, Margueron R, Schneider R
Histone modifications are key regulators of chromatin function. However, little is known to what extent histone modifications can directly impact on chromatin. Here, we address how a modification within the globular domain of histones regulates chromatin function. We demonstrate that H3K122ac can be sufficient to st...

Histone lysine trimethylation or acetylation can be modulated by phytoestrogen, estrogen or anti-HDAC in breast cancer cell lines.
Dagdemir A, Durif J, Ngollo M, Bignon YJ, Bernard-Gallon D
AIM: The isoflavones genistein, daidzein and equol (daidzein metabolite) have been reported to interact with epigenetic modifications, specifically hypermethylation of tumor suppressor genes. The objective of this study was to analyze and understand the mechanisms by which phytoestrogens act on chromatin in breast c...

Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA.
Fadloun A, Le Gras S, Jost B, Ziegler-Birling C, Takahashi H, Gorab E, Carninci P, Torres-Padilla ME
How a more plastic chromatin state is maintained and reversed during development is unknown. Heterochromatin-mediated silencing of repetitive elements occurs in differentiated cells. Here, we used repetitive elements, including retrotransposons, as model loci to address how and when heterochromatin forms during deve...

Ezh2 maintains a key phase of muscle satellite cell expansion but does not regulate terminal differentiation.
Woodhouse S, Pugazhendhi D, Brien P, Pell JM.
Tissue generation and repair requires a stepwise process of cell fate restriction to ensure adult stem cells differentiate in a timely and appropriate manner. A crucial role has been implicated for Polycomb-group (PcG) proteins and the H3K27me3 repressive histone mark, in coordinating the transcriptional programmes ...

Limitations and possibilities of low cell number ChIP-seq.
Gilfillan GD, Hughes T, Sheng Y, Hjorthaug HS, Straub T, Gervin K, Harris JR, Undlien DE, Lyle R
ABSTRACT: BACKGROUND: Chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq) offers high resolution, genome-wide analysis of DNA-protein interactions. However, current standard methods require abundant starting material in the range of 1--20 million cells per immunoprecipitation, and re...

Protein Group Modification and Synergy in the SUMO Pathway as Exemplified in DNA Repair.
Psakhye I, Jentsch S
Protein modification by SUMO affects a wide range of protein substrates. Surprisingly, although SUMO pathway mutants display strong phenotypes, the function of individual SUMO modifications is often enigmatic, and SUMOylation-defective mutants commonly lack notable phenotypes. Here, we use DNA double-strand break re...

IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer.
Baird AM, Leonard J, Naicker KM, Kilmartin L, O'Byrne KJ, Gray SG
BACKGROUND: IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC). METHODS: RT-PCR and chromatin immunopreciptiation (ChIP) were used to examine the levels, epigenetic regulation and effects of various dr...

New partners in regulation of gene expression: the enhancer of trithorax and polycomb corto interacts with methylated ribosomal protein l12 via its chromodomain.
Coléno-Costes A, Jang SM, de Vanssay A, Rougeot J, Bouceba T, Randsholt NB, Gibert JM, Le Crom S, Mouchel-Vielh E, Bloyer S, Peronnet F
Chromodomains are found in many regulators of chromatin structure, and most of them recognize methylated lysines on histones. Here, we investigate the role of the Drosophila melanogaster protein Corto's chromodomain. The Enhancer of Trithorax and Polycomb Corto is involved in both silencing and activation of gene ex...

Extensive promoter hypermethylation and hypomethylation is associated with aberrant microRNA expression in chronic lymphocytic leukemia.
Baer C, Claus R, Frenzel LP, Zucknick M, Park YJ, Gu L, Weichenhan D, Fischer M, Pallasch CP, Herpel E, Rehli M, Byrd JC, Wendtner CM, Plass C
Dysregulated microRNA (miRNA) expression contributes to the pathogenesis of hematopoietic malignancies, including chronic lymphocytic leukemia (CLL). However, an understanding of the mechanisms that cause aberrant miRNA transcriptional control is lacking. In this study, we comprehensively investigated the role and e...

The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells.
Karpiuk O, Najafova Z, Kramer F, Hennion M, Galonska C, König A, Snaidero N, Vogel T, Shchebet A, Begus-Nahrmann Y, Kassem M, Simons M, Shcherbata H, Beissbarth T, Johnsen SA
Extensive changes in posttranslational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly understood. We show tha...

Intronic RNAs mediate EZH2 regulation of epigenetic targets.
Guil S, Soler M, Portela A, Carrère J, Fonalleras E, Gómez A, Villanueva A, Esteller M
Epigenetic deregulation at a number of genomic loci is one of the hallmarks of cancer. A role for some RNA molecules in guiding repressive polycomb complex PRC2 to specific chromatin regions has been proposed. Here we use an in vivo cross-linking method to detect and identify direct PRC2-RNA interactions in human ca...

The transcriptional and epigenomic foundations of ground state pluripotency.
Marks H, Kalkan T, Menafra R, Denissov S, Jones K, Hofemeister H, Nichols J, Kranz A, Francis Stewart A, Smith A, Stunnenberg HG
Mouse embryonic stem (ES) cells grown in serum exhibit greater heterogeneity in morphology and expression of pluripotency factors than ES cells cultured in defined medium with inhibitors of two kinases (Mek and GSK3), a condition known as "2i" postulated to establish a naive ground state. We show that the transcript...

Control of ground-state pluripotency by allelic regulation of Nanog.
Miyanari Y, Torres-Padilla ME
Pluripotency is established through genome-wide reprogramming during mammalian pre-implantation development, resulting in the formation of the naive epiblast. Reprogramming involves both the resetting of epigenetic marks and the activation of pluripotent-cell-specific genes such as Nanog and Oct4 (also known as Pou5...

Prepatterning of developmental gene expression by modified histones before zygotic genome activation.
Lindeman LC, Andersen IS, Reiner AH, Li N, Aanes H, Østrup O, Winata C, Mathavan S, Müller F, Aleström P, Collas P
A hallmark of anamniote vertebrate development is a window of embryonic transcription-independent cell divisions before onset of zygotic genome activation (ZGA). Chromatin determinants of ZGA are unexplored; however, marking of developmental genes by modified histones in sperm suggests a predictive role of histone m...

IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF.
Baird AM, Gray SG, O'Byrne KJ
BACKGROUND: IL-20 is a pleiotrophic member of the IL-10 family and plays a role in skin biology and the development of haematopoietic cells. Recently, IL-20 has been demonstrated to have potential anti-angiogenic effects in non-small cell lung cancer (NSCLC) by down regulating COX-2. METHODS: The expression of IL-20...

H3.5 is a novel hominid-specific histone H3 variant that is specifically expressed in the seminiferous tubules of human testes.
Schenk R, Jenke A, Zilbauer M, Wirth S, Postberg J
The incorporation of histone variants into chromatin plays an important role for the establishment of particular chromatin states. Six human histone H3 variants are known to date, not counting CenH3 variants: H3.1, H3.2, H3.3 and the testis-specific H3.1t as well as the recently described variants H3.X and H3.Y. We ...

Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer
O'Byrne KJ, Baird AM, Kilmartin L, Leonard J, Sacevich C, Gray SG.
Due to their inherently hypoxic environment, cancer cells often resort to glycolysis, or the anaerobic breakdown of glucose to form ATP to provide for their energy needs, known as the Warburg effect. At the same time, overexpression of the insulin receptor in non-small cell lung cancer (NSCLC) is associated with an ...

Characterisation of genome-wide PLZF/RARA target genes.
Spicuglia S, Vincent-Fabert C, Benoukraf T, Tibéri G, Saurin AJ, Zacarias-Cabeza J, Grimwade D, Mills K, Calmels B, Bertucci F, Sieweke M, Ferrier P, Duprez E
The PLZF/RARA fusion protein generated by the t(11;17)(q23;q21) translocation in acute promyelocytic leukaemia (APL) is believed to act as an oncogenic transcriptional regulator recruiting epigenetic factors to genes important for its transforming potential. However, molecular mechanisms associated with PLZF/RARA-de...

Tiling histone H3 lysine 4 and 27 methylation in zebrafish using high-density microarrays.
Lindeman LC, Reiner AH, Mathavan S, Aleström P, Collas P
BACKGROUND: Uncovering epigenetic states by chromatin immunoprecipitation and microarray hybridization (ChIP-chip) has significantly contributed to the understanding of gene regulation at the genome-scale level. Many studies have been carried out in mice and humans; however limited high-resolution information exists...

Autonomous silencing of the imprinted Cdkn1c gene in stem cells
Wood MD, Hiura H, Tunster S, Arima T, Shin J-H, Higgins M, John1 RM
Parent-of-origin specific expression of imprinted genes relies on the differential DNA methylation of specific genomic regions. Differentially methylated regions (DMRs) acquire DNA methylation either during gametogenesis (primary DMR) or after fertilization when allele-specific expression is established (secondary D...

The histone variant macroH2A is an epigenetic regulator of key developmental genes.
Buschbeck M, Uribesalgo I, Wibowo I, Rué P, Martin D, Gutierrez A, Morey L, Guigó R, López-Schier H, Di Croce L
The histone variants macroH2A1 and macroH2A2 are associated with X chromosome inactivation in female mammals. However, the physiological function of macroH2A proteins on autosomes is poorly understood. Microarray-based analysis in human male pluripotent cells uncovered occupancy of both macroH2A variants at many gen...

High-resolution analysis of epigenetic changes associated with X inactivation.
Marks H, Chow JC, Denissov S, Françoijs KJ, Brockdorff N, Heard E, Stunnenberg HG
Differentiation of female murine ES cells triggers silencing of one X chromosome through X-chromosome inactivation (XCI). Immunofluorescence studies showed that soon after Xist RNA coating the inactive X (Xi) undergoes many heterochromatic changes, including the acquisition of H3K27me3. However, the mechanisms that ...

H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming.
Daujat S, Weiss T, Mohn F, Lange UC, Ziegler-Birling C, Zeissler U, Lappe M, Schübeler D, Torres-Padilla ME, Schneider R
Histone modifications are central to the regulation of all DNA-dependent processes. Lys64 of histone H3 (H3K64) lies within the globular domain at a structurally important position. We identify trimethylation of H3K64 (H3K64me3) as a modification that is enriched at pericentric heterochromatin and associated with re...

Epigenetic-Mediated Downregulation of μ-Protocadherin in Colorectal Tumours
Bujko M, Kober P, Statkiewicz M, Mikula M, Ligaj M, Zwierzchowski L, Ostrowski J, Siedlecki JA
Carcinogenesis involves altered cellular interaction and tissue morphology that partly arise from aberrant expression of cadherins. Mucin-like protocadherin is implicated in intercellular adhesion and its expression was found decreased in colorectal cancer (CRC). This study has compared MUPCDH (CDHR5) expression in ...

Analysis of active chromatin modifications in early mammalian embryos reveals uncoupling of H2A.Z acetylation and H3K36 trimethylation from embryonic genome activation
Bošković A, Bender A, Gall L, Ziegler-Birling C, Beaujean N, Torres-Padilla ME
Early embryonic development is characterized by dramatic changes in cell potency and chromatin organization. The role of histone variants in the context of chromatin remodeling during embryogenesis remains under investigated. In particular, the nuclear distribution of the histone variant H2A.Z and its modifications ...

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  H3K4me3 polyclonal antibody

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			'antibody_id' => '115',
			'name' => 'H3K4me3 polyclonal antibody  (sample size)',
			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone H3 containing the trimethylated lysine 4 (H3K4me3), using a KLH-conjugated synthetic peptide.</span></p>
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
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<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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			'id' => '115',
			'name' => 'H3K4me3 polyclonal antibody',
			'description' => 'Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called “histone code”. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Methylation of histone H3K4 is associated with activation of gene transcription.',
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			'lot' => 'A8034D',
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			'reactivity' => 'Human, mouse, pig, zebrafish, trout, Daphnia, Arabidopsis, rice, tomato, maize, poplar, silena latifolia, wide range expected.',
			'type' => 'Polyclonal, <strong>ChIP grade, ChIP-seq grade</strong>',
			'purity' => 'Affinity purified polyclonal antibody.',
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<thead>
<tr>
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<th>Suggested dilution</th>
<th>References</th>
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<td>ChIP/ChIP-seq<sup>*</sup></td>
<td><span style="font-family: Helvetica;">0.5 - 1&nbsp;&micro;g</span></td>
<td>Fig 1, 2</td>
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<tr>
<td>CUT&amp;Tag</td>
<td>0.5 &micro;g</td>
<td>Fig 3</td>
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<tr>
<td>ELISA</td>
<td>1:2,000</td>
<td>Fig 4</td>
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<tr>
<td>Dot Blotting</td>
<td>1:1000</td>
<td>Fig 5</td>
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<tr>
<td>Western Blotting</td>
<td>1:1,000</td>
<td>Fig 6</td>
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<tr>
<td>Immunofluorescence</td>
<td>1:200</td>
<td>Fig 7</td>
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<p></p>
<p><small><sup>*</sup> Please note that the optimal antibody amount per IP should be determined by the end-user. We recommend testing 0.5-5 &micro;g per IP.</small></p>',
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$language = 'jp'
$meta_keywords = ''
$meta_description = 'H3K4me3 polyclonal antibody - Premium (sample size)'
$meta_title = 'H3K4me3 polyclonal antibody - Premium (sample size)'
$product = array(
	'Product' => array(
		'id' => '2172',
		'antibody_id' => '115',
		'name' => 'H3K4me3 polyclonal antibody  (sample size)',
		'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone H3 containing the trimethylated lysine 4 (H3K4me3), using a KLH-conjugated synthetic peptide.</span></p>
<script src="chrome-extension://hhojmcideegachlhfgfdhailpfhgknjm/web_accessible_resources/index.js"></script>',
		'label1' => 'Validation Data',
		'info1' => '<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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</div>
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		'label2' => 'Target Description',
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		'format' => '10 µg',
		'catalog_number' => 'C15410003-10',
		'old_catalog_number' => 'pAb-003-010',
		'sf_code' => 'C15410003-D001-000582',
		'type' => 'FRE',
		'search_order' => '03-Antibody',
		'price_EUR' => '125',
		'price_USD' => '115',
		'price_GBP' => '115',
		'price_JPY' => '19580',
		'price_CNY' => '',
		'price_AUD' => '288',
		'country' => 'ALL',
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		'last_datasheet_update' => '0000-00-00',
		'slug' => 'h3k4me3-polyclonal-antibody-premium-sample-size-10-ug',
		'meta_title' => 'H3K4me3 polyclonal antibody - Premium (sample size)',
		'meta_keywords' => '',
		'meta_description' => 'H3K4me3 polyclonal antibody - Premium (sample size)',
		'modified' => '2022-06-29 14:43:38',
		'created' => '2015-06-29 14:08:20',
		'locale' => 'jpn'
	),
	'Antibody' => array(
		'host' => '*****',
		'id' => '115',
		'name' => 'H3K4me3 polyclonal antibody',
		'description' => 'Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called “histone code”. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Methylation of histone H3K4 is associated with activation of gene transcription.',
		'clonality' => '',
		'isotype' => '',
		'lot' => 'A8034D',
		'concentration' => '1.3 &micro;g/&micro;l',
		'reactivity' => 'Human, mouse, pig, zebrafish, trout, Daphnia, Arabidopsis, rice, tomato, maize, poplar, silena latifolia, wide range expected.',
		'type' => 'Polyclonal, <strong>ChIP grade, ChIP-seq grade</strong>',
		'purity' => 'Affinity purified polyclonal antibody.',
		'classification' => 'Premium',
		'application_table' => '<table>
<thead>
<tr>
<th>Applications</th>
<th>Suggested dilution</th>
<th>References</th>
</tr>
</thead>
<tbody>
<tr>
<td>ChIP/ChIP-seq<sup>*</sup></td>
<td><span style="font-family: Helvetica;">0.5 - 1&nbsp;&micro;g</span></td>
<td>Fig 1, 2</td>
</tr>
<tr>
<td>CUT&amp;Tag</td>
<td>0.5 &micro;g</td>
<td>Fig 3</td>
</tr>
<tr>
<td>ELISA</td>
<td>1:2,000</td>
<td>Fig 4</td>
</tr>
<tr>
<td>Dot Blotting</td>
<td>1:1000</td>
<td>Fig 5</td>
</tr>
<tr>
<td>Western Blotting</td>
<td>1:1,000</td>
<td>Fig 6</td>
</tr>
<tr>
<td>Immunofluorescence</td>
<td>1:200</td>
<td>Fig 7</td>
</tr>
</tbody>
</table>
<p></p>
<p><small><sup>*</sup> Please note that the optimal antibody amount per IP should be determined by the end-user. We recommend testing 0.5-5 &micro;g per IP.</small></p>',
		'storage_conditions' => 'Store at -20°C; for long storage, store at -80°C. Avoid multiple freeze-thaw cycles.',
		'storage_buffer' => 'PBS containing 0.05% azide and 0.05% ProClin 300.',
		'precautions' => 'This product is for research use only. Not for use in diagnostic or therapeutic procedures.',
		'uniprot_acc' => '',
		'slug' => '',
		'meta_keywords' => '',
		'meta_description' => '',
		'modified' => '2022-08-17 11:57:06',
		'created' => '0000-00-00 00:00:00',
		'select_label' => '115 - H3K4me3 polyclonal antibody (A8034D - 1.3 &micro;g/&micro;l - Human, mouse, pig, zebrafish, trout, Daphnia, Arabidopsis, rice, tomato, maize, poplar, silena latifolia, wide range expected. - Affinity purified polyclonal antibody. - Rabbit)'
	),
	'Slave' => array(),
	'Group' => array(
		'Group' => array(
			'id' => '47',
			'name' => 'C15410003',
			'product_id' => '2173',
			'modified' => '2016-02-18 20:50:17',
			'created' => '2016-02-18 20:50:17'
		),
		'Master' => array(
			'id' => '2173',
			'antibody_id' => '115',
			'name' => 'H3K4me3 Antibody',
			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
			'label1' => 'Validation data',
			'info1' => '<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
</div>
</div>
<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
</div>
</div>
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			'label2' => 'Target Description',
			'info2' => '<p>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called "histone code". Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Methylation of histone H3K4 is associated with activation of gene transcription.</p>
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			'label3' => '',
			'info3' => '<p></p>
<script src="chrome-extension://hhojmcideegachlhfgfdhailpfhgknjm/web_accessible_resources/index.js"></script>',
			'format' => '50 µg',
			'catalog_number' => 'C15410003',
			'old_catalog_number' => 'pAb-003-050',
			'sf_code' => 'C15410003-D001-000581',
			'type' => 'FRE',
			'search_order' => '03-Antibody',
			'price_EUR' => '480',
			'price_USD' => '470',
			'price_GBP' => '430',
			'price_JPY' => '75190',
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			'price_AUD' => '1175',
			'country' => 'ALL',
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			'master' => true,
			'last_datasheet_update' => 'January 8, 2021',
			'slug' => 'h3k4me3-polyclonal-antibody-premium-50-ug-50-ul',
			'meta_title' => 'H3K4me3 Antibody - ChIP-seq Grade (C15410003) | Diagenode',
			'meta_keywords' => '',
			'meta_description' => 'H3K4me3 (Histone H3 trimethylated at lysine 4) Polyclonal Antibody validated  in ChIP-seq, ChIP-qPCR, CUT&Tag, ELISA, DB, WB and IF. Specificity confirmed by Peptide array. Batch-specific data available on the website. Sample size available.',
			'modified' => '2024-11-19 16:51:19',
			'created' => '2015-06-29 14:08:20'
		),
		'Product' => array(
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				[maximum depth reached]
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	'Related' => array(
		(int) 0 => array(
			'id' => '1836',
			'antibody_id' => null,
			'name' => 'iDeal ChIP-seq kit for Histones',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/ideal-chipseq-for-histones-complete-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<p>Don&rsquo;t risk wasting your precious sequencing samples. Diagenode&rsquo;s validated <strong>iDeal ChIP-seq kit for Histones</strong> has everything you need for a successful start-to-finish <strong>ChIP of histones prior to Next-Generation Sequencing</strong>. The complete kit contains all buffers and reagents for cell lysis, chromatin shearing, immunoprecipitation and DNA purification. In addition, unlike competing solutions, the kit contains positive and negative control antibodies (H3K4me3 and IgG, respectively) as well as positive and negative control PCR primers pairs (GAPDH TSS and Myoglobin exon 2, respectively) for your convenience and a guarantee of optimal results. The kit has been validated on multiple histone marks.</p>
<p>&nbsp;The &nbsp;iDeal ChIP-seq kit for Histones<strong> </strong>is perfect for <strong>cells</strong> (<strong>100,000 cells</strong> to <strong>1,000,000 cells</strong> per IP) and has been validated for <strong>tissues</strong> (<strong>1.5 mg</strong> to <strong>5 mg</strong> of tissue per IP).</p>
<p>&nbsp;The iDeal ChIP-seq kit is the only kit on the market validated for the major sequencing systems. Our expertise in ChIP-seq tools allows reproducible and efficient results every time.</p>
<p></p>
<p>&nbsp;<strong></strong></p>
<p></p>',
			'label1' => 'Characteristics',
			'info1' => '<ul style="list-style-type: disc;">
<li>Highly <strong>optimized</strong> protocol for ChIP-seq from cells and tissues</li>
<li><strong>Validated</strong> for ChIP-seq with multiple histones marks</li>
<li>Most <strong>complete</strong> kit available (covers all steps, including the control antibodies and primers)</li>
<li>Optimized chromatin preparation in combination with the Bioruptor ensuring the best <strong>epitope integrity</strong></li>
<li>Magnetic beads make ChIP easy, fast and more <strong>reproducible</strong></li>
<li>Combination with Diagenode ChIP-seq antibodies provides high yields with excellent <strong>specificity</strong> and <strong>sensitivity</strong></li>
<li>Purified DNA suitable for any downstream application</li>
<li>Easy-to-follow protocol</li>
</ul>
<p>Note: to obtain optimal results, this kit should be used in combination with the DiaMag1.5 - magnetic rack.</p>
<h3>ChIP-seq on cells</h3>
<p><img src="https://www.diagenode.com/img/product/kits/iDeal-kit-C01010053-figure-1.jpg" alt="Figure 1A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1A. The high consistency of the iDeal ChIP-seq kit on the Ion Torrent&trade; PGM&trade; (Life Technologies) and GAIIx (Illumina<sup>&reg;</sup>)</strong><br /> ChIP was performed on sheared chromatin from 1 million HelaS3 cells using the iDeal ChIP-seq kit and 1 &micro;g of H3K4me3 positive control antibody. Two different biological samples have been analyzed using two different sequencers - GAIIx (Illumina<sup>&reg;</sup>) and PGM&trade; (Ion Torrent&trade;). The expected ChIP-seq profile for H3K4me3 on the GAPDH promoter region has been obtained.<br /> Image A shows a several hundred bp along chr12 with high similarity of read distribution despite the radically different sequencers. Image B is a close capture focusing on the GAPDH that shows that even the peak structure is similar.</p>
<p class="text-center"><strong>Perfect match between ChIP-seq data obtained with the iDeal ChIP-seq workflow and reference dataset</strong></p>
<p><img src="https://www.diagenode.com/img/product/kits/perfect-match-between-chipseq-data.png" alt="Figure 1B" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>
<p><img src="https://www.diagenode.com/img/product/kits/iDeal-kit-C01010053-figure-2.jpg" alt="Figure 2" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 2. Efficient and easy chromatin shearing using the Bioruptor<sup>&reg;</sup> and Shearing buffer iS1 from the iDeal ChIP-seq kit</strong><br /> Chromatin from 1 million of Hela cells was sheared using the Bioruptor<sup>&reg;</sup> combined with the Bioruptor<sup>&reg;</sup> Water cooler (Cat No. BioAcc-cool) during 3 rounds of 10 cycles of 30 seconds &ldquo;ON&rdquo; / 30 seconds &ldquo;OFF&rdquo; at HIGH power setting (position H). Diagenode 1.5 ml TPX tubes (Cat No. M-50001) were used for chromatin shearing. Samples were gently vortexed before and after performing each sonication round (rounds of 10 cycles), followed by a short centrifugation at 4&deg;C to recover the sample volume at the bottom of the tube. The sheared chromatin was then decross-linked as described in the kit manual and analyzed by agarose gel electrophoresis.</p>
<p><img src="https://www.diagenode.com/img/product/kits/iDeal-kit-C01010053-figure-3.jpg" alt="Figure 3" style="display: block; margin-left: auto; margin-right: auto;" width="264" height="320" /></p>
<p><strong>Figure 3. Validation of ChIP by qPCR: reliable results using Diagenode&rsquo;s ChIP-seq grade H3K4me3 antibody, isotype control and sets of validated primers</strong><br /> Specific enrichment on positive loci (GAPDH, EIF4A2, c-fos promoter regions) comparing to no enrichment on negative loci (TSH2B promoter region and Myoglobin exon 2) was detected by qPCR. Samples were prepared using the Diagenode iDeal ChIP-seq kit. Diagenode ChIP-seq grade antibody against H3K4me3 and the corresponding isotype control IgG were used for immunoprecipitation. qPCR amplification was performed with sets of validated primers.</p>
<h3>ChIP-seq on tissue</h3>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-figure-h3k4me3.jpg" alt="Figure 4A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 4A.</strong> Chromatin Immunoprecipitation has been performed using chromatin from mouse liver tissue, the iDeal ChIP-seq kit for Histones and the Diagenode ChIP-seq-grade H3K4me3 (Cat. No. C15410003) antibody. The IP'd DNA was subsequently analysed on an Illumina&reg; HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in a region surrounding the GAPDH positive control gene.</p>
<p><img src="https://www.diagenode.com/img/product/kits/match-of-the-top40-peaks-2.png" alt="Figure 4B" caption="false" style="display: block; margin-left: auto; margin-right: auto;" width="700" height="280" /></p>
<p><strong>Figure 4B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>',
			'label2' => 'Species, cell lines, tissues tested',
			'info2' => '<p>The iDeal ChIP-seq Kit for Histones is compatible with a broad variety of cell lines, tissues and species - some examples are shown below. Other species / cell lines / tissues can be used with this kit.</p>
<p><u>Cell lines:</u></p>
<p>Human: A549, A673, CD8+ T, Blood vascular endothelial cells, Lymphatic endothelial cells, fibroblasts, K562, MDA-MB231</p>
<p>Pig: Alveolar macrophages</p>
<p>Mouse: C2C12, primary HSPC, synovial fibroblasts, HeLa-S3, FACS sorted cells from embryonic kidneys, macrophages, mesodermal cells, myoblasts, NPC, salivary glands, spermatids, spermatocytes, skeletal muscle stem cells, stem cells, Th2</p>
<p>Hamster: CHO</p>
<p>Other cell lines / species: compatible, not tested</p>
<p><u>Tissues</u></p>
<p>Bee &ndash; brain</p>
<p>Daphnia &ndash; whole animal</p>
<p>Horse &ndash; brain, heart, lamina, liver, lung, skeletal muscles, ovary</p>
<p>Human &ndash; Erwing sarcoma tumor samples</p>
<p>Other tissues: compatible, not tested</p>
<p>Did you use the iDeal ChIP-seq for Histones Kit on other cell line / tissue / species? <a href="mailto:agnieszka.zelisko@diagenode.com?subject=Species, cell lines, tissues tested with the iDeal ChIP-seq Kit for TF&amp;body=Dear Customer,%0D%0A%0D%0APlease, leave below your feedback about the iDeal ChIP-seq for Transcription Factors (cell / tissue type, species, other information...).%0D%0A%0D%0AThank you for sharing with us your experience !%0D%0A%0D%0ABest regards,%0D%0A%0D%0AAgnieszka Zelisko-Schmidt, PhD">Let us know!</a></p>',
			'label3' => '  Additional solutions compatible with iDeal ChIP-seq Kit for Histones',
			'info3' => '<p><a href="../p/chromatin-shearing-optimization-kit-low-sds-100-million-cells">Chromatin EasyShear Kit - Ultra Low SDS </a>optimizes chromatin shearing, a critical step for ChIP.</p>
<p>&nbsp;The <a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq">MicroPlex Library Preparation Kit </a>provides easy and optimal &nbsp;library preparation of ChIPed samples.</p>
<p><a href="../categories/chip-seq-grade-antibodies">ChIP-seq grade anti-histone antibodies</a> provide high yields with excellent specificity and sensitivity.</p>
<p>&nbsp;Plus, for our IP-Star Automation users for automated ChIP, check out our <a href="../p/auto-ideal-chip-seq-kit-for-histones-x24-24-rxns">automated</a> version of this kit.</p>',
			'format' => '4 chrom. prep./24 IPs',
			'catalog_number' => 'C01010051',
			'old_catalog_number' => 'AB-001-0024',
			'sf_code' => 'C01010051-',
			'type' => 'RFR',
			'search_order' => '04-undefined',
			'price_EUR' => '915',
			'price_USD' => '1130',
			'price_GBP' => '840',
			'price_JPY' => '143335',
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			'meta_title' => 'iDeal ChIP-seq kit x24',
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			'meta_description' => 'iDeal ChIP-seq kit x24',
			'modified' => '2023-04-20 16:00:20',
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		),
		(int) 1 => array(
			'id' => '1839',
			'antibody_id' => null,
			'name' => 'iDeal ChIP-seq kit for Transcription Factors',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/ideal-chipseq-transcription-factors-x10-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<div class="row">
<div class="small-12 medium-8 large-8 columns"><br />
<p><span style="font-weight: 400;">Diagenode&rsquo;s <strong>iDeal ChIP-seq Kit for Transcription Factors</strong> is a highly validated solution for robust transcription factor and other non-histone proteins ChIP-seq results and contains everything you need for start-to-finish </span><b>ChIP </b><span style="font-weight: 400;">prior to </span><b>Next-Generation Sequencing</b><span style="font-weight: 400;">. This complete solution contains all buffers and reagents for cell lysis, chromatin shearing, immunoprecipitation, and DNA purification. In addition, unlike competing solutions, the kit contains positive and negative control antibodies (CTCF and IgG, respectively) as well as positive and negative control PCR primers pairs (H19 and Myoglobin exon 2, respectively) for your convenience and a guarantee of optimal results. <br /></span></p>
</div>
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<p><span style="font-weight: 400;">The </span><b>&nbsp;iDeal ChIP-seq kit for Transcription Factors </b><span style="font-weight: 400;">is compatible for cells or tissues:</span></p>
<table style="width: 419px; margin-left: auto; margin-right: auto;">
<tbody>
<tr>
<td style="width: 144px;"></td>
<td style="width: 267px; text-align: center;"><span style="font-weight: 400;">Amount per IP</span></td>
</tr>
<tr>
<td style="width: 144px;">Cells</td>
<td style="width: 267px; text-align: center;"><strong>4,000,000</strong></td>
</tr>
<tr>
<td style="width: 144px;">Tissues</td>
<td style="width: 267px; text-align: center;"><strong>30 mg</strong></td>
</tr>
</tbody>
</table>
<p><span style="font-weight: 400;">The iDeal ChIP-seq kit is the only kit on the market validated for major sequencing systems. Our expertise in ChIP-seq tools allows reproducible and efficient results every time. </span></p>
<p></p>
<p></p>',
			'label1' => 'Characteristics',
			'info1' => '<ul>
<li><span style="font-weight: 400;"><strong>Highly optimized protocol</strong> for ChIP-seq from cells and tissues</span></li>
<li><span style="font-weight: 400;"><strong>Validated</strong> for <strong>ChIP-seq</strong> with multiple transcription factors and non-histone targets<br /></span></li>
<li><span style="font-weight: 400;"><strong>Most complete kit</strong> available (covers all steps, including the control antibodies and primers)<br /></span></li>
<li><span style="font-weight: 400;"><strong>Magnetic beads</strong> make ChIP <strong>easy</strong>, <strong>fast</strong> and more <strong>reproducible</strong></span></li>
<li><span style="font-weight: 400;">Combination with Diagenode ChIP-seq antibodies provides <strong>high yields</strong> with excellent <strong>specificity</strong> and <strong>sensitivity</strong><br /></span></li>
<li><span style="font-weight: 400;">Purified DNA suitable for any downstream application</span></li>
<li><span style="font-weight: 400;">Easy-to-follow protocol</span></li>
</ul>
<p><span style="font-weight: 400;"></span></p>
<p>&nbsp;</p>
<h3>ChIP-seq on cells</h3>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-ctcf-diagenode.jpg" alt="CTCF Diagenode" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1.</strong> (A) Chromatin Immunoprecipitation has been performed using chromatin from HeLa cells, the iDeal ChIP-seq kit for Transcription Factors and the Diagenode ChIP-seq-grade CTCF antibody. The IP'd DNA was subsequently analysed on an Illumina<sup>&reg;</sup> HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in a region surrounding the GAPDH positive control gene.</p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-figure-b-total-diagendoe-peaks.png" alt="CTCF Diagenode" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>
<p>&nbsp;</p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-TF-chip-seq-A.png" alt="ChIP-seq figure A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-TF-chip-seq-B.png" alt="ChIP-seq figure B" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-TF-chip-seq-C.png" alt="ChIP-seq figure C" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 2.</strong> Chromatin Immunoprecipitation has been performed using chromatin from HeLa cells, the iDeal ChIP-seq kit for Transcription Factors and the Diagenode ChIP-seq-grade HDAC1 (A), LSD1 (B) and p53 antibody (C). The IP'd DNA was subsequently analysed on an Illumina<sup>&reg;</sup> Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in regions of chromosome 3 (A), chromosome 12 (B) and chromosome 6 (C) respectively.</p>
<p>&nbsp;</p>
<h3>ChIP-seq on tissue</h3>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-figure-3a.jpg" alt="ChIP-seq figure A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 3A.</strong> Chromatin Immunoprecipitation has been performed using chromatin from mouse liver tissue, the iDeal ChIP-seq kit for Transcription Factors and the Diagenode ChIP-seq-grade CTCF antibody. The IP'd DNA was subsequently analysed on an Illumina&reg; HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in a region surrounding the Vwf positive control gene.</p>
<p><img src="https://www.diagenode.com/img/product/kits/match-of-the-top40-peaks.png" alt="Match of the Top40 peaks" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 3B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>',
			'label2' => 'Species, cell lines, tissues tested',
			'info2' => '<p>The iDeal ChIP-seq Kit for Transcription Factors is compatible with a broad variety of cell lines, tissues and species - some examples are shown below. Other species / cell lines / tissues can be used with this kit.</p>
<p><span style="text-decoration: underline;">Cell lines:</span></p>
<p>Human: A549, A673, BT-549, CD4 T, HCC1806, HeLa, HepG2, HFF, HK-GFP-MR, ILC,&nbsp;K562, KYSE-180, LapC4, M14, MCF7, MDA-MB-231, MDA-MB-436, RDES, SKNO1, VCaP, U2-OS, ZR-75-1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;</p>
<p>Mouse: ESC, NPCs, BZ, GT1-7, acinar cells, HSPCs, Th2 cells, keratinocytes</p>
<p>Cattle: pbMEC, <span>MAC-T</span></p>
<p><span>Other cell lines / species: compatible, not tested</span></p>
<p><span style="text-decoration: underline;">Tissues:</span></p>
<p>Mouse: kidney, heart, brain, iris, liver, limbs from E10.5 embryos</p>
<p><span>Horse: l</span>iver, brain, heart, lung, skeletal muscle, lamina, ovary</p>
<p>Other tissues: compatible, not tested</p>
<p><span style="text-decoration: underline;">ChIP on yeast</span></p>
<p>The iDeal ChIP-seq kit for TF is compatible with yeast samples. Check out our <strong><a href="https://www.diagenode.com/files/products/kits/Application_Note-ChIP_on_Yeast.pdf">Application Note</a></strong>&nbsp;presenting an optimized detailed protocol for ChIP on yeast.</p>
<p></p>
<p>Did you use the iDeal ChIP-seq for Transcription Factors Kit on other cell line / tissue / species? <a href="mailto:agnieszka.zelisko@diagenode.com?subject=Species, cell lines, tissues tested with the iDeal ChIP-seq Kit for TF&amp;body=Dear Customer,%0D%0A%0D%0APlease, leave below your feedback about the iDeal ChIP-seq for Transcription Factors (cell / tissue type, species, other information...).%0D%0A%0D%0AThank you for sharing with us your experience !%0D%0A%0D%0ABest regards,%0D%0A%0D%0AAgnieszka Zelisko-Schmidt, PhD">Let us know!</a></p>',
			'label3' => 'Additional solutions compatible with iDeal ChIP-seq kit for Transcription Factors',
			'info3' => '<p><span style="font-weight: 400;">The</span> <a href="https://www.diagenode.com/en/p/chromatin-shearing-optimization-kit-low-sds-for-tfs-25-rxns"><span style="font-weight: 400;">Chromatin EasyShear Kit &ndash; Low SDS </span></a><span style="font-weight: 400;">is the kit compatible with the iDeal ChIP-seq kit for TF, recommended for the optimization of chromatin shearing, a critical step for ChIP.</span></p>
<p><a href="https://www.diagenode.com/en/p/chip-cross-link-gold-600-ul"><span style="font-weight: 400;">ChIP Cross-link Gold</span></a> <span style="font-weight: 400;">should be used in combination with formaldehyde when working with higher order and/or dynamic interactions, for efficient protein-protein fixation.</span></p>
<p><span style="font-weight: 400;">For library preparation of immunoprecipitated samples we recommend to use the </span><b>&nbsp;</b><a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq"><span style="font-weight: 400;">MicroPlex Library Preparation Kit</span></a><span style="font-weight: 400;"> - validated for library preparation from picogram inputs.</span></p>
<p><a href="https://www.diagenode.com/en/categories/chip-seq-grade-antibodies"><span style="font-weight: 400;">ChIP-seq grade antibodies</span></a><span style="font-weight: 400;"> provide high yields with excellent specificity and sensitivity.</span></p>
<p><span style="font-weight: 400;">Check the list of available </span><a href="https://www.diagenode.com/en/categories/primer-pairs"><span style="font-weight: 400;">Primer pairs</span></a><span style="font-weight: 400;"> designed for high specificity to specific genomic regions.</span></p>
<p><span style="font-weight: 400;">Plus, for our <a href="https://www.diagenode.com/en/categories/ip-star">IP-Star Automation</a> users for automated ChIP, check out our <a href="https://www.diagenode.com/en/p/auto-ideal-chip-seq-kit-for-transcription-factors-x24-24-rxns">automated version</a> of this kit.</span></p>',
			'format' => '4 chrom. prep./24 IPs',
			'catalog_number' => 'C01010055',
			'old_catalog_number' => '',
			'sf_code' => 'C01010055-',
			'type' => 'RFR',
			'search_order' => '04-undefined',
			'price_EUR' => '915',
			'price_USD' => '1130',
			'price_GBP' => '840',
			'price_JPY' => '143335',
			'price_CNY' => '',
			'price_AUD' => '2825',
			'country' => 'ALL',
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			'slug' => 'ideal-chip-seq-kit-for-transcription-factors-x24-24-rxns',
			'meta_title' => 'iDeal ChIP-seq kit for Transcription Factors x24',
			'meta_keywords' => '',
			'meta_description' => 'iDeal ChIP-seq kit for Transcription Factors x24',
			'modified' => '2023-06-20 18:27:37',
			'created' => '2015-06-29 14:08:20',
			'ProductsRelated' => array(
				[maximum depth reached]
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			'Image' => array(
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		(int) 2 => array(
			'id' => '1856',
			'antibody_id' => null,
			'name' => 'True MicroChIP-seq Kit',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/truemicrochipseq-kit-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<p>The <b>True </b><b>MicroChIP-seq</b><b> kit </b>provides a robust ChIP protocol suitable for the investigation of histone modifications within chromatin from as few as <b>10 000 cells</b>, including <b>FACS sorted cells</b>. The kit can be used for chromatin preparation for downstream ChIP-qPCR or ChIP-seq analysis. The <b>complete kit</b> contains everything you need for start-to-finish ChIP including all validated buffers and reagents for chromatin shearing, immunoprecipitation and DNA purification for exceptional <strong>ChIP-qPCR</strong> or <strong>ChIP-seq</strong> results. In addition, positive control antibodies and negative control PCR primers are included for your convenience and assurance of result sensitivity and specificity.</p>
<p>The True MicroChIP-seq kit offers unique benefits:</p>
<ul>
<li>An <b>optimized chromatin preparation </b>protocol compatible with low number of cells (<b>10.000</b>) in combination with the Bioruptor&trade; shearing device</li>
<li>Most <b>complete kit </b>available (covers all steps and includes control antibodies and primers)</li>
<li><b>Magnetic beads </b>make ChIP easy, fast, and more reproducible</li>
<li>MicroChIP DiaPure columns (included in the kit) enable the <b>maximum recovery </b>of immunoprecipitation DNA suitable for any downstream application</li>
<li><b>Excellent </b><b>ChIP</b><b>-seq </b>result when combined with <a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq">MicroPlex</a><a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq"> Library Preparation kit </a>adapted for low input</li>
</ul>
<p>For fast ChIP-seq on low input &ndash; check out Diagenode&rsquo;s <a href="https://www.diagenode.com/en/p/uchipmentation-for-histones-24-rxns">&micro;</a><a href="https://www.diagenode.com/en/p/uchipmentation-for-histones-24-rxns">ChIPmentation</a><a href="https://www.diagenode.com/en/p/uchipmentation-for-histones-24-rxns"> for histones</a>.</p>
<p><sub>The True MicroChIP-seq kit, Cat. No. C01010132 is an upgraded version of the kit True MicroChIP, Cat. No. C01010130, with the new validated protocols (e.g. FACS sorted cells) and MicroChIP DiaPure columns included in the kit.</sub></p>',
			'label1' => 'Characteristics',
			'info1' => '<ul>
<li><b>Revolutionary:</b> Only 10,000 cells needed for complete ChIP-seq procedure</li>
<li><b>Validated on</b> studies for histone marks</li>
<li><b>Automated protocol </b>for the IP-Star<sup>&reg;</sup> Compact Automated Platform available</li>
</ul>
<p></p>
<p>The True MicroChIP-seq kit protocol has been optimized for the use of 10,000 - 100,000 cells per immunoprecipitation reaction. Regarding chromatin immunoprecipitation, three protocol variants have been optimized:<br />starting with a batch, starting with an individual sample and starting with the FACS-sorted cells.</p>
<div><button id="readmorebtn" style="background-color: #b02736; color: white; border-radius: 5px; border: none; padding: 5px;">Show Workflow</button></div>
<p><br /> <img src="https://www.diagenode.com/img/product/kits/workflow-microchip.png" id="workflowchip" class="hidden" width="600px" /></p>
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<div class="container">
<div class="row" style="background: rgba(255,255,255,0.1);">
<div class="large-12 columns truemicro-slider" id="truemicro-slider">
<div>
<h3>High efficiency ChIP on 10,000 cells</h3>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><img src="https://www.diagenode.com/img/product/kits/true-micro-chip-histone-results.png" width="800px" /></div>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><center>
<p><small><strong>Figure 1.&nbsp;</strong>ChIP efficiency on 10,000 cells. ChIP was performed on human Hela cells using the Diagenode antibodies <a href="https://www.diagenode.com/en/p/h3k4me3-polyclonal-antibody-premium-50-ug-50-ul">H3K4me3</a> (Cat. No. C15410003), <a href="https://www.diagenode.com/en/p/h3k27ac-polyclonal-antibody-classic-50-mg-42-ml">H3K27ac</a> (C15410174), <a href="https://www.diagenode.com/en/p/h3k9me3-polyclonal-antibody-classic-50-ug">H3K9me3</a> (C15410056) and <a href="https://www.diagenode.com/en/p/h3k27me3-polyclonal-antibody-classic-50-mg-34-ml">H3K27me3</a> (C15410069). Sheared chromatin from 10,000 cells and 0.1 &micro;g (H3K27ac), 0.25 &micro;g (H3K4me3 and H3K27me3) or 0.5 &micro;g (H3K9me3) of the antibody were used per IP. Corresponding amount of IgG was used as control. Quantitative PCR was performed with primers for corresponding positive and negative loci. Figure shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
</center></div>
</div>
<div>
<h3>True MicroChIP-seq protocol in a combination with MicroPlex library preparation kit results in reliable and accurate sequencing data</h3>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><img src="https://www.diagenode.com/img/product/kits/fig2-truemicro.jpg" alt="True MicroChip results" width="800px" /></div>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><center>
<p><small><strong>Figure 2.</strong> Integrative genomics viewer (IGV) visualization of ChIP-seq experiments using 50.000 of K562 cells. ChIP has been performed accordingly to True MicroChIP protocol followed by the library preparation using MicroPlex Library Preparation Kit (C05010001). The above figure shows the peaks from ChIP-seq experiments using the following antibodies: H3K4me1 (C15410194), H3K9/14ac (C15410200), H3K27ac (C15410196) and H3K36me3 (C15410192).</small></p>
</center></div>
</div>
<div>
<h3>Successful chromatin profiling from 10.000 of FACS-sorted cells</h3>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><img src="https://www.diagenode.com/img/product/kits/fig3ab-truemicro.jpg" alt="small non coding RNA" width="800px" /></div>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><center>
<p><small><strong>Figure 3.</strong> (A) Integrative genomics viewer (IGV) visualization of ChIP-seq experiments and heatmap 3kb upstream and downstream of the TSS (B) for H3K4me3. ChIP has been performed using 10.000 of FACS-sorted cells (K562) and H3K4me3 antibody (C15410003) accordingly to True MicroChIP protocol followed by the library preparation using MicroPlex Library Preparation Kit (C05010001). Data were compared to ENCODE standards.</small></p>
</center></div>
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<p>
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			'label2' => 'Additional solutions compatible with the True MicroChIP-seq Kit',
			'info2' => '<p><span style="font-weight: 400;">The <a href="https://www.diagenode.com/en/p/chromatin-shearing-optimization-kit-high-sds-100-million-cells">Chromatin EasyShear Kit &ndash; High SDS</a></span><span style="font-weight: 400;">&nbsp;Recommended for the optimizing chromatin shearing.</span></p>
<p><a href="https://www.diagenode.com/en/categories/chip-seq-grade-antibodies"><span style="font-weight: 400;">ChIP-seq grade antibodies</span></a><span style="font-weight: 400;"> for high yields, specificity, and sensitivity.</span></p>
<p><span style="font-weight: 400;">Check the list of available </span><a href="https://www.diagenode.com/en/categories/primer-pairs"><span style="font-weight: 400;">primer pairs</span></a><span style="font-weight: 400;"> designed for high specificity to specific genomic regions.</span></p>
<p><span style="font-weight: 400;">For library preparation of immunoprecipitated samples we recommend to use the </span><b>&nbsp;</b><a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq"><span style="font-weight: 400;">MicroPlex Library Preparation Kit</span></a><span style="font-weight: 400;"> - validated for library preparation from picogram inputs.</span></p>
<p><span style="font-weight: 400;">For IP-Star Automation users, check out the </span><a href="https://www.diagenode.com/en/p/auto-true-microchip-kit-16-rxns"><span style="font-weight: 400;">automated version</span></a><span style="font-weight: 400;"> of this kit.</span></p>
<p><span style="font-weight: 400;">Application note: </span><a href="https://www.diagenode.com/files/application_notes/Diagenode_AATI_Joint.pdf"><span style="font-weight: 400;">Best Workflow Practices for ChIP-seq Analysis with Small Samples</span></a></p>
<p></p>',
			'label3' => 'Species, cell lines, tissues tested',
			'info3' => '<p>The True MicroChIP-seq kit is compatible with a broad variety of cell lines, tissues and species - some examples are shown below. Other species / cell lines / tissues can be used with this kit.</p>
<p><strong>Cell lines:</strong></p>
<p>Bovine: blastocysts,<br />Drosophila: embryos, salivary glands<br />Human: EndoC-ẞH1 cells, HeLa cells, PBMC, urothelial cells<br />Mouse: adipocytes, B cells, blastocysts, pre-B cells, BMDM cells, chondrocytes, embryonic stem cells, KH2 cells, LSK cells, macrophages, MEP cells, microglia, NK cells, oocytes, pancreatic cells, P19Cl6 cells, RPE cells,</p>
<p>Other cell lines / species: compatible, not tested</p>
<p><strong>Tissues:</strong></p>
<p>Horse: adipose tissue</p>
<p>Mice: intestine tissue</p>
<p>Other tissues: not tested</p>',
			'format' => '20 rxns',
			'catalog_number' => 'C01010132',
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			'type' => 'RFR',
			'search_order' => '04-undefined',
			'price_EUR' => '625',
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			'price_AUD' => '1700',
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			'meta_title' => 'True MicroChIP-seq Kit | Diagenode C01010132',
			'meta_keywords' => '',
			'meta_description' => 'True MicroChIP-seq Kit provides a robust ChIP protocol suitable for the investigation of histone modifications within chromatin from as few as 10 000 cells, including FACS sorted cells. Compatible with ChIP-qPCR as well as ChIP-seq.',
			'modified' => '2023-04-20 16:06:10',
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		(int) 3 => array(
			'id' => '1927',
			'antibody_id' => null,
			'name' => 'MicroPlex Library Preparation Kit v2 (12 indexes)',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/MicroPlex-Libary-Prep-Kit-v2-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<p><span><strong>Specifically optimized for ChIP-seq</strong></span><br /><br /><span>The MicroPlex Library Preparation&trade; kit is the only kit on the market which is validated for ChIP-seq and which allows the preparation of indexed libraries from just picogram inputs. In combination with the&nbsp;</span><a href="./true-microchip-kit-x16-16-rxns">True MicroChIP kit</a><span>, it allows for performing ChIP-seq on as few as 10,000 cells. Less input, fewer steps, fewer supplies, faster time to results!&nbsp;</span></p>
<p>The MicroPlex v2 kit (Cat. No. C05010012) contains all necessary reagents including single indexes for multiplexing up to 12 samples using single barcoding. For higher multiplexing (using dual indexes) check <a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns">MicroPlex Library Preparation Kits v3</a>.</p>',
			'label1' => 'Characteristics',
			'info1' => '<ul>
<li><strong>1 tube, 2 hours, 3 steps</strong> protocol</li>
<li><strong>Input: </strong>50 pg &ndash; 50 ng</li>
<li><strong>Reduce potential bias</strong> - few PCR amplification cycles needed</li>
<li><strong>High sensitivity ChIP-seq</strong> - low PCR duplication rate</li>
<li><strong>Great multiplexing flexibility</strong> with 12 barcodes (8 nt) included</li>
<li><strong>Validated with the <a href="https://www.diagenode.com/p/sx-8g-ip-star-compact-automated-system-1-unit" title="IP-Star Automated System">IP-Star<sup>&reg;</sup> Automated Platform</a></strong></li>
</ul>
<h3>How it works</h3>
<center><img src="https://www.diagenode.com/img/product/kits/microplex-method-overview-v2.png" /></center>
<p style="margin-bottom: 0;"><small><strong>Microplex workflow - protocol with single indexes</strong><br />An input of 50 pg to 50 ng of fragmented dsDNA is converted into sequencing-ready libraries for Illumina&reg; NGS platforms using a fast and simple 3-step protocol</small></p>
<ul class="accordion" data-accordion="" id="readmore" style="margin-left: 0;">
<li class="accordion-navigation"><a href="#first" style="background: #ffffff; padding: 0rem; margin: 0rem; color: #13b2a2;"><small>Read more about MicroPlex workflow</small></a>
<div id="first" class="content">
<p><small><strong>Step 1. Template Preparation</strong> provides efficient repair of the fragmented double-stranded DNA input.</small></p>
<p><small>In this step, the DNA is repaired and yields molecules with blunt ends.</small></p>
<p><small><strong>Step 2. Library Synthesis.</strong> enables ligation of MicroPlex patented stem- loop adapters.</small></p>
<p><small>In the next step, stem-loop adaptors with blocked 5&rsquo; ends are ligated with high efficiency to the 5&rsquo; end of the genomic DNA, leaving a nick at the 3&rsquo; end. The adaptors cannot ligate to each other and do not have single- strand tails, both of which contribute to non-specific background found with many other NGS preparations.</small></p>
<p><small><strong>Step 3. Library Amplification</strong> enables extension of the template, cleavage of the stem-loop adaptors, and amplification of the library. Illumina- compatible indexes are also introduced using a high-fidelity, highly- processive, low-bias DNA polymerase.</small></p>
<p><small>In the final step, the 3&rsquo; ends of the genomic DNA are extended to complete library synthesis and Illumina-compatible indexes are added through a high-fidelity amplification. Any remaining free adaptors are destroyed. Hands-on time and the risk of contamination are minimized by using a single tube and eliminating intermediate purifications.</small></p>
<p><small>Obtained libraries are purified, quantified and sized. The libraries pooling can be performed as well before sequencing.</small></p>
</div>
</li>
</ul>
<p></p>
<h3>Reliable detection of enrichments in ChIP-seq</h3>
<p><img src="https://www.diagenode.com/img/product/kits/microplex-library-prep-kit-figure-a.png" alt="Reliable detection of enrichments in ChIP-seq figure 1" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure A.</strong> ChIP has been peformed with H3K4me3 antibody, amplification of 17 pg of DNA ChIP'd from 10.000 cells and amplification of 35 pg of DNA ChIP'd from 100.000 cells (control experiment). The IP'd DNA was amplified and transformed into a sequencing-ready preparation for the Illumina plateform with the MicroPlex Library Preparation kit. The library was then analysed on an Illumina<sup>&reg;</sup> Genome Analyzer. Cluster generation and sequencing were performed according to the manufacturer's instructions.</p>
<p><img src="https://www.diagenode.com/img/product/kits/microplex-library-prep-kit-figure-b.png" alt="Reliable detection of enrichments in ChIP-seq figure 2" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure B.</strong> We observed a perfect match between the top 40% of True MicroChIP peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>',
			'label2' => '',
			'info2' => '',
			'label3' => '',
			'info3' => '',
			'format' => '12 rxns',
			'catalog_number' => 'C05010012',
			'old_catalog_number' => 'C05010010',
			'sf_code' => 'C05010012-',
			'type' => 'FRE',
			'search_order' => '04-undefined',
			'price_EUR' => '935',
			'price_USD' => '1215',
			'price_GBP' => '835',
			'price_JPY' => '146470',
			'price_CNY' => '',
			'price_AUD' => '3038',
			'country' => 'ALL',
			'except_countries' => 'None',
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			'slug' => 'microplex-library-preparation-kit-v2-x12-12-indices-12-rxns',
			'meta_title' => 'MicroPlex Library Preparation Kit v2 x12 (12 indices)',
			'meta_keywords' => '',
			'meta_description' => 'MicroPlex Library Preparation Kit v2 x12 (12 indices)',
			'modified' => '2023-04-20 15:01:16',
			'created' => '2015-06-29 14:08:20',
			'ProductsRelated' => array(
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			'Image' => array(
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		),
		(int) 4 => array(
			'id' => '2264',
			'antibody_id' => '121',
			'name' => 'H3K9me3 Antibody',
			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone<strong> H3 containing the trimethylated lysine 9</strong> (<strong>H3K9me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
			'label1' => 'Validation Data',
			'info1' => '<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig1.png" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K9me3</strong><br />ChIP assays were performed using human HeLa cells, the Diagenode antibody against H3K9me3 (cat. No. C15410193) and optimized PCR primer sets for qPCR. ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using the &ldquo;iDeal ChIP-seq&rdquo; kit (cat. No. C01010051). A titration of the antibody consisting of 0.5, 1, 2, and 5 &micro;g per ChIP experiment was analysed. IgG (1 &micro;g/IP) was used as negative IP control. QPCR was performed with primers for the heterochromatin marker Sat2 and for the ZNF510 gene, used as positive controls, and for the promoters of the active EIF4A2 and GAPDH genes, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2a.png" width="700" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2b.png" width="700" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2c.png" width="700" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2d.png" width="700" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K9me3</strong><br />ChIP was performed with 0.5 &micro;g of the Diagenode antibody against H3K9me3 (cat. No. C15410193) on sheared chromatin from 1,000,000 HeLa cells using the &ldquo;iDeal ChIP-seq&rdquo; kit as described above. The IP'd DNA was subsequently analysed on an Illumina HiSeq 2000. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 50 bp tags were aligned to the human genome using the BWA algorithm. Figure 2A shows the signal distribution along the long arm of chromosome 19 and a zoomin to an enriched region containing several ZNF repeat genes. The arrows indicate two satellite repeat regions which exhibit a stronger signal. Figures 2B, 2C and 2D show the enrichment along the ZNF510 positive control target and at the H19 and KCNQ1 imprinted genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-CT-Fig3a.png" width="700" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-CT-Fig3b.png" width="700" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K9me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 1 &micro;g of the Diagenode antibody against H3K9me3 (cat. No. C15410193) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in a genomic regions on chromosome 1 containing several ZNF repeat genes and in a genomic region surrounding the KCNQ1 imprinting control gene on chromosome 11 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-Elisa-Fig4.png" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the antibody directed against human H3K9me3 (cat. No. C15410193) in antigen coated wells. The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:87,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-DB-Fig5.png" /></center></div>
<div class="small-8 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K9me3</strong><br />A Dot Blot analysis was performed to test the cross reactivity of the Diagenode antibody against H3K9me3 (cat. No. C15410193) with peptides containing other modifications and unmodified sequences of histone H3 and H4. One hundred to 0.2 pmol of the peptide containing the respective histone modification were spotted on a membrane. The antibody was used at a dilution of 1:20,000. Figure 5 shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-WB-Fig6.png" /></center></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K9me3</strong><br />Western blot was performed on whole cell (25 &micro;g, lane 1) and histone extracts (15 &micro;g, lane 2) from HeLa cells, and on 1 &micro;g of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K9me3 (cat. No. C15410193). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-IF-Fig7.png" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K9me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K9me3 (cat. No. C15410193) and with DAPI. Cells were fixed with 4% formaldehyde for 10&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labelled with the H3K9me3 antibody (middle) diluted 1:500 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The left panel shows staining of the nuclei with DAPI. A merge of both stainings is shown on the right.</small></p>
</div>
</div>',
			'label2' => 'Target Description',
			'info2' => '<p>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called &ldquo;histone code&rdquo;. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Trimethylation of histone H3K9 is associated with inactive genomic regions, satellite repeats and ZNF gene repeats.</p>',
			'label3' => '',
			'info3' => '',
			'format' => '50 μg',
			'catalog_number' => 'C15410193',
			'old_catalog_number' => 'pAb-193-050',
			'sf_code' => 'C15410193-D001-000581',
			'type' => 'FRE',
			'search_order' => '03-Antibody',
			'price_EUR' => '480',
			'price_USD' => '470',
			'price_GBP' => '430',
			'price_JPY' => '75190',
			'price_CNY' => '0',
			'price_AUD' => '1175',
			'country' => 'ALL',
			'except_countries' => 'None',
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			'in_stock' => false,
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			'last_datasheet_update' => 'December 12, 2017',
			'slug' => 'h3k9me3-polyclonal-antibody-premium-50-mg',
			'meta_title' => 'H3K9me3 Antibody - ChIP-seq Grade (C15410193) | Diagenode',
			'meta_keywords' => '',
			'meta_description' => 'H3K9me3  (Histone H3 trimethylated at lysine 9) Polyclonal Antibody validated  in ChIP-seq, ChIP-qPCR, CUT&Tag, ELISA, DB, WB and IF. Specificity confirmed by Peptide array assay. Batch-specific data available on the website. Sample size available.',
			'modified' => '2021-10-20 09:55:53',
			'created' => '2015-06-29 14:08:20',
			'ProductsRelated' => array(
				[maximum depth reached]
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			'Image' => array(
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		(int) 5 => array(
			'id' => '2268',
			'antibody_id' => '70',
			'name' => 'H3K27me3 Antibody',
			'description' => '<p>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 27</strong> (<strong>H3K27me3</strong>), using a KLH-conjugated synthetic peptide.</p>',
			'label1' => 'Validation Data',
			'info1' => '<div class="row">
<div class="small-6 columns">
<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig1.png" alt="H3K27me3 Antibody ChIP Grade" /></p>
<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2.png" alt="H3K27me3 Antibody for ChIP" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K27me3</strong><br />ChIP assays were performed using human HeLa cells, the Diagenode antibody against H3K27me3 (Cat. No. C15410195) and optimized PCR primer pairs for qPCR. ChIP was performed with the &ldquo;iDeal ChIP-seq&rdquo; kit (Cat. No. C01010051), using sheared chromatin from 1 million cells. The chromatin was spiked with a panel of in vitro assembled nucleosomes, each containing a specific lysine methylation. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control.</small></p>
<p><small><strong>Figure 1A.</strong> Quantitative PCR was performed with primers specific for the promoter of the active GAPDH and EIF4A2 genes, used as negative controls, and for the inactive TSH2B and MYT1 genes, used as positive controls. The graph shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
<p><small><strong>Figure 1B.</strong> Recovery of the nucleosomes carrying the H3K27me1, H3K27me2, H3K27me3, H3K4me3, H3K9me3 and H3K36me3 modifications and the unmodified H3K27 as determined by qPCR. The figure clearly shows the antibody is very specific in ChIP for the H3K27me3 modification.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2a.png" alt="H3K27me3 Antibody ChIP-seq Grade" /></p>
</div>
</div>
<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
<div class="row">
<div class="small-12 columns">
<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2b.png" alt="H3K27me3 Antibody for ChIP-seq" /></p>
<p>C. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2c.png" alt="H3K27me3 Antibody for ChIP-seq assay" /></p>
<p>D. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2d.png" alt="H3K27me3 Antibody validated in ChIP-seq" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K27me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLa cells using 1 &micro;g of the Diagenode antibody against H3K27me3 (Cat. No. C15410195) as described above. The IP'd DNA was subsequently analysed on an Illumina HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 50 bp tags were aligned to the human genome using the BWA algorithm. Figure 2 shows the enrichment in genomic regions of chromosome 6 and 20, surrounding the TSH2B and MYT1 positive control genes (fig 2A and 2B, respectively), and in two genomic regions of chromosome 1 and X (figure 2C and D).</small></p>
</div>
</div>
<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
<div class="row">
<div class="small-12 columns">
<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-CUTTAG-Fig3A.png" /></p>
<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-CUTTAG-Fig3B.png" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K27me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 1 &micro;g of the Diagenode antibody against H3K27me3 (cat. No. C15410195) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions on chromosome and 13 and 20 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-ELISA-Fig4.png" alt="H3K27me3 Antibody ELISA Validation " /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody directed against H3K27me3 (Cat. No. C15410195). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:3,000.</small></p>
</div>
</div>
<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-DB-Fig5a.png" alt="H3K27me3 Antibody Dot Blot Validation " /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K27me3</strong><br />A Dot Blot analysis was performed to test the cross reactivity of the Diagenode antibody against H3K27me3 (Cat. No. C15410195) with peptides containing other modifications of histone H3 and H4 and the unmodified H3K27 sequence. One hundred to 0.2 pmol of the peptide containing the respective histone modification were spotted on a membrane. The antibody was used at a dilution of 1:5,000. Figure 5 shows a high specificity of the antibody for the modification of interest. Please note that the antibody also recognizes the modification if S28 is phosphorylated.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-WB-Fig6.png" alt="H3K27me3 Antibody validated in Western Blot" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K27me3</strong><br />Western blot was performed on whole cell (25 &micro;g, lane 1) and histone extracts (15 &micro;g, lane 2) from HeLa cells, and on 1 &micro;g of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K27me3 (cat. No. C15410195) diluted 1:500 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-IF-Fig7.png" alt="H3K27me3 Antibody validated for Immunofluorescence" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K27me3</strong><br />Human HeLa cells were stained with the Diagenode antibody against H3K27me3 (Cat. No. C15410195) and with DAPI. Cells were fixed with 4% formaldehyde for 10&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labelled with the H3K27me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The middle panel shows staining of the nuclei with DAPI. A merge of the two stainings is shown on the right.</small></p>
</div>
</div>',
			'label2' => 'Target Description',
			'info2' => '<p><small>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which alter chromatin structure to facilitate transcriptional activation, repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called &ldquo;histone code&rdquo;. Histone methylation and demethylation is regulated by histone methyl transferases and histone demethylases. Methylation of histone H3K27 is associated with inactive genomic regions.</small></p>',
			'label3' => '',
			'info3' => '',
			'format' => '50 μg',
			'catalog_number' => 'C15410195',
			'old_catalog_number' => 'pAb-195-050',
			'sf_code' => 'C15410195-D001-000581',
			'type' => 'FRE',
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			'slug' => 'h3k27me3-polyclonal-antibody-premium-50-mg-27-ml',
			'meta_title' => 'H3K27me3 Antibody - ChIP-seq Grade (C15410195) | Diagenode',
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			'meta_description' => 'H3K27me3 (Histone H3 trimethylated at lysine 27) Polyclonal Antibody validated  in ChIP-seq, ChIP-qPCR, CUT&Tag, ELISA, DB, WB and IF. Specificity confirmed by Peptide array assay. Batch-specific data available on the website. Sample size available.',
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			'id' => '2262',
			'antibody_id' => '74',
			'name' => 'H3K36me3 Antibody',
			'description' => '<p>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 36</strong> (<strong>H3K36me3</strong>), using a KLH-conjugated synthetic peptide.</p>',
			'label1' => 'Validation Data',
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<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig1.png" alt="H3K36me3 Antibody ChIP Grade" caption="false" width="432" height="674" /></p>
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<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K36me3</strong><br /> <strong>Figure 1A</strong> ChIP assays were performed using human HeLa cells, the Diagenode antibody against H3K36me3 (Cat. No. C15410192) and optimized PCR primer pairs for qPCR. ChIP was performed with the &ldquo;Auto Histone ChIP-seq&rdquo; kit (Cat. No. C01010022) on the IP-Star automated system, using sheared chromatin from 1,000,000 cells. A titration consisting of 1, 2, 5 and 10 &micro;g of antibody per ChIP experiment was analyzed. IgG (2 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers for the coding region of the active GAPDH and ACTB genes, used as positive controls, and for the promoter and a region located 1 kb upstream of the promoter of the GAPDH gene, used as negative controls.<br /><br /> <strong>Figure 1B</strong> ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K36me3 (Cat. No. C15410192) and optimized PCR primer pairs for qPCR. ChIP was performed with the &ldquo;iDeal ChIP-seq&rdquo; kit (Cat. No. C01010051), using sheared chromatin from 100,000 cells. A titration consisting of 0.2, 0.5, 1 and 2 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers for the coding region of the active GAPDH and ACTB genes, used as positive controls, and for the coding region of the inactive MB gene and the Sat satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig2-2.jpg" alt="H3K36me3 Antibody SNAP-ChIP validation" caption="false" width="432" height="298" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 2. ChIP results obtained with the Diagenode antibody directed against H3K36me3</strong><br /> ChIP assays were performed on sheared chromatin from 1 million human HeLa cells as described above. The chromatin was spiked with a panel of in vitro assembled nucleosomes, each containing a specific lysine methylation (SNAP-ChIP K-MetStat Panel, Epicypher). A titration consisting of 0.2, 0.5, 1 and 2 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the nucleosomes carrying the H3K36me1, H3K36me2, H3K36me3, H3K4me3, H3K9me3, H3K27me3 and H4K20me3 modifications and the unmodified H3K4. The graph shows the recovery, expressed as a % of input. These results demonstrate a high specificity of the H3K36me3 antibody for the modification of interest.</small></p>
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</div>
<div class="row">
<div class="small-12 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig2.png" alt="H3K36me3 Antibody for ChIP-seq" caption="false" width="893" height="702" /></p>
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</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. ChIP-seq results obtained with the Diagenode antibody directed against H3K36me3</strong><br /> ChIP was performed on sheared chromatin from 100,000 K562 cells with the &ldquo;iDeal ChIP-seq&rdquo; kit (Cat. No. C01010051) using 0.5 &micro;g of the Diagenode antibody against H3K36me3 (Cat. No. C15410192) as described above. The IP&rsquo;d DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer&rsquo;s instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 3 shows the H3K36me3 signal distribution along the complete sequence and a zoomin of human chromosome 12 (figure 2A and B) and in 2 genomic regions containing the GAPDH and ACTB positive control genes (figure 3C and D).</small></p>
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</div>
<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig3.png" alt="H3K36me3 Antibody ELISA validation" caption="false" width="432" height="328" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K36me3 (Cat. No. C15410192). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:132,000.</small></p>
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<div class="row">
<div class="small-6 columns">
<p>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig4-a.png" alt="H3K36me3 Antibody Dot Blot Validation" caption="false" width="432" height="162" /></p>
<p>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig4-b.png" alt="H3K36me3 Antibody Peptide Array validation" caption="false" width="432" height="257" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K36me3</strong><br /> <strong>Figure 5A.</strong> To test the cross reactivity of the Diagenode antibody against H3K36me3 (Cat. No. C15410192), a Dot Blot analysis was performed with peptides containing other modifications or unmodified sequences of histone H3 and H4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:20,000. Figure 5A shows a high specificity of the antibody for the modification of interest. <strong>Figure 5B.</strong> The specificity of the antibody was further demonstrated by peptide array analyses on an array containing 384 peptides with different combinations of modifications from histone H3, H4, H2A and H2B. The antibody was used at a dilution of 1:10,000. Figure 5B shows the specificity factor, calculated as the ratio of the average intensity of all spots containing the mark, divided by the average intensity of all spots not containing the mark. The peptide array analysis shows a slight cross reaction with H4K20me3 that was not observed in dot blot.</small></p>
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<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig5.png" alt="H3K36me3 Antibody for Western Blot" caption="false" width="432" height="346" /></p>
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<div class="small-6 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K36me3</strong><br /> Western blot was performed on whole cell (25 &micro;g, lane 1) and histone extracts (15 &micro;g, lane 2) from HeLa cells, and on 1 &micro;g of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K36me3 (Cat. No. C15410192). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is shown on the right, the marker (in kDa) is shown on the left.</small></p>
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<div class="row">
<div class="small-12 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig6.png" alt="H3K36me3 Antibody for Immunofluorescence " caption="false" width="893" height="232" /></p>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K36me3</strong><br /> HeLa cells were stained with the Diagenode antibody against H3K36me3 (Cat. C15410192) and with DAPI. Cells were fixed with 4% formaldehyde for 10&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labeled with the H3K36me3 antibody (left) diluted 1:500 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The middle panel shows staining of the nuclei with DAPI. A merge of the two stainings is shown on the right.</small></p>
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			'info2' => '<p>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called &ldquo;histone code&rdquo;. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Trimethylation of histone H3K36 is associated with active genes.</p>',
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			'meta_description' => 'H3K36me3 (Histone H3 trimethylated at lysine 36) Polyclonal Antibody validated  in ChIP-seq, ChIP-grade, ELISA, DB, WB and IF. Specificity confirmed by Peptide array. Batch-specific data available on the website. Sample size available. ',
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			'antibody_id' => '115',
			'name' => 'H3K4me3 Antibody',
			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
			'label1' => 'Validation data',
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
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<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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<p>Learn more about: <a href="https://www.diagenode.com/applications/western-blot">Loading control, MW marker visualization</a><em>. <br /></em></p>
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			'name' => 'IF',
			'description' => '<p><strong>Immunofluorescence</strong>:</p>
<p>Diagenode offers huge selection of highly sensitive antibodies validated in IF.</p>
<p><img src="https://www.diagenode.com/img/product/antibodies/C15200229-IF.jpg" alt="" height="245" width="256" /></p>
<p><sup><strong>Immunofluorescence using the Diagenode monoclonal antibody directed against CRISPR/Cas9</strong></sup></p>
<p><sup>HeLa cells transfected with a Cas9 expression vector (left) or untransfected cells (right) were fixed in methanol at -20&deg;C, permeabilized with acetone at -20&deg;C and blocked with PBS containing 2% BSA. The cells were stained with the Cas9 C-terminal antibody (Cat. No. C15200229) diluted 1:400, followed by incubation with an anti-mouse secondary antibody coupled to AF488. The bottom images show counter-staining of the nuclei with Hoechst 33342.</sup></p>
<h5><sup>Check our selection of antibodies validated in IF.</sup></h5>',
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			'meta_description' => 'Diagenode offers a wide range of antibodies and technical support for ChIP Sequencing applications',
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			'description' => '<p>CUT＆Tagアッセイを成功させるための重要な要素の1つは使用される抗体の品質です。 特異性高い抗体は、目的のタンパク質のみをターゲットとした確実な結果を可能にします。 CUT＆Tagで検証済みの抗体のセレクションはこちらからご覧ください。</p>
<p>Read more:</p>
<p><a href="https://www.diagenode.com/en/categories/cutandtag">Products for CUT&amp;Tag assay</a></p>
<p><a href="https://www.diagenode.com/en/pages/cut-and-tag">Performance of Diagenode's antibodies in CUT&amp;Tag</a></p>
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			'description' => '<p><b>Unparalleled ChIP-Seq results with the most rigorously validated antibodies</b></p>
<p><span style="font-weight: 400;">Diagenode provides leading solutions for epigenetic research. Because ChIP-seq is a widely-used technique, we validate our antibodies in ChIP and ChIP-seq experiments (in addition to conventional methods like Western blot, Dot blot, ELISA, and immunofluorescence) to provide the highest quality antibody. We standardize our validation and production to guarantee high product quality without technical bias. Diagenode guarantees ChIP-seq grade antibody performance under our suggested conditions.</span></p>
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<div class="small-12 medium-9 large-9 columns">
<p><strong>ChIP-seq profile</strong> of active (H3K4me3 and H3K36me3) and inactive (H3K27me3) marks using Diagenode antibodies.</p>
<img src="https://www.diagenode.com/img/categories/antibodies/chip-seq-grade-antibodies.png" /></div>
<div class="small-12 medium-3 large-3 columns">
<p><small> ChIP was performed on sheared chromatin from 100,000 K562 cells using iDeal ChIP-seq kit for Histones (cat. No. C01010051) with 1 &micro;g of the Diagenode antibodies against H3K27me3 (cat. No. C15410195) and H3K4me3 (cat. No. C15410003), and 0.5 &micro;g of the antibody against H3K36me3 (cat. No. C15410192). The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. The figure shows the signal distribution along the complete sequence of human chromosome 3, a zoomin to a 10 Mb region and a further zoomin to a 1.5 Mb region. </small></p>
</div>
</div>
<p>Diagenode&rsquo;s highly validated antibodies:</p>
<ul>
<li>Highly sensitive and specific</li>
<li>Cost-effective (requires less antibody per reaction)</li>
<li>Batch-specific data is available on the website</li>
<li>Expert technical support</li>
<li>Sample sizes available</li>
<li>100% satisfaction guarantee</li>
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			'description' => '<p>Histones are the main protein components of chromatin involved in the compaction of DNA into nucleosomes, the basic units of chromatin. A <strong>nucleosome</strong> consists of one pair of each of the core histones (<strong>H2A</strong>, <strong>H2B</strong>, <strong>H3</strong> and <strong>H4</strong>) forming an octameric structure wrapped by 146 base pairs of DNA. The different nucleosomes are linked by the linker histone<strong> H1, </strong>allowing for further condensation of chromatin.</p>
<p>The core histones have a globular structure with large unstructured N-terminal tails protruding from the nucleosome.&nbsp; They can undergo to multiple post-translational modifications (PTM), mainly at the N-terminal tails. These <strong>post-translational modifications </strong>include&nbsp; methylation, acetylation, phosphorylation, ubiquitinylation, citrullination, sumoylation, deamination and crotonylation.&nbsp; The most well characterized PTMs are <strong>methylation,</strong> <strong>acetylation and phosphorylation</strong>. Histone methylation occurs mainly on lysine (K) residues, which can be mono-, di- or tri-methylated, and on arginines (R), which can be mono-methylated and symmetrically or asymmetrically di-methylated. Histone acetylation occurs on lysines and histone phosphorylation mainly on serines (S), threonines (T) and tyrosines (Y).</p>
<p>The PTMs of the different residues are involved in numerous processes such as DNA repair, DNA replication and chromosome condensation. They influence the chromatin organization and can be positively or negatively associated with gene expression. Trimethylation of H3K4, H3K36 and H3K79, and lysine acetylation generally result in an open chromatin configuration (figure below) and are therefore associated with <strong>euchromatin</strong> and gene activation. Trimethylation of H3K9, K3K27 and H4K20, on the other hand, is enriched in <strong>heterochromatin </strong>and associated with gene silencing. The combination of different histone modifications is called the "<strong>histone code</strong>&rdquo;, analogous to the genetic code.</p>
<p><img src="https://www.diagenode.com/img/categories/antibodies/histone-marks-illustration.png" /></p>
<p>Diagenode is proud to offer a large range of antibodies against histones and histone modifications. Our&nbsp; antibodies are highly specific and have been validated in many applications, including <strong>ChIP</strong> and <strong>ChIP-seq</strong>.</p>
<p>Diagenode&rsquo;s collection includes antibodies recognizing:</p>
<ul>
<li><strong>Histone H1 variants</strong></li>
<li><strong>Histone H2A, H2A variants and histone H2A</strong> <strong>modifications</strong> (serine phosphorylation, lysine acetylation, lysine ubiquitinylation)</li>
<li><strong>Histone H2B and H2B</strong> <strong>modifications </strong>(serine phosphorylation, lysine acetylation)</li>
<li><strong>Histone H3 and H3 modifications </strong>(lysine methylation (mono-, di- and tri-methylated), lysine acetylation, serine phosphorylation, threonine phosphorylation, arginine methylation (mono-methylated, symmetrically and asymmetrically di-methylated))</li>
<li><strong>Histone H4 and H4 modifications (</strong>lysine methylation (mono-, di- and tri-methylated), lysine acetylation, arginine methylation (mono-methylated and symmetrically di-methylated), serine phosphorylation )</li>
</ul>
<p><span style="font-weight: 400;"><strong>HDAC's HAT's, HMT's and other</strong> <strong>enzymes</strong> which modify histones can be found in the category <a href="../categories/chromatin-modifying-proteins-histone-transferase">Histone modifying enzymes</a><br /></span></p>
<p><span style="font-weight: 400;"> Diagenode&rsquo;s highly validated antibodies:</span></p>
<ul>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Highly sensitive and specific</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Cost-effective (requires less antibody per reaction)</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Batch-specific data is available on the website</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Expert technical support</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Sample sizes available</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 100% satisfaction guarantee</span></li>
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			'description' => '<h1><strong>Validated epigenetics antibodies</strong>&nbsp;&ndash; care for a sample?<br />&nbsp;</h1>
<p>Diagenode has partnered with leading epigenetics experts and numerous epigenetics consortiums to bring to you a validated and comprehensive collection of epigenetic antibodies. As an expert in epigenetics, we are committed to offering highly-specific antibodies validated for ChIP/ChIP-seq and many other applications. All batch-specific validation data is available on our website.<br /><a href="../categories/antibodies">Read about our expertise in antibody production</a>.</p>
<ul>
<li><strong>Focused</strong> -&nbsp;Diagenode's selection of antibodies is exclusively dedicated for epigenetic research. <a title="See the full collection." href="../categories/all-antibodies">See the full collection.</a></li>
<li><strong>Strict quality standards</strong>&nbsp;with rigorous QC and validation</li>
<li><strong>Classified</strong>&nbsp;based on level of validation for flexibility of application</li>
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<p>Existing sample sizes are listed below. We will soon expand our collection. &nbsp;Are you looking for a sample size of another antibody? Just <a href="mailto:agnieszka.zelisko@diagenode.com?Subject=Sample%20Size%20Request" target="_top">Contact us</a>.</p>',
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			'description' => '<p><span style="font-weight: 400;">All Diagenode&rsquo;s antibodies are listed below. Please, use our Quick search field to find the antibody of interest by target name, application, purity.</span></p>
<p><span style="font-weight: 400;">Diagenode&rsquo;s highly validated antibodies:</span></p>
<ul>
<li>Highly sensitive and specific</li>
<li>Cost-effective (requires less antibody per reaction)</li>
<li>Batch-specific data is available on the website</li>
<li>Expert technical support</li>
<li>Sample sizes available</li>
<li>100% satisfaction guarantee</li>
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			'name' => 'ChIP-grade antibodies',
			'description' => '<div class="row">
<div class="small-12 columns"><center></center>
<p><br />Chromatin immunoprecipitation (<b>ChIP</b>) is a technique to study the associations of proteins with the specific genomic regions in intact cells. One of the most important steps of this protocol is the immunoprecipitation of targeted protein using the antibody specifically recognizing it. The quality of antibodies used in ChIP is essential for the success of the experiment. Diagenode offers extensively validated ChIP-grade antibodies, confirmed for their specificity, and high level of performance in ChIP. Each batch is validated, and batch-specific data are available on the website.</p>
<p></p>
</div>
</div>
<p><strong>ChIP results</strong> obtained with the antibody directed against H3K4me3 (Cat. No. <a href="../p/h3k4me3-polyclonal-antibody-premium-50-ug-50-ul">C15410003</a>).&nbsp;</p>
<div class="row">
<div class="small-12 medium-6 large-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" alt="" width="400" height="315" />&nbsp;</div>
<div class="small-12 medium-6 large-6 columns">
<p></p>
<p></p>
<p></p>
</div>
</div>
<p></p>
<p>Our aim at Diagenode is to offer the largest collection of highly specific <strong>ChIP-grade antibodies</strong>. We add new antibodies monthly. Find your ChIP-grade antibody in the list below and check more information about tested applications, extensive validation data, and product information.</p>',
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			'name' => 'Claudin-1 as a potential marker of stress-induced premature senescence in vascular smooth muscle cells',
			'authors' => 'Agnieszka Gadecka et al.',
			'description' => '<p><span>Cellular senescence, a permanent state of cell cycle arrest, can result either from external stress and is then called stress-induced premature senescence (SIPS), or from the exhaustion of cell division potential giving rise to replicative senescence (RS). Despite numerous biomarkers distinguishing SIPS from RS remains challenging. We propose claudin-1 (CLDN1) as a potential cell-specific marker of SIPS in vascular smooth muscle cells (VSMCs). In our study, VSMCs subjected to RS or SIPS exhibited significantly higher levels of CLDN1 expression exclusively in SIPS. Moreover, nuclear accumulation of this protein was also characteristic only of prematurely senescent cells. ChIP-seq results suggest that higher CLDN1 expression in SIPS might be a result of a more open chromatin state, as evidenced by a broader H3K4me3 peak in the gene promoter region. However, the broad H3K4me3 peak and relatively high&nbsp;</span><em>CLDN1</em><span><span>&nbsp;</span>expression in RS did not translate into protein level, which implies a different regulatory mechanism in this type of senescence. Elevated CLDN1 levels were also observed in VSMCs isolated from atherosclerotic plaques, although this was highly donor dependent. These findings indicate that increased CLDN1 level in prematurely senescent cells may serve as a promising cell-specific marker of SIPS in VSMCs, both in vitro and ex vivo.</span></p>',
			'date' => '2024-11-07',
			'pmid' => 'https://www.researchsquare.com/article/rs-5192437/v1',
			'doi' => 'https://doi.org/10.21203/rs.3.rs-5192437/v1',
			'modified' => '2024-11-12 09:27:24',
			'created' => '2024-11-12 09:27:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 1 => array(
			'id' => '4965',
			'name' => 'Trained immunity is regulated by T cell-induced CD40-TRAF6 signaling',
			'authors' => 'Jacobs M.M.E. et al.',
			'description' => '<p><span>Trained immunity is characterized by histone modifications and metabolic changes in innate immune cells following exposure to inflammatory signals, leading to heightened responsiveness to secondary stimuli. Although our understanding of the molecular regulation of trained immunity has increased, the role of adaptive immune cells herein remains largely unknown. Here, we show that T&nbsp;cells modulate trained immunity via cluster of differentiation 40-tissue necrosis factor receptor-associated factor 6 (CD40-TRAF6) signaling. CD40-TRAF6 inhibition modulates functional, transcriptomic, and metabolic reprogramming and modifies histone 3 lysine 4 trimethylation associated with trained immunity. Besides&nbsp;</span><i>in&nbsp;vitro</i><span><span>&nbsp;</span>studies, we reveal that single-nucleotide polymorphisms in the proximity of<span>&nbsp;</span></span><i>CD40</i><span><span>&nbsp;</span>are linked to trained immunity responses<span>&nbsp;</span></span><i>in&nbsp;vivo</i><span><span>&nbsp;</span>and that combining CD40-TRAF6 inhibition with cytotoxic T lymphocyte antigen 4-immunoglobulin (CTLA4-Ig)-mediated co-stimulatory blockade induces long-term graft acceptance in a murine heart transplantation model. Combined, our results reveal that trained immunity is modulated by CD40-TRAF6 signaling between myeloid and adaptive immune cells and that this can be leveraged for therapeutic purposes.</span></p>',
			'date' => '2024-09-24',
			'pmid' => 'https://www.cell.com/cell-reports/fulltext/S2211-1247(24)01015-5',
			'doi' => '',
			'modified' => '2024-09-02 10:23:11',
			'created' => '2024-09-02 10:23:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 2 => array(
			'id' => '4958',
			'name' => 'Legionella pneumophila modulates macrophage functions through epigenetic reprogramming via the C-type lectin receptor Mincle',
			'authors' => 'Stegmann F. et al.',
			'description' => '<p><em>Legionella pneumophila</em><span><span>&nbsp;</span>is a pathogen which can lead to a severe form of pneumonia in humans known as Legionnaires disease after replication in alveolar macrophages. Viable<span>&nbsp;</span></span><em>L.&nbsp;pneumophila</em><span><span>&nbsp;</span>actively secrete effector molecules to modulate the host&rsquo;s immune response. Here, we report that<span>&nbsp;</span></span><em>L.&nbsp;pneumophila</em><span>-derived factors reprogram macrophages into a tolerogenic state, a process to which the C-type lectin receptor Mincle (CLEC4E) markedly contributes. The underlying epigenetic state is characterized by increases of the closing mark H3K9me3 and decreases of the opening mark H3K4me3, subsequently leading to the reduced secretion of the cytokines TNF, IL-6, IL-12, the production of reactive oxygen species, and cell-surface expression of MHC-II and CD80 upon re-stimulation. In summary, these findings provide important implications for our understanding of Legionellosis and the contribution of Mincle to reprogramming of macrophages by<span>&nbsp;</span></span><em>L.&nbsp;pneumophila</em><span>.</span></p>',
			'date' => '2024-09-20',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S2589004224019254#:~:text=L.,crucial%20for%20mediating%20tolerance%20induction.',
			'doi' => 'https://doi.org/10.1016/j.isci.2024.110700',
			'modified' => '2024-09-02 10:06:00',
			'created' => '2024-09-02 10:06:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 3 => array(
			'id' => '4974',
			'name' => 'Systematic prioritization of functional variants and effector genes underlying colorectal cancer risk',
			'authors' => 'Law P.J. et al.',
			'description' => '<p><span>Genome-wide association studies of colorectal cancer (CRC) have identified 170 autosomal risk loci. However, for most of these, the functional variants and their target genes are unknown. Here, we perform statistical fine-mapping incorporating tissue-specific epigenetic annotations and massively parallel reporter assays to systematically prioritize functional variants for each CRC risk locus. We identify plausible causal variants for the 170 risk loci, with a single variant for 40. We link these variants to 208 target genes by analyzing colon-specific quantitative trait loci and implementing the activity-by-contact model, which integrates epigenomic features and Micro-C data, to predict enhancer&ndash;gene connections. By deciphering CRC risk loci, we identify direct links between risk variants and target genes, providing further insight into the molecular basis of CRC susceptibility and highlighting potential pharmaceutical targets for prevention and treatment.</span></p>',
			'date' => '2024-09-16',
			'pmid' => 'https://www.nature.com/articles/s41588-024-01900-w',
			'doi' => 'https://doi.org/10.1038/s41588-024-01900-w',
			'modified' => '2024-09-23 10:14:18',
			'created' => '2024-09-23 10:14:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 4 => array(
			'id' => '4971',
			'name' => 'Bivalent chromatin accommodates survivin and BRG1/SWI complex to activate DNA damage response in CD4+ cells',
			'authors' => 'Chandrasekaran V. et al.',
			'description' => '<section aria-labelledby="Abs1" data-title="Abstract" lang="en">
<div class="c-article-section" id="Abs1-section">
<div class="c-article-section__content" id="Abs1-content">
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Background</h3>
<p>Bivalent regions of chromatin (BvCR) are characterized by trimethylated lysine 4 (H3K4me3) and lysine 27 on histone H3 (H3K27me3) deposition which aid gene expression control during cell differentiation. The role of BvCR in post-transcriptional DNA damage response remains unidentified. Oncoprotein survivin binds chromatin and mediates IFN&gamma; effects in CD4<sup>+</sup><span>&nbsp;</span>cells. In this study, we explored the role of BvCR in DNA damage response of autoimmune CD4<sup>+</sup><span>&nbsp;</span>cells in rheumatoid arthritis (RA).</p>
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Methods</h3>
<p>We performed deep sequencing of the chromatin bound to survivin, H3K4me3, H3K27me3, and H3K27ac, in human CD4<sup>+</sup><span>&nbsp;</span>cells and identified BvCR, which possessed all three histone H3 modifications. Protein partners of survivin on chromatin were predicted by integration of motif enrichment analysis, computational machine-learning, and structural modeling, and validated experimentally by mass spectrometry and peptide binding array. Survivin-dependent change in BvCR and transcription of genes controlled by the BvCR was studied in CD4<sup>+</sup><span>&nbsp;</span>cells treated with survivin inhibitor, which revealed survivin-dependent biological processes. Finally, the survivin-dependent processes were mapped to the transcriptome of CD4<sup>+</sup><span>&nbsp;</span>cells in blood and in synovial tissue of RA patients and the effect of modern immunomodulating drugs on these processes was explored.</p>
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Results</h3>
<p>We identified that BvCR dominated by H3K4me3 (H3K4me3-BvCR) accommodated survivin within<span>&nbsp;</span><i>cis</i>-regulatory elements of the genes controlling DNA damage. Inhibition of survivin or JAK-STAT signaling enhanced H3K4me3-BvCR dominance, which improved DNA damage recognition and arrested cell cycle progression in cultured CD4<sup>+</sup><span>&nbsp;</span>cells. Specifically, BvCR accommodating survivin aided sequence-specific anchoring of the BRG1/SWI chromatin-remodeling complex coordinating DNA damage response. Mapping survivin interactome to BRG1/SWI complex demonstrated interaction of survivin with the subunits anchoring the complex to chromatin. Co-expression of BRG1, survivin and IFN&gamma; in CD4<sup>+</sup><span>&nbsp;</span>cells rendered complete deregulation of DNA damage response in RA. Such cells possessed strong ability of homing to RA joints. Immunomodulating drugs inhibited the anchoring subunits of BRG1/SWI complex, which affected arthritogenic profile of CD4<sup>+</sup><span>&nbsp;</span>cells.</p>
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Conclusions</h3>
<p>BvCR execute DNA damage control to maintain genome fidelity in IFN-activated CD4<sup>+</sup><span>&nbsp;</span>cells. Survivin anchors the BRG1/SWI complex to BvCR to repress DNA damage response. These results offer a platform for therapeutic interventions targeting survivin and BRG1/SWI complex in autoimmunity.</p>
</div>
</div>
</section>
<section data-title="Background">
<div class="c-article-section" id="Sec1-section">
<h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec1"></h2>
</div>
</section>',
			'date' => '2024-09-11',
			'pmid' => 'https://biosignaling.biomedcentral.com/articles/10.1186/s12964-024-01814-4',
			'doi' => 'https://doi.org/10.1186/s12964-024-01814-4',
			'modified' => '2024-09-16 10:02:18',
			'created' => '2024-09-16 10:02:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 5 => array(
			'id' => '4951',
			'name' => 'LL37/self-DNA complexes mediate monocyte reprogramming',
			'authors' => 'Aman Damara et al.',
			'description' => '<p><span>LL37 alone and in complex with self-DNA triggers inflammatory responses in myeloid cells and plays a crucial role in the development of systemic autoimmune diseases, like psoriasis and systemic lupus erythematosus. We demonstrated that LL37/self-DNA complexes induce long-term metabolic and epigenetic changes in monocytes, enhancing their responsiveness to subsequent stimuli. Monocytes trained with LL37/self-DNA complexes and those derived from psoriatic patients exhibited heightened glycolytic and oxidative phosphorylation rates, elevated release of proinflammatory cytokines, and affected na&iuml;ve CD4</span><sup>+</sup><span><span>&nbsp;</span>T cells. Additionally, KDM6A/B, a demethylase of lysine 27 on histone 3, was upregulated in psoriatic monocytes and monocytes treated with LL37/self-DNA complexes. Inhibition of KDM6A/B reversed the trained immune phenotype by reducing proinflammatory cytokine production, metabolic activity, and the induction of IL-17-producing T cells by LL37/self-DNA-treated monocytes. Our findings highlight the role of LL37/self-DNA-induced innate immune memory in psoriasis pathogenesis, uncovering its impact on monocyte and T cell dynamics.</span></p>',
			'date' => '2024-08-01',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S1521661624003966',
			'doi' => 'https://doi.org/10.1016/j.clim.2024.110287',
			'modified' => '2024-07-04 15:53:17',
			'created' => '2024-07-04 15:53:17',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 6 => array(
			'id' => '4968',
			'name' => 'Innate immune training restores pro-reparative myeloid functions to promote remyelination in the aged central nervous system',
			'authors' => 'Tiwari V. et al.',
			'description' => '<p><span>The reduced ability of the central nervous system to regenerate with increasing age limits functional recovery following demyelinating injury. Previous work has shown that myelin debris can overwhelm the metabolic capacity of microglia, thereby impeding tissue regeneration in aging, but the underlying mechanisms are unknown. In a model of demyelination, we found that a substantial number of genes that were not effectively activated in aged myeloid cells displayed epigenetic modifications associated with restricted chromatin accessibility. Ablation of two class I histone deacetylases in microglia was sufficient to restore the capacity of aged mice to remyelinate lesioned tissue. We used Bacillus Calmette-Guerin (BCG), a live-attenuated vaccine, to train the innate immune system and detected epigenetic reprogramming of brain-resident myeloid cells and functional restoration of myelin debris clearance and lesion recovery. Our results provide insight into aging-associated decline in myeloid function and how this decay can be prevented by innate immune reprogramming.</span></p>',
			'date' => '2024-07-24',
			'pmid' => 'https://www.cell.com/immunity/fulltext/S1074-7613(24)00348-0',
			'doi' => '',
			'modified' => '2024-09-02 17:05:54',
			'created' => '2024-09-02 17:05:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 7 => array(
			'id' => '4954',
			'name' => 'A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment',
			'authors' => 'Perez R. F. at al. ',
			'description' => '<p><span>Aging involves the deterioration of organismal function, leading to the emergence of multiple pathologies. Environmental stimuli, including lifestyle, can influence the trajectory of this process and may be used as tools in the pursuit of healthy aging. To evaluate the role of epigenetic mechanisms in this context, we have generated bulk tissue and single cell multi-omic maps of the male mouse dorsal hippocampus in young and old animals exposed to environmental stimulation in the form of enriched environments. We present a molecular atlas of the aging process, highlighting two distinct axes, related to inflammation and to the dysregulation of mRNA metabolism, at the functional RNA and protein level. Additionally, we report the alteration of heterochromatin domains, including the loss of bivalent chromatin and the uncovering of a heterochromatin-switch phenomenon whereby constitutive heterochromatin loss is partially mitigated through gains in facultative heterochromatin. Notably, we observed the multi-omic reversal of a great number of aging-associated alterations in the context of environmental enrichment, which was particularly linked to glial and oligodendrocyte pathways. In conclusion, our work describes the epigenomic landscape of environmental stimulation in the context of aging and reveals how lifestyle intervention can lead to the multi-layered reversal of aging-associated decline.</span></p>',
			'date' => '2024-07-16',
			'pmid' => 'https://www.nature.com/articles/s41467-024-49608-z',
			'doi' => 'https://doi.org/10.1038/s41467-024-49608-z',
			'modified' => '2024-07-29 11:33:49',
			'created' => '2024-07-29 11:33:49',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 8 => array(
			'id' => '4946',
			'name' => 'The landscape of RNA-chromatin interaction reveals small non-coding RNAs as essential mediators of leukemia maintenance',
			'authors' => 'Haiyang Yun et al.',
			'description' => '<p><span>RNA constitutes a large fraction of chromatin. Spatial distribution and functional relevance of most of RNA-chromatin interactions remain unknown. We established a landscape analysis of RNA-chromatin interactions in human acute myeloid leukemia (AML). In total more than 50 million interactions were captured in an AML cell line. Protein-coding mRNAs and long non-coding RNAs exhibited a substantial number of interactions with chromatin in&nbsp;</span><i>cis</i><span><span>&nbsp;</span>suggesting transcriptional activity. In contrast, small nucleolar RNAs (snoRNAs) and small nuclear RNAs (snRNAs) associated with chromatin predominantly in<span>&nbsp;</span></span><i>trans</i><span><span>&nbsp;</span>suggesting chromatin specific functions. Of note, snoRNA-chromatin interaction was associated with chromatin modifications and occurred independently of the classical snoRNA-RNP complex. Two C/D box snoRNAs, namely<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span>, displayed high frequency of<span>&nbsp;</span></span><i>trans</i><span>-association with chromatin. The transcription of<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span><span>&nbsp;</span>was increased upon leukemia transformation and enriched in leukemia stem cells, but decreased during myeloid differentiation. Suppression of<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span><span>&nbsp;</span>impaired leukemia cell proliferation and colony forming capacity in AML cell lines and primary patient samples. Notably, this effect was leukemia specific with less impact on healthy CD34+ hematopoietic stem and progenitor cells. These findings highlight the functional importance of chromatin-associated RNAs overall and in particular of<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span><span>&nbsp;</span>in maintaining leukemia propagation.</span></p>',
			'date' => '2024-06-28',
			'pmid' => 'https://www.nature.com/articles/s41375-024-02322-7',
			'doi' => 'https://doi.org/10.1038/s41375-024-02322-7',
			'modified' => '2024-07-04 14:32:41',
			'created' => '2024-07-04 14:32:41',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 9 => array(
			'id' => '4948',
			'name' => 'Single-cell epigenomic reconstruction of developmental trajectories from pluripotency in human neural organoid systems',
			'authors' => 'Fides Zenk et al.',
			'description' => '<p><span>Cell fate progression of pluripotent progenitors is strictly regulated, resulting in high human cell diversity. Epigenetic modifications also orchestrate cell fate restriction. Unveiling the epigenetic mechanisms underlying human cell diversity has been difficult. In this study, we use human brain and retina organoid models and present single-cell profiling of H3K27ac, H3K27me3 and H3K4me3 histone modifications from progenitor to differentiated neural fates to reconstruct the epigenomic trajectories regulating cell identity acquisition. We capture transitions from pluripotency through neuroepithelium to retinal and brain region and cell type specification. Switching of repressive and activating epigenetic modifications can precede and predict cell fate decisions at each stage, providing a temporal census of gene regulatory elements and transcription factors. Removing H3K27me3 at the neuroectoderm stage disrupts fate restriction, resulting in aberrant cell identity acquisition. Our single-cell epigenome-wide map of human neural organoid development serves as a blueprint to explore human cell fate determination.</span></p>',
			'date' => '2024-06-24',
			'pmid' => 'https://www.nature.com/articles/s41593-024-01652-0',
			'doi' => 'https://doi.org/10.1038/s41593-024-01652-0',
			'modified' => '2024-07-04 14:54:14',
			'created' => '2024-07-04 14:54:14',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 10 => array(
			'id' => '4924',
			'name' => 'SURVIVIN IN SYNERGY WITH BAF/SWI COMPLEX BINDS BIVALENT CHROMATIN REGIONS AND ACTIVATES DNA DAMAGE RESPONSE IN CD4+ T CELLS',
			'authors' => 'Chandrasekaran V. et al.',
			'description' => '<p id="p-2">This study explores a regulatory role of oncoprotein survivin on the bivalent regions of chromatin (BvCR) characterized by concomitant deposition of trimethylated lysine of histone H3 at position 4 (H3K4me3) and 27 (H3K27me3).</p>
<p id="p-3">Intersect between BvCR and chromatin sequences bound to survivin demonstrated their co-localization on<span>&nbsp;</span><em>cis</em>-regulatory elements of genes which execute DNA damage control in primary human CD4<sup>+</sup><span>&nbsp;</span>cells. Survivin anchored BRG1-complex to BvCR to repress DNA damage repair genes in IFN&gamma;-stimulated CD4<sup>+</sup><span>&nbsp;</span>cells. In contrast, survivin inhibition shifted the functional balance of BvCR in favor of H3K4me3, which activated DNA damage recognition and repair. Co-expression of BRG1, survivin and IFN&gamma; in CD4<sup>+</sup><span>&nbsp;</span>cells of patients with rheumatoid arthritis identified arthritogenic BRG1<sup>hi</sup><span>&nbsp;</span>cells abundant in autoimmune synovia. Immunomodulating drugs inhibited the subunits anchoring BRG1-complex to BvCR, which changed the arthritogenic profile.</p>
<p id="p-4">Together, this study demonstrates the function of BvCR in DNA damage control of CD4<sup>+</sup><span>&nbsp;</span>cells offering an epigenetic platform for survivin and BRG1-complex targeting interventions to combat autoimmunity.</p>
<div id="sec-1" class="subsection">
<p id="p-5"><strong>Summary</strong><span>&nbsp;</span>This study shows that bivalent chromatin regions accommodate survivin which represses DNA repair enzymes in IFN&gamma;-stimulated CD4<sup>+</sup><span>&nbsp;</span>T cells. Survivin anchors BAF/SWI complex to these regions and supports autoimmune profile of T cells, providing novel targets for therapeutic intervention.</p>
</div>',
			'date' => '2024-03-10',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/2024.03.05.583464v1',
			'doi' => 'https://doi.org/10.1101/2024.03.05.583464',
			'modified' => '2024-03-13 17:07:31',
			'created' => '2024-03-13 17:07:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 11 => array(
			'id' => '4911',
			'name' => 'Multiomics uncovers the epigenomic and transcriptomic response to viral and bacterial stimulation in turbot',
			'authors' => 'Aramburu O. et al.',
			'description' => '<p><span>Uncovering the epigenomic regulation of immune responses is essential for a comprehensive understanding of host defence mechanisms but remains poorly described in farmed fish. Here, we report the first annotation of the innate immune regulatory response in the genome of turbot (</span><em>Scophthalmus maximus</em><span>), a farmed flatfish. We integrated RNA-Seq with ATAC-Seq and ChIP-Seq (histone marks H3K4me3, H3K27ac and H3K27me3) using samples from head kidney. Sampling was performed 24 hours post-stimulation with viral (poly I:C) and bacterial (inactivate<span>&nbsp;</span></span><em>Vibrio anguillarum</em><span>) mimics<span>&nbsp;</span></span><em>in vivo</em><span><span>&nbsp;</span>and<span>&nbsp;</span></span><em>in vitro</em><span><span>&nbsp;</span>(primary leukocyte cultures). Among the 8,797 differentially expressed genes (DEGs), we observed enrichment of transcriptional activation pathways in response to<span>&nbsp;</span></span><em>Vibrio</em><span><span>&nbsp;</span>and immune response pathways - including interferon stimulated genes - for poly I:C. Meanwhile, metabolic and cell cycle were downregulated by both mimics. We identified notable differences in chromatin accessibility (20,617<span>&nbsp;</span></span><em>in vitro</em><span>, 59,892<span>&nbsp;</span></span><em>in vivo</em><span>) and H3K4me3 bound regions (11,454<span>&nbsp;</span></span><em>in vitro</em><span>, 10,275<span>&nbsp;</span></span><em>in viv</em><span>o) - i.e. marking active promoters - between stimulations and controls. Overlaps of DEGs with promoters showing differential accessibility or histone mark binding revealed a significant coupling of the transcriptome and chromatin state. DEGs with activation marks in their promoters were enriched for similar functions to the global DEG set, but not in all cases, suggesting key regulatory genes were in poised or bivalent states. Active promoters and putative enhancers were differentially enriched in transcription factor binding motifs, many of them common to viral and bacterial responses. Finally, an in-depth analysis of immune response changes in chromatin state surrounding key DEGs encoding transcription factors was performed. This comprehensive multi-omics investigation provides an improved understanding of the epigenomic basis for the turbot immune responses and provides novel functional genomic information that can be leveraged in selective breeding towards enhanced disease resistance.</span></p>',
			'date' => '2024-02-15',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/2024.02.15.580452v1',
			'doi' => 'https://doi.org/10.1101/2024.02.15.580452',
			'modified' => '2024-02-22 11:41:27',
			'created' => '2024-02-22 11:41:27',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 12 => array(
			'id' => '4842',
			'name' => 'Alterations in the hepatocyte epigenetic landscape in steatosis.',
			'authors' => 'Maji  Ranjan K. et al.',
			'description' => '<p>Fatty liver disease or the accumulation of fat in the liver, has been reported to affect the global population. This comes with an increased risk for the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Yet, little is known about the effects of a diet containing high fat and alcohol towards epigenetic aging, with respect to changes in transcriptional and epigenomic profiles. In this study, we took up a multi-omics approach and integrated gene expression, methylation signals, and chromatin signals to study the epigenomic effects of a high-fat and alcohol-containing diet on mouse hepatocytes. We identified four relevant gene network clusters that were associated with relevant pathways that promote steatosis. Using a machine learning approach, we predict specific transcription factors that might be responsible to modulate the functionally relevant clusters. Finally, we discover four additional CpG loci and validate aging-related differential CpG methylation. Differential CpG methylation linked to aging showed minimal overlap with altered methylation in steatosis.</p>',
			'date' => '2023-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37415213',
			'doi' => '10.1186/s13072-023-00504-8',
			'modified' => '2023-08-01 14:08:16',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 13 => array(
			'id' => '4859',
			'name' => 'Sexual differentiation in human malaria parasites is regulated bycompetition between phospholipid metabolism and histone methylation.',
			'authors' => 'Harris  C. T. et al.',
			'description' => '<p>For Plasmodium falciparum, the most widespread and virulent malaria parasite that infects humans, persistence depends on continuous asexual replication in red blood cells, while transmission to their mosquito vector requires asexual blood-stage parasites to differentiate into non-replicating gametocytes. This decision is controlled by stochastic derepression of a heterochromatin-silenced locus encoding AP2-G, the master transcription factor of sexual differentiation. The frequency of ap2-g derepression was shown to be responsive to extracellular phospholipid precursors but the mechanism linking these metabolites to epigenetic regulation of ap2-g was unknown. Through a combination of molecular genetics, metabolomics and chromatin profiling, we show that this response is mediated by metabolic competition for the methyl donor S-adenosylmethionine between histone methyltransferases and phosphoethanolamine methyltransferase, a critical enzyme in the parasite's pathway for de novo phosphatidylcholine synthesis. When phosphatidylcholine precursors are scarce, increased consumption of SAM for de novo phosphatidylcholine synthesis impairs maintenance of the histone methylation responsible for silencing ap2-g, increasing the frequency of derepression and sexual differentiation. This provides a key mechanistic link that explains how LysoPC and choline availability can alter the chromatin status of the ap2-g locus controlling sexual differentiation.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37277533',
			'doi' => '10.1038/s41564-023-01396-w',
			'modified' => '2023-08-01 14:48:21',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 14 => array(
			'id' => '4862',
			'name' => 'Mutant FUS induces chromatin reorganization in the hippocampus andalters memory processes.',
			'authors' => 'Tzeplaeff  L. et al.',
			'description' => '<p>Cytoplasmic mislocalization of the nuclear Fused in Sarcoma (FUS) protein is associated to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cytoplasmic FUS accumulation is recapitulated in the frontal cortex and spinal cord of heterozygous Fus mice. Yet, the mechanisms linking FUS mislocalization to hippocampal function and memory formation are still not characterized. Herein, we show that in these mice, the hippocampus paradoxically displays nuclear FUS accumulation. Multi-omic analyses showed that FUS binds to a set of genes characterized by the presence of an ETS/ELK-binding motifs, and involved in RNA metabolism, transcription, ribosome/mitochondria and chromatin organization. Importantly, hippocampal nuclei showed a decompaction of the neuronal chromatin at highly expressed genes and an inappropriate transcriptomic response was observed after spatial training of Fus mice. Furthermore, these mice lacked precision in a hippocampal-dependent spatial memory task and displayed decreased dendritic spine density. These studies shows that mutated FUS affects epigenetic regulation of the chromatin landscape in hippocampal neurons, which could participate in FTD/ALS pathogenic events. These data call for further investigation in the neurological phenotype of FUS-related diseases and open therapeutic strategies towards epigenetic drugs.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37327984',
			'doi' => '10.1016/j.pneurobio.2023.102483',
			'modified' => '2023-08-01 14:55:49',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 15 => array(
			'id' => '4820',
			'name' => 'The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cellfate.',
			'authors' => 'Lackner  A. et al.',
			'description' => '<p><span>Placental development relies on coordinated cell fate decisions governed by signalling inputs. However, little is known about how signalling cues are transformed into repressive mechanisms triggering lineage-specific transcriptional signatures. Here, we demonstrate that upon inhibition of the Fgf/Erk pathway in mouse trophoblast stem cells (TSCs), the Ets2 repressor factor (Erf) interacts with the Nuclear Receptor Co-Repressor Complex 1 and 2 (NCoR1/2) and recruits it to key trophoblast genes. Genetic ablation of Erf or Tbl1x (a component of the NCoR1/2 complex) abrogates the Erf/NCoR1/2 interaction. This leads to mis-expression of Erf/NCoR1/2 target genes, resulting in a TSC differentiation defect. Mechanistically, Erf regulates expression of these genes by recruiting the NCoR1/2 complex and decommissioning their H3K27ac-dependent enhancers. Our findings uncover how the Fgf/Erf/NCoR1/2 repressive axis governs cell fate and placental development, providing a paradigm for Fgf-mediated transcriptional control.</span></p>',
			'date' => '2023-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37137875',
			'doi' => '10.1038/s41467-023-38101-8',
			'modified' => '2023-06-19 10:10:38',
			'created' => '2023-06-13 21:11:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 16 => array(
			'id' => '4778',
			'name' => 'Comprehensive epigenomic profiling reveals the extent of disease-specificchromatin states and informs target discovery in ankylosing spondylitis',
			'authors' => 'Brown  A.C. et al.',
			'description' => '<p>Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterized by enthesitis of the spine and sacroiliac joints. Genome-wide association studies (GWASs) have revealed more than 100 genetic associations whose functional effects remain largely unresolved. Here, we present a comprehensive transcriptomic and epigenomic map of disease-relevant blood immune cell subsets from AS patients and healthy controls.We find that, while CD14+ monocytes and CD4+ and CD8+ T cells show disease-specific differences at the RNA level, epigenomic differences are only apparent upon multi-omics integration. The latter reveals enrichment at disease-associated loci in monocytes. We link putative functional SNPs to genes using high-resolution Capture-C at 10 loci, including PTGER4 and ETS1, and show how disease-specific functional genomic data can be integrated with GWASs to enhance therapeutic target discovery. This study combines epigenetic and transcriptional analysis with GWASs to identify disease-relevant cell types and gene regulation of likely pathogenic relevance and prioritize drug targets.</p>',
			'date' => '2023-04-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.xgen.2023.100306',
			'doi' => '10.1016/j.xgen.2023.100306',
			'modified' => '2023-06-13 09:14:26',
			'created' => '2023-05-05 12:34:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 17 => array(
			'id' => '4763',
			'name' => 'Chromatin profiling identifies transcriptional readthrough as a conservedmechanism for piRNA biogenesis in mosquitoes.',
			'authors' => 'Qu  J. et al.',
			'description' => '<p>The piRNA pathway in mosquitoes differs substantially from other model organisms, with an expanded PIWI gene family and functions in antiviral defense. Here, we define core piRNA clusters as genomic loci that show ubiquitous piRNA expression in both somatic and germline tissues. These core piRNA clusters are enriched for non-retroviral endogenous viral elements (nrEVEs) in antisense orientation and depend on key biogenesis factors, Veneno, Tejas, Yb, and Shutdown. Combined transcriptome and chromatin state analyses identify transcriptional readthrough as a conserved mechanism for cluster-derived piRNA biogenesis in the vector mosquitoes Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and Anopheles gambiae. Comparative analyses between the two Aedes species suggest that piRNA clusters function as traps for nrEVEs, allowing adaptation to environmental challenges such as virus infection. Our systematic transcriptome and chromatin state analyses lay the foundation for studies of gene regulation, genome evolution, and piRNA function in these important vector species.</p>',
			'date' => '2023-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36930642',
			'doi' => '10.1016/j.celrep.2023.112257',
			'modified' => '2023-04-17 09:12:37',
			'created' => '2023-04-14 13:41:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 18 => array(
			'id' => '4765',
			'name' => 'Epigenetic dosage identifies two major and functionally distinct beta cells ubtypes.',
			'authors' => 'Dror  E.et al.',
			'description' => '<p>The mechanisms that specify and stabilize cell subtypes remain poorly understood. Here, we identify two major subtypes of pancreatic &Icirc;&sup2; cells based on histone mark heterogeneity (beta HI and beta LO). Beta HI cells exhibit 4-fold higher levels of H3K27me3, distinct chromatin organization and compaction, and a specific transcriptional pattern. B<span>eta HI and beta LO</span> cells also differ in size, morphology, cytosolic and nuclear ultrastructure, epigenomes, cell surface marker expression, and function, and can be FACS separated into CD24 and CD24 fractions. Functionally, &Icirc;&sup2; cells have increased mitochondrial mass, activity, and insulin secretion in vivo and ex vivo. Partial loss of function indicates that H3K27me3 dosage regulates <span>beta HI/beta LO&nbsp;</span>ratio in vivo, suggesting that control of <span>beta HI&nbsp;</span>cell subtype identity and ratio is at least partially uncoupled. Both subtypes are conserved in humans, with <span>beta HI</span> cells enriched in humans with type 2 diabetes. Thus, epigenetic dosage is a novel regulator of cell subtype specification and identifies two functionally distinct&nbsp;beta cell subtypes.</p>',
			'date' => '2023-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36948185',
			'doi' => '10.1016/j.cmet.2023.03.008',
			'modified' => '2023-04-17 09:26:02',
			'created' => '2023-04-14 13:41:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 19 => array(
			'id' => '4667',
			'name' => 'Detailed molecular and epigenetic characterization of the Pig IPECJ2and Chicken SL-29 cell lines',
			'authors' => 'de Vos  J. et al.',
			'description' => '<p>The pig IPECJ2 and chicken SL-29 cell lines are of interest because of their untransformed nature and wide use in functional studies. Molecular characterization of these cell lines is important to gain insight into possible molecular aberrations. The aims of this paper are providing a molecular and epigenetic characterization of the IPEC-J2 and SL-29 cell lines and providing a cell-line reference for the FAANG community, and future biomedical research. Whole genome sequencing , gene expression, DNA methylation , chromatin accessibility and ChIP-seq of four histone marks (H3K4me1, H3K4me3, H3K27ac, H3K27me3) and an insulator (CTCF) are used to achieve these aims. Heteroploidy (aneuploidy) of various chromosomes was observed from whole genome sequencing analysis in both cell lines. Furthermore, higher gene expression for genes located on chromosomes with aneuploidy in comparison to diploid chromosomes was observed. Regulatory complexity of gene expression, DNA methylation and chromatin accessibility was investigated through an integrative approach.</p>',
			'date' => '2023-02-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.isci.2023.106252',
			'doi' => '10.1016/j.isci.2023.106252',
			'modified' => '2023-04-07 16:52:26',
			'created' => '2023-02-28 12:19:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 20 => array(
			'id' => '4669',
			'name' => 'Histone remodeling reflects conserved mechanisms of bovine and humanpreimplantation development.',
			'authors' => 'Zhou  C. et al.',
			'description' => '<p>How histone modifications regulate changes in gene expression during preimplantation development in any species remains poorly understood. Using CUT\&amp;Tag to overcome limiting amounts of biological material, we profiled two activating (H3K4me3 and H3K27ac) and two repressive (H3K9me3 and H3K27me3) marks in bovine oocytes, 2-, 4-, and 8-cell embryos, morula, blastocysts, inner cell mass, and trophectoderm. In oocytes, broad bivalent domains mark developmental genes, and prior to embryonic genome activation (EGA), H3K9me3 and H3K27me3 co-occupy gene bodies, suggesting a global mechanism for transcription repression. During EGA, chromatin accessibility is established before canonical H3K4me3 and H3K27ac signatures. Embryonic transcription is required for this remodeling, indicating that maternally provided products alone are insufficient for reprogramming. Last, H3K27me3 plays a major role in restriction of cellular potency, as blastocyst lineages are defined by differential polycomb repression and transcription factor activity. Notably, inferred regulators of EGA and blastocyst formation strongly resemble those described in humans, as opposed to mice. These similarities suggest that cattle are a better model than rodents to investigate the molecular basis of human preimplantation development.</p>',
			'date' => '2023-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36779365',
			'doi' => '10.15252/embr.202255726',
			'modified' => '2023-04-14 09:34:12',
			'created' => '2023-02-28 12:19:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 21 => array(
			'id' => '4605',
			'name' => 'Gene Regulatory Interactions at Lamina-Associated Domains',
			'authors' => 'Madsen-Østerbye  J. et al.',
			'description' => '<p>The nuclear lamina provides a repressive chromatin environment at the nuclear periphery. However, whereas most genes in lamina-associated domains (LADs) are inactive, over ten percent reside in local euchromatic contexts and are expressed. How these genes are regulated and whether they are able to interact with regulatory elements remain unclear. Here, we integrate publicly available enhancer-capture Hi-C data with our own chromatin state and transcriptomic datasets to show that inferred enhancers of active genes in LADs are able to form connections with other enhancers within LADs and outside LADs. Fluorescence in situ hybridization analyses show proximity changes between differentially expressed genes in LADs and distant enhancers upon the induction of adipogenic differentiation. We also provide evidence of involvement of lamin A/C, but not lamin B1, in repressing genes at the border of an in-LAD active region within a topological domain. Our data favor a model where the spatial topology of chromatin at the nuclear lamina is compatible with gene expression in this dynamic nuclear compartment.</p>',
			'date' => '2023-01-01',
			'pmid' => 'https://doi.org/10.3390%2Fgenes14020334',
			'doi' => '10.3390/genes14020334',
			'modified' => '2023-04-04 08:57:32',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 22 => array(
			'id' => '4802',
			'name' => 'Analyzing the Genome-Wide Distribution of Histone Marks byCUT\&Tag in Drosophila Embryos.',
			'authors' => 'Zenk  F. et al.',
			'description' => '<p><span>CUT&amp;Tag is a method to map the genome-wide distribution of histone modifications and some chromatin-associated proteins. CUT&amp;Tag relies on antibody-targeted chromatin tagmentation and can easily be scaled up or automatized. This protocol provides clear experimental guidelines and helpful considerations when planning and executing CUT&amp;Tag experiments.</span></p>',
			'date' => '2023-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37212984',
			'doi' => '10.1007/978-1-0716-3143-0_1',
			'modified' => '2023-06-15 08:43:40',
			'created' => '2023-06-13 21:11:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 23 => array(
			'id' => '4545',
			'name' => 'Histone Deacetylases 1 and 2 target gene regulatory networks of nephronprogenitors to control nephrogenesis.',
			'authors' => 'Liu  Hongbing et al.',
			'description' => '<p>Our studies demonstrated the critical role of Histone deacetylases (HDACs) in the regulation of nephrogenesis. To better understand the key pathways regulated by HDAC1/2 in early nephrogenesis, we performed chromatin immunoprecipitation sequencing (ChIP-Seq) of Hdac1/2 on isolated nephron progenitor cells (NPCs) from mouse E16.5 kidneys. Our analysis revealed that 11802 (40.4\%) of Hdac1 peaks overlap with Hdac2 peaks, further demonstrates the redundant role of Hdac1 and Hdac2 during nephrogenesis. Common Hdac1/2 peaks are densely concentrated close to the transcriptional start site (TSS). GREAT Gene Ontology analysis of overlapping Hdac1/2 peaks reveals that Hdac1/2 are associated with metanephric nephron morphogenesis, chromatin assembly or disassembly, as well as other DNA checkpoints. Pathway analysis shows that negative regulation of Wnt signaling pathway is one of Hdac1/2's most significant function in NPCs. Known motif analysis indicated that Hdac1 is enriched in motifs for Six2, Hox family, and Tcf family members, which are essential for self-renewal and differentiation of nephron progenitors. Interestingly, we found the enrichment of HDAC1/2 at the enhancer and promoter regions of actively transcribed genes, especially those concerned with NPC self-renewal. HDAC1/2 simultaneously activate or repress the expression of different genes to maintain the cellular state of nephron progenitors. We used the Integrative Genomics Viewer to visualize these target genes associated with each function and found that Hdac1/2 co-bound to the enhancers or/and promoters of genes associated with nephron morphogenesis, differentiation, and cell cycle control. Taken together, our ChIP-Seq analysis demonstrates that Hdac1/2 directly regulate the molecular cascades essential for nephrogenesis.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36356658',
			'doi' => '10.1016/j.bcp.2022.115341',
			'modified' => '2022-11-24 10:24:07',
			'created' => '2022-11-24 08:49:52',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 24 => array(
			'id' => '4658',
			'name' => 'Balance between autophagy and cell death is maintained byPolycomb-mediated regulation during stem cell differentiation.',
			'authors' => 'Puri  Deepika et al.',
			'description' => '<p>Autophagy is a conserved cytoprotective process, aberrations in which lead to numerous degenerative disorders. While the cytoplasmic components of autophagy have been extensively studied, the epigenetic regulation of autophagy genes, especially in stem cells, is less understood. Deciphering the epigenetic regulation of autophagy genes becomes increasingly relevant given the therapeutic benefits of small-molecule epigenetic inhibitors in novel treatment modalities. We observe that, during retinoic acid-mediated differentiation of mouse embryonic stem cells (mESCs), autophagy is induced, and identify the Polycomb group histone methyl transferase EZH2 as a regulator of this process. In mESCs, EZH2 represses several autophagy genes, including the autophagy regulator DNA damage-regulated autophagy modulator protein 1 (Dram1). EZH2 facilitates the formation of a bivalent chromatin domain at the Dram1 promoter, allowing gene expression and autophagy induction during differentiation while retaining the repressive H3K27me3 mark. EZH2 inhibition leads to loss of the bivalent domain, with consequent "hyper-expression" of Dram1, accompanied by extensive cell death. This study shows that Polycomb group proteins help maintain a balance between autophagy and cell death during stem cell differentiation, in part by regulating the expression of the Dram1 gene.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36380631',
			'doi' => '10.1111/febs.16656',
			'modified' => '2023-03-07 08:59:36',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 25 => array(
			'id' => '4788',
			'name' => 'Dietary methionine starvation impairs acute myeloid leukemia progression.',
			'authors' => 'Cunningham  A. et al.',
			'description' => '<p>Targeting altered tumor cell metabolism might provide an attractive opportunity for patients with acute myeloid leukemia (AML). An amino acid dropout screen on primary leukemic stem cells and progenitor populations revealed a number of amino acid dependencies, of which methionine was one of the strongest. By using various metabolite rescue experiments, nuclear magnetic resonance-based metabolite quantifications and 13C-tracing, polysomal profiling, and chromatin immunoprecipitation sequencing, we identified that methionine is used predominantly for protein translation and to provide methyl groups to histones via S-adenosylmethionine for epigenetic marking. H3K36me3 was consistently the most heavily impacted mark following loss of methionine. Methionine depletion also reduced total RNA levels, enhanced apoptosis, and induced a cell cycle block. Reactive oxygen species levels were not increased following methionine depletion, and replacement of methionine with glutathione or N-acetylcysteine could not rescue phenotypes, excluding a role for methionine in controlling redox balance control in AML. Although considered to be an essential amino acid, methionine can be recycled from homocysteine. We uncovered that this is primarily performed by the enzyme methionine synthase and only when methionine availability becomes limiting. In&Acirc;&nbsp;vivo, dietary methionine starvation was not only tolerated by mice, but also significantly delayed both cell line and patient-derived AML progression. Finally, we show that inhibition of the H3K36-specific methyltransferase SETD2 phenocopies much of the cytotoxic effects of methionine depletion, providing a more targeted therapeutic approach. In conclusion, we show that methionine depletion is a vulnerability in AML that can be exploited therapeutically, and we provide mechanistic insight into how cells metabolize and recycle methionine.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://doi.org/10.33612%2Fdiss.205032978',
			'doi' => '10.1182/blood.2022017575',
			'modified' => '2023-06-12 09:01:21',
			'created' => '2023-05-05 12:34:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 26 => array(
			'id' => '4499',
			'name' => 'Trained Immunity Provides Long-Term Protection againstBacterial Infections in Channel Catfish.',
			'authors' => 'Petrie-Hanson  L. et al.',
			'description' => '<p>Beta glucan exposure induced trained immunity in channel catfish that conferred long-term protection against and infections one month post exposure. Flow cytometric analyses demonstrated that isolated macrophages and neutrophils phagocytosed higher amounts of and . Beta glucan induced changes in the distribution of histone modifications in the monomethylation and trimethylation of H3K4 and modifications in the acetylation and trimethylation of H3K27. KEGG pathway analyses revealed that these modifications affected expressions of genes controlling phagocytosis, phagosome functions and enhanced immune cell signaling. These analyses correlate the histone modifications with gene functions and to the observed enhanced phagocytosis and to the increased survival following bacterial challenge in channel catfish. These data suggest the chromatin reconfiguration that directs trained immunity as demonstrated in mammals also occurs in channel catfish. Understanding the mechanisms underlying trained immunity can help us design prophylactic and non-antibiotic based therapies and develop broad-based vaccines to limit bacterial disease outbreaks in catfish production.</p>',
			'date' => '2022-10-01',
			'pmid' => 'https://doi.org/10.3390%2Fpathogens11101140',
			'doi' => '10.3390/pathogens11101140',
			'modified' => '2022-11-21 10:31:12',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 27 => array(
			'id' => '4451',
			'name' => 'bESCs from cloned embryos do not retain transcriptomic or epigenetic memory from somatic donor cells.',
			'authors' => 'Navarro  M. et al.',
			'description' => '<p>Embryonic stem cells (ESC) indefinitely maintain the pluripotent state of the blastocyst epiblast. Stem cells are invaluable for studying development and lineage commitment, and in livestock they constitute a useful tool for genomic improvement and in vitro breeding programs. Although these cells have been recently derived from bovine blastocysts, a detailed characterization of their molecular state is still lacking. Here, we apply cutting-edge technologies to analyze the transcriptomic and epigenomic landscape of bovine ESC (bESC) obtained from in vitro fertilized (IVF) and somatic cell nuclear transfer (SCNT) embryos. Bovine ESC were efficiently derived from SCNT and IVF embryos and expressed pluripotency markers while retaining genome stability. Transcriptome analysis revealed that only 46 genes were differentially expressed between IVF- and SCNT-derived bESC, which did not reflect significant deviation in cellular function. Interrogating the histone marks H3K4me3, H3K9me3 and H3K27me3 with CUT\&amp;Tag, we found that the epigenomes of both bESC groups were virtually indistinguishable. Minor epigenetic differences were randomly distributed throughout the genome and were not associated with differentially expressed or developmentally important genes. Finally, categorization of genomic regions according to their combined histone mark signal demonstrated that all bESC shared the same epigenomic signatures, especially at promoters. Overall, we conclude that bESC derived from SCNT and IVF are transcriptomically and epigenetically analogous, allowing for the production of an unlimited source of pluripotent cells from high genetic merit organisms without resorting to genome editing techniques.</p>',
			'date' => '2022-08-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/35951478/',
			'doi' => '10.1530/REP-22-0063',
			'modified' => '2022-10-21 09:31:32',
			'created' => '2022-09-28 09:53:13',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 28 => array(
			'id' => '4416',
			'name' => 'Large-scale manipulation of promoter DNA methylation revealscontext-specific transcriptional responses and stability.',
			'authors' => 'de Mendoza  A. et al. ',
			'description' => '<p>BACKGROUND: Cytosine DNA methylation is widely described as a transcriptional repressive mark with the capacity to silence promoters. Epigenome engineering techniques enable direct testing of the effect of induced DNA methylation on endogenous promoters; however, the downstream effects have not yet been comprehensively assessed. RESULTS: Here, we simultaneously induce methylation at thousands of promoters in human cells using an engineered zinc finger-DNMT3A fusion protein, enabling us to test the effect of forced DNA methylation upon transcription, chromatin accessibility, histone modifications, and DNA methylation persistence after the removal of the fusion protein. We find that transcriptional responses to DNA methylation are highly context-specific, including lack of repression, as well as cases of increased gene expression, which appears to be driven by the eviction of methyl-sensitive transcriptional repressors. Furthermore, we find that some regulatory networks can override DNA methylation and that promoter methylation can cause alternative promoter usage. DNA methylation deposited at promoter and distal regulatory regions is rapidly erased after removal of the zinc finger-DNMT3A fusion protein, in a process combining passive and TET-mediated demethylation. Finally, we demonstrate that induced DNA methylation can exist simultaneously on promoter nucleosomes that possess the active histone modification H3K4me3, or DNA bound by the initiated form of RNA polymerase II. CONCLUSIONS: These findings have important implications for epigenome engineering and demonstrate that the response of promoters to DNA methylation is more complex than previously appreciated.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35883107',
			'doi' => '10.1186/s13059-022-02728-5',
			'modified' => '2022-09-15 09:01:24',
			'created' => '2022-09-08 16:32:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 29 => array(
			'id' => '4417',
			'name' => 'HOTAIR interacts with PRC2 complex regulating the regional preadipocytetranscriptome and human fat distribution.',
			'authors' => 'Kuo  Feng-Chih et al.',
			'description' => '<p>Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA HOTAIR (HOX transcript antisense RNA) is exclusively expressed in gluteofemoral AT, where it is essential for adipocyte development. We find that HOTAIR interacts with polycomb repressive complex 2 (PRC2) and we identify core HOTAIR-PRC2 target genes involved in adipocyte lineage determination. Repression of target genes coincides with PRC2 promoter occupancy and H3K27 trimethylation. HOTAIR is also involved in modifying the gluteal adipocyte transcriptome through alternative splicing. Gluteal-specific expression of HOTAIR is maintained by defined regions of open chromatin across the HOTAIR promoter. HOTAIR expression levels can be modified by hormonal (estrogen, glucocorticoids) and genetic variation (rs1443512 is a HOTAIR eQTL associated with reduced gynoid fat mass). These data identify HOTAIR as a dynamic regulator of the gluteal adipocyte transcriptome and epigenome with functional importance for human regional AT development.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35905723',
			'doi' => '10.1016/j.celrep.2022.111136',
			'modified' => '2022-09-27 14:41:23',
			'created' => '2022-09-08 16:32:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 30 => array(
			'id' => '4458',
			'name' => 'Epiblast inducers capture mouse trophectoderm stem cells in vitro andpattern blastoids for implantation in utero.',
			'authors' => 'Seong  Jinwoo et al.',
			'description' => '<p>The embryo instructs the allocation of cell states to spatially regulate functions. In the blastocyst, patterning of trophoblast (TR) cells ensures successful implantation and placental development. Here, we defined an optimal set of molecules secreted by the epiblast (inducers) that captures in&nbsp;vitro stable, highly self-renewing mouse trophectoderm stem cells (TESCs) resembling the blastocyst stage. When exposed to suboptimal inducers, these stem cells fluctuate to form interconvertible subpopulations with reduced self-renewal and facilitated differentiation, resembling peri-implantation cells, known as TR stem cells (TSCs). TESCs have enhanced capacity to form blastoids that implant more efficiently in utero due to inducers maintaining not only local TR proliferation and self-renewal, but also WNT6/7B secretion that stimulates uterine decidualization. Overall, the epiblast maintains sustained growth and decidualization potential of abutting TR cells, while, as known, distancing imposed by the blastocyst cavity differentiates TR cells for uterus adhesion, thus patterning the essential functions of implantation.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35803228',
			'doi' => '10.1016/j.stem.2022.06.002',
			'modified' => '2022-10-21 09:44:00',
			'created' => '2022-09-28 09:53:13',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 31 => array(
			'id' => '4386',
			'name' => 'Epigenomic analysis reveals a dynamic and context-specific macrophageenhancer landscape associated with innate immune activation and tolerance.',
			'authors' => 'Zhang  P. et al.',
			'description' => '<p>BACKGROUND: Chromatin states and enhancers associate gene expression, cell identity and disease. Here, we systematically delineate the acute innate immune response to endotoxin in terms of human macrophage enhancer activity and contrast with endotoxin tolerance, profiling the coding and non-coding transcriptome, chromatin accessibility and epigenetic modifications. RESULTS: We describe the spectrum of enhancers under acute and tolerance conditions and the regulatory networks between these enhancers and biological processes including gene expression, splicing regulation, transcription factor binding and enhancer RNA signatures. We demonstrate that the vast majority of differentially regulated enhancers on acute stimulation are subject to tolerance and that expression quantitative trait loci, disease-risk variants and eRNAs are enriched in these regulatory regions and related to context-specific gene expression. We find enrichment for context-specific eQTL involving endotoxin response and specific infections and delineate specific differential regions informative for GWAS variants in inflammatory bowel disease and multiple sclerosis, together with a context-specific enhancer involving a bacterial infection eQTL for KLF4. We show enrichment in differential enhancers for tolerance involving transcription factors NF&kappa;B-p65, STATs and IRFs and prioritize putative causal genes directly linking genetic variants and disease risk enhancers. We further delineate similarities and differences in epigenetic landscape between stem cell-derived macrophages and primary cells and characterize the context-specific enhancer activities for key innate immune response genes KLF4, SLAMF1 and IL2RA. CONCLUSIONS: Our study demonstrates the importance of context-specific macrophage enhancers in gene regulation and utility for interpreting disease associations, providing a roadmap to link genetic variants with molecular and cellular functions.</p>',
			'date' => '2022-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35751107',
			'doi' => '10.1186/s13059-022-02702-1',
			'modified' => '2022-08-11 14:07:03',
			'created' => '2022-08-11 12:14:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 32 => array(
			'id' => '4221',
			'name' => 'Epigenetic Mechanisms Mediating Cell State Transitions in Chondrocytes',
			'authors' => 'Wuelling M. et al.',
			'description' => '<p><span>Epigenetic modifications play critical roles in regulating cell lineage differentiation, but the epigenetic mechanisms guiding specific differentiation steps within a cell lineage have rarely been investigated. To decipher such mechanisms, we used the defined transition from proliferating (PC) into hypertrophic chondrocytes (HC) during endochondral ossification as a model. We established a map of activating and repressive histone modifications for each cell type. ChromHMM state transition analysis and Pareto-based integration of differential levels of mRNA and epigenetic marks revealed that differentiation-associated gene repression is initiated by the addition of H3K27me3 to promoters still carrying substantial levels of activating marks. Moreover, the integrative analysis identified genes specifically expressed in cells undergoing the transition into hypertrophy. Investigation of enhancer profiles detected surprising differences in enhancer number, location, and transcription factor binding sites between the two closely related cell types. Furthermore, cell type-specific upregulation of gene expression was associated with increased numbers of H3K27ac peaks. Pathway analysis identified PC-specific enhancers associated with chondrogenic genes, whereas HC-specific enhancers mainly control metabolic pathways linking epigenetic signature to biological functions. Since HC-specific enhancers show a higher conservation in postnatal tissues, the switch to metabolic pathways seems to be a hallmark of differentiated tissues. Surprisingly, the analysis of H3K27ac levels at super-enhancers revealed a rapid adaption of H3K27ac occupancy to changes in gene expression, supporting the importance of enhancer modulation for acute alterations in gene expression. &copy; 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).</span></p>',
			'date' => '2022-05-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/33534175/',
			'doi' => '10.1002/jbmr.4263',
			'modified' => '2022-04-25 11:46:32',
			'created' => '2022-04-21 12:00:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 33 => array(
			'id' => '4446',
			'name' => 'Variation in PU.1 binding and chromatin looping at neutrophil enhancersinfluences autoimmune disease susceptibility',
			'authors' => 'Watt  S. et al. ',
			'description' => '<p>Neutrophils play fundamental roles in innate inflammatory response, shape adaptive immunity1, and have been identified as a potentially causal cell type underpinning genetic associations with immune system traits and diseases2,3 The majority of these variants are non-coding and the underlying mechanisms are not fully understood. Here, we profiled the binding of one of the principal myeloid transcriptional regulators, PU.1, in primary neutrophils across nearly a hundred volunteers, and elucidate the coordinated genetic effects of PU.1 binding variation, local chromatin state, promoter-enhancer interactions and gene expression. We show that PU.1 binding and the associated chain of molecular changes underlie genetically-driven differences in cell count and autoimmune disease susceptibility. Our results advance interpretation for genetic loci associated with neutrophil biology and immune disease.</p>',
			'date' => '2022-05-01',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/620260v1.abstract',
			'doi' => '10.1101/620260',
			'modified' => '2022-10-14 16:39:03',
			'created' => '2022-09-28 09:53:13',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 34 => array(
			'id' => '4402',
			'name' => 'The CpG Island-Binding Protein SAMD1 Contributes to anUnfavorable Gene Signature in HepG2 Hepatocellular CarcinomaCells.',
			'authors' => 'Simon  C. et al.',
			'description' => '<p>The unmethylated CpG island-binding protein SAMD1 is upregulated in many human cancer types, but its cancer-related role has not yet been investigated. Here, we used the hepatocellular carcinoma cell line HepG2 as a cancer model and investigated the cellular and transcriptional roles of SAMD1 using ChIP-Seq and RNA-Seq. SAMD1 targets several thousand gene promoters, where it acts predominantly as a transcriptional repressor. HepG2 cells with SAMD1 deletion showed slightly reduced proliferation, but strongly impaired clonogenicity. This phenotype was accompanied by the decreased expression of pro-proliferative genes, including MYC target genes. Consistently, we observed a decrease in the active H3K4me2 histone mark at most promoters, irrespective of SAMD1 binding. Conversely, we noticed an increase in interferon response pathways and a gain of H3K4me2 at a subset of enhancers that were enriched for IFN-stimulated response elements (ISREs). We identified key transcription factor genes, such as , , and , that were directly repressed by SAMD1. Moreover, SAMD1 deletion also led to the derepression of the PI3K-inhibitor , contributing to diminished mTOR signaling and ribosome biogenesis pathways. Our work suggests that SAMD1 is involved in establishing a pro-proliferative setting in hepatocellular carcinoma cells. Inhibiting SAMD1's function in liver cancer cells may therefore lead to a more favorable gene signature.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35453756',
			'doi' => '10.3390/biology11040557',
			'modified' => '2022-08-11 14:45:43',
			'created' => '2022-08-11 12:14:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 35 => array(
			'id' => '4524',
			'name' => 'Local euchromatin enrichment in lamina-associated domains anticipatestheir repositioning in the adipogenic lineage.',
			'authors' => 'Madsen-Østerbye  J. et al.',
			'description' => '<p>BACKGROUND: Interactions of chromatin with the nuclear lamina via lamina-associated domains (LADs) confer structural stability to the genome. The dynamics of positioning of LADs during differentiation, and how LADs impinge on developmental gene expression, remains, however, elusive. RESULTS: We examined changes in the association of lamin B1 with the genome in the first 72 h of differentiation of adipose stem cells into adipocytes. We demonstrate a repositioning of entire stand-alone LADs and of LAD edges as a prominent nuclear structural feature of early adipogenesis. Whereas adipogenic genes are released from LADs, LADs sequester downregulated or repressed genes irrelevant for the adipose lineage. However, LAD repositioning only partly concurs with gene expression changes. Differentially expressed genes in LADs, including LADs conserved throughout differentiation, reside in local euchromatic and lamin-depleted sub-domains. In these sub-domains, pre-differentiation histone modification profiles correlate with the LAD versus inter-LAD outcome of these genes during adipogenic commitment. Lastly, we link differentially expressed genes in LADs to short-range enhancers which overall co-partition with these genes in LADs versus inter-LADs during differentiation. CONCLUSIONS: We conclude that LADs are predictable structural features of adipose nuclear architecture that restrain non-adipogenic genes in a repressive environment.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35410387',
			'doi' => '10.1186/s13059-022-02662-6',
			'modified' => '2022-11-24 09:08:01',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 36 => array(
			'id' => '4528',
			'name' => 'ZWC complex-mediated SPT5 phosphorylation suppresses divergentantisense RNA transcription at active gene promoters.',
			'authors' => 'Park  K. et al.',
			'description' => '<p>The human genome encodes large numbers of non-coding RNAs, including divergent antisense transcripts at transcription start sites (TSSs). However, molecular mechanisms by which divergent antisense transcription is regulated have not been detailed. Here, we report a novel ZWC complex composed of ZC3H4, WDR82&nbsp;and CK2 that suppresses divergent antisense transcription. The ZWC complex preferentially localizes at TSSs of active genes through direct interactions of ZC3H4 and WDR82 subunits with the S5p RNAPII C-terminal domain. ZC3H4 depletion leads to increased divergent antisense transcription, especially at genes that naturally produce divergent antisense transcripts. We further demonstrate that the ZWC complex phosphorylates the previously uncharacterized N-terminal acidic domain of SPT5, a subunit of the transcription-elongation factor DSIF, and that this phosphorylation is responsible for suppressing divergent antisense transcription. Our study provides evidence that the newly identified ZWC-DSIF axis regulates the direction of transcription during the transition from early to productive elongation.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35325203',
			'doi' => '10.1093/nar/gkac193',
			'modified' => '2022-11-24 09:24:05',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 37 => array(
			'id' => '4857',
			'name' => 'Broad domains of histone marks in the highly compact  macronucleargenome.',
			'authors' => 'Drews  F. et al.',
			'description' => '<p>The unicellular ciliate contains a large vegetative macronucleus with several unusual characteristics, including an extremely high coding density and high polyploidy. As macronculear chromatin is devoid of heterochromatin, our study characterizes the functional epigenomic organization necessary for gene regulation and proper Pol II activity. Histone marks (H3K4me3, H3K9ac, H3K27me3) reveal no narrow peaks but broad domains along gene bodies, whereas intergenic regions are devoid of nucleosomes. Our data implicate H3K4me3 levels inside ORFs to be the main factor associated with gene expression, and H3K27me3 appears in association with H3K4me3 in plastic genes. Silent and lowly expressed genes show low nucleosome occupancy, suggesting that gene inactivation does not involve increased nucleosome occupancy and chromatin condensation. Because of a high occupancy of Pol II along highly expressed ORFs, transcriptional elongation appears to be quite different from that of other species. This is supported by missing heptameric repeats in the C-terminal domain of Pol II and a divergent elongation system. Our data imply that unoccupied DNA is the default state, whereas gene activation requires nucleosome recruitment together with broad domains of H3K4me3. In summary, gene activation and silencing in run counter to the current understanding of chromatin biology.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35264449',
			'doi' => '10.1101/gr.276126.121',
			'modified' => '2023-08-01 14:45:37',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 38 => array(
			'id' => '4367',
			'name' => 'Cell-type specific transcriptional networks in root xylem adjacent celllayers',
			'authors' => 'Asensi Fabado  Maria Amparo et al.',
			'description' => '<p>Transport of water, ions and signals from roots to leaves via the xylem vessels is essential for plant life and needs to be tightly regulated. The final composition of the transpiration stream before passage into the shoots is controlled by the xylem-adjacent cell layers, namely xylem parenchyma and pericycle, in the upper part of the root. To unravel regulatory networks in this strategically important location, we generated Arabidopsis lines expressing a nuclear tag under the control of the HKT1 promoter. HKT1 retrieves sodium from the xylem to prevent toxic levels in the shoot, and this function depends on its specific expression in upper root xylem-adjacent tissues. Based on FACS RNA-sequencing and INTACT ChIP-sequencing, we identified the gene repertoire that is preferentially expressed in the tagged cell types and discovered transcription factors experiencing cell-type specific loss of H3K27me3 demethylation. For one of these, ZAT6, we show that H3K27me3-demethylase REF6 is required for de-repression. Analysis of zat6 mutants revealed that ZAT6 activates a suite of cell-type specific downstream genes and restricts Na+ accumulation in the shoots. The combined Files open novel opportunities for &lsquo;bottom-up&rsquo; causal dissection of cell-type specific regulatory networks that control root-to-shoot communication under environmental challenge.</p>',
			'date' => '2022-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2022.02.04.479129',
			'doi' => '10.1101/2022.02.04.479129',
			'modified' => '2022-08-04 16:17:32',
			'created' => '2022-08-04 14:55:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 39 => array(
			'id' => '4214',
			'name' => 'Comprehensive characterization of the epigenetic landscape in Multiple Myeloma',
			'authors' => 'Elina Alaterre et al.',
			'description' => '<p>Background: Human multiple myeloma (MM) cell lines (HMCLs) have been widely used to understand the<br />molecular processes that drive MM biology. Epigenetic modifications are involved in MM development,<br />progression, and drug resistance. A comprehensive characterization of the epigenetic landscape of MM would<br />advance our understanding of MM pathophysiology and may attempt to identify new therapeutic targets.<br />Methods: We performed chromatin immunoprecipitation sequencing to analyze histone mark changes<br />(H3K4me1, H3K4me3, H3K9me3, H3K27ac, H3K27me3 and H3K36me3) on 16 HMCLs.<br />Results: Differential analysis of histone modification profiles highlighted links between histone modifications<br />and cytogenetic abnormalities or recurrent mutations. Using histone modifications associated to enhancer<br />regions, we identified super-enhancers (SE) associated with genes involved in MM biology. We also identified<br />promoters of genes enriched in H3K9me3 and H3K27me3 repressive marks associated to potential tumor<br />suppressor functions. The prognostic value of genes associated with repressive domains and SE was used to<br />build two distinct scores identifying high-risk MM patients in two independent cohorts (CoMMpass cohort; n =<br />674 and Montpellier cohort; n = 69). Finally, we explored H3K4me3 marks comparing drug-resistant and<br />-sensitive HMCLs to identify regions involved in drug resistance. From these data, we developed epigenetic<br />biomarkers based on the H3K4me3 modification predicting MM cell response to lenalidomide and histone<br />deacetylase inhibitors (HDACi).<br />Conclusions: The epigenetic landscape of MM cells represents a unique resource for future biological studies.<br />Furthermore, risk-scores based on SE and repressive regions together with epigenetic biomarkers of drug<br />response could represent new tools for precision medicine in MM.</p>',
			'date' => '2022-01-16',
			'pmid' => 'https://www.thno.org/v12p1715',
			'doi' => '10.7150/thno.54453',
			'modified' => '2022-01-27 13:17:28',
			'created' => '2022-01-27 13:14:17',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 40 => array(
			'id' => '4225',
			'name' => 'Comprehensive characterization of the epigenetic landscape in Multiple
Myeloma',
			'authors' => 'Alaterre, Elina and Ovejero, Sara and Herviou, Laurie and de
Boussac, Hugues and Papadopoulos, Giorgio and Kulis, Marta and
Boireau, Stéphanie and Robert, Nicolas and Requirand, Guilhem
and Bruyer, Angélique and Cartron, Guillaume and Vincent,
Laure and M',
			'description' => 'Background: Human multiple myeloma (MM) cell lines (HMCLs) have
been widely used to understand the molecular processes that drive MM
biology. Epigenetic modifications are involved in MM development,
progression, and drug resistance. A comprehensive characterization of the
epigenetic landscape of MM would advance our understanding of MM
pathophysiology and may attempt to identify new therapeutic
targets.

Methods: We performed chromatin immunoprecipitation
sequencing to analyze histone mark changes (H3K4me1, H3K4me3,
H3K9me3, H3K27ac, H3K27me3 and H3K36me3) on 16
HMCLs.

Results: Differential analysis of histone modification
profiles highlighted links between histone modifications and cytogenetic
abnormalities or recurrent mutations. Using histone modifications
associated to enhancer regions, we identified super-enhancers (SE)
associated with genes involved in MM biology. We also identified
promoters of genes enriched in H3K9me3 and H3K27me3 repressive
marks associated to potential tumor suppressor functions. The prognostic
value of genes associated with repressive domains and SE was used to
build two distinct scores identifying high-risk MM patients in two
independent cohorts (CoMMpass cohort; n = 674 and Montpellier cohort;
n = 69). Finally, we explored H3K4me3 marks comparing drug-resistant
and -sensitive HMCLs to identify regions involved in drug resistance.
From these data, we developed epigenetic biomarkers based on the
H3K4me3 modification predicting MM cell response to lenalidomide and
histone deacetylase inhibitors (HDACi).

Conclusions: The epigenetic
landscape of MM cells represents a unique resource for future biological
studies. Furthermore, risk-scores based on SE and repressive regions
together with epigenetic biomarkers of drug response could represent new
tools for precision medicine in MM.',
			'date' => '2022-01-01',
			'pmid' => 'https://www.thno.org/v12p1715.htm',
			'doi' => '10.7150/thno.54453',
			'modified' => '2022-05-19 10:41:50',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 41 => array(
			'id' => '4326',
			'name' => 'Loss of KMT2C reprograms the epigenomic landscape in hPSCsresulting in NODAL overexpression and a failure of hemogenic endotheliumspecification.',
			'authors' => 'Maurya Shailendra et al.',
			'description' => '<p>Germline or somatic variation in the family of KMT2 lysine methyltransferases have been associated with a variety of congenital disorders and cancers. Notably, -fusions are prevalent in 70\% of infant leukaemias but fail to phenocopy short latency leukaemogenesis in mammalian models, suggesting additional factors are necessary for transformation. Given the lack of additional somatic mutation, the role of epigenetic regulation in cell specification, and our prior results of germline variation in infant leukaemia patients, we hypothesized that germline dysfunction of KMT2C altered haematopoietic specification. In isogenic KO hPSCs, we found genome-wide differences in histone modifications at active and poised enhancers, leading to gene expression profiles akin to mesendoderm rather than mesoderm highlighted by a significant increase in NODAL expression and WNT inhibition, ultimately resulting in a lack of hemogenic endothelium specification. These unbiased multi-omic results provide new evidence for germline mechanisms increasing risk of early leukaemogenesis.</p>',
			'date' => '2022-01-01',
			'pmid' => 'https://doi.org/10.1080%2F15592294.2021.1954780',
			'doi' => '10.1080/15592294.2021.1954780',
			'modified' => '2022-06-20 09:27:45',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 42 => array(
			'id' => '4238',
			'name' => 'The long noncoding RNA H19 regulates tumor plasticity inneuroendocrine prostate cancer',
			'authors' => 'Singh N. et al.',
			'description' => '<p>Neuroendocrine (NE) prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (PCa) arising either de novo or from transdifferentiated prostate adenocarcinoma following androgen deprivation therapy (ADT). Extensive computational analysis has identified a high degree of association between the long noncoding RNA (lncRNA) H19 and NEPC, with the longest isoform highly expressed in NEPC. H19 regulates PCa lineage plasticity by driving a bidirectional cell identity of NE phenotype (H19 overexpression) or luminal phenotype (H19 knockdown). It contributes to treatment resistance, with the knockdown of H19 re-sensitizing PCa to ADT. It is also essential for the proliferation and invasion of NEPC. H19 levels are negatively regulated by androgen signaling via androgen receptor (AR). When androgen is absent SOX2 levels increase, driving H19 transcription and facilitating transdifferentiation. H19 facilitates the PRC2 complex in regulating methylation changes at H3K27me3/H3K4me3 histone sites of AR-driven and NEPC-related genes. Additionally, this lncRNA induces alterations in genome-wide DNA methylation on CpG sites, further regulating genes associated with the NEPC phenotype. Our clinical data identify H19 as a candidate diagnostic marker and predictive marker of NEPC with elevated H19 levels associated with an increased probability of biochemical recurrence and metastatic disease in patients receiving ADT. Here we report H19 as an early upstream regulator of cell fate, plasticity, and treatment resistance in NEPC that can reverse/transform cells to a treatable form of PCa once therapeutically deactivated.</p>',
			'date' => '2021-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34934057',
			'doi' => '10.1038/s41467-021-26901-9',
			'modified' => '2022-05-19 17:06:50',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 43 => array(
			'id' => '4239',
			'name' => 'Epromoters function as a hub to recruit key transcription factorsrequired for the inflammatory response',
			'authors' => 'Santiago-Algarra D. et al. ',
			'description' => '<p>Gene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. Our previous results demonstrated that a subset of gene promoters, termed Epromoters, work as bona fide enhancers and regulate distal gene expression. Here, we hypothesized that Epromoters play a key role in the coordination of rapid gene induction during the inflammatory response. Using a high-throughput reporter assay we explored the function of Epromoters in response to type I interferon. We find that clusters of IFNa-induced genes are frequently associated with Epromoters and that these regulatory elements preferentially recruit the STAT1/2 and IRF transcription factors and distally regulate the activation of interferon-response genes. Consistently, we identified and validated the involvement of Epromoter-containing clusters in the regulation of LPS-stimulated macrophages. Our findings suggest that Epromoters function as a local hub recruiting the key TFs required for coordinated regulation of gene clusters during the inflammatory response.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34795220',
			'doi' => '10.1038/s41467-021-26861-0',
			'modified' => '2022-05-19 17:10:30',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 44 => array(
			'id' => '4251',
			'name' => 'Comparing the epigenetic landscape in myonuclei purified with a PCM1antibody from a fast/glycolytic and a slow/oxidative muscle.',
			'authors' => 'Bengtsen Mads et al.',
			'description' => '<p>Muscle cells have different phenotypes adapted to different usage, and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of the epigenetic landscape by ChIP-Seq in two muscle extremes, the fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where up to 60\% of the nuclei can be of a different origin. Since cellular homogeneity is critical in epigenome-wide association studies we developed a new method for purifying skeletal muscle nuclei from whole tissue, based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labelling and a magnetic-assisted sorting approach, we were able to sort out myonuclei with 95\% purity in muscles from mice, rats and humans. The sorting eliminated influence from the other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the differences in the functional properties of the two muscles, and revealed distinct regulatory programs involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles were also regulated by different sets of transcription factors; e.g. in soleus, binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SIX1 binding sites were found to be overrepresented. In addition, more novel transcription factors for muscle regulation such as members of the MAF family, ZFX and ZBTB14 were identified.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/34752468/',
			'doi' => '10.1371/journal.pgen.1009907',
			'modified' => '2022-05-20 09:39:35',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 45 => array(
			'id' => '4241',
			'name' => 'Rhesus macaques self-curing from a schistosome infection can displaycomplete immunity to challenge',
			'authors' => 'Amaral MS et al.  ',
			'description' => '<p>The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict \&gt;200 million people worldwide. By monitoring bloodstream levels of parasite-gut-derived antigen, we show that from week 10 onwards an established infection with Schistosoma mansoni is cleared in an exponential manner, eliciting resistance to reinfection. Secondary challenge at week 42 demonstrates that protection is strong in all animals and complete in some. Antibody profiles suggest that antigens mediating protection are the released products of developing schistosomula. In culture they are killed by addition of rhesus plasma, collected from week 8 post-infection onwards, and even more efficiently with post-challenge plasma. Furthermore, cultured schistosomula lose chromatin activating marks at the transcription start site of genes related to worm development and show decreased expression of genes related to lysosomes and lytic vacuoles involved with autophagy. Overall, our results indicate that enhanced antibody responses against the challenge migrating larvae mediate the naturally acquired protective immunity and will inform the route to an effective vaccine.</p>',
			'date' => '2021-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34702841',
			'doi' => '10.1038/s41467-021-26497-0',
			'modified' => '2022-05-19 17:15:53',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 46 => array(
			'id' => '4268',
			'name' => 'p300 suppresses the transition of myelodysplastic syndromes to acutemyeloid leukemia',
			'authors' => 'Man Na et al.',
			'description' => '<p>Myelodysplastic syndromes (MDS) are hematopoietic stem and progenitor cell (HSPC) malignancies characterized by ineffective hematopoiesis and an increased risk of leukemia transformation. Epigenetic regulators are recurrently mutated in MDS, directly implicating epigenetic dysregulation in MDS pathogenesis. Here, we identified a tumor suppressor role of the acetyltransferase p300 in clinically relevant MDS models driven by mutations in the epigenetic regulators TET2, ASXL1, and SRSF2. The loss of p300 enhanced the proliferation and self-renewal capacity of Tet2-deficient HSPCs, resulting in an increased HSPC pool and leukemogenicity in primary and transplantation mouse models. Mechanistically, the loss of p300 in Tet2-deficient HSPCs altered enhancer accessibility and the expression of genes associated with differentiation, proliferation, and leukemia development. Particularly, p300 loss led to an increased expression of Myb, and the depletion of Myb attenuated the proliferation of HSPCs and improved the survival of leukemia-bearing mice. Additionally, we show that chemical inhibition of p300 acetyltransferase activity phenocopied Ep300 deletion in Tet2-deficient HSPCs, whereas activation of p300 activity with a small molecule impaired the self-renewal and leukemogenicity of Tet2-deficient cells. This suggests a potential therapeutic application of p300 activators in the treatment of MDS with TET2 inactivating mutations.</p>',
			'date' => '2021-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34622806',
			'doi' => '10.1172/jci.insight.138478',
			'modified' => '2022-05-23 09:44:16',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 47 => array(
			'id' => '4231',
			'name' => 'Differential contribution to gene expression prediction of histonemodifications at enhancers or promoters.',
			'authors' => 'González-Ramírez M. et al.',
			'description' => '<p>The ChIP-seq signal of histone modifications at promoters is a good predictor of gene expression in different cellular contexts, but whether this is also true at enhancers is not clear. To address this issue, we develop quantitative models to characterize the relationship of gene expression with histone modifications at enhancers or promoters. We use embryonic stem cells (ESCs), which contain a full spectrum of active and repressed (poised) enhancers, to train predictive models. As many poised enhancers in ESCs switch towards an active state during differentiation, predictive models can also be trained on poised enhancers throughout differentiation and in development. Remarkably, we determine that histone modifications at enhancers, as well as promoters, are predictive of gene expression in ESCs and throughout differentiation and development. Importantly, we demonstrate that their contribution to the predictive models varies depending on their location in enhancers or promoters. Moreover, we use a local regression (LOESS) to normalize sequencing data from different sources, which allows us to apply predictive models trained in a specific cellular context to a different one. We conclude that the relationship between gene expression and histone modifications at enhancers is universal and different from promoters. Our study provides new insight into how histone modifications relate to gene expression based on their location in enhancers or promoters.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/34473698/',
			'doi' => '10.1371/journal.pcbi.1009368',
			'modified' => '2022-05-19 16:50:59',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 48 => array(
			'id' => '4294',
			'name' => 'DOT1L O-GlcNAcylation promotes its protein stability andMLL-fusion leukemia cell proliferation.',
			'authors' => 'Song Tanjing et al.',
			'description' => '<p>Histone lysine methylation functions at the interface of the extracellular environment and intracellular gene expression. DOT1L is a versatile histone H3K79 methyltransferase with a prominent role in MLL-fusion leukemia, yet little is known about how DOT1L responds to extracellular stimuli. Here, we report that DOT1L protein stability is regulated by the extracellular glucose level through the hexosamine biosynthetic pathway (HBP). Mechanistically, DOT1L is O-GlcNAcylated at evolutionarily conserved S1511 in its C terminus. We identify UBE3C as a DOT1L E3 ubiquitin ligase promoting DOT1L degradation whose interaction with DOT1L is susceptible to O-GlcNAcylation. Consequently, HBP enhances H3K79 methylation and expression of critical DOT1L target genes such as HOXA9/MEIS1, promoting cell proliferation in MLL-fusion leukemia. Inhibiting HBP or O-GlcNAc transferase (OGT) increases cellular sensitivity to DOT1L inhibitor. Overall, our work uncovers O-GlcNAcylation and UBE3C as critical determinants of DOT1L protein abundance, revealing a mechanism by which glucose metabolism affects malignancy progression through histone methylation.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34551297',
			'doi' => '10.1016/j.celrep.2021.109739',
			'modified' => '2022-05-24 09:20:37',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 49 => array(
			'id' => '4297',
			'name' => 'INTS11 regulates hematopoiesis by promoting PRC2 function.',
			'authors' => 'Zhang Peng et al.',
			'description' => '<p>INTS11, the catalytic subunit of the Integrator (INT) complex, is crucial for the biogenesis of small nuclear RNAs and enhancer RNAs. However, the role of INTS11 in hematopoietic stem and progenitor cell (HSPC) biology is unknown. Here, we report that INTS11 is required for normal hematopoiesis and hematopoietic-specific genetic deletion of leads to cell cycle arrest and impairment of fetal and adult HSPCs. We identified a novel INTS11-interacting protein complex, Polycomb repressive complex 2 (PRC2), that maintains HSPC functions. Loss of INTS11 destabilizes the PRC2 complex, decreases the level of histone H3 lysine 27 trimethylation (H3K27me3), and derepresses PRC2 target genes. Reexpression of INTS11 or PRC2 proteins in -deficient HSPCs restores the levels of PRC2 and H3K27me3 as well as HSPC functions. Collectively, our data demonstrate that INTS11 is an essential regulator of HSPC homeostasis through the INTS11-PRC2 axis.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34516911',
			'doi' => '10.1126/sciadv.abh1684',
			'modified' => '2022-05-30 09:31:00',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 50 => array(
			'id' => '4282',
			'name' => 'Enhanced targeted DNA methylation of the CMV and endogenous promoterswith dCas9-DNMT3A3L entails distinct subsequent histonemodification changes in CHO cells.',
			'authors' => 'Marx Nicolas et al. ',
			'description' => '<p>With the emergence of new CRISPR/dCas9 tools that enable site specific modulation of DNA methylation and histone modifications, more detailed investigations of the contribution of epigenetic regulation to the precise phenotype of cells in culture, including recombinant production subclones, is now possible. These also allow a wide range of applications in metabolic engineering once the impact of such epigenetic modifications on the chromatin state is available. In this study, enhanced DNA methylation tools were targeted to a recombinant viral promoter (CMV), an endogenous promoter that is silenced in its native state in CHO cells, but had been reactivated previously (&beta;-galactoside &alpha;-2,6-sialyltransferase 1) and an active endogenous promoter (&alpha;-1,6-fucosyltransferase), respectively. Comparative ChIP-analysis of histone modifications revealed a general loss of active promoter histone marks and the acquisition of distinct repressive heterochromatin marks after targeted methylation. On the other hand, targeted demethylation resulted in autologous acquisition of active promoter histone marks and loss of repressive heterochromatin marks. These data suggest that DNA methylation directs the removal or deposition of specific histone marks associated with either active, poised or silenced chromatin. Moreover, we show that de novo methylation of the CMV promoter results in reduced transgene expression in CHO cells. Although targeted DNA methylation is not efficient, the transgene is repressed, thus offering an explanation for seemingly conflicting reports about the source of CMV promoter instability in CHO cells. Importantly, modulation of epigenetic marks enables to nudge the cell into a specific gene expression pattern or phenotype, which is stabilized in the cell by autologous addition of further epigenetic marks. Such engineering strategies have the added advantage of being reversible and potentially tunable to not only turn on or off a targeted gene, but also to achieve the setting of a desirable expression level.</p>',
			'date' => '2021-07-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.ymben.2021.04.014',
			'doi' => '10.1016/j.ymben.2021.04.014',
			'modified' => '2022-05-23 10:09:24',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 51 => array(
			'id' => '4118',
			'name' => 'ChIP-seq protocol for sperm cells and embryos to assess environmentalimpacts and epigenetic inheritance',
			'authors' => 'Lismer, Ariane and Lambrot, Romain and Lafleur, Christine and Dumeaux,Vanessa and Kimmins, Sarah',
			'description' => '<p>In the field of epigenetic inheritance, delineating molecular mechanisms implicated in the transfer of paternal environmental conditions to descendants has been elusive. This protocol details how to track sperm chromatin intergenerationally. We describe mouse model design to probe chromatin states in single mouse sperm and techniques to assess pre-implantation embryo chromatin and gene expression. We place emphasis on how to obtain high-quality and quantifiable data sets in sperm and embryos, as well as highlight the limitations of working with low input.</p>',
			'date' => '2021-06-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.xpro.2021.100602',
			'doi' => '10.1016/j.xpro.2021.100602',
			'modified' => '2021-12-06 17:59:57',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 52 => array(
			'id' => '4318',
			'name' => 'E2F6 initiates stable epigenetic silencing of germline genes duringembryonic development',
			'authors' => 'Dahlet T. et al.',
			'description' => '<p>In mouse development, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes; however, the molecular mechanisms of this specificity remain unclear. Here, we demonstrate that the transcription factor E2F6, a member of the polycomb repressive complex 1.6 (PRC1.6), is critical to target and initiate epigenetic silencing at germline genes in early embryogenesis. Genome-wide, E2F6 binds preferentially to CpG islands in embryonic cells. E2F6 cooperates with MGA to silence a subgroup of germline genes in mouse embryonic stem cells and in embryos, a function that critically depends on the E2F6 marked box domain. Inactivation of E2f6 leads to a failure to deposit CpG island DNA methylation at these genes during implantation. Furthermore, E2F6 is required to initiate epigenetic silencing in early embryonic cells but becomes dispensable for the maintenance in differentiated cells. Our findings elucidate the mechanisms of epigenetic targeting of germline genes and provide a paradigm for how transient repression signals by DNA-binding factors in early embryonic cells are translated into long-term epigenetic silencing during mouse development.</p>',
			'date' => '2021-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34117224',
			'doi' => '10.1038/s41467-021-23596-w',
			'modified' => '2022-08-02 16:53:03',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 53 => array(
			'id' => '4349',
			'name' => 'Lasp1 regulates adherens junction dynamics and fibroblast transformationin destructive arthritis',
			'authors' => 'Beckmann D. et al.',
			'description' => '<p>The LIM and SH3 domain protein 1 (Lasp1) was originally cloned from metastatic breast cancer and characterised as an adaptor molecule associated with tumourigenesis and cancer cell invasion. However, the regulation of Lasp1 and its function in the aggressive transformation of cells is unclear. Here we use integrative epigenomic profiling of invasive fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and from mouse models of the disease, to identify Lasp1 as an epigenomically co-modified region in chronic inflammatory arthritis and a functionally important binding partner of the Cadherin-11/&beta;-Catenin complex in zipper-like cell-to-cell contacts. In vitro, loss or blocking of Lasp1 alters pathological tissue formation, migratory behaviour and platelet-derived growth factor response of arthritic FLS. In arthritic human TNF transgenic mice, deletion of Lasp1 reduces arthritic joint destruction. Therefore, we show a function of Lasp1 in cellular junction formation and inflammatory tissue remodelling and identify Lasp1 as a potential target for treating inflammatory joint disorders associated with aggressive cellular transformation.</p>',
			'date' => '2021-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34131132',
			'doi' => '10.1038/s41467-021-23706-8',
			'modified' => '2022-08-03 17:02:30',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 54 => array(
			'id' => '4143',
			'name' => 'Placental uptake and metabolism of 25(OH)Vitamin D determines itsactivity within the fetoplacental unit',
			'authors' => 'Ashley, B. et al.',
			'description' => '<p>Pregnancy 25-hydroxyvitamin D (25(OH)D) concentrations are associated with maternal and fetal health outcomes, but the underlying mechanisms have not been elucidated. Using physiological human placental perfusion approaches and intact villous explants we demonstrate a role for the placenta in regulating the relationships between maternal 25(OH)D concentrations and fetal physiology. Here, we demonstrate active placental uptake of 25(OH)D3 by endocytosis and placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the fetal and maternal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than solely the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer, including transcriptional activation and inflammatory responses. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta; with widespread effects on the placenta itself. These data show complex and synergistic interplay between vitamin D and the placenta, and inform possible interventions to optimise placental function to better support fetal growth and the maternal adaptations to pregnancy.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.03.01.431439',
			'doi' => '10.1101/2021.03.01.431439',
			'modified' => '2021-12-13 09:29:25',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 55 => array(
			'id' => '4160',
			'name' => 'Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.',
			'authors' => 'Pettinato, Anthony M. et al. ',
			'description' => '<p>Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization by unclear mechanisms. To study this process, we engineer a human cardiomyocyte model to track replication and polyploidization using fluorescently tagged cyclin B1 and cardiac troponin T. Using time-lapse imaging, in&nbsp;vitro cardiomyocyte replication patterns recapitulate the progressive mononuclear polyploidization and replicative arrest observed in&nbsp;vivo. Single-cell transcriptomics and chromatin state analyses reveal that polyploidization is preceded by sarcomere assembly, enhanced oxidative metabolism, a DNA damage response, and p53 activation. CRISPR knockout screening reveals p53 as a driver of cell-cycle arrest and polyploidization. Inhibiting sarcomere function, or scavenging ROS, inhibits cell-cycle arrest and polyploidization. Finally, we show that cardiomyocyte engraftment in infarcted rat hearts is enhanced 4-fold by the increased proliferation of troponin-knockout cardiomyocytes. Thus, the sarcomere inhibits cell division through a DNA damage response that can be targeted to improve cardiomyocyte replacement strategies.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33951429',
			'doi' => '10.1016/j.celrep.2021.109088',
			'modified' => '2021-12-16 10:58:59',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 56 => array(
			'id' => '4343',
			'name' => 'The SAM domain-containing protein 1 (SAMD1) acts as a repressivechromatin regulator at unmethylated CpG islands',
			'authors' => 'Stielow B. et al. ',
			'description' => '<p>CpG islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here, we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 has an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. The absence of SAMD1 impairs ES cell differentiation processes, leading to misregulation of key biological pathways. Together, our work establishes SAMD1 as a newly identified chromatin regulator acting at unmethylated CGIs.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33980486',
			'doi' => '10.1126/sciadv.abf2229',
			'modified' => '2022-08-03 16:34:24',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 57 => array(
			'id' => '4350',
			'name' => 'Simplification of culture conditions and feeder-free expansion of bovineembryonic stem cells',
			'authors' => 'Soto D. A. et al. ',
			'description' => '<p>Bovine embryonic stem cells (bESCs) extend the lifespan of the transient pluripotent bovine inner cell mass in vitro. After years of research, derivation of stable bESCs was only recently reported. Although successful, bESC culture relies on complex culture conditions that require a custom-made base medium and mouse embryonic fibroblasts (MEF) feeders, limiting the widespread use of bESCs. We report here simplified bESC culture conditions based on replacing custom base medium with a commercially available alternative and eliminating the need for MEF feeders by using a chemically-defined substrate. bESC lines were cultured and derived using a base medium consisting of N2B27 supplements and 1\% BSA (NBFR-bESCs). Newly derived bESC lines were easy to establish, simple to propagate and stable after long-term culture. These cells expressed pluripotency markers and actively proliferated for more than 35 passages while maintaining normal karyotype and the ability to differentiate into derivatives of all three germ lineages in embryoid bodies and teratomas. In addition, NBFR-bESCs grew for multiple passages in a feeder-free culture system based on vitronectin and Activin A medium supplementation while maintaining pluripotency. Simplified conditions will facilitate the use of bESCs for gene editing applications and pluripotency and lineage commitment studies.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34040070',
			'doi' => '10.1038/s41598-021-90422-0',
			'modified' => '2022-08-03 16:38:27',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 58 => array(
			'id' => '4161',
			'name' => 'The anti-inflammatory cytokine interleukin-37 is an inhibitor of trainedimmunity.',
			'authors' => 'Cavalli, Giulio and Tengesdal, Isak W and Gresnigt, Mark and Nemkov, Travisand Arts, Rob J W and Domínguez-Andrés, Jorge and Molteni, Raffaella andStefanoni, Davide and Cantoni, Eleonora and Cassina, Laura and Giugliano,Silvia and Schraa, Kiki and Mill',
			'description' => '<p>Trained immunity (TI) is a de facto innate immune memory program induced in monocytes/macrophages by exposure to pathogens or vaccines, which evolved as protection against infections. TI is characterized by immunometabolic changes and histone post-translational modifications, which enhance production of pro-inflammatory cytokines. As aberrant activation of TI is implicated in inflammatory diseases, tight regulation is critical; however, the mechanisms responsible for this modulation remain elusive. Interleukin-37 (IL-37) is an anti-inflammatory cytokine that curbs inflammation and modulates metabolic pathways. In this study, we show that administration of recombinant IL-37 abrogates the protective effects of TI in&nbsp;vivo, as revealed by reduced host pro-inflammatory responses and survival to disseminated candidiasis. Mechanistically, IL-37 reverses the immunometabolic changes and histone post-translational modifications characteristic of TI in monocytes, thus suppressing cytokine production in response to infection. IL-37 thereby emerges as an inhibitor of TI and as a potential therapeutic target in immune-mediated pathologies.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33826894',
			'doi' => '10.1016/j.celrep.2021.108955',
			'modified' => '2021-12-21 15:16:27',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 59 => array(
			'id' => '4178',
			'name' => 'Comparative analysis of histone H3K4me3 modifications between blastocystsand somatic tissues in cattle.',
			'authors' => 'Ishibashi, Mao et al.',
			'description' => '<p>Epigenetic changes induced in the early developmental stages by the surrounding environment can have not only short-term but also long-term consequences throughout life. This concept constitutes the "Developmental Origins of Health and Disease" (DOHaD) hypothesis and encompasses the possibility of controlling livestock health and diseases by epigenetic regulation during early development. As a preliminary step for examining changes of epigenetic modifications in early embryos and their long-lasting effects in fully differentiated somatic tissues, we aimed to obtain high-throughput genome-wide histone H3 lysine 4 trimethylation (H3K4me3) profiles of bovine blastocysts and to compare these data with those from adult somatic tissues in order to extract common and typical features between these tissues in terms of H3K4me3 modifications. Bovine blastocysts were produced in vitro and subjected to chromatin immunoprecipitation-sequencing analysis of H3K4me3. Comparative analysis of the blastocyst-derived H3K4me3 profile with publicly available data from adult liver and muscle tissues revealed that the blastocyst profile could be used as a "sieve" to extract somatic tissue-specific modifications in genes closely related to tissue-specific functions. Furthermore, principal component analysis of the level of common modifications between blastocysts and somatic tissues in meat production-related and imprinted genes well characterized inter- and intra-tissue differences. The results of this study produced a referential genome-wide H3K4me3 profile of bovine blastocysts within the limits of their in vitro source and revealed its common and typical features in relation to the profiles of adult tissues.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33859293',
			'doi' => '10.1038/s41598-021-87683-0',
			'modified' => '2021-12-21 16:40:41',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 60 => array(
			'id' => '4181',
			'name' => 'Genetic perturbation of PU.1 binding and chromatin looping at neutrophilenhancers associates with autoimmune disease.',
			'authors' => 'Watt, Stephen et al.',
			'description' => '<p>Neutrophils play fundamental roles in innate immune response, shape adaptive immunity, and are a potentially causal cell type underpinning genetic associations with immune system traits and diseases. Here, we profile the binding of myeloid master regulator PU.1 in primary neutrophils across nearly a hundred volunteers. We show that variants associated with differential PU.1 binding underlie genetically-driven differences in cell count and susceptibility to autoimmune and inflammatory diseases. We integrate these results with other multi-individual genomic readouts, revealing coordinated effects of PU.1 binding variants on the local chromatin state, enhancer-promoter contacts and downstream gene expression, and providing a functional interpretation for 27 genes underlying immune traits. Collectively, these results demonstrate the functional role of PU.1 and its target enhancers in neutrophil transcriptional control and immune disease susceptibility.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33863903',
			'doi' => '10.1038/s41467-021-22548-8',
			'modified' => '2021-12-21 16:50:30',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 61 => array(
			'id' => '4138',
			'name' => 'Loss of SETD1B results in the redistribution of genomic H3K4me3 in theoocyte',
			'authors' => 'Hanna, C. W. et al. ',
			'description' => '<p>Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransferases SETD1B and MLL2 are essential for oogenesis. We investigated changes in H3K4me3 in Setd1b conditional knockout (cKO) GV oocytes using ultra-low input ChIP-seq, in conjunction with DNA methylation and gene expression analysis. Setd1b cKO oocytes showed a redistribution of H3K4me3, with a marked loss at active gene promoters associated with downregulated gene expression. Remarkably, many regions gained H3K4me3 in Setd1b cKOs, in particular those that were DNA hypomethylated, transcriptionally inactive and CpGrich - hallmarks of MLL2 targets. Thus, loss of SETD1B appears to enable enhanced MLL2 activity. Our work reveals two distinct, complementary mechanisms of genomic targeting of H3K4me3 in oogenesis, with SETD1B linked to gene expression in the oogenic program and MLL2 to CpG content.</p>',
			'date' => '2021-03-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.03.11.434836',
			'doi' => '10.1101/2021.03.11.434836',
			'modified' => '2021-12-13 09:15:06',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 62 => array(
			'id' => '4162',
			'name' => 'Epigenomic tensor predicts disease subtypes and reveals constrained tumorevolution.',
			'authors' => 'Leistico, Jacob R et al.',
			'description' => '<p>Understanding the epigenomic evolution and specificity of disease subtypes from complex patient data remains a major biomedical problem. We here present DeCET (decomposition and classification of epigenomic tensors), an integrative computational approach for simultaneously analyzing hierarchical heterogeneous data, to identify robust epigenomic differences among tissue types, differentiation states, and disease subtypes. Applying DeCET to our own data from 21 uterine benign tumor (leiomyoma) patients identifies distinct epigenomic features discriminating normal myometrium and leiomyoma subtypes. Leiomyomas possess preponderant alterations in distal enhancers and long-range histone modifications confined to chromatin contact domains that constrain the evolution of pathological epigenomes. Moreover, we demonstrate the power and advantage of DeCET on multiple publicly available epigenomic datasets representing different cancers and cellular states. Epigenomic features extracted by DeCET can thus help improve our understanding of disease states, cellular development, and differentiation, thereby facilitating future therapeutic, diagnostic, and prognostic strategies.</p>',
			'date' => '2021-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33789109',
			'doi' => '10.1016/j.celrep.2021.108927',
			'modified' => '2021-12-21 15:19:13',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 63 => array(
			'id' => '4196',
			'name' => 'Functional annotations of three domestic animal genomes provide vitalresources for comparative and agricultural research.',
			'authors' => 'Kern C. et al.',
			'description' => '<p>Gene regulatory elements are central drivers of phenotypic variation and thus of critical importance towards understanding the genetics of complex traits. The Functional Annotation of Animal Genomes consortium was formed to collaboratively annotate the functional elements in animal genomes, starting with domesticated animals. Here we present an expansive collection of datasets from eight diverse tissues in three important agricultural species: chicken (Gallus gallus), pig (Sus scrofa), and cattle (Bos taurus). Comparative analysis of these datasets and those from the human and mouse Encyclopedia of DNA Elements projects reveal that a core set of regulatory elements are functionally conserved independent of divergence between species, and that tissue-specific transcription factor occupancy at regulatory elements and their predicted target genes are also conserved. These datasets represent a unique opportunity for the emerging field of comparative epigenomics, as well as the agricultural research community, including species that are globally important food resources.</p>',
			'date' => '2021-03-01',
			'pmid' => 'https://doi.org/10.1038%2Fs41467-021-22100-8',
			'doi' => '10.1038/s41467-021-22100-8',
			'modified' => '2022-01-06 14:30:41',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 64 => array(
			'id' => '4127',
			'name' => 'The histone modification H3K4me3 is altered at the  locus in Alzheimer'sdisease brain.',
			'authors' => 'Smith, Adam et al.',
			'description' => '<p>Several epigenome-wide association studies of DNA methylation have highlighted altered DNA methylation in the gene in Alzheimer's disease (AD) brain samples. However, no study has specifically examined histone modifications in the disease. We use chromatin immunoprecipitation-qPCR to quantify tri-methylation at histone 3 lysine 4 (H3K4me3) and 27 (H3K27me3) in the gene in entorhinal cortex from donors with high (n&nbsp;=&nbsp;59) or low (n&nbsp;=&nbsp;29) Alzheimer's disease&nbsp;pathology. We demonstrate decreased levels of H3K4me3, a marker of active gene transcription, with no change in H3K27me3, a marker of inactive genes. H3K4me3 is negatively correlated with DNA methylation in specific regions of the gene. Our study suggests that the gene shows altered epigenetic marks indicative of reduced gene activation in Alzheimer's disease.</p>',
			'date' => '2021-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33815817',
			'doi' => '10.2144/fsoa-2020-0161',
			'modified' => '2021-12-07 10:16:08',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 65 => array(
			'id' => '4146',
			'name' => 'The G2-phase enriched lncRNA SNHG26 is necessary for proper cell cycleprogression and proliferation',
			'authors' => 'Samdal, H. et al.',
			'description' => '<p>Long noncoding RNAs (lncRNAs) are involved in the regulation of cell cycle, although only a few have been functionally characterized. By combining RNA sequencing and ChIP sequencing of cell cycle synchronized HaCaT cells we have previously identified lncRNAs highly enriched for cell cycle functions. Based on a cyclic expression profile and an overall high correlation to histone 3 lysine 4 trimethylation (H3K4me3) and RNA polymerase II (Pol II) signals, the lncRNA SNHG26 was identified as a top candidate. In the present study we report that downregulation of SNHG26 affects mitochondrial stress, proliferation, cell cycle phase distribution, and gene expression in cis- and in trans, and that this effect is reversed by upregulation of SNHG26. We also find that the effect on cell cycle phase distribution is cell type specific and stable over time. Results indicate an oncogenic role of SNHG26, possibly by affecting cell cycle progression through the regulation of downstream MYC-responsive genes.</p>',
			'date' => '2021-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.02.22.432245',
			'doi' => '10.1101/2021.02.22.432245',
			'modified' => '2021-12-14 09:21:27',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 66 => array(
			'id' => '4151',
			'name' => 'The epigenetic landscape in purified myonuclei from fast and slow muscles',
			'authors' => 'Bengtsen, M. et al.',
			'description' => '<p>Muscle cells have different phenotypes adapted to different usage and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of chromatin environment by ChIP-Seq in two muscle extremes, the almost completely fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where less than 60\% of the nuclei are inside muscle fibers. Since cellular homogeneity is critical in epigenome-wide association studies we devised a new method for purifying skeletal muscle nuclei from whole tissue based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labeling and a magnetic-assisted sorting approach we were able to sort out myonuclei with 95\% purity. The sorting eliminated influence from other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the functional properties of the two muscles each with a distinct regulatory program involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles are also regulated by different sets of transcription factors; e.g. in soleus binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SOX1 binding sites were found to be overrepresented. In addition, novel factors for muscle regulation such as MAF, ZFX and ZBTB14 were identified.</p>',
			'date' => '2021-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.02.04.429545',
			'doi' => '10.1101/2021.02.04.429545',
			'modified' => '2021-12-14 09:40:02',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 67 => array(
			'id' => '4198',
			'name' => 'WAPL maintains a cohesin loading cycle to preserve cell-type-specificdistal gene regulation.',
			'authors' => 'Liu N. Q.et al.',
			'description' => '<p>The cohesin complex has an essential role in maintaining genome organization. However, its role in gene regulation remains largely unresolved. Here we report that the cohesin release factor WAPL creates a pool of free cohesin, in a process known as cohesin turnover, which reloads it to cell-type-specific binding sites. Paradoxically, stabilization of cohesin binding, following WAPL ablation, results in depletion of cohesin from these cell-type-specific regions, loss of gene expression and differentiation. Chromosome conformation capture experiments show that cohesin turnover is important for maintaining promoter-enhancer loops. Binding of cohesin to cell-type-specific sites is dependent on the pioneer transcription factors OCT4 (POU5F1) and SOX2, but not NANOG. We show the importance of cohesin turnover in controlling transcription and propose that a cycle of cohesin loading and off-loading, instead of static cohesin binding, mediates promoter and enhancer interactions critical for gene regulation.</p>',
			'date' => '2020-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33318687',
			'doi' => '10.1038/s41588-020-00744-4',
			'modified' => '2022-01-06 14:38:26',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 68 => array(
			'id' => '4061',
			'name' => 'Dissecting Herpes Simplex Virus 1-Induced Host Shutoff at the RNA Level.',
			'authors' => 'Friedel, Caroline C and Whisnant, Adam W and Djakovic, Lara and Rutkowski,Andrzej J and Friedl, Marie-Sophie and Kluge, Michael and Williamson, JamesC and Sai, Somesh and Vidal, Ramon Oliveira and Sauer, Sascha and Hennig,Thomas and Grothey, Arnhild an',
			'description' => '<p>Herpes simplex virus 1 (HSV-1) induces a profound host shut-off during lytic infection. The virion host shut-off () protein plays a key role in this process by efficiently cleaving host and viral mRNAs. Furthermore, the onset of viral DNA replication is accompanied by a rapid decline in host transcriptional activity. To dissect relative contributions of both mechanisms and elucidate gene-specific host transcriptional responses throughout the first 8h of lytic HSV-1 infection, we employed RNA-seq of total, newly transcribed (4sU-labelled) and chromatin-associated RNA in wild-type (WT) and &Delta; infection of primary human fibroblasts. Following virus entry, v activity rapidly plateaued at an elimination rate of around 30\% of cellular mRNAs per hour until 8h p.i. In parallel, host transcriptional activity dropped to 10-20\%. While the combined effects of both phenomena dominated infection-induced changes in total RNA, extensive gene-specific transcriptional regulation was observable in chromatin-associated RNA and was surprisingly concordant between WT and &Delta; infection. Both induced strong transcriptional up-regulation of a small subset of genes that were poorly expressed prior to infection but already primed by H3K4me3 histone marks at their promoters. Most interestingly, analysis of chromatin-associated RNA revealed -nuclease-activity-dependent transcriptional down-regulation of at least 150 cellular genes, in particular of many integrin adhesome and extracellular matrix components. This was accompanied by a -dependent reduction in protein levels by 8h p.i. for many of these genes. In summary, our study provides a comprehensive picture of the molecular mechanisms that govern cellular RNA metabolism during the first 8h of lytic HSV-1 infection. The HSV-1 virion host shut-off () protein efficiently cleaves both host and viral mRNAs in a translation-dependent manner. In this study, we model and quantify changes in activity as well as virus-induced global loss of host transcriptional activity during productive HSV-1 infection. In general, HSV-1-induced alterations in total RNA levels were dominated by these two global effects. In contrast, chromatin-associated RNA depicted gene-specific transcriptional changes. This revealed highly concordant transcriptional changes in WT and infection, confirmed DUX4 as a key transcriptional regulator in HSV-1 infection and depicted -dependent, transcriptional down-regulation of the integrin adhesome and extracellular matrix components. The latter explained seemingly gene-specific effects previously attributed to -mediated mRNA degradation and resulted in a concordant loss in protein levels by 8h p.i. for many of the respective genes.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33148793',
			'doi' => '10.1128/JVI.01399-20',
			'modified' => '2021-02-19 17:31:53',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 69 => array(
			'id' => '4069',
			'name' => 'Increased H3K4me3 methylation and decreased miR-7113-5p expression lead toenhanced Wnt/β-catenin signaling in immune cells from PTSD patientsleading to inflammatory phenotype.',
			'authors' => 'Bam, Marpe and Yang, Xiaoming and Busbee, Brandon P and Aiello, Allison Eand Uddin, Monica and Ginsberg, Jay P and Galea, Sandro and Nagarkatti,Prakash S and Nagarkatti, Mitzi',
			'description' => '<p>BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric disorder accompanied by chronic peripheral inflammation. What triggers inflammation in PTSD is currently unclear. In the present study, we identified potential defects in signaling pathways in peripheral blood mononuclear cells (PBMCs) from individuals with PTSD. METHODS: RNAseq (5 samples each for controls and PTSD), ChIPseq (5 samples each) and miRNA array (6 samples each) were used in combination with bioinformatics tools to identify dysregulated genes in PBMCs. Real time qRT-PCR (24 samples each) and in vitro assays were employed to validate our primary findings and hypothesis. RESULTS: By RNA-seq analysis of PBMCs, we found that Wnt signaling pathway was upregulated in PTSD when compared to normal controls. Specifically, we found increased expression of WNT10B in the PTSD group when compared to controls. Our findings were confirmed using NCBI's GEO database involving a larger sample size. Additionally, in vitro activation studies revealed that activated but not na&iuml;ve PBMCs from control individuals expressed more IFN&gamma; in the presence of recombinant WNT10B suggesting that Wnt signaling played a crucial role in exacerbating inflammation. Next, we investigated the mechanism of induction of WNT10B and found that increased expression of WNT10B may result from epigenetic modulation involving downregulation of hsa-miR-7113-5p which targeted WNT10B. Furthermore, we also observed that WNT10B overexpression was linked to higher expression of H3K4me3 histone modification around the promotor of WNT10B. Additionally, knockdown of histone demethylase specific to H3K4me3, using siRNA, led to increased expression of WNT10B providing conclusive evidence that H3K4me3 indeed controlled WNT10B expression. CONCLUSIONS: In summary, our data demonstrate for the first time that Wnt signaling pathway is upregulated in PBMCs of PTSD patients resulting from epigenetic changes involving microRNA dysregulation and histone modifications, which in turn may promote the inflammatory phenotype in such cells.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33189141',
			'doi' => '10.1186/s10020-020-00238-3',
			'modified' => '2021-02-19 17:54:52',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 70 => array(
			'id' => '4084',
			'name' => 'BCG Vaccination Induces Long-Term Functional Reprogramming of HumanNeutrophils.',
			'authors' => 'Moorlag, Simone J C F M and Rodriguez-Rosales, Yessica Alina and Gillard,Joshua and Fanucchi, Stephanie and Theunissen, Kate and Novakovic, Borisand de Bont, Cynthia M and Negishi, Yutaka and Fok, Ezio T and Kalafati,Lydia and Verginis, Panayotis and M',
			'description' => '<p>The tuberculosis vaccine bacillus Calmette-Gu&eacute;rin (BCG) protects against some heterologous infections, probably via induction of non-specific innate immune memory in monocytes and natural killer (NK) cells, a process known as trained immunity. Recent studies have revealed that the induction of trained immunity is associated with a bias toward granulopoiesis in bone marrow hematopoietic progenitor cells, but it is unknown whether BCG vaccination also leads to functional reprogramming of mature neutrophils. Here, we show that BCG vaccination of healthy humans induces long-lasting changes in neutrophil phenotype, characterized by increased expression of activation markers and antimicrobial function. The enhanced function of human neutrophils persists for at least 3&nbsp;months after vaccination and is associated with genome-wide epigenetic modifications in trimethylation at histone 3 lysine 4. Functional reprogramming of neutrophils by the induction of trained immunity might offer novel therapeutic strategies in clinical conditions that could benefit from modulation of neutrophil effector function.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33207187',
			'doi' => '10.1016/j.celrep.2020.108387',
			'modified' => '2021-03-15 17:07:29',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 71 => array(
			'id' => '4095',
			'name' => 'ZNF354C is a transcriptional repressor that inhibits endothelialangiogenic sprouting.',
			'authors' => 'Oo, James A and Irmer, Barnabas and Günther, Stefan and Warwick, Timothyand Pálfi, Katalin and Izquierdo Ponce, Judit and Teichmann, Tom andPflüger-Müller, Beatrice and Gilsbach, Ralf and Brandes, Ralf P andLeisegang, Matthias S',
			'description' => '<p>Zinc finger proteins (ZNF) are a large group of transcription factors with diverse functions. We recently discovered that endothelial cells harbour a specific mechanism to limit the action of ZNF354C, whose function in endothelial cells is unknown. Given that ZNF354C&nbsp;has so far only been studied in bone and tumour, its function was determined in endothelial cells. ZNF354C is expressed in vascular cells and localises to the nucleus and cytoplasm. Overexpression of ZNF354C in human endothelial cells results in a marked inhibition of endothelial sprouting. RNA-sequencing of human microvascular endothelial cells with and without overexpression of ZNF354C revealed that the protein is a potent transcriptional repressor. ZNF354C contains an active KRAB domain which mediates this suppression as shown by mutagenesis analysis. ZNF354C interacts with dsDNA, TRIM28 and histones, as observed by proximity ligation and immunoprecipitation. Moreover, chromatin immunoprecipitation revealed that the ZNF binds to specific endothelial-relevant target-gene promoters. ZNF354C suppresses these genes as shown by CRISPR/Cas knockout and RNAi. Inhibition of endothelial sprouting by ZNF354C is dependent on the amino acids DV and MLE of the KRAB domain. These results demonstrate that ZNF354C is a repressive transcription factor which acts through a KRAB domain to inhibit endothelial angiogenic sprouting.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33154469',
			'doi' => '10.1038/s41598-020-76193-0',
			'modified' => '2021-03-17 17:19:53',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 72 => array(
			'id' => '4197',
			'name' => 'Derivation of Intermediate Pluripotent Stem Cells Amenable to PrimordialGerm Cell Specification.',
			'authors' => 'Yu L. et al.',
			'description' => '<p>Dynamic pluripotent stem cell (PSC) states are in&nbsp;vitro adaptations of pluripotency continuum in&nbsp;vivo. Previous studies have generated a number of PSCs with distinct properties. To date, however, no known PSCs have demonstrated dual competency for chimera formation and direct responsiveness to primordial germ cell (PGC) specification, a unique functional feature of formative pluripotency. Here, by modulating fibroblast growth factor (FGF), transforming growth factor &beta; (TGF-&beta;), and WNT pathways, we derived PSCs from mice, horses, and humans (designated as XPSCs) that are permissive for direct PGC-like cell induction in&nbsp;vitro and are capable of contributing to intra- or inter-species chimeras in&nbsp;vivo. XPSCs represent a pluripotency state between naive and primed pluripotency and harbor molecular, cellular, and phenotypic features characteristic of formative pluripotency. XPSCs open new avenues for studying mammalian pluripotency and dissecting the molecular mechanisms governing PGC specification. Our method may be broadly applicable for the derivation of analogous stem cells from other mammalian species.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33271070',
			'doi' => '10.1016/j.stem.2020.11.003',
			'modified' => '2022-01-06 14:35:44',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 73 => array(
			'id' => '4201',
			'name' => 'The epigenetic regulator RINF (CXXC5) maintains SMAD7 expression in human immature erythroid cells and sustains red blood cellsexpansion.',
			'authors' => 'Astori A. et al.',
			'description' => '<p>The gene CXXC5, encoding a Retinoid-Inducible Nuclear Factor (RINF), is located within a region at 5q31.2 commonly deleted in myelodysplastic syndrome (MDS) and adult acute myeloid leukemia (AML). RINF may act as an epigenetic regulator and has been proposed as a tumor suppressor in hematopoietic malignancies. However, functional studies in normal hematopoiesis are lacking, and its mechanism of action is unknow. Here, we evaluated the consequences of RINF silencing on cytokineinduced erythroid differentiation of human primary CD34+ progenitors. We found that RINF is expressed in immature erythroid cells and that RINF-knockdown accelerated erythropoietin-driven maturation, leading to a significant reduction (~45\%) in the number of red blood cells (RBCs), without affecting cell viability. The phenotype induced by RINF-silencing was TGF&beta;-dependent and mediated by SMAD7, a TGF&beta;- signaling inhibitor. RINF upregulates SMAD7 expression by direct binding to its promoter and we found a close correlation between RINF and SMAD7 mRNA levels both in CD34+ cells isolated from bone marrow of healthy donors and MDS patients with del(5q). Importantly, RINF knockdown attenuated SMAD7 expression in primary cells and ectopic SMAD7 expression was sufficient to prevent the RINF knockdowndependent erythroid phenotype. Finally, RINF silencing affects 5&rsquo;-hydroxymethylation of human erythroblasts, in agreement with its recently described role as a Tet2- anchoring platform in mouse. Altogether, our data bring insight into how the epigenetic factor RINF, as a transcriptional regulator of SMAD7, may fine-tune cell sensitivity to TGF&beta; superfamily cytokines and thus play an important role in both normal and pathological erythropoiesis.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33241676',
			'doi' => '10.3324/haematol.2020.263558',
			'modified' => '2022-01-06 14:46:32',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 74 => array(
			'id' => '4052',
			'name' => 'StE(z)2, a Polycomb group methyltransferase and deposition of H3K27me3 andH3K4me3 regulate the expression of tuberization genes in potato.',
			'authors' => 'Kumar, Amit and Kondhare, Kirtikumar R and Malankar, Nilam N and Banerjee,Anjan K',
			'description' => '<p>Polycomb Repressive Complex (PRC) group proteins regulate various developmental processes in plants by repressing the target genes via H3K27 trimethylation, whereas their function is antagonized by Trithorax group proteins-mediated H3K4 trimethylation. Tuberization in potato is widely studied, but the role of histone modifications in this process is unknown. Recently, we showed that overexpression of StMSI1 (a PRC2 member) alters the expression of tuberization genes in potato. As MSI1 lacks histone-modification activity, we hypothesized that this altered expression could be caused by another PRC2 member, StE(z)2 (a potential H3K27 methyltransferase in potato). Here, we demonstrate that short-day photoperiod influences StE(z)2 expression in leaf and stolon. Moreover, StE(z)2 overexpression alters plant architecture and reduces tuber yield, whereas its knockdown enhanced the yield. ChIP-sequencing using short-day induced stolons revealed that several tuberization and phytohormone-related genes, such as StBEL5/11/29, StSWEET11B, StGA2OX1 and StPIN1 carry H3K4me3 or H3K27me3 marks and/or are StE(z)2 targets. Interestingly, we noticed that another important tuberization gene, StSP6A is targeted by StE(z)2 in leaves and had increased deposition of H3K27me3 under non-induced (long-day) conditions compared to SD. Overall, we show that StE(z)2 and deposition of H3K27me3 and/or H3K4me3 marks could regulate the expression of key tuberization genes in potato.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33048134',
			'doi' => '10.1093/jxb/eraa468',
			'modified' => '2021-02-19 14:55:34',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 75 => array(
			'id' => '4053',
			'name' => 'Priming for enhanced ARGONAUTE2 activation accompanies induced resistanceto cucumber mosaic virus in Arabidopsis thaliana.',
			'authors' => 'Ando, Sugihiro and Jaskiewicz, Michal and Mochizuki, Sei and Koseki, Saekoand Miyashita, Shuhei and Takahashi, Hideki and Conrath, Uwe',
			'description' => '<p>Systemic acquired resistance (SAR) is a broad-spectrum disease resistance response that can be induced upon infection from pathogens or by chemical treatment, such as with benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH). SAR involves priming for more robust activation of defence genes upon pathogen attack. Whether priming for SAR would involve components of RNA silencing remained unknown. Here, we show that upon leaf infiltration of water, BTH-primed Arabidopsis thaliana plants accumulate higher amounts of mRNA of ARGONAUTE (AGO)2 and AGO3, key components of RNA silencing. The enhanced AGO2 expression is associated with prior-to-activation trimethylation of lysine 4 in histone H3 and acetylation of histone H3 in the AGO2 promoter and with induced resistance to the yellow strain of cucumber mosaic virus (CMV[Y]). The results suggest that priming A.&nbsp;thaliana for enhanced defence involves modification of histones in the AGO2 promoter that condition AGO2 for enhanced activation, associated with resistance to CMV(Y). Consistently, the fold-reduction in CMV(Y) coat protein accumulation by BTH pretreatment was lower in ago2 than in wild type, pointing to reduced capacity of ago2 to activate BTH-induced CMV(Y) resistance. A role of AGO2 in pathogen-induced SAR is suggested by the enhanced activation of AGO2 after infiltrating systemic leaves of plants expressing a localized hypersensitive response upon CMV(Y) infection. In addition, local inoculation of SAR-inducing Pseudomonas syringae pv. maculicola causes systemic priming for enhanced AGO2 expression. Together our results indicate that defence priming targets the AGO2 component of RNA silencing whose enhanced expression is likely to contribute to SAR.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33073913',
			'doi' => '10.1111/mpp.13005',
			'modified' => '2021-02-19 14:57:21',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 76 => array(
			'id' => '4062',
			'name' => 'Digging Deeper into Breast Cancer Epigenetics: Insights from ChemicalInhibition of Histone Acetyltransferase TIP60 .',
			'authors' => 'Idrissou, Mouhamed and Lebert, Andre and Boisnier, Tiphanie and Sanchez,Anna and Houfaf Khoufaf, Fatma Zohra and Penault-Llorca, Frédérique andBignon, Yves-Jean and Bernard-Gallon, Dominique',
			'description' => '<p>Breast cancer is often sporadic due to several factors. Among them, the deregulation of epigenetic proteins may be involved. TIP60 or KAT5 is an acetyltransferase that regulates gene transcription through the chromatin structure. This pleiotropic protein acts in several cellular pathways by acetylating proteins. RNA and protein expressions of TIP60 were shown to decrease in some breast cancer subtypes, particularly in triple-negative breast cancer (TNBC), where a low expression of TIP60 was exhibited compared with luminal subtypes. In this study, the inhibition of the residual activity of TIP60 in breast cancer cell lines was investigated by using two chemical inhibitors, TH1834 and NU9056, first on the acetylation of the specific target, lysine 4 of histone 3 (H3K4) by immunoblotting, and second, by chromatin immunoprecipitation (ChIP)-qPCR (-quantitative Polymerase Chain Reaction). Subsequently, significant decreases or a trend toward decrease of H3K4ac in the different chromatin compartments were observed. In addition, the expression of 48 human nuclear receptors was studied with TaqMan Low-Density Array in these breast cancer cell lines treated with TIP60 inhibitors. The statistical analysis allowed us to comprehensively characterize the androgen receptor and receptors in TNBC cell lines after TH1834 or NU9056 treatment. The understanding of the residual activity of TIP60 in the evolution of breast cancer might be a major asset in the fight against this disease, and could allow TIP60 to be used as a biomarker or therapeutic target for breast cancer progression in the future.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32960142',
			'doi' => '10.1089/omi.2020.0104',
			'modified' => '2021-02-19 17:39:52',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 77 => array(
			'id' => '4073',
			'name' => 'NSD1-deposited H3K36me2 directs de novo methylation in the mouse malegermline and counteracts Polycomb-associated silencing.',
			'authors' => 'Shirane, Kenjiro and Miura, Fumihito and Ito, Takashi and Lorincz, MatthewC',
			'description' => '<p>De novo DNA methylation (DNAme) in mammalian germ cells is dependent on DNMT3A and DNMT3L. However, oocytes and spermatozoa show distinct patterns of DNAme. In mouse oocytes, de novo DNAme requires the lysine methyltransferase (KMTase) SETD2, which deposits H3K36me3. We show here that SETD2 is dispensable for de novo DNAme in the male germline. Instead, the lysine methyltransferase NSD1, which broadly deposits H3K36me2 in euchromatic regions, plays a critical role in de novo DNAme in prospermatogonia, including at imprinted genes. However, males deficient in germline NSD1 show a more severe defect in spermatogenesis than Dnmt3l males. Notably, unlike DNMT3L, NSD1 safeguards a subset of genes against H3K27me3-associated transcriptional silencing. In contrast, H3K36me2 in oocytes is predominantly dependent on SETD2 and coincides with H3K36me3. Furthermore, females with NSD1-deficient oocytes are fertile. Thus, the sexually dimorphic pattern of DNAme in mature mouse gametes is orchestrated by distinct profiles of H3K36 methylation.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32929285',
			'doi' => '10.1038/s41588-020-0689-z',
			'modified' => '2021-02-19 18:02:40',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 78 => array(
			'id' => '4078',
			'name' => 'Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth andPotentiates Checkpoint Inhibition.',
			'authors' => 'Priem, Bram and van Leent, Mandy M T and Teunissen, Abraham J P and Sofias,Alexandros Marios and Mourits, Vera P and Willemsen, Lisa and Klein, Emma Dand Oosterwijk, Roderick S and Meerwaldt, Anu E and Munitz, Jazz andPrévot, Geoffrey and Vera Verschuu',
			'description' => '<p>Trained immunity, a functional state of myeloid cells, has been proposed as a compelling immune-oncological target. Its efficient induction requires direct engagement of myeloid progenitors in the bone marrow. For this purpose, we developed a bone marrow-avid nanobiologic platform designed specifically to induce trained immunity. We established the potent anti-tumor capabilities of our lead candidate MTP-HDL in a B16F10 mouse melanoma model. These anti-tumor effects result from trained immunity-induced myelopoiesis caused by epigenetic rewiring of multipotent progenitors in the bone marrow, which overcomes the immunosuppressive tumor microenvironment. Furthermore, MTP-HDL nanotherapy potentiates checkpoint inhibition in this melanoma model refractory to anti-PD-1 and anti-CTLA-4 therapy. Finally, we determined MTP-HDL's favorable biodistribution and safety profile in non-human primates. In conclusion, we show that rationally designed nanobiologics can promote trained immunity and elicit a durable anti-tumor response either as a monotherapy or in combination with checkpoint inhibitor drugs.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33125893',
			'doi' => '10.1016/j.cell.2020.09.059',
			'modified' => '2021-03-15 16:51:03',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 79 => array(
			'id' => '4092',
			'name' => 'Formation of the CenH3-Deficient Holocentromere in Lepidoptera AvoidsActive Chromatin.',
			'authors' => 'Senaratne, Aruni P and Muller, Héloïse and Fryer, Kelsey A and Kawamoto,Munetaka and Katsuma, Susumu and Drinnenberg, Ines A',
			'description' => '<p>Despite the essentiality for faithful chromosome segregation, centromere architectures are diverse among eukaryotes and embody two main configurations: mono- and holocentromeres, referring, respectively, to localized or unrestricted distribution of centromeric activity. Of the two, some holocentromeres offer the curious condition of having arisen independently in multiple insects, most of which have lost the otherwise essential centromere-specifying factor CenH3 (first described as CENP-A in humans). The loss of CenH3 raises intuitive questions about how holocentromeres are organized and regulated in CenH3-lacking insects. Here, we report the first chromatin-level description of CenH3-deficient holocentromeres by leveraging recently identified centromere components and genomics approaches to map and characterize the holocentromeres of the silk moth Bombyx mori, a representative lepidopteran insect lacking CenH3. This uncovered a robust correlation between the distribution of centromere sites and regions of low chromatin activity along B.&nbsp;mori chromosomes. Transcriptional perturbation experiments recapitulated the exclusion of B.&nbsp;mori centromeres from active chromatin. Based on reciprocal centromere occupancy patterns observed along differentially expressed orthologous genes of Lepidoptera, we further found that holocentromere formation in a manner that is recessive to chromatin dynamics is evolutionarily conserved. Our results help us discuss the plasticity of centromeres in the context of a role for the chromosome-wide chromatin landscape in conferring centromere identity rather than the presence of CenH3. Given the co-occurrence of CenH3 loss and holocentricity in insects, we further propose that the evolutionary establishment of holocentromeres in insects was facilitated through the loss of a CenH3-specified centromere.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33125865',
			'doi' => '10.1016/j.cub.2020.09.078',
			'modified' => '2021-03-17 17:13:50',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 80 => array(
			'id' => '4091',
			'name' => 'Epigenetic regulation of the lineage specificity of primary human dermallymphatic and blood vascular endothelial cells.',
			'authors' => 'Tacconi, Carlotta and He, Yuliang and Ducoli, Luca and Detmar, Michael',
			'description' => '<p>Lymphatic and blood vascular endothelial cells (ECs) share several molecular and developmental features. However, these two cell types possess distinct phenotypic signatures, reflecting their different biological functions. Despite significant advances in elucidating how the specification of lymphatic and blood vascular ECs is regulated at the transcriptional level during development, the key molecular mechanisms governing their lineage identity under physiological or pathological conditions remain poorly understood. To explore the epigenomic signatures in the maintenance of EC lineage specificity, we compared the transcriptomic landscapes, histone composition (H3K4me3 and H3K27me3) and DNA methylomes of cultured matched human primary dermal lymphatic and blood vascular ECs. Our findings reveal that blood vascular lineage genes manifest a more 'repressed' histone composition in lymphatic ECs, whereas DNA methylation at promoters is less linked to the differential transcriptomes of lymphatic versus blood vascular ECs. Meta-analyses identified two transcriptional regulators, BCL6 and MEF2C, which potentially govern endothelial lineage specificity. Notably, the blood vascular endothelial lineage markers CD34, ESAM and FLT1 and the lymphatic endothelial lineage markers PROX1, PDPN and FLT4 exhibited highly differential epigenetic profiles and responded in distinct manners to epigenetic drug treatments. The perturbation of histone and DNA methylation selectively promoted the expression of blood vascular endothelial markers in lymphatic endothelial cells, but not vice versa. Overall, our study reveals that the fine regulation of lymphatic and blood vascular endothelial transcriptomes is maintained via several epigenetic mechanisms, which are crucial to the maintenance of endothelial cell identity.</p>',
			'date' => '2020-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32918672',
			'doi' => '10.1007/s10456-020-09743-9',
			'modified' => '2021-03-17 17:09:36',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 81 => array(
			'id' => '3978',
			'name' => 'OxLDL-mediated immunologic memory in endothelial cells.',
			'authors' => 'Sohrabi Y, Lagache SMM, Voges VC, Semo D, Sonntag G, Hanemann I, Kahles F, Waltenberger J, Findeisen HM',
			'description' => '<p>Trained innate immunity describes the metabolic reprogramming and long-term proinflammatory activation of innate immune cells in response to different pathogen or damage associated molecular patterns, such as oxidized low-density lipoprotein (oxLDL). Here, we have investigated whether the regulatory networks of trained innate immunity also control endothelial cell activation following oxLDL treatment. Human aortic endothelial cells (HAECs) were primed with oxLDL for 24 h. After a resting time of 4 days, cells were restimulated with the TLR2-agonist PAM3cys4. OxLDL priming induced a proinflammatory memory with increased production of inflammatory cytokines such as IL-6, IL-8 and MCP-1 in response to PAM3cys4 restimulation. This memory formation was dependent on TLR2 activation. Furthermore, oxLDL priming of HAECs caused characteristic metabolic and epigenetic reprogramming, including activated mTOR-HIF1&alpha;-signaling with increases in glucose consumption and lactate production, as well as epigenetic modifications in inflammatory gene promoters. Inhibition of mTOR-HIF1&alpha;-signaling or histone methyltransferases blocked the observed phenotype. Furthermore, primed HAECs showed epigenetic activation of ICAM-1 and increased ICAM-1 expression in a HIF1&alpha;-dependent manner. Accordingly, live cell imaging revealed increased monocyte adhesion and transmigration following oxLDL priming. In summary, we demonstrate that oxLDL-mediated endothelial cell activation represents an immunologic event, which triggers metabolic and epigenetic reprogramming. Molecular mechanisms regulating trained innate immunity in innate immune cells also regulate this sustained proinflammatory phenotype in HAECs with enhanced atheroprone cell functions. Further research is necessary to elucidate the detailed metabolic regulation and the functional relevance for atherosclerosis formation in vivo.</p>',
			'date' => '2020-07-26',
			'pmid' => 'http://www.pubmed.gov/32726647',
			'doi' => '10.1016/j.yjmcc.2020.07.006',
			'modified' => '2020-08-10 13:08:21',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 82 => array(
			'id' => '3997',
			'name' => 'The Human Integrator Complex Facilitates Transcriptional Elongation by Endonucleolytic Cleavage of Nascent Transcripts.',
			'authors' => 'Beckedorff F, Blumenthal E, daSilva LF, Aoi Y, Cingaram PR, Yue J, Zhang A, Dokaneheifard S, Valencia MG, Gaidosh G, Shilatifard A, Shiekhattar R',
			'description' => '<p>Transcription by RNA polymerase II (RNAPII) is pervasive in the human genome. However, the mechanisms controlling transcription at promoters and enhancers remain enigmatic. Here, we demonstrate that Integrator subunit 11 (INTS11), the catalytic subunit of the Integrator complex, regulates transcription at these loci through its endonuclease activity. Promoters of genes require INTS11 to cleave nascent transcripts associated with paused RNAPII and induce their premature termination in the proximity of the&nbsp;+1 nucleosome. The turnover of RNAPII permits the subsequent recruitment of an elongation-competent RNAPII complex, leading to productive elongation. In contrast, enhancers require INTS11 catalysis not to evict paused RNAPII but rather to terminate enhancer RNA transcription beyond the&nbsp;+1 nucleosome. These findings are supported by the differential occupancy of negative elongation factor (NELF), SPT5, and tyrosine-1-phosphorylated RNAPII. This study elucidates the role of Integrator in mediating transcriptional elongation at human promoters through the endonucleolytic cleavage of nascent transcripts and the dynamic turnover of RNAPII.</p>',
			'date' => '2020-07-21',
			'pmid' => 'http://www.pubmed.gov/32697989',
			'doi' => '10.1016/j.celrep.2020.107917',
			'modified' => '2020-09-01 14:44:33',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 83 => array(
			'id' => '3996',
			'name' => 'Prostate cancer reactivates developmental epigenomic programs during metastatic progression.',
			'authors' => 'Pomerantz MM, Qiu X, Zhu Y, Takeda DY, Pan W, Baca SC, Gusev A, Korthauer KD, Severson TM, Ha G, Viswanathan SR, Seo JH, Nguyen HM, Zhang B, Pasaniuc B, Giambartolomei C, Alaiwi SA, Bell CA, O'Connor EP, Chabot MS, Stillman DR, Lis R, Font-Tello A, Li L, ',
			'description' => '<p>Epigenetic processes govern prostate cancer (PCa) biology, as evidenced by the dependency of PCa cells on the androgen receptor (AR), a prostate master transcription factor. We generated 268 epigenomic datasets spanning two state transitions-from normal prostate epithelium to localized PCa to metastases-in specimens derived from human tissue. We discovered that reprogrammed AR sites in metastatic PCa are not created de novo; rather, they are prepopulated by the transcription factors FOXA1 and HOXB13 in normal prostate epithelium. Reprogrammed regulatory elements commissioned in metastatic disease hijack latent developmental programs, accessing sites that are implicated in prostate organogenesis. Analysis of reactivated regulatory elements enabled the identification and functional validation of previously unknown metastasis-specific enhancers at HOXB13, FOXA1 and NKX3-1. Finally, we observed that prostate lineage-specific regulatory elements were strongly associated with PCa risk heritability and somatic mutation density. Examining prostate biology through an epigenomic lens is fundamental for understanding the mechanisms underlying tumor progression.</p>',
			'date' => '2020-07-20',
			'pmid' => 'http://www.pubmed.gov/32690948',
			'doi' => '10.1038/s41588-020-0664-8',
			'modified' => '2020-09-01 14:45:54',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 84 => array(
			'id' => '3987',
			'name' => 'The hypomethylation of imprinted genes in IVF/ICSI placenta samples is associated with concomitant changes in histone modifications.',
			'authors' => 'Choux C, Petazzi P, Sanchez-Delgado M, Hernandez Mora JR, Monteagudo A, Sagot P, Monk D, Fauque P',
			'description' => '<p>Although more and more children are born by Assisted Reproductive Technologies (ART), ART safety has not fully been demonstrated. Notably, ART could disturb the delicate step of implantation, and trigger placenta-related adverse outcomes with potential long-term effects, through disrupted epigenetic regulation. We have previously demonstrated that placental DNA methylation was significantly lower after IVF/ICSI than following natural conception at two differentially methylated regions (DMRs) associated with imprinted genes (IGs): and . As histone modifications are critical for placental physiology, the aim of this study was to profile permissive and repressive histone marks in placenta biopsies to reveal a better understanding of the epigenetic changes in the context of ART. Utilizing chromatin immunoprecipitation (ChIP) coupled with quantitative PCR, permissive (H3K4me3, H3K4me2, and H3K9ac) and repressive (H3K9me3 and H3K9me2) post-translational histone modifications were quantified. The analyses revealed a significantly higher quantity of H3K4me2 precipitation in the IVF/ICSI group than in the natural conception group for and DMRs (P&nbsp;=&nbsp;0.016 and 0.003, respectively). Conversely, the quantity of both repressive marks at and DMRs was significantly lower in the IVF/ICSI group than in the natural conception group (P&nbsp;=&nbsp;0.011 and 0.027 for ; and P&nbsp;=&nbsp;0.010 and 0.035 for ). These novel findings highlight that DNA hypomethylation at imprinted DMRs following ART is linked with increased permissive/decreased repressive histone marks, altogether promoting a more permissive chromatin conformation. This concomitant change in epigenetic state at IGs at birth might be an important developmental event because of ART manipulations.</p>',
			'date' => '2020-06-23',
			'pmid' => 'http://www.pubmed.gov/32573317',
			'doi' => '10.1080/15592294.2020.1783168',
			'modified' => '2020-09-01 15:10:37',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 85 => array(
			'id' => '3986',
			'name' => 'Epigenetic priming by Dppa2 and 4 in pluripotency facilitates multi-lineage commitment.',
			'authors' => 'Eckersley-Maslin MA, Parry A, Blotenburg M, Krueger C, Ito Y, Franklin VNR, Narita M, D'Santos CS, Reik W',
			'description' => '<p>How the epigenetic landscape is established in development is still being elucidated. Here, we uncover developmental pluripotency associated 2 and 4 (DPPA2/4) as epigenetic priming factors that establish a permissive epigenetic landscape at a subset of developmentally important bivalent promoters characterized by low expression and poised RNA-polymerase. Differentiation assays reveal that Dppa2/4 double knockout mouse embryonic stem cells fail to exit pluripotency and differentiate efficiently. DPPA2/4 bind both H3K4me3-marked and bivalent gene promoters and associate with COMPASS- and Polycomb-bound chromatin. Comparing knockout and inducible knockdown systems, we find that acute depletion of DPPA2/4 results in rapid loss of H3K4me3 from key bivalent genes, while H3K27me3 is initially more stable but lost following extended culture. Consequently, upon DPPA2/4 depletion, these promoters gain DNA methylation and are unable to be activated upon differentiation. Our findings uncover a novel epigenetic priming mechanism at developmental promoters, poising them for future lineage-specific activation.</p>',
			'date' => '2020-06-22',
			'pmid' => 'http://www.pubmed.gov/32572255',
			'doi' => '10.1038/s41594-020-0443-3',
			'modified' => '2020-09-01 15:12:03',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 86 => array(
			'id' => '3982',
			'name' => 'Genomic deregulation of PRMT5 supports growth and stress tolerance in chronic lymphocytic leukemia.',
			'authors' => 'Schnormeier AK, Pommerenke C, Kaufmann M, Drexler HG, Koeppel M',
			'description' => '<p>Patients suffering from chronic lymphocytic leukemia (CLL) display highly diverse clinical courses ranging from indolent cases to aggressive disease, with genetic and epigenetic features resembling this diversity. Here, we developed a comprehensive approach combining a variety of molecular and clinical data to pinpoint translocation events disrupting long-range chromatin interactions and causing cancer-relevant transcriptional deregulation. Thereby, we discovered a B cell specific cis-regulatory element restricting the expression of genes in the associated locus, including PRMT5 and DAD1, two factors with oncogenic potential. Experimental PRMT5 inhibition identified transcriptional programs similar to those in patients with differences in PRMT5 abundance, especially MYC-driven and stress response pathways. In turn, such inhibition impairs factors involved in DNA repair, sensitizing cells for apoptosis. Moreover, we show that artificial deletion of the regulatory element from its endogenous context resulted in upregulation of corresponding genes, including PRMT5. Furthermore, such disruption renders PRMT5 transcription vulnerable to additional stimuli and subsequently alters the expression of downstream PRMT5 targets. These studies provide a mechanism of PRMT5 deregulation in CLL and the molecular dependencies identified might have therapeutic implementations.</p>',
			'date' => '2020-06-17',
			'pmid' => 'http://www.pubmed.gov/32555249',
			'doi' => '10.1038/s41598-020-66224-1',
			'modified' => '2020-09-01 15:17:40',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 87 => array(
			'id' => '4360',
			'name' => 'The hypomethylation of imprinted genes in IVF/ICSI placenta samplesis associated with concomitant changes in histone modifications.',
			'authors' => 'Choux C. et al. ',
			'description' => '<p>Although more and more children are born by Assisted Reproductive Technologies (ART), ART safety has not fully been demonstrated. Notably, ART could disturb the delicate step of implantation, and trigger placenta-related adverse outcomes with potential long-term effects, through disrupted epigenetic regulation. We have previously demonstrated that placental DNA methylation was significantly lower after IVF/ICSI than following natural conception at two differentially methylated regions (DMRs) associated with imprinted genes (IGs): and . As histone modifications are critical for placental physiology, the aim of this study was to profile permissive and repressive histone marks in placenta biopsies to reveal a better understanding of the epigenetic changes in the context of ART. Utilizing chromatin immunoprecipitation (ChIP) coupled with quantitative PCR, permissive (H3K4me3, H3K4me2, and H3K9ac) and repressive (H3K9me3 and H3K9me2) post-translational histone modifications were quantified. The analyses revealed a significantly higher quantity of H3K4me2 precipitation in the IVF/ICSI group than in the natural conception group for and DMRs (P = 0.016 and 0.003, respectively). Conversely, the quantity of both repressive marks at and DMRs was significantly lower in the IVF/ICSI group than in the natural conception group (P = 0.011 and 0.027 for ; and P = 0.010 and 0.035 for ). These novel findings highlight that DNA hypomethylation at imprinted DMRs following ART is linked with increased permissive/decreased repressive histone marks, altogether promoting a more permissive chromatin conformation. This concomitant change in epigenetic state at IGs at birth might be an important developmental event because of ART manipulations.</p>',
			'date' => '2020-06-01',
			'pmid' => 'http://www.pubmed.gov/32573317',
			'doi' => '10.1080/15592294.2020.1783168',
			'modified' => '2022-08-03 17:14:32',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 88 => array(
			'id' => '4005',
			'name' => 'Measuring Histone Modifications in the Human Parasite Schistosoma mansoni ',
			'authors' => 'de Carvalho Augusto R, Roquis D, Al Picard M, Chaparro C, Cosseau C, Grunau C.',
			'description' => '<p>DNA-binding proteins play critical roles in many major processes such as development and sexual biology of Schistosoma mansoni and are important for the pathogenesis of schistosomiasis. Chromatin immunoprecipitation (ChIP) experiments followed by sequencing (ChIP-seq) are useful to characterize the association of genomic regions with posttranslational chemical modifications of histone proteins. Challenges in the standard ChIP protocol have motivated recent enhancements in this approach, such as reducing the number of cells required and increasing the resolution. In this chapter, we describe the latest advances made by our group in the ChIP methods to improve the standard ChIP protocol to reduce the number of input cells required and to increase the resolution and robustness of ChIP in S. mansoni.</p>',
			'date' => '2020-05-26',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/32451999/',
			'doi' => '10.1007/978-1-0716-0635-3_9 ',
			'modified' => '2020-09-11 15:31:21',
			'created' => '2020-09-11 15:25:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 89 => array(
			'id' => '3965',
			'name' => 'Histone post-translational modifications in Silene latifolia X and Y chromosomes suggest a mammal-like dosage compensation system',
			'authors' => 'Luis Rodríguez Lorenzo José, Hubinský Marcel, Vyskot Boris, Hobza Roman',
			'description' => '<p>Silene latifolia is a model organism to study evolutionary young heteromorphic sex chromosome evolution in plants. Previous research indicates a Y-allele gene degeneration and a dosage compensation system already operating. Here, we propose an epigenetic approach based on analysis of several histone post-translational modifications (PTMs) to find the first epigenetic hints of the X:Y sex chromosome system regulation in S. latifolia. Through chromatin immunoprecipitation we interrogated six genes from X and Y alleles. Several histone PTMS linked to DNA methylation and transcriptional repression (H3K27me3, H3K23me, H3K9me2 and H3K9me3) and to transcriptional activation (H3K4me3 and H4K5, 8, 12, 16ac) were used. DNA enrichment (Immunoprecipitated DNA/input DNA) was analyzed and showed three main results: i) promoters of the Y allele are associated with heterochromatin marks, ii) promoters of the X allele in males are associated with activation of transcription marks and finally, iii) promoters of X alleles in females are associated with active and repressive marks. Our finding indicates a transcription activation of X allele and transcription repression of Y allele in males. In females we found a possible differential regulation (up X1, down X2) of each female X allele. These results agree with the mammal-like epigenetic dosage compensation regulation.</p>',
			'date' => '2020-05-24',
			'pmid' => 'https://www.sciencedirect.com/science/article/abs/pii/S0168945220301333',
			'doi' => '10.1016/j.plantsci.2020.110528',
			'modified' => '2020-08-12 09:42:21',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 90 => array(
			'id' => '3952',
			'name' => 'TET3 controls the expression of the H3K27me3 demethylase Kdm6b during neural commitment.',
			'authors' => 'Montibus B, Cercy J, Bouschet T, Charras A, Maupetit-Méhouas S, Nury D, Gonthier-Guéret C, Chauveau S, Allegre N, Chariau C, Hong CC, Vaillant I, Marques CJ, Court F, Arnaud P',
			'description' => '<p>The acquisition of cell identity is associated with developmentally regulated changes in the cellular histone methylation signatures. For instance, commitment to neural differentiation relies on the tightly controlled gain or loss of H3K27me3, a hallmark of polycomb-mediated transcriptional gene silencing, at specific gene sets. The KDM6B demethylase, which removes H3K27me3 marks at defined promoters and enhancers, is a key factor in neurogenesis. Therefore, to better understand the epigenetic regulation of neural fate acquisition, it is important to determine how Kdm6b expression is regulated. Here, we investigated the molecular mechanisms involved in the induction of Kdm6b expression upon neural commitment of mouse embryonic stem cells. We found that the increase in Kdm6b expression is linked to a rearrangement between two 3D configurations defined by the promoter contact with two different regions in the Kdm6b locus. This is associated with changes in 5-hydroxymethylcytosine (5hmC) levels at these two regions, and requires a functional ten-eleven-translocation (TET) 3 protein. Altogether, our data support a model whereby Kdm6b induction upon neural commitment relies on an intronic enhancer the activity of which is defined by its TET3-mediated 5-hmC level. This original observation reveals an unexpected interplay between the 5-hmC and H3K27me3 pathways during neural lineage commitment in mammals. It also questions to which extent KDM6B-mediated changes in H3K27me3 level account for the TET-mediated effects on gene expression.</p>',
			'date' => '2020-05-14',
			'pmid' => 'http://www.pubmed.gov/32405722',
			'doi' => '10.1007/s00018-020-03541-8',
			'modified' => '2020-08-17 09:53:08',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 91 => array(
			'id' => '3951',
			'name' => 'In vitro capture and characterization of embryonic rosette-stage pluripotency between naive and primed states.',
			'authors' => 'Neagu A, van Genderen E, Escudero I, Verwegen L, Kurek D, Lehmann J, Stel J, Dirks RAM, van Mierlo G, Maas A, Eleveld C, Ge Y, den Dekker AT, Brouwer RWW, van IJcken WFJ, Modic M, Drukker M, Jansen JH, Rivron NC, Baart EB, Marks H, Ten Berge D',
			'description' => '<p>Following implantation, the naive pluripotent epiblast of the mouse blastocyst generates a rosette, undergoes lumenogenesis and forms the primed pluripotent egg cylinder, which is able to generate the embryonic tissues. How pluripotency progression and morphogenesis are linked and whether intermediate pluripotent states exist remain controversial. We identify here a rosette pluripotent state defined by the co-expression of naive factors with the transcription factor OTX2. Downregulation of blastocyst WNT signals drives the transition into rosette pluripotency by inducing OTX2. The rosette then activates MEK signals that induce lumenogenesis and drive progression to primed pluripotency. Consequently, combined WNT and MEK inhibition supports rosette-like stem cells, a self-renewing naive-primed intermediate. Rosette-like stem cells erase constitutive heterochromatin marks and display a primed chromatin landscape, with bivalently marked primed pluripotency genes. Nonetheless, WNT induces reversion to naive pluripotency. The rosette is therefore a reversible pluripotent intermediate whereby control over both pluripotency progression and morphogenesis pivots from WNT to MEK signals.</p>',
			'date' => '2020-05-01',
			'pmid' => 'http://www.pubmed.gov/32367046',
			'doi' => '10.1038/s41556-020-0508-x',
			'modified' => '2020-08-17 09:55:37',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 92 => array(
			'id' => '3929',
			'name' => 'The TGF-β profibrotic cascade targets ecto-5'-nucleotidase gene in proximal tubule epithelial cells and is a traceable marker of progressive diabetic kidney disease.',
			'authors' => 'Cappelli C, Tellez A, Jara C, Alarcón S, Torres A, Mendoza P, Podestá L, Flores C, Quezada C, Oyarzún C, Martín RS',
			'description' => '<p>Progressive diabetic nephropathy (DN) and loss of renal function correlate with kidney fibrosis. Crosstalk between TGF-&beta; and adenosinergic signaling contributes to the phenotypic transition of cells and to renal fibrosis in DN models. We evaluated the role of TGF-&beta; on NT5E gene expression coding for the ecto-5`-nucleotidase CD73, the limiting enzyme in extracellular adenosine production. We showed that high d-glucose may predispose HK-2 cells towards active transcription of the proximal promoter region of the NT5E gene while additional TGF-&beta; results in full activation. The epigenetic landscape of the NT5E gene promoter was modified by concurrent TGF-&beta; with occupancy by the p300 co-activator and the phosphorylated forms of the Smad2/3 complex and RNA Pol II. Transcriptional induction at NT5E in response to TGF-&beta; was earlier compared to the classic responsiveness genes PAI-1 and Fn1. CD73 levels and AMPase activity were concomitantly increased by TGF-&beta; in HK-2 cells. Interestingly, we found increased CD73 content in urinary extracellular vesicles only in diabetic patients with renal repercussions. Further, CD73-mediated AMPase activity was increased in the urinary sediment of DN patients. We conclude that the NT5E gene is a target of the profibrotic TGF-&beta; cascade and is a traceable marker of progressive DN.</p>',
			'date' => '2020-04-11',
			'pmid' => 'http://www.pubmed.gov/32289379',
			'doi' => '10.1016/j.bbadis.2020.165796',
			'modified' => '2020-08-17 10:46:30',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 93 => array(
			'id' => '3889',
			'name' => 'LXR Activation Induces a Proinflammatory Trained Innate Immunity-Phenotype in Human Monocytes',
			'authors' => 'Sohrabi Yahya, Sonntag Glenn V. H., Braun Laura C., Lagache Sina M. M., Liebmann Marie, Klotz Luisa, Godfrey Rinesh, Kahles Florian, Waltenberger Johannes, Findeisen Hannes M.',
			'description' => '<p>The concept of trained innate immunity describes a long-term proinflammatory memory in innate immune cells. Trained innate immunity is regulated through reprogramming of cellular metabolic pathways including cholesterol and fatty acid synthesis. Here, we have analyzed the role of Liver X Receptor (LXR), a key regulator of cholesterol and fatty acid homeostasis, in trained innate immunity.</p>',
			'date' => '2020-03-10',
			'pmid' => 'https://www.frontiersin.org/articles/10.3389/fimmu.2020.00353/full',
			'doi' => '10.3389/ﬁmmu.2020.00353',
			'modified' => '2020-03-20 17:19:37',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 94 => array(
			'id' => '3884',
			'name' => 'A MORC-driven transcriptional switch controls Toxoplasma developmental trajectories and sexual commitment.',
			'authors' => 'Farhat DC, Swale C, Dard C, Cannella D, Ortet P, Barakat M, Sindikubwabo F, Belmudes L, De Bock PJ, Couté Y, Bougdour A, Hakimi MA',
			'description' => '<p>Toxoplasma gondii has a complex life cycle that is typified by asexual development that takes place in vertebrates, and sexual reproduction, which occurs exclusively in felids and is therefore less studied. The developmental transitions rely on changes in the patterns of gene expression, and recent studies have assigned roles for chromatin shapers, including histone modifications, in establishing specific epigenetic programs for each given stage. Here, we identified the T. gondii microrchidia (MORC) protein as an upstream transcriptional repressor of sexual commitment. MORC, in a complex with Apetala 2 (AP2) transcription factors, was shown to recruit the histone deacetylase HDAC3, thereby impeding the accessibility of chromatin at the genes that are exclusively expressed during sexual stages. We found that MORC-depleted cells underwent marked transcriptional changes, resulting in the expression of a specific repertoire of genes, and revealing a shift from asexual proliferation to sexual differentiation. MORC acts as a master regulator that directs the hierarchical expression of secondary AP2 transcription factors, and these transcription factors potentially contribute to the unidirectionality of the life cycle. Thus, MORC plays a cardinal role in the T. gondii life cycle, and its conditional depletion offers a method to study the sexual development of the parasite in vitro, and is proposed as an alternative to the requirement of T. gondii infections in cats.</p>',
			'date' => '2020-02-24',
			'pmid' => 'http://www.pubmed.gov/32094587',
			'doi' => '10.1038/s41564-020-0674-4',
			'modified' => '2020-03-20 17:27:25',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 95 => array(
			'id' => '3874',
			'name' => 'Recombination may occur in the absence of transcription in the immunoglobulin heavy chain recombination centre.',
			'authors' => 'Oudinet C, Braikia FZ, Dauba A, Khamlichi AA',
			'description' => '<p>Developing B cells undergo V(D)J recombination to generate a vast repertoire of Ig molecules. V(D)J recombination is initiated by the RAG1/RAG2 complex in recombination centres (RCs), where gene segments become accessible to the complex. Whether transcription is the causal factor of accessibility or whether it is a side product of other processes that generate accessibility remains a controversial issue. At the IgH locus, V(D)J recombination is controlled by E&mu; enhancer, which directs the transcriptional, epigenetic and recombinational events in the IgH RC. Deletion of E&mu; enhancer affects both transcription and recombination, making it difficult to conclude if E&mu; controls the two processes through the same or different mechanisms. By using a mouse line carrying a CpG-rich sequence upstream of E&mu; enhancer and analyzing transcription and recombination at the single-cell level, we found that recombination could occur in the RC in the absence of detectable transcription, suggesting that E&mu; controls transcription and recombination through distinct mechanisms. Moreover, while the normally E&mu;-dependent transcription and demethylating activities were impaired, recruitment of chromatin remodeling complexes was unaffected. RAG1 was efficiently recruited, thus compensating for the defective transcription-associated recruitment of RAG2, and providing a mechanistic basis for RAG1/RAG2 assembly to initiate V(D)J recombination.</p>',
			'date' => '2020-02-22',
			'pmid' => 'http://www.pubmed.gov/32086526',
			'doi' => '10.1093/nar/gkaa108',
			'modified' => '2020-03-20 17:40:41',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 96 => array(
			'id' => '3873',
			'name' => 'Inhibition of methyltransferase activity of enhancer of zeste 2 leads to enhanced lipid accumulation and altered chromatin status in zebrafish.',
			'authors' => 'den Broeder MJ, Ballangby J, Kamminga LM, Aleström P, Legler J, Lindeman LC, Kamstra JH',
			'description' => '<p>BACKGROUND: Recent studies indicate that exposure to environmental chemicals may increase susceptibility to developing metabolic diseases. This susceptibility may in part be caused by changes to the epigenetic landscape which consequently affect gene expression and lead to changes in lipid metabolism. The epigenetic modifier enhancer of zeste 2 (Ezh2) is a histone H3K27 methyltransferase implicated to play a role in lipid metabolism and adipogenesis. In this study, we used the zebrafish (Danio rerio) to investigate the role of Ezh2 on lipid metabolism and chromatin status following developmental exposure to the Ezh1/2 inhibitor PF-06726304 acetate. We used the environmental chemical tributyltin (TBT) as a positive control, as this chemical is known to act on lipid metabolism via EZH-mediated pathways in mammals. RESULTS: Zebrafish embryos (0-5&nbsp;days post-fertilization, dpf) exposed to non-toxic concentrations of PF-06726304 acetate (5&nbsp;&mu;M) and TBT (1&nbsp;nM) exhibited increased lipid accumulation. Changes in chromatin were analyzed by the assay for transposase-accessible chromatin sequencing (ATAC-seq) at 50% epiboly (5.5 hpf). We observed 349 altered chromatin regions, predominantly located at H3K27me3 loci and mostly more open chromatin in the exposed samples. Genes associated to these loci were linked to metabolic pathways. In addition, a selection of genes involved in lipid homeostasis, adipogenesis and genes specifically targeted by PF-06726304 acetate via altered chromatin accessibility were differentially expressed after TBT and PF-06726304 acetate exposure at 5 dpf, but not at 50% epiboly stage. One gene, cebpa, did not show a change in chromatin, but did show a change in gene expression at 5 dpf. Interestingly, underlying H3K27me3 marks were significantly decreased at this locus at 50% epiboly. CONCLUSIONS: Here, we show for the first time the applicability of ATAC-seq as a tool to investigate toxicological responses in zebrafish. Our analysis indicates that Ezh2 inhibition leads to a partial primed state of chromatin linked to metabolic pathways which results in gene expression changes later in development, leading to enhanced lipid accumulation. Although ATAC-seq seems promising, our in-depth assessment of the cebpa locus indicates that we need to consider underlying epigenetic marks as well.</p>',
			'date' => '2020-02-12',
			'pmid' => 'http://www.pubmed.gov/32051014',
			'doi' => '10.1186/s13072-020-0329-y',
			'modified' => '2020-03-20 17:42:02',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 97 => array(
			'id' => '3883',
			'name' => 'Targeting Macrophage Histone H3 Modification as a Leishmania Strategy to Dampen the NF-κB/NLRP3-Mediated Inflammatory Response.',
			'authors' => 'Lecoeur H, Prina E, Rosazza T, Kokou K, N'Diaye P, Aulner N, Varet H, Bussotti G, Xing Y, Milon G, Weil R, Meng G, Späth GF',
			'description' => '<p>Aberrant macrophage activation during intracellular infection generates immunopathologies that can cause severe human morbidity. A better understanding of immune subversion strategies and macrophage phenotypic and functional responses is necessary to design host-directed intervention strategies. Here, we uncover a fine-tuned transcriptional response that is induced in primary and lesional macrophages infected by the parasite Leishmania amazonensis and dampens NF-&kappa;B and NLRP3 inflammasome activation. Subversion is amastigote-specific and characterized by a decreased expression of activating and increased expression of de-activating components of these pro-inflammatory pathways, thus revealing a regulatory dichotomy that abrogates the anti-microbial response. Changes in transcript abundance correlate with histone H3K9/14 hypoacetylation and H3K4 hypo-trimethylation in infected primary and lesional macrophages at promoters of NF-&kappa;B-related, pro-inflammatory genes. Our results reveal a Leishmania immune subversion strategy targeting host cell epigenetic regulation to establish conditions beneficial for parasite survival and open avenues for host-directed, anti-microbial drug discovery.</p>',
			'date' => '2020-02-11',
			'pmid' => 'http://www.pubmed.gov/32049017',
			'doi' => '10.1016/j.celrep.2020.01.030',
			'modified' => '2020-03-20 17:29:47',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 98 => array(
			'id' => '3868',
			'name' => 'Replicational Dilution of H3K27me3 in Mammalian Cells and the Role of Poised Promoters.',
			'authors' => 'Jadhav U, Manieri E, Nalapareddy K, Madha S, Chakrabarti S, Wucherpfennig K, Barefoot M, Shivdasani RA',
			'description' => '<p>Polycomb repressive complex 2 (PRC2) places H3K27me3 at developmental genes and is causally implicated in keeping bivalent genes silent. It is unclear if that silence requires minimum H3K27me3 levels and how the mark transmits faithfully across mammalian somatic cell generations. Mouse intestinal cells lacking EZH2 methyltransferase reduce H3K27me3 proportionately at all PRC2 target sites, but &sim;40% uniform residual levels keep target genes inactive. These genes, derepressed in PRC2-null villus cells, remain silent in intestinal stem cells (ISCs). Quantitative chromatin immunoprecipitation and computational modeling indicate that because unmodified histones dilute H3K27me3 by 50% each time DNA replicates, PRC2-deficient ISCs initially retain sufficient H3K27me3 to avoid gene derepression. EZH2 mutant human lymphoma cells also require multiple divisions before H3K27me3 dilution relieves gene silencing. In both cell types, promoters with high basal H3K4me2/3 activate in spite of some residual H3K27me3, compared to less-poised promoters. These findings have implications for PRC2 inhibition in cancer therapy.</p>',
			'date' => '2020-01-29',
			'pmid' => 'http://www.pubmed.gov/32027840',
			'doi' => '10.1016/j.molcel.2020.01.017',
			'modified' => '2020-03-20 17:46:30',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 99 => array(
			'id' => '3848',
			'name' => 'A comprehensive epigenomic analysis of phenotypically distinguishable, genetically identical female and male Daphnia pulex.',
			'authors' => 'Kvist J, Athanàsio CG, Pfrender ME, Brown JB, Colbourne JK, Mirbahai L',
			'description' => '<p>BACKGROUND: Daphnia species reproduce by cyclic parthenogenesis involving both sexual and asexual reproduction. The sex of the offspring is environmentally determined and mediated via endocrine signalling by the mother. Interestingly, male and female Daphnia can be genetically identical, yet display large differences in behaviour, morphology, lifespan and metabolic activity. Our goal was to integrate multiple omics datasets, including gene expression, splicing, histone modification and DNA methylation data generated from genetically identical female and male Daphnia pulex under controlled laboratory settings with the aim of achieving a better understanding of the underlying epigenetic factors that may contribute to the phenotypic differences observed between the two genders. RESULTS: In this study we demonstrate that gene expression level is positively correlated with increased DNA methylation, and histone H3 trimethylation at lysine&thinsp;4 (H3K4me3) at predicted promoter regions. Conversely, elevated histone H3 trimethylation at lysine&thinsp;27 (H3K27me3), distributed across the entire transcript length, is negatively correlated with gene expression level. Interestingly, male Daphnia are dominated with epigenetic modifications that globally promote elevated gene expression, while female Daphnia are dominated with epigenetic modifications that reduce gene expression globally. For examples, CpG methylation (positively correlated with gene expression level) is significantly higher in almost all differentially methylated sites in male compared to female Daphnia. Furthermore, H3K4me3 modifications are higher in male compared to female Daphnia in more than 3/4 of the differentially regulated promoters. On the other hand, H3K27me3 is higher in female compared to male Daphnia in more than 5/6 of differentially modified sites. However, both sexes demonstrate roughly equal number of genes that are up-regulated in one gender compared to the other sex. Since, gene expression analyses typically assume that most genes are expressed at equal level among samples and different conditions, and thus cannot detect global changes affecting most genes. CONCLUSIONS: The epigenetic differences between male and female in Daphnia pulex are vast and dominated by changes that promote elevated gene expression in male Daphnia. Furthermore, the differences observed in both gene expression changes and epigenetic modifications between the genders relate to pathways that are physiologically relevant to the observed phenotypic differences.</p>',
			'date' => '2020-01-06',
			'pmid' => 'http://www.pubmed.gov/31906859',
			'doi' => '10.1186/s12864-019-6415-5',
			'modified' => '2020-02-20 11:34:47',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 100 => array(
			'id' => '3802',
			'name' => 'Analysis of Histone Modifications in Rodent Pancreatic Islets by Native Chromatin Immunoprecipitation.',
			'authors' => 'Sandovici I, Nicholas LM, O'Neill LP',
			'description' => '<p>The islets of Langerhans are clusters of cells dispersed throughout the pancreas that produce several hormones essential for controlling a variety of metabolic processes, including glucose homeostasis and lipid metabolism. Studying the transcriptional control of pancreatic islet cells has important implications for understanding the mechanisms that control their normal development, as well as the pathogenesis of metabolic diseases such as diabetes. Histones represent the main protein components of the chromatin and undergo diverse covalent modifications that are very important for gene regulation. Here we describe the isolation of pancreatic islets from rodents and subsequently outline the methods used to immunoprecipitate and analyze the native chromatin obtained from these cells.</p>',
			'date' => '2020-01-01',
			'pmid' => 'http://www.pubmed.gov/31586329',
			'doi' => '10.1007/978-1-4939-9882-1',
			'modified' => '2019-12-05 11:28:01',
			'created' => '2019-12-02 15:25:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 101 => array(
			'id' => '4096',
			'name' => 'Changes in H3K27ac at Gene Regulatory Regions in Porcine AlveolarMacrophages Following LPS or PolyIC Exposure.',
			'authors' => 'Herrera-Uribe, Juber and Liu, Haibo and Byrne, Kristen A and Bond, Zahra Fand Loving, Crystal L and Tuggle, Christopher K',
			'description' => '<p>Changes in chromatin structure, especially in histone modifications (HMs), linked with chromatin accessibility for transcription machinery, are considered to play significant roles in transcriptional regulation. Alveolar macrophages (AM) are important immune cells for protection against pulmonary pathogens, and must readily respond to bacteria and viruses that enter the airways. Mechanism(s) controlling AM innate response to different pathogen-associated molecular patterns (PAMPs) are not well defined in pigs. By combining RNA sequencing (RNA-seq) with chromatin immunoprecipitation and sequencing (ChIP-seq) for four histone marks (H3K4me3, H3K4me1, H3K27ac and H3K27me3), we established a chromatin state map for AM stimulated with two different PAMPs, lipopolysaccharide (LPS) and Poly(I:C), and investigated the potential effect of identified histone modifications on transcription factor binding motif (TFBM) prediction and RNA abundance changes in these AM. The integrative analysis suggests that the differential gene expression between non-stimulated and stimulated AM is significantly associated with changes in the H3K27ac level at active regulatory regions. Although global changes in chromatin states were minor after stimulation, we detected chromatin state changes for differentially expressed genes involved in the TLR4, TLR3 and RIG-I signaling pathways. We found that regions marked by H3K27ac genome-wide were enriched for TFBMs of TF that are involved in the inflammatory response. We further documented that TF whose expression was induced by these stimuli had TFBMs enriched within H3K27ac-marked regions whose chromatin state changed by these same stimuli. Given that the dramatic transcriptomic changes and minor chromatin state changes occurred in response to both stimuli, we conclude that regulatory elements (i.e. active promoters) that contain transcription factor binding motifs were already active/poised in AM for immediate inflammatory response to PAMPs. In summary, our data provides the first chromatin state map of porcine AM in response to bacterial and viral PAMPs, contributing to the Functional Annotation of Animal Genomes (FAANG) project, and demonstrates the role of HMs, especially H3K27ac, in regulating transcription in AM in response to LPS and Poly(I:C).</p>',
			'date' => '2020-01-01',
			'pmid' => 'https://www.frontiersin.org/articles/10.3389/fgene.2020.00817/full',
			'doi' => '10.3389/fgene.2020.00817',
			'modified' => '2021-03-17 17:22:56',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 102 => array(
			'id' => '3839',
			'name' => 'Functionally Annotating Regulatory Elements in the Equine Genome Using Histone Mark ChIP-Seq.',
			'authors' => 'Kingsley NB, Kern C, Creppe C, Hales EN, Zhou H, Kalbfleisch TS, MacLeod JN, Petersen JL, Finno CJ, Bellone RR',
			'description' => '<p>One of the primary aims of the Functional Annotation of ANimal Genomes (FAANG) initiative is to characterize tissue-specific regulation within animal genomes. To this end, we used chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to map four histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me3) in eight prioritized tissues collected as part of the FAANG equine biobank from two thoroughbred mares. Data were generated according to optimized experimental parameters developed during quality control testing. To ensure that we obtained sufficient ChIP and successful peak-calling, data and peak-calls were assessed using six quality metrics, replicate comparisons, and site-specific evaluations. Tissue specificity was explored by identifying binding motifs within unique active regions, and motifs were further characterized by gene ontology (GO) and protein-protein interaction analyses. The histone marks identified in this study represent some of the first resources for tissue-specific regulation within the equine genome. As such, these publicly available annotation data can be used to advance equine studies investigating health, performance, reproduction, and other traits of economic interest in the horse.</p>',
			'date' => '2019-12-18',
			'pmid' => 'http://www.pubmed.gov/31861495',
			'doi' => '10.3390/genes11010003',
			'modified' => '2020-02-20 11:20:25',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 103 => array(
			'id' => '3837',
			'name' => 'H3K4me1 Supports Memory-like NK Cells Induced by Systemic Inflammation.',
			'authors' => 'Rasid O, Chevalier C, Camarasa TM, Fitting C, Cavaillon JM, Hamon MA',
			'description' => '<p>Natural killer (NK) cells are unique players in innate immunity and, as such, an attractive target for immunotherapy. NK cells display immune memory properties in certain models, but the long-term status of NK cells following systemic inflammation is unknown. Here we show that following LPS-induced endotoxemia in mice, NK cells acquire cell-intrinsic memory-like properties, showing increased production of IFN&gamma; upon specific secondary stimulation. The NK cell memory response is detectable for at least 9&nbsp;weeks and contributes to protection from E.&nbsp;coli infection upon adoptive transfer. Importantly, we reveal a mechanism essential for NK cell memory, whereby an H3K4me1-marked latent enhancer is uncovered at the ifng locus. Chemical inhibition of histone methyltransferase activity erases the enhancer and abolishes NK cell memory. Thus, NK cell memory develops after endotoxemia in a histone methylation-dependent manner, ensuring a heightened response to secondary stimulation.</p>',
			'date' => '2019-12-17',
			'pmid' => 'http://www.pubmed.gov/31851924',
			'doi' => '10.1016/j.celrep.2019.11.043',
			'modified' => '2020-02-20 11:24:10',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 104 => array(
			'id' => '3830',
			'name' => 'Trained immunity modulates inflammation-induced fibrosis.',
			'authors' => 'Jeljeli M, Riccio LGC, Doridot L, Chêne C, Nicco C, Chouzenoux S, Deletang Q, Allanore Y, Kavian N, Batteux F',
			'description' => '<p>Chronic inflammation and fibrosis can result from inappropriately activated immune responses that are mediated by macrophages. Macrophages can acquire memory-like characteristics in response to antigen exposure. Here, we show the effect of BCG or low-dose LPS stimulation on macrophage phenotype, cytokine production, chromatin and metabolic modifications. Low-dose LPS training alleviates fibrosis and inflammation in a mouse model of systemic sclerosis (SSc), whereas BCG-training exacerbates disease in this model. Adoptive transfer of low-dose LPS-trained or BCG-trained macrophages also has beneficial or harmful effects, respectively. Furthermore, coculture with low-dose LPS trained macrophages reduces the fibro-inflammatory profile of fibroblasts from mice and patients with SSc, indicating that trained immunity might be a phenomenon that can be targeted to treat SSc and other autoimmune and inflammatory fibrotic disorders.</p>',
			'date' => '2019-12-11',
			'pmid' => 'http://www.pubmed.gov/31827093',
			'doi' => '10.1038/s41467-019-13636-x',
			'modified' => '2020-02-25 13:32:01',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 105 => array(
			'id' => '3826',
			'name' => 'MicroRNA-708 is a novel regulator of the Hoxa9 program in myeloid cells.',
			'authors' => 'Schneider E, Pochert N, Ruess C, MacPhee L, Escano L, Miller C, Krowiorz K, Delsing Malmberg E, Heravi-Moussavi A, Lorzadeh A, Ashouri A, Grasedieck S, Sperb N, Kumar Kopparapu P, Iben S, Staffas A, Xiang P, Rösler R, Kanduri M, Larsson E, Fogelstrand L, ',
			'description' => '<p>MicroRNAs (miRNAs) are commonly deregulated in acute myeloid leukemia (AML), affecting critical genes not only through direct targeting, but also through modulation of downstream effectors. Homeobox (Hox) genes balance self-renewal, proliferation, cell death, and differentiation in many tissues and aberrant Hox gene expression can create a predisposition to leukemogenesis in hematopoietic cells. However, possible linkages between the regulatory pathways of Hox genes and miRNAs are not yet fully resolved. We identified miR-708 to be upregulated in Hoxa9/Meis1 AML inducing cell lines as well as in AML patients. We further showed Meis1 directly targeting miR-708 and modulating its expression through epigenetic transcriptional regulation. CRISPR/Cas9 mediated knockout of miR-708 in Hoxa9/Meis1 cells delayed disease onset in vivo, demonstrating for the first time a pro-leukemic contribution of miR-708 in this context. Overexpression of miR-708 however strongly impeded Hoxa9 mediated transformation and homing capacity in vivo through modulation of adhesion factors and induction of myeloid differentiation. Taken together, we reveal miR-708, a putative tumor suppressor miRNA and direct target of Meis1, as a potent antagonist of the Hoxa9 phenotype but an effector of transformation in Hoxa9/Meis1. This unexpected finding highlights the yet unexplored role of miRNAs as indirect regulators of the Hox program during normal and aberrant hematopoiesis.</p>',
			'date' => '2019-11-25',
			'pmid' => 'http://www.pubmed.gov/31768018',
			'doi' => '10.1038/s41375-019-0651-1',
			'modified' => '2020-02-25 13:36:10',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 106 => array(
			'id' => '3807',
			'name' => 'Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.',
			'authors' => 'Aloia L, McKie MA, Vernaz G, Cordero-Espinoza L, Aleksieva N, van den Ameele J, Antonica F, Font-Cunill B, Raven A, Aiese Cigliano R, Belenguer G, Mort RL, Brand AH, Zernicka-Goetz M, Forbes SJ, Miska EA, Huch M',
			'description' => '<p>Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal cells. However, the molecular mechanisms by which adult ductal-committed cells acquire cellular plasticity, initiate organoids and regenerate the damaged tissue remain largely unknown. Here, we describe that ductal cells undergo a transient, genome-wide, remodelling of their transcriptome and epigenome during organoid initiation and in vivo following tissue damage. TET1-mediated hydroxymethylation licences differentiated ductal cells to initiate organoids and activate the regenerative programme through the transcriptional regulation of stem-cell genes and regenerative pathways including the YAP-Hippo signalling. Our results argue in favour of the remodelling of genomic methylome/hydroxymethylome landscapes as a general mechanism by which differentiated cells exit a committed state in response to tissue damage.</p>',
			'date' => '2019-11-04',
			'pmid' => 'http://www.pubmed.gov/31685987',
			'doi' => '10.1038/s41556-019-0402-6',
			'modified' => '2019-12-05 11:19:34',
			'created' => '2019-12-02 15:25:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 107 => array(
			'id' => '3824',
			'name' => 'Transcriptional alterations in glioma result primarily from DNA methylation-independent mechanisms.',
			'authors' => 'Court F, Le Boiteux E, Fogli A, Müller-Barthélémy M, Vaurs-Barrière C, Chautard E, Pereira B, Biau J, Kemeny JL, Khalil T, Karayan-Tapon L, Verrelle P, Arnaud P',
			'description' => '<p>In cancer cells, aberrant DNA methylation is commonly associated with transcriptional alterations, including silencing of tumor suppressor genes. However, multiple epigenetic mechanisms, including polycomb repressive marks, contribute to gene deregulation in cancer. To dissect the relative contribution of DNA methylation-dependent and -independent mechanisms to transcriptional alterations at CpG island/promoter-associated genes in cancer, we studied 70 samples of adult glioma, a widespread type of brain tumor, classified according to their isocitrate dehydrogenase () mutation status. We found that most transcriptional alterations in tumor samples were DNA methylation-independent. Instead, altered histone H3 trimethylation at lysine 27 (H3K27me3) was the predominant molecular defect at deregulated genes. Our results also suggest that the presence of a bivalent chromatin signature at CpG island promoters in stem cells predisposes not only to hypermethylation, as widely documented, but more generally to all types of transcriptional alterations in transformed cells. In addition, the gene expression strength in healthy brain cells influences the choice between DNA methylation- and H3K27me3-associated silencing in glioma. Highly expressed genes were more likely to be repressed by H3K27me3 than by DNA methylation. Our findings support a model in which altered H3K27me3 dynamics, more specifically defects in the interplay between polycomb protein complexes and the brain-specific transcriptional machinery, is the main cause of transcriptional alteration in glioma cells. Our study provides the first comprehensive description of epigenetic changes in glioma and their relative contribution to transcriptional changes. It may be useful for the design of drugs targeting cancer-related epigenetic defects.</p>',
			'date' => '2019-10-01',
			'pmid' => 'http://www.pubmed.gov/31533980',
			'doi' => '10.1101/gr.249219.119.',
			'modified' => '2020-02-25 13:41:40',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 108 => array(
			'id' => '3781',
			'name' => 'Functional analyses of a low-penetrance risk variant rs6702619/1p21.2 associating with colorectal cancer in Polish population.',
			'authors' => 'Statkiewicz M, Maryan N, Kulecka M, Kuklinska U, Ostrowski J, Mikula M',
			'description' => '<p>Several studies employed the genome-wide association (GWA) analysis of single-nucleotide polymorphisms (SNPs) to identify susceptibility regions in colorectal cancer (CRC). However, the functional studies exploring the role of associating SNPs with cancer biology are limited. Herein, using chromatin immunoprecipitation assay (ChIP), reporter assay and chromosome conformation capture sequencing (3C-Seq) augmented with publically available genomic and epigenomic databases we aimed to define the function of rs6702619/1p21.2 region associated with CRC in the Polish population. Using ChIP we confirmed that rs6702619 region is occupied by a CTCF, a master regulator of long-range genomic interactions, and is decorated with enhancer-like histone modifications. The enhancer blocking assay revealed that rs6702619 region acts as an insulator with activity dependent on the SNP genotype. Finally, a 3C-Seq survey indicated more than a hundred loci in the rs6702619 locus interactome, including GNAS gene that is frequently amplified in CRC. Taken together, we showed that the CRC-associated rs6702619 region has in vitro and in vivo properties of an insulator that demonstrates long-range physical interactions with CRC-relevant loci.</p>',
			'date' => '2019-09-17',
			'pmid' => 'http://www.pubmed.gov/31531420',
			'doi' => '10.1093/nar/gkm875.',
			'modified' => '2019-10-02 16:51:42',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 109 => array(
			'id' => '3776',
			'name' => 'β-Glucan-Induced Trained Immunity Protects against Leishmania braziliensis Infection: a Crucial Role for IL-32.',
			'authors' => 'Dos Santos JC, Barroso de Figueiredo AM, Teodoro Silva MV, Cirovic B, de Bree LCJ, Damen MSMA, Moorlag SJCFM, Gomes RS, Helsen MM, Oosting M, Keating ST, Schlitzer A, Netea MG, Ribeiro-Dias F, Joosten LAB',
			'description' => '<p>American tegumentary leishmaniasis is a vector-borne parasitic disease caused by Leishmania protozoans. Innate immune cells undergo long-term functional reprogramming in response to infection or Bacillus Calmette-Gu&eacute;rin (BCG) vaccination via a process called trained immunity, conferring non-specific protection from secondary infections. Here, we demonstrate that monocytes trained with the fungal cell wall component &beta;-glucan confer enhanced protection against infections caused by Leishmania braziliensis through the enhanced production of proinflammatory cytokines. Mechanistically, this augmented immunological response is dependent on increased expression of interleukin 32 (IL-32). Studies performed using a humanized IL-32 transgenic mouse highlight the clinical implications of these findings in&nbsp;vivo. This study represents a definitive characterization of the role of IL-32&gamma; in the trained phenotype induced by &beta;-glucan or BCG, the results of which improve our understanding of the molecular mechanisms governing trained immunity and Leishmania infection control.</p>',
			'date' => '2019-09-03',
			'pmid' => 'http://www.pubmed.gov/31484076',
			'doi' => '10.1016/j.celrep.2019.08.004',
			'modified' => '2019-10-02 17:00:49',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 110 => array(
			'id' => '3774',
			'name' => 'Reactivation of super-enhancers by KLF4 in human Head and Neck Squamous Cell Carcinoma.',
			'authors' => 'Tsompana M, Gluck C, Sethi I, Joshi I, Bard J, Nowak NJ, Sinha S, Buck MJ',
			'description' => '<p>Head and neck squamous cell carcinoma (HNSCC) is a disease of significant morbidity and mortality and rarely diagnosed in early stages. Despite extensive genetic and genomic characterization, targeted therapeutics and diagnostic markers of HNSCC are lacking due to the inherent heterogeneity and complexity of the disease. Herein, we have generated the global histone mark based epigenomic and transcriptomic cartogram of SCC25, a representative cell type of mesenchymal HNSCC and its normal oral keratinocyte counterpart. Examination of genomic regions marked by differential chromatin states and associated with misregulated gene expression led us to identify SCC25 enriched regulatory sequences and transcription factors (TF) motifs. These findings were further strengthened by ATAC-seq based open chromatin and TF footprint analysis which unearthed Kr&uuml;ppel-like Factor 4 (KLF4) as a potential key regulator of the SCC25 cistrome. We reaffirm the results obtained from in silico and chromatin studies in SCC25 by ChIP-seq of KLF4 and identify &Delta;Np63 as a co-oncogenic driver of the cancer-specific gene expression milieu. Taken together, our results lead us to propose a model where elevated KLF4 levels sustains the oncogenic state of HNSCC by reactivating repressed chromatin domains at key downstream genes, often by targeting super-enhancers.</p>',
			'date' => '2019-09-02',
			'pmid' => 'http://www.pubmed.gov/31477832',
			'doi' => '10.1038/s41388-019-0990-4',
			'modified' => '2019-10-02 17:05:36',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 111 => array(
			'id' => '3777',
			'name' => 'Nucleome Dynamics during Retinal Development.',
			'authors' => 'Norrie JL, Lupo MS, Xu B, Al Diri I, Valentine M, Putnam D, Griffiths L, Zhang J, Johnson D, Easton J, Shao Y, Honnell V, Frase S, Miller S, Stewart V, Zhou X, Chen X, Dyer MA',
			'description' => '<p>More than 8,000 genes are turned on or off as progenitor cells produce the 7 classes of retinal cell types during development. Thousands of enhancers are also active in the developing retinae, many having features of cell- and developmental stage-specific activity. We studied dynamic changes in the 3D chromatin landscape important for precisely orchestrated changes in gene expression during retinal development by ultra-deep in situ Hi-C analysis on murine retinae. We identified developmental-stage-specific changes in chromatin compartments and enhancer-promoter interactions. We developed a machine learning-based algorithm to map euchromatin and heterochromatin domains genome-wide and overlaid it with chromatin compartments identified by Hi-C. Single-cell ATAC-seq and RNA-seq were integrated with our Hi-C and previous ChIP-seq data to identify cell- and developmental-stage-specific super-enhancers (SEs). We identified a bipolar neuron-specific core regulatory circuit SE upstream of Vsx2, whose deletion in mice led to the loss of bipolar neurons.</p>',
			'date' => '2019-08-21',
			'pmid' => 'http://www.pubmed.gov/31493975',
			'doi' => '10.1016/j.neuron.2019.08.002',
			'modified' => '2019-10-02 16:58:50',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 112 => array(
			'id' => '3742',
			'name' => 'Development and epigenetic plasticity of murine Müller glia.',
			'authors' => 'Dvoriantchikova G, Seemungal RJ, Ivanov D',
			'description' => '<p>The ability to regenerate the entire retina and restore lost sight after injury is found in some species and relies mostly on the epigenetic plasticity of M&uuml;ller glia. To understand the role of mammalian M&uuml;ller glia as a source of progenitors for retinal regeneration, we investigated changes in gene expression during differentiation of retinal progenitor cells (RPCs) into M&uuml;ller glia. We also analyzed the global epigenetic profile of adult M&uuml;ller glia. We observed significant changes in gene expression during differentiation of RPCs into M&uuml;ller glia in only a small group of genes. We found a high similarity between RPCs and M&uuml;ller glia on the transcriptomic and epigenomic levels. Our findings also indicate that M&uuml;ller glia are epigenetically very close to late-born retinal neurons, but not early-born retinal neurons. Importantly, we found that key genes required for phototransduction were highly methylated. Thus, our data suggest that M&uuml;ller glia are epigenetically very similar to late RPCs. Meanwhile, obstacles for regeneration of the entire mammalian retina from M&uuml;ller glia may consist of repressive chromatin and highly methylated DNA in the promoter regions of many genes required for the development of early-born retinal neurons. In addition, DNA demethylation may be required for proper reprogramming and differentiation of M&uuml;ller glia into rod photoreceptors.</p>
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<div id="ConnectiveDocSignExtentionInstalled" data-extension-version="1.0.4"></div>',
			'date' => '2019-07-02',
			'pmid' => 'http://www.pubmed.gov/31276697',
			'doi' => '10.1016/j.bbamcr.2019.06.019',
			'modified' => '2019-08-13 10:50:24',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 113 => array(
			'id' => '3754',
			'name' => 'The alarmin S100A9 hampers osteoclast differentiation from human circulating precursors by reducing the expression of RANK.',
			'authors' => 'Di Ceglie I, Blom AB, Davar R, Logie C, Martens JHA, Habibi E, Böttcher LM, Roth J, Vogl T, Goodyear CS, van der Kraan PM, van Lent PL, van den Bosch MH',
			'description' => '<p>The alarmin S100A8/A9 is implicated in sterile inflammation-induced bone resorption and has been shown to increase the bone-resorptive capacity of mature osteoclasts. Here, we investigated the effects of S100A9 on osteoclast differentiation from human CD14 circulating precursors. Hereto, human CD14 monocytes were isolated and differentiated toward osteoclasts with M-CSF and receptor activator of NF-&kappa;B (RANK) ligand (RANKL) in the presence or absence of S100A9. Tartrate-resistant acid phosphatase staining showed that exposure to S100A9 during monocyte-to-osteoclast differentiation strongly decreased the numbers of multinucleated osteoclasts. This was underlined by a decreased resorption of a hydroxyapatite-like coating. The thus differentiated cells showed a high mRNA and protein production of proinflammatory factors after 16 h of exposure. In contrast, at d 4, the cells showed a decreased production of the osteoclast-promoting protein TNF-&alpha;. Interestingly, S100A9 exposure during the first 16 h of culture only was sufficient to reduce osteoclastogenesis. Using fluorescently labeled RANKL, we showed that, within this time frame, S100A9 inhibited the M-CSF-mediated induction of RANK. Chromatin immunoprecipitation showed that this was associated with changes in various histone marks at the epigenetic level. This S100A9-induced reduction in RANK was in part recovered by blocking TNF-&alpha; but not IL-1. Together, our data show that S100A9 impedes monocyte-to-osteoclast differentiation, probably a reduction in RANK expression.-Di Ceglie, I., Blom, A. B., Davar, R., Logie, C., Martens, J. H. A., Habibi, E., B&ouml;ttcher, L.-M., Roth, J., Vogl, T., Goodyear, C. S., van der Kraan, P. M., van Lent, P. L., van den Bosch, M. H. The alarmin S100A9 hampers osteoclast differentiation from human circulating precursors by reducing the expression of RANK.</p>',
			'date' => '2019-06-14',
			'pmid' => 'http://www.pubmed.gov/31199668',
			'doi' => '10.1096/fj.201802691RR',
			'modified' => '2019-10-03 12:20:02',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 114 => array(
			'id' => '3737',
			'name' => 'Probing the Tumor Suppressor Function of BAP1 in CRISPR-Engineered Human Liver Organoids.',
			'authors' => 'Artegiani B, van Voorthuijsen L, Lindeboom RGH, Seinstra D, Heo I, Tapia P, López-Iglesias C, Postrach D, Dayton T, Oka R, Hu H, van Boxtel R, van Es JH, Offerhaus J, Peters PJ, van Rheenen J, Vermeulen M, Clevers H',
			'description' => '<p>The deubiquitinating enzyme BAP1 is a tumor suppressor, among others involved in cholangiocarcinoma. BAP1 has many proposed molecular targets, while its Drosophila homolog is known to deubiquitinate histone H2AK119. We introduce BAP1 loss-of-function by CRISPR/Cas9 in normal human cholangiocyte organoids. We find that BAP1 controls&nbsp;the expression of junctional and cytoskeleton components by regulating chromatin accessibility. Consequently, we observe loss of multiple epithelial characteristics while motility increases. Importantly, restoring the catalytic activity of BAP1 in the nucleus rescues these cellular and molecular changes. We engineer human liver organoids to combine four common cholangiocarcinoma mutations (TP53, PTEN, SMAD4, and NF1). In this genetic background, BAP1 loss results in acquisition of malignant features upon xenotransplantation. Thus, control of epithelial identity through the regulation of chromatin accessibility appears to be a key aspect of BAP1's tumor suppressor function. Organoid technology combined with CRISPR/Cas9 provides an experimental platform for mechanistic studies of cancer gene function in a human context.</p>',
			'date' => '2019-06-06',
			'pmid' => 'http://www.pubmed.gov/31130514',
			'doi' => '10.1016/j.stem.2019.04.017',
			'modified' => '2019-08-06 16:58:50',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 115 => array(
			'id' => '3713',
			'name' => 'Complementary Activity of ETV5, RBPJ, and TCF3 Drives Formative Transition from Naive Pluripotency.',
			'authors' => 'Kalkan T, Bornelöv S, Mulas C, Diamanti E, Lohoff T, Ralser M, Middelkamp S, Lombard P, Nichols J, Smith A',
			'description' => '<p>The gene regulatory network (GRN) of naive mouse embryonic stem cells (ESCs) must be reconfigured to enable lineage commitment. TCF3 sanctions rewiring by suppressing components of the ESC transcription factor circuitry. However, TCF3 depletion only delays and does not prevent transition to formative pluripotency. Here, we delineate additional contributions of the ETS-family transcription factor ETV5 and the repressor RBPJ. In response to ERK signaling, ETV5 switches activity from supporting self-renewal and undergoes genome relocation linked to commissioning of enhancers activated in formative epiblast. Independent upregulation of RBPJ prevents re-expression of potent naive factors, TBX3 and NANOG, to secure exit from the naive state. Triple deletion of Etv5, Rbpj, and Tcf3 disables ESCs, such that they remain largely undifferentiated and locked in self-renewal, even in the presence of differentiation stimuli. Thus, genetic elimination of three complementary drivers of network transition stalls developmental progression, emulating environmental insulation by small-molecule inhibitors.</p>',
			'date' => '2019-05-02',
			'pmid' => 'http://www.pubmed.gov/31031137',
			'doi' => '10.1016/j.stem.2019.03.017',
			'modified' => '2019-07-05 14:28:38',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 116 => array(
			'id' => '3692',
			'name' => 'PML modulates H3.3 targeting to telomeric and centromeric repeats in mouse fibroblasts.',
			'authors' => 'Spirkoski J, Shah A, Reiner AH, Collas P, Delbarre E',
			'description' => '<p>Targeted deposition of histone variant H3.3 into chromatin is paramount for proper regulation of chromatin integrity, particularly in heterochromatic regions including repeats. We have recently shown that the promyelocytic leukemia (PML) protein prevents H3.3 from being deposited in large heterochromatic PML-associated domains (PADs). However, to what extent PML modulates H3.3 loading on chromatin in other areas of the genome remains unexplored. Here, we examined the impact of PML on targeting of H3.3 to genes and repeat regions that reside outside PADs. We show that loss of PML increases H3.3 deposition in subtelomeric, telomeric, pericentric and centromeric repeats in mouse embryonic fibroblasts, while other repeat classes are not affected. Expression of major satellite, minor satellite and telomeric non-coding transcripts is altered in Pml-null cells. In particular, telomeric Terra transcripts are strongly upregulated, in concordance with a marked reduction in H4K20me3 at these sites. Lastly, for most genes H3.3 enrichment or gene expression outcomes are independent of PML. Our data argue towards the importance of a PML-H3.3 axis in preserving a heterochromatin state at centromeres and telomeres.</p>',
			'date' => '2019-04-16',
			'pmid' => 'http://www.pubmed.gov/30850162',
			'doi' => '10.1016/j.bbrc.2019.02.087',
			'modified' => '2019-06-28 13:50:40',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 117 => array(
			'id' => '3711',
			'name' => 'Long intergenic non-coding RNAs regulate human lung fibroblast function: Implications for idiopathic pulmonary fibrosis.',
			'authors' => 'Hadjicharalambous MR, Roux BT, Csomor E, Feghali-Bostwick CA, Murray LA, Clarke DL, Lindsay MA',
			'description' => '<p>Phenotypic changes in lung fibroblasts are believed to contribute to the development of Idiopathic Pulmonary Fibrosis (IPF), a progressive and fatal lung disease. Long intergenic non-coding RNAs (lincRNAs) have been identified as novel regulators of gene expression and protein activity. In non-stimulated cells, we observed reduced proliferation and inflammation but no difference in the fibrotic response of IPF fibroblasts. These functional changes in non-stimulated cells were associated with changes in the expression of the histone marks, H3K4me1, H3K4me3 and H3K27ac indicating a possible involvement of epigenetics. Following activation with TGF-&beta;1 and IL-1&beta;, we demonstrated an increased fibrotic but reduced inflammatory response in IPF fibroblasts. There was no significant difference in proliferation following PDGF exposure. The lincRNAs, LINC00960 and LINC01140 were upregulated in IPF fibroblasts. Knockdown studies showed that LINC00960 and LINC01140 were positive regulators of proliferation in both control and IPF fibroblasts but had no effect upon the fibrotic response. Knockdown of LINC01140 but not LINC00960 increased the inflammatory response, which was greater in IPF compared to control fibroblasts. Overall, these studies demonstrate for the first time that lincRNAs are important regulators of proliferation and inflammation in human lung fibroblasts and that these might mediate the reduced inflammatory response observed in IPF-derived fibroblasts.</p>',
			'date' => '2019-04-15',
			'pmid' => 'http://www.pubmed.gov/30988425',
			'doi' => '10.1038/s41598-019-42292-w',
			'modified' => '2019-07-05 14:31:28',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 118 => array(
			'id' => '3702',
			'name' => 'Identification of ADGRE5 as discriminating MYC target between Burkitt lymphoma and diffuse large B-cell lymphoma.',
			'authors' => 'Kleo K, Dimitrova L, Oker E, Tomaszewski N, Berg E, Taruttis F, Engelmann JC, Schwarzfischer P, Reinders J, Spang R, Gronwald W, Oefner PJ, Hummel M',
			'description' => '<p>BACKGROUND: MYC is a heterogeneously expressed transcription factor that plays a multifunctional role in many biological processes such as cell proliferation and differentiation. It is also associated with many types of cancer including the malignant lymphomas. There are two types of aggressive B-cell lymphoma, namely Burkitt lymphoma (BL) and a subgroup of diffuse large cell lymphoma (DLBCL), which both carry MYC translocations and overexpress MYC but both differ significantly in their clinical outcome. In DLBCL, MYC translocations are associated with an aggressive behavior and poor outcome, whereas MYC-positive BL show a superior outcome. METHODS: To shed light on this phenomenon, we investigated the different modes of actions of MYC in aggressive B-cell lymphoma cell lines subdivided into three groups: (i) MYC-positive BL, (ii) DLBCL with MYC translocation (DLBCLpos) and (iii) DLBCL without MYC translocation (DLBCLneg) for control. In order to identify genome-wide MYC-DNA binding sites a chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) was performed. In addition, ChIP-Seq for H3K4me3 was used for determination of genomic regions accessible for transcriptional activity. These data were supplemented with gene expression data derived from RNA-Seq. RESULTS: Bioinformatics integration of all data sets revealed different MYC-binding patterns and transcriptional profiles in MYC-positive BL and DLBCL cell lines indicating different functional roles of MYC for gene regulation in aggressive B-cell lymphomas. Based on this multi-omics analysis we identified ADGRE5 (alias CD97) - a member of the EGF-TM7 subfamily of adhesion G protein-coupled receptors - as a MYC target gene, which is specifically expressed in BL but not in DLBCL regardless of MYC translocation. CONCLUSION: Our study describes a diverse genome-wide MYC-DNA binding pattern in BL and DLBCL cell lines with and without MYC translocations. Furthermore, we identified ADREG5 as a MYC target gene able to discriminate between BL and DLBCL irrespectively of the presence of MYC breaks in DLBCL. Since ADGRE5 plays an important role in tumor cell formation, metastasis and invasion, it might also be instrumental to better understand the different pathobiology of BL and DLBCL and help to explain discrepant clinical characteristics of BL and DLBCL.</p>',
			'date' => '2019-04-05',
			'pmid' => 'http://www.pubmed.gov/30953469',
			'doi' => '10.1186/s12885-019-5537-0',
			'modified' => '2019-07-05 14:41:38',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 119 => array(
			'id' => '3732',
			'name' => 'Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis.',
			'authors' => 'Mallaney C, Ostrander EL, Celik H, Kramer AC, Martens A, Kothari A, Koh WK, Haussler E, Iwamori N, Gontarz P, Zhang B, Challen GA',
			'description' => '<p>The histone demethylase KDM6B (JMJD3) is upregulated in blood disorders, suggesting that it may have important pathogenic functions. Here we examined the function of Kdm6b in hematopoietic stem cells (HSC) to evaluate its potential as a therapeutic target. Loss of Kdm6b lead to depletion of phenotypic and functional HSCs in adult mice, and Kdm6b is necessary for HSC self-renewal in response to inflammatory and proliferative stress. Loss of Kdm6b leads to a pro-differentiation poised state in HSCs due to the increased expression of the AP-1 transcription factor complex (Fos and Jun) and immediate early response (IER) genes. These gene expression changes occurred independently of chromatin modifications. Targeting AP-1 restored function of Kdm6b-deficient HSCs, suggesting that Kdm6b regulates this complex during HSC stress response. We also show Kdm6b supports developmental context-dependent leukemogenesis for T-cell acute lymphoblastic leukemia (T-ALL) and M5 acute myeloid leukemia (AML). Kdm6b is required for effective fetal-derived T-ALL and adult-derived AML, but not vice versa. These studies identify a crucial role for Kdm6b in regulating HSC self-renewal in different contexts, and highlight the potential of KDM6B as a therapeutic target in different hematopoietic malignancies.</p>',
			'date' => '2019-04-01',
			'pmid' => 'http://www.pubmed.gov/30936419',
			'doi' => '10.1038/s41375-019-0462-4',
			'modified' => '2019-08-07 09:14:05',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 120 => array(
			'id' => '3700',
			'name' => 'A critical regulator of Bcl2 revealed by systematic transcript discovery of lncRNAs associated with T-cell differentiation.',
			'authors' => 'Saadi W, Kermezli Y, Dao LTM, Mathieu E, Santiago-Algarra D, Manosalva I, Torres M, Belhocine M, Pradel L, Loriod B, Aribi M, Puthier D, Spicuglia S',
			'description' => '<p>Normal T-cell differentiation requires a complex regulatory network which supports a series of maturation steps, including lineage commitment, T-cell receptor (TCR) gene rearrangement, and thymic positive and negative selection. However, the underlying molecular mechanisms are difficult to assess due to limited T-cell models. Here we explore the use of the pro-T-cell line P5424 to study early T-cell differentiation. Stimulation of P5424 cells by the calcium ionophore ionomycin together with PMA resulted in gene regulation of T-cell differentiation and activation markers, partially mimicking the CD4CD8 double negative (DN) to double positive (DP) transition and some aspects of subsequent T-cell maturation and activation. Global analysis of gene expression, along with kinetic experiments, revealed a significant association between the dynamic expression of coding genes and neighbor lncRNAs including many newly-discovered transcripts, thus suggesting potential co-regulation. CRISPR/Cas9-mediated genetic deletion of Robnr, an inducible lncRNA located downstream of the anti-apoptotic gene Bcl2, demonstrated a critical role of the Robnr locus in the induction of Bcl2. Thus, the pro-T-cell line P5424 is a powerful model system to characterize regulatory networks involved in early T-cell differentiation and maturation.</p>',
			'date' => '2019-03-18',
			'pmid' => 'http://www.pubmed.gov/30886319',
			'doi' => '10.1038/s41598-019-41247-5',
			'modified' => '2019-07-05 14:43:51',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 121 => array(
			'id' => '3571',
			'name' => 'The role of TCF3 as potential master regulator in blastemal Wilms tumors.',
			'authors' => 'Kehl T, Schneider L, Kattler K, Stöckel D, Wegert J, Gerstner N, Ludwig N, Distler U, Tenzer S, Gessler M, Walter J, Keller A, Graf N, Meese E, Lenhof HP',
			'description' => '<p>Wilms tumors are the most common type of pediatric kidney tumors. While the overall prognosis for patients is favorable, especially tumors that exhibit a blastemal subtype after preoperative chemotherapy have a poor prognosis. For an improved risk assessment and therapy stratification, it is essential to identify the driving factors that are distinctive for this aggressive subtype. In our study, we compared gene expression profiles of 33 tumor biopsies (17 blastemal and 16 other tumors) after neoadjuvant chemotherapy. The analysis of this dataset using the Regulator Gene Association Enrichment algorithm successfully identified several biomarkers and associated molecular mechanisms that distinguish between blastemal and nonblastemal Wilms tumors. Specifically, regulators involved in embryonic development and epigenetic processes like chromatin remodeling and histone modification play an essential role in blastemal tumors. In this context, we especially identified TCF3 as the central regulatory element. Furthermore, the comparison of ChIP-Seq data of Wilms tumor cell cultures from a blastemal mouse xenograft and a stromal tumor provided further evidence that the chromatin states of blastemal cells share characteristics with embryonic stem cells that are not present in the stromal tumor cell line. These stem-cell like characteristics could potentially add to the increased malignancy and chemoresistance of the blastemal subtype. Along with TCF3, we detected several additional biomarkers that are distinctive for blastemal Wilms tumors after neoadjuvant chemotherapy and that may provide leads for new therapeutic regimens.</p>',
			'date' => '2019-03-15',
			'pmid' => 'http://www.pubmed.gov/30155889',
			'doi' => '10.1002/ijc.31834',
			'modified' => '2019-03-21 17:10:17',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 122 => array(
			'id' => '3611',
			'name' => 'Extensive Recovery of Embryonic Enhancer and Gene Memory Stored in Hypomethylated Enhancer DNA.',
			'authors' => 'Jadhav U, Cavazza A, Banerjee KK, Xie H, O'Neill NK, Saenz-Vash V, Herbert Z, Madha S, Orkin SH, Zhai H, Shivdasani RA',
			'description' => '<p>Developing and adult tissues use different cis-regulatory elements. Although DNA at some decommissioned embryonic enhancers is hypomethylated in adult cells, it is unknown whether this putative epigenetic memory is complete and recoverable. We find that, in adult mouse cells, hypomethylated CpG dinucleotides preserve a nearly complete archive of tissue-specific developmental enhancers. Sites that carry the active histone mark H3K4me1, and are therefore considered "primed," are mainly cis elements that act late in organogenesis. In contrast, sites decommissioned early in development retain hypomethylated DNA as a singular property. In adult intestinal and blood cells, sustained absence of polycomb repressive complex 2 indirectly reactivates most-and only-hypomethylated developmental enhancers. Embryonic and fetal transcriptional programs re-emerge as a result, in reverse chronology to cis element inactivation during development. Thus, hypomethylated DNA in adult cells preserves a "fossil record" of tissue-specific developmental enhancers, stably marking decommissioned sites and enabling recovery of this epigenetic memory.</p>',
			'date' => '2019-03-15',
			'pmid' => 'http://www.pubmed.gov/30905509',
			'doi' => '10.1016/j.molcel.2019.02.024',
			'modified' => '2019-04-17 14:46:15',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 123 => array(
			'id' => '3569',
			'name' => 'The epigenetic basis for the impaired ability of adult murine retinal pigment epithelium cells to regenerate retinal tissue.',
			'authors' => 'Dvoriantchikova G, Seemungal RJ, Ivanov D',
			'description' => '<p>The epigenetic plasticity of amphibian retinal pigment epithelium (RPE) allows them to regenerate the entire retina, a trait known to be absent in mammals. In this study, we investigated the epigenetic plasticity of adult murine RPE to identify possible mechanisms that prevent mammalian RPE from regenerating retinal tissue. RPE were analyzed using microarray, ChIP-seq, and whole-genome bisulfite sequencing approaches. We found that the majority of key genes required for progenitor phenotypes were in a permissive chromatin state and unmethylated in RPE. We observed that the majority of non-photoreceptor genes had promoters in a repressive chromatin state, but these promoters were in unmethylated or low-methylated regions. Meanwhile, the majority of promoters for photoreceptor genes were found in a permissive chromatin state, but were highly-methylated. Methylome states of photoreceptor-related genes in adult RPE and embryonic retina (which mostly contain progenitors) were very similar. However, promoters of these genes were demethylated and activated during retinal development. Our data suggest that, epigenetically, adult murine RPE cells are a progenitor-like cell type. Most likely two mechanisms prevent adult RPE from reprogramming and differentiating into retinal neurons: 1) repressive chromatin in the promoter regions of non-photoreceptor retinal neuron genes; 2) highly-methylated promoters of photoreceptor-related genes.</p>',
			'date' => '2019-03-07',
			'pmid' => 'http://www.pubmed.gov/30846751',
			'doi' => '10.1038/s41598-019-40262-w',
			'modified' => '2019-05-09 17:33:09',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 124 => array(
			'id' => '3671',
			'name' => 'Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes.',
			'authors' => 'Yi G, Wierenga ATJ, Petraglia F, Narang P, Janssen-Megens EM, Mandoli A, Merkel A, Berentsen K, Kim B, Matarese F, Singh AA, Habibi E, Prange KHM, Mulder AB, Jansen JH, Clarke L, Heath S, van der Reijden BA, Flicek P, Yaspo ML, Gut I, Bock C, Schuringa JJ',
			'description' => '<p>Global investigation of histone marks in acute myeloid leukemia (AML) remains limited. Analyses of 38 AML samples through integrated transcriptional and chromatin mark analysis exposes 2 major subtypes. One subtype is dominated by patients with&nbsp;NPM1 mutations or MLL-fusion genes, shows activation of the regulatory pathways involving HOX-family genes as targets, and displays high self-renewal capacity and stemness. The second subtype is enriched for RUNX1 or spliceosome mutations, suggesting potential interplay between the 2 aberrations, and mainly depends on IRF family regulators. Cellular consequences in prognosis predict a relatively worse outcome for the first subtype. Our integrated profiling establishes a rich resource to probe AML subtypes on the basis of expression and chromatin data.</p>',
			'date' => '2019-01-22',
			'pmid' => 'http://www.pubmed.gov/30673601',
			'doi' => '10.1016/j.celrep.2018.12.098',
			'modified' => '2019-07-01 11:30:31',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 125 => array(
			'id' => '3629',
			'name' => 'Comprehensive Analysis of Chromatin States in Atypical Teratoid/Rhabdoid Tumor Identifies Diverging Roles for SWI/SNF and Polycomb in Gene Regulation.',
			'authors' => 'Erkek S, Johann PD, Finetti MA, Drosos Y, Chou HC, Zapatka M, Sturm D, Jones DTW, Korshunov A, Rhyzova M, Wolf S, Mallm JP, Beck K, Witt O, Kulozik AE, Frühwald MC, Northcott PA, Korbel JO, Lichter P, Eils R, Gajjar A, Roberts CWM, Williamson D, Hasselbla',
			'description' => '<p>Biallelic inactivation of SMARCB1, encoding a member of the SWI/SNF chromatin remodeling complex, is the hallmark genetic aberration of atypical teratoid rhabdoid tumors (ATRT). Here, we report how loss of SMARCB1 affects the epigenome in these tumors. Using chromatin immunoprecipitation sequencing (ChIP-seq) on primary tumors for a series of active and repressive histone marks, we identified the chromatin states differentially represented in ATRTs compared with other brain tumors and non-neoplastic brain. Re-expression of SMARCB1 in ATRT cell lines enabled confirmation of our genome-wide findings for the chromatin states. Additional generation of ChIP-seq data for SWI/SNF and Polycomb group proteins and the transcriptional repressor protein REST determined differential dependencies of SWI/SNF and Polycomb complexes in regulation of diverse gene sets in ATRTs.</p>',
			'date' => '2019-01-14',
			'pmid' => 'http://www.pubmed.gov/30595504',
			'doi' => '10.1016/j.ccell.2018.11.014',
			'modified' => '2019-05-08 12:27:57',
			'created' => '2019-04-25 11:11:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 126 => array(
			'id' => '3658',
			'name' => 'The Wnt-Driven Mll1 Epigenome Regulates Salivary Gland and Head and Neck Cancer.',
			'authors' => 'Zhu Q, Fang L, Heuberger J, Kranz A, Schipper J, Scheckenbach K, Vidal RO, Sunaga-Franze DY, Müller M, Wulf-Goldenberg A, Sauer S, Birchmeier W',
			'description' => '<p>We identified a regulatory system that acts downstream of Wnt/&beta;-catenin signaling in salivary gland and head and neck carcinomas. We show in a mouse tumor model of K14-Cre-induced Wnt/&beta;-catenin gain-of-function and Bmpr1a loss-of-function mutations that tumor-propagating cells exhibit increased Mll1 activity and genome-wide increased H3K4 tri-methylation at promoters. Null mutations of Mll1 in tumor mice and in xenotransplanted human head and neck tumors resulted in loss of self-renewal of tumor-propagating cells and in block of tumor formation but did not alter normal tissue homeostasis. CRISPR/Cas9 mutagenesis and pharmacological interference of Mll1 at sequences that inhibit essential protein-protein interactions or the SET enzyme active site also blocked the self-renewal of mouse and human tumor-propagating cells. Our work provides strong genetic evidence for a crucial role of Mll1 in solid tumors. Moreover, inhibitors targeting specific Mll1 interactions might offer additional directions for therapies to treat these aggressive tumors.</p>',
			'date' => '2019-01-08',
			'pmid' => 'http://www.pubmed.gov/30625324',
			'doi' => '10.1016/j.celrep.2018.12.059',
			'modified' => '2019-06-07 09:00:14',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 127 => array(
			'id' => '3686',
			'name' => 'Gamma radiation induces locus specific changes to histone modification enrichment in zebrafish and Atlantic salmon.',
			'authors' => 'Lindeman LC, Kamstra JH, Ballangby J, Hurem S, Martín LM, Brede DA, Teien HC, Oughton DH, Salbu B, Lyche JL, Aleström P',
			'description' => '<p>Ionizing radiation is a recognized genotoxic agent, however, little is known about the role of the functional form of DNA in these processes. Post translational modifications on histone proteins control the organization of chromatin and hence control transcriptional responses that ultimately affect the phenotype. The purpose of this study was to investigate effects on chromatin caused by ionizing radiation in fish. Direct exposure of zebrafish (Danio rerio) embryos to gamma radiation (10.9 mGy/h for 3h) induced hyper-enrichment of H3K4me3 at the genes hnf4a, gmnn and vegfab. A similar relative hyper-enrichment was seen at the hnf4a loci of irradiated Atlantic salmon (Salmo salar) embryos (30 mGy/h for 10 days). At the selected genes in ovaries of adult zebrafish irradiated during gametogenesis (8.7 and 53 mGy/h for 27 days), a reduced enrichment of H3K4me3 was observed, which was correlated with reduced levels of histone H3 was observed. F1 embryos of the exposed parents showed hyper-methylation of H3K4me3, H3K9me3 and H3K27me3 on the same three loci, while these differences were almost negligible in F2 embryos. Our results from three selected loci suggest that ionizing radiation can affect chromatin structure and organization, and that these changes can be detected in F1 offspring, but not in subsequent generations.</p>',
			'date' => '2019-01-01',
			'pmid' => 'http://www.pubmed.gov/30759148',
			'doi' => '10.1371/journal.pone.0212123',
			'modified' => '2019-06-28 13:57:39',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 128 => array(
			'id' => '3607',
			'name' => 'Mutant p63 Affects Epidermal Cell Identity through Rewiring the Enhancer Landscape.',
			'authors' => 'Qu J, Tanis SEJ, Smits JPH, Kouwenhoven EN, Oti M, van den Bogaard EH, Logie C, Stunnenberg HG, van Bokhoven H, Mulder KW, Zhou H',
			'description' => '<p>Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Mutations in the p63 DNA-binding domain are associated with ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome. However, the underlying molecular mechanism of these mutations remains unclear. Here, we characterized the transcriptome and epigenome of p63 mutant keratinocytes derived from EEC patients. The transcriptome of p63 mutant keratinocytes deviated from the normal epidermal cell identity. Epigenomic analyses showed an altered enhancer landscape in p63 mutant keratinocytes contributed by loss of p63-bound active enhancers and unexpected gain of enhancers. The gained enhancers were frequently bound by deregulated transcription factors such as RUNX1. Reversing RUNX1 overexpression partially rescued deregulated gene expression and the altered enhancer landscape. Our findings identify a disease mechanism whereby mutant p63 rewires the enhancer landscape and affects epidermal cell identity, consolidating the pivotal role of p63 in controlling the enhancer landscape of epidermal keratinocytes.</p>',
			'date' => '2018-12-18',
			'pmid' => 'http://www.pubmed.gov/30566872',
			'doi' => '10.1016/j.celrep.2018.11.039',
			'modified' => '2019-04-17 14:51:18',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 129 => array(
			'id' => '3509',
			'name' => 'Promoter bivalency favors an open chromatin architecture in embryonic stem cells.',
			'authors' => 'Mas G, Blanco E, Ballaré C, Sansó M, Spill YG, Hu D, Aoi Y, Le Dily F, Shilatifard A, Marti-Renom MA, Di Croce L',
			'description' => '<p>In embryonic stem cells (ESCs), developmental gene promoters are characterized by their bivalent chromatin state, with simultaneous modification by MLL2 and Polycomb complexes. Although essential for embryogenesis, bivalency is functionally not well understood. Here, we show that MLL2 plays a central role in ESC genome organization. We generate a catalog of bona fide bivalent genes in ESCs and demonstrate that loss of MLL2 leads to increased Polycomb occupancy. Consequently, promoters lose accessibility, long-range interactions are redistributed, and ESCs fail to differentiate. We pose that bivalency balances accessibility and long-range connectivity of promoters, allowing developmental gene expression to be properly modulated.</p>',
			'date' => '2018-10-17',
			'pmid' => 'http://www.pubmed.gov/30224650',
			'doi' => '10.1038/s41588-018-0218-5',
			'modified' => '2019-02-27 15:45:37',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 130 => array(
			'id' => '3552',
			'name' => 'PRC2 targeting is a therapeutic strategy for EZ score defined high-risk multiple myeloma patients and overcome resistance to IMiDs.',
			'authors' => 'Herviou L, Kassambara A, Boireau S, Robert N, Requirand G, Müller-Tidow C, Vincent L, Seckinger A, Goldschmidt H, Cartron G, Hose D, Cavalli G, Moreaux J',
			'description' => '<p>BACKGROUND: Multiple myeloma (MM) is a malignant plasma cell disease with a poor survival, characterized by the accumulation of myeloma cells (MMCs) within the bone marrow. Epigenetic modifications in MM are associated not only with cancer development and progression, but also with drug resistance. METHODS: We identified a significant upregulation of the polycomb repressive complex 2 (PRC2) core genes in MM cells in association with proliferation. We used EPZ-6438, a specific small molecule inhibitor of EZH2 methyltransferase activity, to evaluate its effects on MM cells phenotype and gene expression prolile. RESULTS: PRC2 targeting results in growth inhibition due to cell cycle arrest and apoptosis together with polycomb, DNA methylation, TP53, and RB1 target genes induction. Resistance to EZH2 inhibitor is mediated by DNA methylation of PRC2 target genes. We also demonstrate a synergistic effect of EPZ-6438 and lenalidomide, a conventional drug used for MM treatment, activating B cell transcription factors and tumor suppressor gene expression in concert with MYC repression. We establish a gene expression-based EZ score allowing to identify poor prognosis patients that could benefit from EZH2 inhibitor treatment. CONCLUSIONS: These data suggest that PRC2 targeting in association with IMiDs could have a therapeutic interest in MM patients characterized by high EZ score values, reactivating B cell transcription factors, and tumor suppressor genes.</p>',
			'date' => '2018-10-03',
			'pmid' => 'http://www.pubmed.org/30285865',
			'doi' => '10.1186/s13148-018-0554-4',
			'modified' => '2019-03-21 16:45:55',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 131 => array(
			'id' => '3396',
			'name' => 'The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity',
			'authors' => 'Domínguez-Andrés Jorge, Novakovic Boris, Li Yang, Scicluna Brendon P., Gresnigt Mark S., Arts Rob J.W., Oosting Marije, Moorlag Simone J.C.F.M., Groh Laszlo A., Zwaag Jelle, Koch Rebecca M., ter Horst Rob, Joosten Leo A.B., Wijmenga Cisca, Michelucci Ales',
			'description' => '<p>Sepsis involves simultaneous hyperactivation of the immune system and immune paralysis, leading to both organ dysfunction and increased susceptibility to secondary infections. Acute activation of myeloid cells induced itaconate synthesis, which subsequently mediated innate immune tolerance in human monocytes. In contrast, induction of trained immunity by b-glucan counteracted tolerance induced in a model of human endotoxemia by inhibiting the expression of immune-responsive gene 1 (IRG1), the enzyme that controls itaconate synthesis. b-Glucan also increased the expression of succinate dehydrogenase (SDH), contributing to the integrity of the TCA cycle and leading to an enhanced innate immune response after secondary stimulation. The role of itaconate was further validated by IRG1 and SDH polymorphisms that modulate induction of tolerance and trained immunity in human monocytes. These data demonstrate the importance of the IRG1-itaconateSDH axis in the development of immune tolerance and training and highlight the potential of b-glucaninduced trained immunity to revert immunoparalysis.</p>',
			'date' => '2018-10-01',
			'pmid' => 'http://www.pubmed.gov/30293776',
			'doi' => '10.1016/j.cmet.2018.09.003',
			'modified' => '2018-11-22 15:18:30',
			'created' => '2018-11-08 12:59:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 132 => array(
			'id' => '3566',
			'name' => 'Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes.',
			'authors' => 'Ferguson GB, Van Handel B, Bay M, Fiziev P, Org T, Lee S, Shkhyan R, Banks NW, Scheinberg M, Wu L, Saitta B, Elphingstone J, Larson AN, Riester SM, Pyle AD, Bernthal NM, Mikkola HK, Ernst J, van Wijnen AJ, Bonaguidi M, Evseenko D',
			'description' => '<p>Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application of cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differentiation. Network analysis delineated five tissue-specific gene modules; these modules and chromatin state analysis defined broad similarities in gene expression during cartilage specification and maturation in vitro and in vivo, including early expression and progressive silencing of muscle- and bone-specific genes. Finally, ontogenetic analysis of freshly isolated and pluripotent stem cell-derived articular chondrocytes identified that integrin alpha 4 defines 2 subsets of functionally and molecularly distinct chondrocytes characterized by their gene expression, osteochondral potential in vitro and proliferative signature in vivo. These analyses provide new insight into human musculoskeletal development and provide an essential comparative resource for disease modeling and regenerative medicine.</p>',
			'date' => '2018-09-07',
			'pmid' => 'http://www.pubmed.gov/30194383',
			'doi' => '10.1038/s41467-018-05573-y',
			'modified' => '2019-03-25 11:14:45',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 133 => array(
			'id' => '3596',
			'name' => 'RNA Sequencing and Pathway Analysis Identify Important Pathways Involved in Hypertrichosis and Intellectual Disability in Patients with Wiedemann-Steiner Syndrome.',
			'authors' => 'Mietton L, Lebrun N, Giurgea I, Goldenberg A, Saintpierre B, Hamroune J, Afenjar A, Billuart P, Bienvenu T',
			'description' => '<p>A growing number of histone modifiers are involved in human neurodevelopmental disorders, suggesting that proper regulation of chromatin state is essential for the development of the central nervous system. Among them, heterozygous de novo variants in KMT2A, a gene coding for histone methyltransferase, have been associated with Wiedemann-Steiner syndrome (WSS), a rare developmental disorder mainly characterized by intellectual disability (ID) and hypertrichosis. As KMT2A is known to regulate the expression of multiple target genes through methylation of lysine 4 of histone 3 (H3K4me), we sought to investigate the transcriptomic consequences of KMT2A variants involved in WSS. Using fibroblasts from four WSS patients harboring loss-of-function KMT2A variants, we performed RNA sequencing and identified a number of genes for which transcription was altered in KMT2A-mutated cells compared to the control ones. Strikingly, analysis of the pathways and biological functions significantly deregulated between patients with WSS and healthy individuals revealed a number of processes predicted to be altered that are relevant for hypertrichosis and intellectual disability, the cardinal signs of this disease.</p>',
			'date' => '2018-09-01',
			'pmid' => 'http://www.pubmed.gov/30014449',
			'doi' => '10.1007/s12017-018-8502-1',
			'modified' => '2019-04-17 15:10:22',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 134 => array(
			'id' => '3564',
			'name' => 'Atopic asthma after rhinovirus-induced wheezing is associated with DNA methylation change in the SMAD3 gene promoter.',
			'authors' => 'Lund RJ, Osmala M, Malonzo M, Lukkarinen M, Leino A, Salmi J, Vuorikoski S, Turunen R, Vuorinen T, Akdis C, Lähdesmäki H, Lahesmaa R, Jartti T',
			'description' => '<p>Children with rhinovirus-induced severe early wheezing have an increased risk of developing asthma later in life. The exact molecular mechanisms for this association are still mostly unknown. To identify potential changes in the transcriptional and epigenetic regulation in rhinovirus-associated atopic or nonatopic asthma, we analyzed a cohort of 5-year-old children (n&nbsp;=&nbsp;45) according to the virus etiology of the first severe wheezing episode at the mean age of 13&nbsp;months and to 5-year asthma outcome. The development of atopic asthma in children with early rhinovirus-induced wheezing was associated with DNA methylation changes at several genomic sites in chromosomal regions previously linked to asthma. The strongest changes in atopic asthma were detected in the promoter region of SMAD3 gene at chr 15q22.33 and introns of DDO/METTL24 genes at 6q21. These changes were validated to be present also at the average age of 8&nbsp;years.</p>',
			'date' => '2018-08-01',
			'pmid' => 'http://www.pubmed.gov/29729188',
			'doi' => '10.1111/all.13473',
			'modified' => '2019-03-25 11:19:56',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 135 => array(
			'id' => '3515',
			'name' => 'Integrative multi-omics analysis of intestinal organoid differentiation',
			'authors' => 'Rik GH Lindeboom, Lisa van Voorthuijsen1, Koen C Oost, Maria J Rodríguez-Colman, Maria V Luna-Velez, Cristina Furlan, Floriane Baraille, Pascal WTC Jansen, Agnès Ribeiro, Boudewijn MT Burgering, Hugo J Snippert, & Michiel Vermeulen',
			'description' => '<p>Intestinal organoids accurately recapitulate epithelial homeostasis in vivo, thereby representing a powerful in vitro system to investigate lineage specification and cellular differentiation. Here, we applied a multi-omics framework on stem cell-enriched and stem cell-depleted mouse intestinal organoids to obtain a holistic view of the molecular mechanisms that drive differential gene expression during adult intestinal stem cell differentiation. Our data revealed a global rewiring of the transcriptome and proteome between intestinal stem cells and enterocytes, with the majority of dynamic protein expression being transcription-driven. Integrating absolute mRNA and protein copy numbers revealed post-transcriptional regulation of gene expression. Probing the epigenetic landscape identified a large number of cell-type-specific regulatory elements, which revealed Hnf4g as a major driver of enterocyte differentiation. In summary, by applying an integrative systems biology approach, we uncovered multiple layers of gene expression regulation, which contribute to lineage specification and plasticity of the mouse small intestinal epithelium.</p>',
			'date' => '2018-06-26',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/29945941/',
			'doi' => '10.15252/msb.20188227',
			'modified' => '2022-05-18 18:45:53',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 136 => array(
			'id' => '3423',
			'name' => 'The Polycomb-Dependent Epigenome Controls β Cell Dysfunction, Dedifferentiation, and Diabetes.',
			'authors' => 'Lu TT, Heyne S, Dror E, Casas E, Leonhardt L, Boenke T, Yang CH, Sagar , Arrigoni L, Dalgaard K, Teperino R, Enders L, Selvaraj M, Ruf M, Raja SJ, Xie H, Boenisch U, Orkin SH, Lynn FC, Hoffman BG, Grün D, Vavouri T, Lempradl AM, Pospisilik JA',
			'description' => '<p>To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single-cell transcriptomics to mine for evidence of chromatin dysregulation in type 2 diabetes. We find two chromatin-state signatures that track &beta; cell dysfunction in mice and humans: ectopic activation of bivalent Polycomb-silenced domains and loss of expression at an epigenomically unique class of lineage-defining genes. &beta; cell-specific Polycomb (Eed/PRC2) loss of function in mice triggers diabetes-mimicking transcriptional signatures and highly penetrant, hyperglycemia-independent dedifferentiation, indicating that PRC2 dysregulation contributes to disease. The work provides novel resources for exploring &beta;&nbsp;cell transcriptional regulation and identifies PRC2 as necessary for long-term maintenance of &beta; cell identity. Importantly, the data suggest a two-hit (chromatin and hyperglycemia) model for loss of &beta;&nbsp;cell identity in diabetes.</p>',
			'date' => '2018-06-05',
			'pmid' => 'http://www.pubmed.gov/29754954',
			'doi' => '10.1016/j.cmet.2018.04.013',
			'modified' => '2018-12-31 11:43:24',
			'created' => '2018-12-04 09:51:07',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 137 => array(
			'id' => '3380',
			'name' => 'The reference epigenome and regulatory chromatin landscape of chronic lymphocytic leukemia',
			'authors' => 'Beekman R. et al.',
			'description' => '<p>Chronic lymphocytic leukemia (CLL) is a frequent hematological neoplasm in which underlying epigenetic alterations are only partially understood. Here, we analyze the reference epigenome of seven primary CLLs and the regulatory chromatin landscape of 107 primary cases in the context of normal B cell differentiation. We identify that the CLL chromatin landscape is largely influenced by distinct dynamics during normal B cell maturation. Beyond this, we define extensive catalogues of regulatory elements de novo reprogrammed in CLL as a whole and in its major clinico-biological subtypes classified by IGHV somatic hypermutation levels. We uncover that IGHV-unmutated CLLs harbor more active and open chromatin than IGHV-mutated cases. Furthermore, we show that de novo active regions in CLL are enriched for NFAT, FOX and TCF/LEF transcription factor family binding sites. Although most genetic alterations are not associated with consistent epigenetic profiles, CLLs with MYD88 mutations and trisomy 12 show distinct chromatin configurations. Furthermore, we observe that non-coding mutations in IGHV-mutated CLLs are enriched in H3K27ac-associated regulatory elements outside accessible chromatin. Overall, this study provides an integrative portrait of the CLL epigenome, identifies extensive networks of altered regulatory elements and sheds light on the relationship between the genetic and epigenetic architecture of the disease.</p>',
			'date' => '2018-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29785028',
			'doi' => '',
			'modified' => '2018-07-27 17:10:43',
			'created' => '2018-07-27 17:10:43',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 138 => array(
			'id' => '3469',
			'name' => 'Increased H3K9 methylation and impaired expression of Protocadherins are associated with the cognitive dysfunctions of the Kleefstra syndrome.',
			'authors' => 'Iacono G, Dubos A, Méziane H, Benevento M, Habibi E, Mandoli A, Riet F, Selloum M, Feil R, Zhou H, Kleefstra T, Kasri NN, van Bokhoven H, Herault Y, Stunnenberg HG',
			'description' => '<p>Kleefstra syndrome, a disease with intellectual disability, autism spectrum disorders and other developmental defects is caused in humans by haploinsufficiency of EHMT1. Although EHMT1 and its paralog EHMT2 were shown to be histone methyltransferases responsible for deposition of the di-methylated H3K9 (H3K9me2), the exact nature of epigenetic dysfunctions in Kleefstra syndrome remains unknown. Here, we found that the epigenome of Ehmt1+/- adult mouse brain displays a marked increase of H3K9me2/3 which correlates with impaired expression of protocadherins, master regulators of neuronal diversity. Increased H3K9me3 was present already at birth, indicating that aberrant methylation patterns are established during embryogenesis. Interestingly, we found that Ehmt2+/- mice do not present neither the marked increase of H3K9me2/3 nor the cognitive deficits found in Ehmt1+/- mice, indicating an evolutionary diversification of functions. Our finding of increased H3K9me3 in Ehmt1+/- mice is the first one supporting the notion that EHMT1 can quench the deposition of tri-methylation by other Histone methyltransferases, ultimately leading to impaired neurocognitive functioning. Our insights into the epigenetic pathophysiology of Kleefstra syndrome may offer guidance for future developments of therapeutic strategies for this disease.</p>',
			'date' => '2018-06-01',
			'pmid' => 'http://www.pubmed.gov/29554304',
			'doi' => '10.1093/nar/gky196',
			'modified' => '2019-02-15 21:04:02',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 139 => array(
			'id' => '3478',
			'name' => 'Pro-inflammatory cytokines activate hypoxia-inducible factor 3α via epigenetic changes in mesenchymal stromal/stem cells.',
			'authors' => 'Cuomo F, Coppola A, Botti C, Maione C, Forte A, Scisciola L, Liguori G, Caiafa I, Ursini MV, Galderisi U, Cipollaro M, Altucci L, Cobellis G',
			'description' => '<p>Human mesenchymal stromal/stem cells (hMSCs) emerged as a promising therapeutic tool for ischemic disorders, due to their ability to regenerate damaged tissues, promote angiogenesis and reduce inflammation, leading to encouraging, but still limited results. The outcomes in clinical trials exploring hMSC therapy are influenced by low cell retention and survival in affected tissues, partially influenced by lesion's microenvironment, where low oxygen conditions (i.e. hypoxia) and inflammation coexist. Hypoxia and inflammation are pathophysiological stresses, sharing common activators, such as hypoxia-inducible factors (HIFs) and NF-&kappa;B. HIF1&alpha; and HIF2&alpha; respond essentially to hypoxia, activating pathways involved in tissue repair. Little is known about the regulation of HIF3&alpha;. Here we investigated the role of HIF3&alpha; in vitro and in vivo. Human MSCs expressed HIF3&alpha;, differentially regulated by pro-inflammatory cytokines in an oxygen-independent manner, a novel and still uncharacterized mechanism, where NF-&kappa;B is critical for its expression. We investigated if epigenetic modifications are involved in HIF3&alpha; expression by methylation-specific PCR and histone modifications. Robust hypermethylation of histone H3 was observed across HIF3A locus driven by pro-inflammatory cytokines. Experiments in a murine model of arteriotomy highlighted the activation of Hif3&alpha; expression in infiltrated inflammatory cells, suggesting a new role for Hif3&alpha; in inflammation in vivo.</p>',
			'date' => '2018-04-11',
			'pmid' => 'http://www.pubmed.gov/29643458',
			'doi' => '10.1038/s41598-018-24221-5',
			'modified' => '2019-02-15 20:21:28',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 140 => array(
			'id' => '3463',
			'name' => 'Epigenetic modifiers promote mitochondrial biogenesis and oxidative metabolism leading to enhanced differentiation of neuroprogenitor cells.',
			'authors' => 'Martine Uittenbogaard, Christine A. Brantner, Anne Chiaramello1',
			'description' => '<p>During neural development, epigenetic modulation of chromatin acetylation is part of a dynamic, sequential and critical process to steer the fate of multipotent neural progenitors toward a specific lineage. Pan-HDAC inhibitors (HDCis) trigger neuronal differentiation by generating an "acetylation" signature and promoting the expression of neurogenic bHLH transcription factors. Our studies and others have revealed a link between neuronal differentiation and increase of mitochondrial mass. However, the neuronal regulation of mitochondrial biogenesis has remained largely unexplored. Here, we show that the HDACi, sodium butyrate (NaBt), promotes mitochondrial biogenesis via the NRF-1/Tfam axis in embryonic hippocampal progenitor cells and neuroprogenitor-like PC12-NeuroD6 cells, thereby enhancing their neuronal differentiation competency. Increased mitochondrial DNA replication by several pan-HDACis indicates a common mechanism by which they regulate mitochondrial biogenesis. NaBt also induces coordinates mitochondrial ultrastructural changes and enhanced OXPHOS metabolism, thereby increasing key mitochondrial bioenergetics parameters in neural progenitor cells. NaBt also endows the neuronal cells with increased mitochondrial spare capacity to confer resistance to oxidative stress associated with neuronal differentiation. We demonstrate that mitochondrial biogenesis is under HDAC-mediated epigenetic regulation, the timing of which is consistent with its integrative role during neuronal differentiation. Thus, our findings add a new facet to our mechanistic understanding of how pan-HDACis induce differentiation of neuronal progenitor cells. Our results reveal the concept that epigenetic modulation of the mitochondrial pool prior to neurotrophic signaling dictates the efficiency of initiation of neuronal differentiation during the transition from progenitor to differentiating neuronal cells. The histone acetyltransferase CREB-binding protein plays a key role in regulating the mitochondrial biomass. By ChIP-seq analysis, we show that NaBt confers an H3K27ac epigenetic signature in several interconnected nodes of nuclear genes vital for neuronal differentiation and mitochondrial reprogramming. Collectively, our study reports a novel developmental epigenetic layer that couples mitochondrial biogenesis to neuronal differentiation.</p>',
			'date' => '2018-03-02',
			'pmid' => 'http://www.pubmed.gov/29500414',
			'doi' => '10.1038/s41419-018-0396-1',
			'modified' => '2019-02-15 21:21:45',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 141 => array(
			'id' => '3361',
			'name' => 'Micro-ribonucleic acid-155 is a direct target of Meis1, but not a driver in acute myeloid leukemia',
			'authors' => 'Schneider E. et al.',
			'description' => '<p>Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute myeloid leukemia. The additional overexpression of miR-155 accelerated the formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells <i>in vivo</i> However, in the absence or following the removal of miR-155, leukemia onset and progression were unaffected. Although miR-155 accelerated growth and homing in addition to impairing differentiation, our data underscore the pathophysiological relevance of miR-155 as an accelerator rather than a driver of leukemogenesis. This further highlights the complexity of the oncogenic program of Meis1 to compensate for the loss of a potent oncogene such as miR-155. These findings are highly relevant to current and developing approaches for targeting miR-155 in acute myeloid leukemia.</p>',
			'date' => '2018-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29217774',
			'doi' => '',
			'modified' => '2018-04-06 15:39:36',
			'created' => '2018-04-06 15:39:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 142 => array(
			'id' => '3446',
			'name' => 'Metabolic Induction of Trained Immunity through the Mevalonate Pathway.',
			'authors' => 'Bekkering S, Arts RJW, Novakovic B, Kourtzelis I, van der Heijden CDCC, Li Y, Popa CD, Ter Horst R, van Tuijl J, Netea-Maier RT, van de Veerdonk FL, Chavakis T, Joosten LAB, van der Meer JWM, Stunnenberg H, Riksen NP, Netea MG',
			'description' => '<p>Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that activation of the cholesterol synthesis pathway, but not the synthesis of cholesterol itself, is essential for training of myeloid cells. Rather, the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways. Statins, which block mevalonate generation, prevent trained immunity induction. Furthermore, monocytes of patients with hyper immunoglobulin D syndrome (HIDS), who are mevalonate kinase deficient and accumulate mevalonate, have a constitutive trained immunity phenotype at both immunological and epigenetic levels, which could explain the attacks of sterile inflammation that these patients experience. Unraveling the role of mevalonate in trained immunity contributes to our understanding of the pathophysiology of HIDS and identifies novel therapeutic targets for clinical conditions with excessive activation of trained immunity.</p>',
			'date' => '2018-01-11',
			'pmid' => 'http://www.pubmed.gov/29328908',
			'doi' => '10.1016/j.cell.2017.11.025',
			'modified' => '2019-02-15 21:37:39',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 143 => array(
			'id' => '3408',
			'name' => 'BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity.',
			'authors' => 'Arts RJW, Moorlag SJCFM, Novakovic B, Li Y, Wang SY, Oosting M, Kumar V, Xavier RJ, Wijmenga C, Joosten LAB, Reusken CBEM, Benn CS, Aaby P, Koopmans MP, Stunnenberg HG, van Crevel R, Netea MG',
			'description' => '<p>The tuberculosis vaccine bacillus Calmette-Gu&eacute;rin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was accompanied by functional changes indicative of trained immunity. Reduction of viremia was highly correlated with the upregulation of IL-1&beta;, a heterologous cytokine associated with the induction of trained immunity, but not with&nbsp;the specific IFN&gamma; response. The importance of IL-1&beta; for the induction of trained immunity was validated through genetic, epigenetic, and immunological studies. In conclusion, BCG induces epigenetic reprogramming in human monocytes in&nbsp;vivo, followed by functional reprogramming and protection against non-related viral infections, with a key role for IL-1&beta; as a mediator of trained immunity responses.</p>',
			'date' => '2018-01-10',
			'pmid' => 'http://www.pubmed.gov/29324233',
			'doi' => '10.1016/j.chom.2017.12.010',
			'modified' => '2018-11-22 15:15:09',
			'created' => '2018-11-08 12:59:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 144 => array(
			'id' => '3440',
			'name' => 'Senescence-associated reprogramming promotes cancer stemness.',
			'authors' => 'Milanovic M, Fan DNY, Belenki D, Däbritz JHM, Zhao Z, Yu Y, Dörr JR, Dimitrova L, Lenze D, Monteiro Barbosa IA, Mendoza-Parra MA, Kanashova T, Metzner M, Pardon K, Reimann M, Trumpp A, Dörken B, Zuber J, Gronemeyer H, Hummel M, Dittmar G, Lee S, Schmitt C',
			'description' => '<p>Cellular senescence is a stress-responsive cell-cycle arrest program that terminates the further expansion of (pre-)malignant cells. Key signalling components of the senescence machinery, such as p16, p21 and p53, as well as trimethylation of lysine 9 at histone H3 (H3K9me3), also operate as critical regulators of stem-cell functions (which are collectively termed 'stemness'). In cancer cells, a gain of stemness may have profound implications for tumour aggressiveness and clinical outcome. Here we investigated whether chemotherapy-induced senescence could change stem-cell-related properties of malignant cells. Gene expression and functional analyses comparing senescent and non-senescent B-cell lymphomas from E&mu;-Myc transgenic mice revealed substantial upregulation of an adult tissue stem-cell signature, activated Wnt signalling, and distinct stem-cell markers in senescence. Using genetically switchable models of senescence targeting H3K9me3 or p53 to mimic spontaneous escape from the arrested condition, we found that cells released from senescence re-entered the cell cycle with strongly enhanced and Wnt-dependent clonogenic growth potential compared to virtually identical populations that had been equally exposed to chemotherapy but had never been senescent. In vivo, these previously senescent cells presented with a much higher tumour initiation potential. Notably, the temporary enforcement of senescence in p53-regulatable models of acute lymphoblastic leukaemia and acute myeloid leukaemia was found to reprogram non-stem bulk leukaemia cells into self-renewing, leukaemia-initiating stem cells. Our data, which are further supported by consistent results in human cancer cell lines and primary samples of human haematological malignancies, reveal that senescence-associated stemness is an unexpected, cell-autonomous feature that exerts its detrimental, highly aggressive growth potential upon escape from cell-cycle blockade, and is enriched in relapse tumours. These findings have profound implications for cancer therapy, and provide new mechanistic insights into the plasticity of cancer cells.</p>',
			'date' => '2018-01-04',
			'pmid' => 'http://www.pubmed.org/29258294',
			'doi' => '10.1038/nature25167',
			'modified' => '2019-02-15 21:39:11',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 145 => array(
			'id' => '3385',
			'name' => 'MLL2 conveys transcription-independent H3K4 trimethylation in oocytes',
			'authors' => 'Hanna C.W. et al.',
			'description' => '<p>Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyte provides an attractive system to investigate these mechanisms, because extensive H3K4me3 acquisition occurs in nondividing cells. We developed low-input chromatin immunoprecipitation to interrogate H3K4me3, H3K27ac and H3K27me3 marks throughout oogenesis. In nongrowing oocytes, H3K4me3 was restricted to active promoters, but as oogenesis progressed, H3K4me3 accumulated in a transcription-independent manner and was targeted to intergenic regions, putative enhancers and silent H3K27me3-marked promoters. Ablation of the H3K4 methyltransferase&nbsp;gene Mll2 resulted in loss of transcription-independent H3K4 trimethylation but had limited effects on transcription-coupled H3K4 trimethylation or gene expression. Deletion of Dnmt3a and Dnmt3b showed that DNA methylation protects regions from acquiring H3K4me3. Our findings reveal two independent mechanisms of targeting H3K4me3 to genomic elements, with MLL2 recruited to unmethylated CpG-rich regions independently of transcription.</p>',
			'date' => '2018-01-02',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29323282',
			'doi' => '',
			'modified' => '2018-08-07 10:26:20',
			'created' => '2018-08-07 10:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 146 => array(
			'id' => '3330',
			'name' => 'The histone code reader Spin1 controls skeletal muscle development',
			'authors' => 'Greschik H. et al.',
			'description' => '<p>While several studies correlated increased expression of the histone code reader Spin1 with tumor formation or growth, little is known about physiological functions of the protein. We generated Spin1<sup>M5</sup> mice with ablation of Spin1 in myoblast precursors using the Myf5-Cre deleter strain. Most Spin1<sup>M5</sup> mice die shortly after birth displaying severe sarcomere disorganization and necrosis. Surviving Spin1<sup>M5</sup> mice are growth-retarded and exhibit the most prominent defects in soleus, tibialis anterior, and diaphragm muscle. Transcriptome analyses of limb muscle at embryonic day (E) 15.5, E16.5, and at three weeks of age provided evidence for aberrant fetal myogenesis and identified deregulated skeletal muscle (SkM) functional networks. Determination of genome-wide chromatin occupancy in primary myoblast revealed direct Spin1 target genes and suggested that deregulated basic helix-loop-helix transcription factor networks account for developmental defects in Spin1<sup>M5</sup> fetuses. Furthermore, correlating histological and transcriptome analyses, we show that aberrant expression of titin-associated proteins, abnormal glycogen metabolism, and neuromuscular junction defects contribute to SkM pathology in Spin1<sup>M5</sup> mice. Together, we describe the first example of a histone code reader controlling SkM development in mice, which hints at Spin1 as a potential player in human SkM disease.</p>',
			'date' => '2017-11-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29168801',
			'doi' => '',
			'modified' => '2018-02-07 10:20:01',
			'created' => '2018-02-07 10:20:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 147 => array(
			'id' => '3322',
			'name' => 'In Situ Fixation Redefines Quiescence and Early Activation of Skeletal Muscle Stem Cells',
			'authors' => 'Machado L. et al.',
			'description' => '<div class="abstract">
<h2 class="sectionTitle" tabindex="0">Summary</h2>
<div class="content">
<p>State of the art techniques have been developed to isolate and analyze cells from various tissues, aiming to capture their <em>in&nbsp;vivo</em> state. However, the majority of cell isolation protocols involve lengthy mechanical and enzymatic dissociation steps followed by flow cytometry, exposing cells to stress and disrupting their physiological niche. Focusing on adult skeletal muscle stem cells, we have developed a protocol that circumvents the impact of isolation procedures and captures cells in their native quiescent state. We show that current isolation protocols induce major transcriptional changes accompanied by specific histone modifications while having negligible effects on DNA methylation. In addition to proposing a protocol to avoid isolation-induced artifacts, our study reveals previously undetected quiescence and early activation genes of potential biological interest.</p>
</div>
</div>',
			'date' => '2017-11-14',
			'pmid' => 'http://www.cell.com/cell-reports/abstract/S2211-1247(17)31543-7',
			'doi' => '',
			'modified' => '2022-05-19 16:11:43',
			'created' => '2018-02-02 16:36:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 148 => array(
			'id' => '3309',
			'name' => 'GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency',
			'authors' => 'Krendl C. et al.',
			'description' => '<p>To elucidate the molecular basis of BMP4-induced differentiation of human pluripotent stem cells (PSCs) toward progeny with trophectoderm characteristics, we produced transcriptome, epigenome H3K4me3, H3K27me3, and CpG methylation maps of trophoblast progenitors, purified using the surface marker APA. We combined them with the temporally resolved transcriptome of the preprogenitor phase and of single APA+ cells. This revealed a circuit of bivalent TFAP2A, TFAP2C, GATA2, and GATA3 transcription factors, coined collectively the "trophectoderm four" (TEtra), which are also present in human trophectoderm in vivo. At the onset of differentiation, the TEtra factors occupy multiple sites in epigenetically inactive placental genes and in <i>OCT4</i> Functional manipulation of <i>GATA3</i> and <i>TFAP2A</i> indicated that they directly couple trophoblast-specific gene induction with suppression of pluripotency. In accordance, knocking down <i>GATA3</i> in primate embryos resulted in a failure to form trophectoderm. The discovery of the TEtra circuit indicates how trophectoderm commitment is regulated in human embryogenesis.</p>',
			'date' => '2017-11-07',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29078328',
			'doi' => '',
			'modified' => '2018-01-04 10:23:33',
			'created' => '2018-01-04 10:23:33',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 149 => array(
			'id' => '3302',
			'name' => 'The mixed lineage leukemia 4 (MLL4) methyltransferase complex is involved in transforming growth factor beta (TGF-β)-activated gene transcription.',
			'authors' => 'Baas R. et al.',
			'description' => '<p>Sma and Mad related (SMAD)-mediated Transforming Growth Factor &beta; (TGF-&beta;) and Bone Morphogenetic Protein (BMP) signaling is required for various cellular processes. The activated heterotrimeric SMAD protein complexes associate with nuclear proteins such as the histone acetyltransferases p300, PCAF and the Mixed Lineage Leukemia 4 (MLL4) subunit Pax Transactivation domain-Interacting Protein (PTIP) to regulate gene transcription. We investigated the functional role of PTIP and PTIP Interacting protein 1 (PA1) in relation to TGF-&beta;-activated SMAD signaling. We immunoprecipitated PTIP and PA1 with all SMAD family members to identify the TGF-&beta; and not BMP-specific SMADs as interacting proteins. Gene silencing experiments of MLL4 and the subunits PA1 and PTIP confirm TGF-&beta;-specific genes to be regulated by the MLL4 complex, which links TGF-&beta; signaling to transcription regulation by the MLL4 methyltransferase complex.</p>',
			'date' => '2017-10-04',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28976802',
			'doi' => '',
			'modified' => '2017-12-05 10:50:08',
			'created' => '2017-12-05 10:50:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 150 => array(
			'id' => '3296',
			'name' => 'Predicting stimulation-dependent enhancer-promoter interactions from ChIP-Seq time course data',
			'authors' => 'Dzida T. et al.',
			'description' => '<p>We have developed a machine learning approach to predict stimulation-dependent enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ER&alpha;), RNA polymerase (Pol II) and histone marks H2AZ and H3K4me3 were measured over time using ChIP-Seq experiments in MCF7 cells stimulated with estrogen. A Bayesian classifier was developed which uses the correlation of temporal binding patterns at enhancers and promoters and genomic proximity as features to predict interactions. This method was trained using experimentally determined interactions from the same system and was shown to achieve much higher precision than predictions based on the genomic proximity of nearest ER&alpha;&nbsp;binding. We use the method to identify a genome-wide confident set of ER&alpha;&nbsp;target genes and their regulatory enhancers genome-wide. Validation with publicly available GRO-Seq data demonstrates that our predicted targets are much more likely to show early nascent transcription than predictions based on genomic ER&alpha;&nbsp;binding proximity alone.</p>',
			'date' => '2017-09-28',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28970965',
			'doi' => '',
			'modified' => '2017-12-04 11:06:11',
			'created' => '2017-12-04 11:06:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 151 => array(
			'id' => '3303',
			'name' => 'Genetic Predisposition to Multiple Myeloma at 5q15 Is Mediated by an ELL2 Enhancer Polymorphism',
			'authors' => 'Li N. et al.',
			'description' => '<p>Multiple myeloma (MM) is a malignancy of plasma cells. Genome-wide association studies have shown that variation at 5q15 influences MM risk. Here, we have sought to decipher the causal variant at 5q15 and the mechanism by which it influences tumorigenesis. We show that rs6877329&nbsp;G &gt; C resides in a predicted enhancer element that physically interacts with the transcription start site of ELL2. The rs6877329-C risk allele is associated with reduced enhancer activity and lowered ELL2 expression. Since ELL2 is critical to the B cell differentiation process, reduced ELL2 expression is consistent with inherited genetic variation contributing to arrest of plasma cell development, facilitating MM clonal expansion. These data provide evidence for a biological mechanism underlying a hereditary risk of MM at 5q15.</p>',
			'date' => '2017-09-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28903037',
			'doi' => '',
			'modified' => '2018-01-02 17:58:38',
			'created' => '2018-01-02 17:58:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 152 => array(
			'id' => '3298',
			'name' => 'Chromosome contacts in activated T cells identify autoimmune disease candidate genes',
			'authors' => 'Burren OS et al.',
			'description' => '<div class="abstr">
<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Autoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4<sup>+</sup> T cells. Linking such regulatory regions to gene promoters in disease-relevant cell contexts facilitates identification of candidate disease genes.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Within 4&nbsp;h, activation of CD4<sup>+</sup> T cells invokes changes in histone modifications and enhancer RNA transcription that correspond to altered expression of the interacting genes identified by promoter capture Hi-C. By integrating promoter capture Hi-C data with genetic associations for five autoimmune diseases, we prioritised 245 candidate genes with a median distance from peak signal to prioritised gene of 153&nbsp;kb. Just under half (108/245) prioritised genes related to activation-sensitive interactions. This included IL2RA, where allele-specific expression analyses were consistent with its interaction-mediated regulation, illustrating the utility of the approach.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">Our systematic experimental framework offers an alternative approach to candidate causal gene identification for variants with cell state-specific functional effects, with achievable sample sizes.</abstracttext></p>
</div>
</div>',
			'date' => '2017-09-04',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28870212',
			'doi' => '',
			'modified' => '2017-12-04 11:25:15',
			'created' => '2017-12-04 11:25:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 153 => array(
			'id' => '3262',
			'name' => 'A lncRNA fine tunes the dynamics of a cell state transition involving Lin28, let-7 and de novo DNA methylation',
			'authors' => 'Li M.A. et al.',
			'description' => '<p>Execution of pluripotency requires progression from the na&iuml;ve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) <em>linc1281,</em> hereafter <em>Ephemeron</em> (<em>Eprn</em>), that modulates the dynamics of exit from na&iuml;ve pluripotency. <em>Eprn</em> deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression. In the absence of <em>Eprn</em>, <em>Lin28a</em> expression is reduced which results in persistence of <em>let-7 microRNAs, and</em> the up-regulation of de novo methyltransferases Dnmt3a/b is delayed. <em>Dnmt3a/b</em> deletion retards ES cell transition, correlating with delayed <em>Nanog</em> promoter methylation and phenocopying loss of <em>Eprn</em> or <em>Lin28a</em>. The connection from lncRNA to miRNA and DNA methylation facilitates the acute extinction of na&iuml;ve pluripotency, a pre-requisite for rapid progression from preimplantation epiblast to gastrulation in rodents. <em>Eprn</em> illustrates how lncRNAs may introduce species-specific network modulations.</p>',
			'date' => '2017-08-18',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562443/',
			'doi' => '',
			'modified' => '2017-10-09 15:55:39',
			'created' => '2017-10-09 15:55:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 154 => array(
			'id' => '3240',
			'name' => 'Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation',
			'authors' => 'Pünzeler S. et al.',
			'description' => '<p>Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine the comprehensive interactome of H2A.Z and identify PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A is a functionally uncharacterized, vertebrate-specific protein that binds very tightly to chromatin through a concerted multivalent binding mode. Two internal protein regions mediate H2A.Z-specificity and nucleosome interaction, whereas the PWWP domain exhibits direct DNA binding. Genome-wide mapping reveals that PWWP2A binds selectively to H2A.Z-containing nucleosomes with strong preference for promoters of highly transcribed genes. In human cells, its depletion affects gene expression and impairs proliferation via a mitotic delay. While PWWP2A does not influence H2A.Z occupancy, the C-terminal tail of H2A.Z is one important mediator to recruit PWWP2A to chromatin. Knockdown of PWWP2A in <i>Xenopus</i> results in severe cranial facial defects, arising from neural crest cell differentiation and migration problems. Thus, PWWP2A is a novel H2A.Z-specific multivalent chromatin binder providing a surprising link between H2A.Z, chromosome segregation, and organ development.</p>',
			'date' => '2017-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28645917',
			'doi' => '',
			'modified' => '2017-08-29 09:45:44',
			'created' => '2017-08-29 09:45:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 155 => array(
			'id' => '3270',
			'name' => 'Mouse models of 17q21.31 microdeletion and microduplication syndromes highlight the importance of Kansl1 for cognition',
			'authors' => 'Arbogast T. et al.',
			'description' => '<p>Koolen-de Vries syndrome (KdVS) is a multi-system disorder characterized by intellectual disability, friendly behavior, and congenital malformations. The syndrome is caused either by microdeletions in the 17q21.31 chromosomal region or by variants in the KANSL1 gene. The reciprocal 17q21.31 microduplication syndrome is associated with psychomotor delay, and reduced social interaction. To investigate the pathophysiology of 17q21.31 microdeletion and microduplication syndromes, we generated three mouse models: 1) the deletion (Del/+); or 2) the reciprocal duplication (Dup/+) of the 17q21.31 syntenic region; and 3) a heterozygous Kansl1 (Kans1+/-) model. We found altered weight, general activity, social behaviors, object recognition, and fear conditioning memory associated with craniofacial and brain structural changes observed in both Del/+ and Dup/+ animals. By investigating hippocampus function, we showed synaptic transmission defects in Del/+ and Dup/+ mice. Mutant mice with a heterozygous loss-of-function mutation in Kansl1 displayed similar behavioral and anatomical phenotypes compared to Del/+ mice with the exception of sociability phenotypes. Genes controlling chromatin organization, synaptic transmission and neurogenesis were upregulated in the hippocampus of Del/+ and Kansl1+/- animals. Our results demonstrate the implication of KANSL1 in the manifestation of KdVS phenotypes and extend substantially our knowledge about biological processes affected by these mutations. Clear differences in social behavior and gene expression profiles between Del/+ and Kansl1+/- mice suggested potential roles of other genes affected by the 17q21.31 deletion. Together, these novel mouse models provide new genetic tools valuable for the development of therapeutic approaches.</p>',
			'date' => '2017-07-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28704368',
			'doi' => '',
			'modified' => '2017-10-10 17:25:37',
			'created' => '2017-10-10 17:25:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 156 => array(
			'id' => '3339',
			'name' => 'Platelet function is modified by common sequence variation in megakaryocyte super enhancers',
			'authors' => 'Petersen R. et al.',
			'description' => '<p>Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quantitative traits using cell type-matched epigenomic data and promoter long-range interactions. We identify potential regulatory functions for 423 of 565 (75%) non-coding variants associated with platelet traits and we demonstrate, through <em>ex vivo</em> and proof of principle genome editing validation, that variants in super enhancers play an important role in controlling archetypical platelet functions.</p>',
			'date' => '2017-07-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511350/#S1',
			'doi' => '',
			'modified' => '2018-02-15 10:25:39',
			'created' => '2018-02-15 10:25:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 157 => array(
			'id' => '3234',
			'name' => 'Chromatin Immunoprecipitation (ChIP) in Mouse T-cell Lines',
			'authors' => 'Giaimo B.D. et al.',
			'description' => '<p>Signaling pathways regulate gene expression programs via the modulation of the chromatin structure at different levels, such as by post-translational modifications (PTMs) of histone tails, the exchange of canonical histones with histone variants, and nucleosome eviction. Such regulation requires the binding of signal-sensitive transcription factors (TFs) that recruit chromatin-modifying enzymes at regulatory elements defined as enhancers. Understanding how signaling cascades regulate enhancer activity requires a comprehensive analysis of the binding of TFs, chromatin modifying enzymes, and the occupancy of specific histone marks and histone variants. Chromatin immunoprecipitation (ChIP) assays utilize highly specific antibodies to immunoprecipitate specific protein/DNA complexes. The subsequent analysis of the purified DNA allows for the identification the region occupied by the protein recognized by the antibody. This work describes a protocol to efficiently perform ChIP of histone proteins in a mature mouse T-cell line. The presented protocol allows for the performance of ChIP assays in a reasonable timeframe and with high reproducibility.</p>',
			'date' => '2017-06-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28654055',
			'doi' => '',
			'modified' => '2017-08-24 10:13:18',
			'created' => '2017-08-24 10:13:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 158 => array(
			'id' => '3222',
			'name' => 'DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats',
			'authors' => 'Brocks D. et al.',
			'description' => '<p>Several mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known about their genome-wide transcriptional and epigenomic consequences. By mapping global transcription start site (TSS) and chromatin dynamics, we observed the cryptic transcription of thousands of treatment-induced non-annotated TSSs (TINATs) following DNMTi and HDACi treatment. The resulting transcripts frequently splice into protein-coding exons and encode truncated or chimeric ORFs translated into products with predicted abnormal or immunogenic functions. TINAT transcription after DNMTi treatment coincided with DNA hypomethylation and gain of classical promoter histone marks, while HDACi specifically induced a subset of TINATs in association with H2AK9ac, H3K14ac, and H3K23ac. Despite this mechanistic difference, both inhibitors convergently induced transcription from identical sites, as we found TINATs to be encoded in solitary long terminal repeats of the ERV9/LTR12 family, which are epigenetically repressed in virtually all normal cells.</p>',
			'date' => '2017-06-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28604729',
			'doi' => '',
			'modified' => '2017-08-18 14:14:48',
			'created' => '2017-08-18 14:14:48',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 159 => array(
			'id' => '3241',
			'name' => 'Evolutionary re-wiring of p63 and the epigenomic regulatory landscape in keratinocytes and its potential implications on species-specific gene expression and phenotypes',
			'authors' => 'Sethi I. et al.',
			'description' => '<p>Although epidermal keratinocyte development and differentiation proceeds in similar fashion between humans and mice, evolutionary pressures have also wrought significant species-specific physiological differences. These differences between species could arise in part, by the rewiring of regulatory network due to changes in the global targets of lineage-specific transcriptional master regulators such as p63. Here we have performed a systematic and comparative analysis of the p63 target gene network within the integrated framework of the transcriptomic and epigenomic landscape of mouse and human keratinocytes. We determined that there exists a core set of &sim;1600 genomic regions distributed among enhancers and super-enhancers, which are conserved and occupied by p63 in keratinocytes from both species. Notably, these DNA segments are typified by consensus p63 binding motifs under purifying selection and are associated with genes involved in key keratinocyte and skin-centric biological processes. However, the majority of the p63-bound mouse target regions consist of either murine-specific DNA elements that are not alignable to the human genome or exhibit no p63 binding in the orthologous syntenic regions, typifying an occupancy lost subset. Our results suggest that these evolutionarily divergent regions have undergone significant turnover of p63 binding sites and are associated with an underlying inactive and inaccessible chromatin state, indicative of their selective functional activity in the transcriptional regulatory network in mouse but not human. Furthermore, we demonstrate that this selective targeting of genes by p63 correlates with subtle, but measurable transcriptional differences in mouse and human keratinocytes that converges on major metabolic processes, which often exhibit species-specific trends. Collectively our study offers possible molecular explanation for the observable phenotypic differences between the mouse and human skin and broadly informs on the prevailing principles that govern the tug-of-war between evolutionary forces of rigidity and plasticity over transcriptional regulatory programs.</p>',
			'date' => '2017-05-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28505376',
			'doi' => '',
			'modified' => '2017-08-29 12:01:20',
			'created' => '2017-08-29 12:01:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 160 => array(
			'id' => '3201',
			'name' => 'RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA(+) and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells.',
			'authors' => 'Lund R.J. et al.',
			'description' => '<p>POLR3G is expressed at high levels in human pluripotent stem cells (hPSCs) and is required for maintenance of stem cell state through mechanisms not known in detail. To explore how POLR3G regulates stem cell state, we carried out deep-sequencing analysis&nbsp;of polyA<sup>+</sup> and smallRNA transcriptomes present in hPSCs and regulated in POLR3G-dependent manner. Our data reveal that&nbsp;POLR3G regulates a specific subset of the hPSC transcriptome, including multiple transcript types, such as protein-coding genes,&nbsp;long intervening non-coding RNAs, microRNAs and small nucleolar RNAs, and affects RNA splicing. The primary function of POLR3G is in the maintenance rather than repression of transcription. The majority of POLR3G polyA<sup>+</sup> transcriptome is regulated&nbsp;during differentiation, and the key pluripotency factors bind to the promoters of at least 30% of the POLR3G-regulated transcripts. Among the direct targets of POLR3G, POLG is potentially important in sustaining stem cell status in a POLR3G-dependent manner.</p>',
			'date' => '2017-05-09',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28494942',
			'doi' => '',
			'modified' => '2017-07-03 10:04:16',
			'created' => '2017-07-03 10:04:16',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 161 => array(
			'id' => '3211',
			'name' => 'The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis.',
			'authors' => 'Aldiri I. et al.',
			'description' => '<p>In the developing retina, multipotent neural progenitors undergo unidirectional differentiation in a precise spatiotemporal order. Here we profile the epigenetic and transcriptional changes that occur during retinogenesis in mice and humans. Although some progenitor genes and cell cycle genes were epigenetically silenced during retinogenesis, the most dramatic change was derepression of cell-type-specific differentiation programs. We identified developmental-stage-specific super-enhancers and showed that most epigenetic changes are conserved in humans and mice. To determine how the epigenome changes during tumorigenesis and reprogramming, we performed integrated epigenetic analysis of murine and human retinoblastomas and induced pluripotent stem cells (iPSCs) derived from murine rod photoreceptors. The retinoblastoma epigenome mapped to the developmental stage when retinal progenitors switch from neurogenic to terminal patterns of cell division. The epigenome of retinoblastomas was more similar to that of the normal retina than that of retina-derived iPSCs, and we identified retina-specific epigenetic memory.</p>',
			'date' => '2017-05-03',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28472656',
			'doi' => '',
			'modified' => '2017-07-07 17:04:39',
			'created' => '2017-07-07 17:04:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 162 => array(
			'id' => '3187',
			'name' => 'Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions',
			'authors' => 'Frank-Bertoncelj M, Trenkmann M, Klein K, Karouzakis E, Rehrauer H, Bratus A, Kolling C, Armaka M, Filer A, Michel BA, Gay RE, Buckley CD, Kollias G, Gay S, Ospelt C',
			'description' => '<p>A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNF, creating a unique microenvironment in each joint. These findings indicate that local stroma might control positional disease patterns not only in arthritis but in any disease with a prominent stromal component.</p>',
			'date' => '2017-03-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28332497',
			'doi' => '',
			'modified' => '2017-05-24 17:07:07',
			'created' => '2017-05-24 17:07:07',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 163 => array(
			'id' => '3159',
			'name' => 'Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells',
			'authors' => 'Tumber A. et al.',
			'description' => '<p>Methylation of lysine residues on histone tail is a dynamic epigenetic modification that plays a key role in chromatin structure and gene regulation. Members of the KDM5 (also known as JARID1) sub-family are 2-oxoglutarate (2-OG) and Fe<sup>2+</sup>-dependent oxygenases acting as histone 3 lysine 4 trimethyl (H3K4me3) demethylases, regulating proliferation, stem cell self-renewal, and differentiation. Here we present the characterization of KDOAM-25, an inhibitor of KDM5 enzymes. KDOAM-25 shows biochemical half maximal inhibitory concentration values of&nbsp;&lt;100&nbsp;nM for KDM5A-D in&nbsp;vitro, high selectivity toward other 2-OG oxygenases sub-families, and no off-target activity on a panel of 55 receptors and enzymes. In human cell assay systems, KDOAM-25 has a half maximal effective concentration of &sim;50&nbsp;&mu;M and good selectivity toward other demethylases. KDM5B is overexpressed in multiple myeloma and negatively correlated with the overall survival. Multiple myeloma MM1S cells treated with KDOAM-25 show increased global H3K4 methylation at transcriptional start sites and impaired proliferation.</p>',
			'date' => '2017-03-16',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28262558',
			'doi' => '',
			'modified' => '2017-04-12 14:51:37',
			'created' => '2017-04-12 14:51:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 164 => array(
			'id' => '3172',
			'name' => 'Decoupling of DNA methylation and activity of intergenic LINE-1 promoters in colorectal cancer',
			'authors' => 'Vafadar-Isfahani N. et al.',
			'description' => '<p>Hypomethylation of LINE-1 repeats in cancer has been proposed as the main mechanism behind their activation; this assumption, however, was based on findings from early studies that were biased toward young and transpositionally active elements. Here, we investigate the relationship between methylation of 2 intergenic, transpositionally inactive LINE-1 elements and expression of the LINE-1 chimeric transcript (LCT) 13 and LCT14 driven by their antisense promoters (L1-ASP). Our data from DNA modification, expression, and 5'RACE analyses suggest that colorectal cancer methylation in the regions analyzed is not always associated with LCT repression. Consistent with this, in HCT116 colorectal cancer cells lacking DNA methyltransferases DNMT1 or DNMT3B, LCT13 expression decreases, while cells lacking both DNMTs or treated with the DNMT inhibitor 5-azacytidine (5-aza) show no change in LCT13 expression. Interestingly, levels of the H4K20me3 histone modification are inversely associated with LCT13 and LCT14 expression. Moreover, at these LINE-1s, H4K20me3 levels rather than DNA methylation seem to be good predictor of their sensitivity to 5-aza treatment. Therefore, by studying individual LINE-1 promoters we have shown that in some cases these promoters can be active without losing methylation; in addition, we provide evidence that other factors (e.g., H4K20me3 levels) play prominent roles in their regulation.</p>',
			'date' => '2017-03-16',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28300471',
			'doi' => '',
			'modified' => '2017-05-10 16:26:24',
			'created' => '2017-05-10 16:26:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 165 => array(
			'id' => '3165',
			'name' => 'Assessing histone demethylase inhibitors in cells: lessons learned',
			'authors' => 'Hatch S.B. et al.',
			'description' => '<div xmlns="http://www.w3.org/1999/xhtml" class="AbstractSection" id="ASec1">
<h3 xmlns="" class="Heading">Background</h3>
<p id="Par1" class="Para">Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The first KDM inhibitors for KDM1 have entered clinical trials, and efforts are ongoing to develop potent, selective and cell-active &lsquo;probe&rsquo; molecules for this target class. Robust cellular assays to assess the specific engagement of KDM inhibitors in cells as well as their cellular selectivity are a prerequisite for the development of high-quality inhibitors. Here we describe the use of a high-content cellular immunofluorescence assay as a method for demonstrating target engagement in cells.</p>
</div>
<div xmlns="http://www.w3.org/1999/xhtml" class="AbstractSection" id="ASec2">
<h3 xmlns="" class="Heading">Results</h3>
<p id="Par2" class="Para">A panel of assays for the Jumonji C subfamily of KDMs was developed to encompass all major branches of the JmjC phylogenetic tree. These assays compare compound activity against wild-type KDM proteins to a catalytically inactive version of the KDM, in which residues involved in the active-site iron coordination are mutated to inactivate the enzyme activity. These mutants are critical for assessing the specific effect of KDM inhibitors and for revealing indirect effects on histone methylation status. The reported assays make use of ectopically expressed demethylases, and we demonstrate their use to profile several recently identified classes of KDM inhibitors and their structurally matched inactive controls. The generated data correlate well with assay results assessing endogenous KDM inhibition and confirm the selectivity observed in biochemical assays with isolated enzymes. We find that both cellular permeability and competition with 2-oxoglutarate affect the translation of biochemical activity to cellular inhibition.</p>
</div>
<div xmlns="http://www.w3.org/1999/xhtml" class="AbstractSection" id="ASec3">
<h3 xmlns="" class="Heading">Conclusions</h3>
<p id="Par3" class="Para">High-content-based immunofluorescence assays have been established for eight KDM members of the 2-oxoglutarate-dependent oxygenases covering all major branches of the JmjC-KDM phylogenetic tree. The usage of both full-length, wild-type and catalytically inactive mutant ectopically expressed protein, as well as structure-matched inactive control compounds, allowed for detection of nonspecific effects causing changes in histone methylation as a result of compound toxicity. The developed assays offer a histone lysine demethylase family-wide tool for assessing KDM inhibitors for cell activity and on-target efficacy. In addition, the presented data may inform further studies to assess the cell-based activity of histone lysine methylation inhibitors.</p>
</div>',
			'date' => '2017-03-01',
			'pmid' => 'https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-017-0116-6',
			'doi' => '',
			'modified' => '2017-05-09 10:02:47',
			'created' => '2017-05-09 10:02:47',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 166 => array(
			'id' => '3149',
			'name' => 'RNF40 regulates gene expression in an epigenetic context-dependent manner',
			'authors' => 'Xie W. et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlates with increased gene expression. In contrast, depletion of the H2B ubiquitin ligases RNF20 or RNF40 alters the expression of only a subset of genes.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Using conditional Rnf40 knockout mouse embryo fibroblasts, we show that genes occupied by low to moderate amounts of H2Bub1 are selectively regulated in response to Rnf40 deletion, whereas genes marked by high levels of H2Bub1 are mostly unaffected by Rnf40 loss. Furthermore, we find that decreased expression of RNF40-dependent genes is highly associated with widespread narrowing of H3K4me3 peaks. H2Bub1 promotes the broadening of H3K4me3 to increase transcriptional elongation, which together lead to increased tissue-specific gene transcription. Notably, genes upregulated following Rnf40 deletion, including Foxl2, are enriched for H3K27me3, which is decreased following Rnf40 deletion due to decreased expression of the Ezh2 gene. As a consequence, increased expression of some RNF40-"suppressed" genes is associated with enhancer activation via FOXL2.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">Together these findings reveal the complexity and context-dependency whereby one histone modification can have divergent effects on gene transcription. Furthermore, we show that these effects are dependent upon the activity of other epigenetic regulatory proteins and histone modifications.</abstracttext></p>
</div>',
			'date' => '2017-02-16',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28209164',
			'doi' => '',
			'modified' => '2017-03-24 17:22:20',
			'created' => '2017-03-24 17:22:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 167 => array(
			'id' => '3140',
			'name' => 'Menin regulates Inhbb expression through an Akt/Ezh2-mediated H3K27 histone modification',
			'authors' => 'Gherardi S. et al.',
			'description' => '<p>Although Men1 is a well-known tumour suppressor gene, little is known about the functions of Menin, the protein it encodes for. Since few years, numerous publications support a major role of Menin in the control of epigenetics gene regulation. While Menin interaction with MLL complex favours transcriptional activation of target genes through H3K4me3 marks, Menin also represses gene expression via mechanisms involving the Polycomb repressing complex (PRC). Interestingly, Ezh2, the PRC-methyltransferase that catalyses H3K27me3 repressive marks and Menin have been shown to co-occupy a large number of promoters. However, lack of binding between Menin and Ezh2 suggests that another member of the PRC complex is mediating this indirect interaction. Having found that ActivinB - a TGF&beta; superfamily member encoded by the Inhbb gene - is upregulated in insulinoma tumours caused by Men1 invalidation, we hypothesize that Menin could directly participate in the epigenetic-repression of Inhbb gene expression. Using Animal model and cell lines, we report that loss of Menin is directly associated with ActivinB-induced expression both in vivo and in vitro. Our work further reveals that ActivinB expression is mediated through a direct modulation of H3K27me3 marks on the Inhbb locus in Menin-KO cell lines. More importantly, we show that Menin binds on the promoter of Inhbb gene where it favours the recruitment of Ezh2 via an indirect mechanism involving Akt-phosphorylation. Our data suggests therefore that Menin could take an important part to the Ezh2-epigenetic repressive landscape in many cells and tissues through its capacity to modulate Akt phosphorylation.</p>',
			'date' => '2017-02-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28215965',
			'doi' => '',
			'modified' => '2017-03-22 12:07:48',
			'created' => '2017-03-22 12:07:48',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 168 => array(
			'id' => '3139',
			'name' => 'A novel DLX3-PKC integrated signaling network drives keratinocyte differentiation',
			'authors' => 'Palazzo E. et al.',
			'description' => '<p>Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regulate cell cycle-related signaling and that this mechanism is functionally involved in cutaneous squamous cell carcinoma development. Here we show that DLX3 expression and its downstream signaling depend on protein kinase C &alpha; (PKC&alpha;) activity in skin. We found that following 12-O-tetradecanoyl-phorbol-13-acetate (TPA) topical treatment, DLX3 expression is significantly upregulated in the epidermis and keratinocytes from mice overexpressing PKC&alpha; by transgenic targeting (K5-PKC&alpha;), resulting in cell cycle block and terminal differentiation. Epidermis lacking DLX3 (DLX3cKO), which is linked to the development of a DLX3-dependent epidermal hyperplasia with hyperkeratosis and dermal leukocyte recruitment, displays enhanced PKC&alpha; activation, suggesting a feedback regulation of DLX3 and PKC&alpha;. Of particular significance, transcriptional activation of epidermal barrier, antimicrobial peptide and cytokine genes is significantly increased in DLX3cKO skin and further increased by TPA-dependent PKC activation. Furthermore, when inhibiting PKC activity, we show that epidermal thickness, keratinocyte proliferation and inflammatory cell infiltration are reduced and the PKC-DLX3-dependent gene expression signature is normalized. Independently of PKC, DLX3 expression specifically modulates regulatory networks such as Wnt signaling, phosphatase activity and cell adhesion. Chromatin immunoprecipitation sequencing analysis of primary suprabasal keratinocytes showed binding of DLX3 to the proximal promoter regions of genes associated with cell cycle regulation, and of structural proteins and transcription factors involved in epidermal differentiation. These results indicate that Dlx3 potentially regulates a set of crucial genes necessary during the epidermal differentiation process. Altogether, we demonstrate the existence of a robust DLX3-PKC&alpha; signaling pathway in keratinocytes that is crucial to epidermal differentiation control and cutaneous homeostasis.</p>',
			'date' => '2017-02-10',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28186503',
			'doi' => '',
			'modified' => '2017-03-22 12:00:37',
			'created' => '2017-03-22 12:00:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 169 => array(
			'id' => '3100',
			'name' => 'Muscle catabolic capacities and global hepatic epigenome are modified in juvenile rainbow trout fed different vitamin levels at first feeding',
			'authors' => 'Panserat S. et al.',
			'description' => '<p>Based on the concept of nutritional programming in mammals, we tested whether a short term hyper or hypo vitamin stimulus during first-feeding could induce long-lasting changes in nutrient metabolism in rainbow trout. Trout alevins received during the 4 first weeks of exogenous feeding a diet either without supplemental vitamins (NOSUP), a diet supplemented with a vitamin premix to satisfy the minimal requirement in all the vitamins (NRC) or a diet with a vitamin premix corresponding to an optimal vitamin nutrition (OVN). Following a common rearing period on the control diet, all three groups were then evaluated in terms of metabolic marker gene expressions at the end of the feeding period (day 119). Whereas no gene modifications for proteins involved in energy and lipid metabolism were observed in whole alevins (short-term effect), some of these genes showed a long-term molecular adaptation in the muscle of juveniles (long-term effect). Indeed, muscle of juveniles subjected at an early feeding of the OVN diet displayed up-regulated expression of markers of lipid catabolism (3-hydroxyacyl-CoA dehydrogenase &ndash; HOAD - enzyme) and mitochondrial energy metabolism (Citrate synthase - <em>cs</em>, Ubiquitinol cytochrome <em>c</em> reductase core protein 2 - QCR2, cytochrome oxidase 4 - COX4, ATP synthase form 5 - ATP5A) compared to fish fed the NOSUP diet. Moreover, some key enzymes involved in glucose catabolism (Muscle Pyruvate kinase - PKM) and amino acid catabolism (Glutamate dehydrogenase - GDH3) were also up regulated in muscle of juvenile fish fed with the OVN diet at first-feeding compared to fish fed the NOSUP diet. We researched if these permanently modified gene expressions could be related to global modifications of epigenetic marks (global DNA methylation and global histone acetylation and methylation). There was no variation of the epigenetic marks in muscle. However, we found changes in hepatic DNA methylation, global H3 acetylation and H3K4 methylation, dependent on the vitamin intake at early life. In summary, our data show, for the first time in fish, that a short-term vitamin-stimulus during early life may durably influence muscle energy and lipid metabolism as well as some hepatic epigenetic marks in rainbow trout.</p>',
			'date' => '2017-02-01',
			'pmid' => 'http://www.sciencedirect.com/science/article/pii/S0044848616309693',
			'doi' => '',
			'modified' => '2017-01-03 15:01:50',
			'created' => '2017-01-03 15:01:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 170 => array(
			'id' => '3131',
			'name' => 'DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma',
			'authors' => 'Sheffield N.C. et al.',
			'description' => '<p>Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genetically homogeneous cancers. We performed genome-scale DNA methylation sequencing for a large cohort of Ewing sarcoma tumors and analyzed epigenetic heterogeneity on three levels: between cancers, between tumors, and within tumors. We observed consistent DNA hypomethylation at enhancers regulated by the disease-defining EWS-FLI1 fusion protein, thus establishing epigenomic enhancer reprogramming as a ubiquitous and characteristic feature of Ewing sarcoma. DNA methylation differences between tumors identified a continuous disease spectrum underlying Ewing sarcoma, which reflected the strength of an EWS-FLI1 regulatory signature and a continuum between mesenchymal and stem cell signatures. There was substantial epigenetic heterogeneity within tumors, particularly in patients with metastatic disease. In summary, our study provides a comprehensive assessment of epigenetic heterogeneity in Ewing sarcoma and thereby highlights the importance of considering nongenetic aspects of tumor heterogeneity in the context of cancer biology and personalized medicine.</p>',
			'date' => '2017-01-30',
			'pmid' => 'http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4273.html',
			'doi' => '',
			'modified' => '2017-03-07 15:33:50',
			'created' => '2017-03-07 15:33:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 171 => array(
			'id' => '3144',
			'name' => 'MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct enhancer repertoire and target the RUNX1 program in 11q23 acute myeloid leukemia.',
			'authors' => 'Prange KH et al.',
			'description' => '<p>In 11q23 leukemias, the N-terminal part of the mixed lineage leukemia (MLL) gene is fused to &gt;60 different partner genes. In order to define a core set of MLL rearranged targets, we investigated the genome-wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and associated epigenetic signatures in acute myeloid leukemia (AML) cell lines THP-1 and MV4-11. We uncovered both common as well as specific MLL-AF9 and MLL-AF4 target genes, which were all marked by H3K79me2, H3K27ac and H3K4me3. Apart from promoter binding, we also identified MLL-AF9 and MLL-AF4 binding at specific subsets of non-overlapping active distal regulatory elements. Despite this differential enhancer binding, MLL-AF9 and MLL-AF4 still direct a common gene program, which represents part of the RUNX1 gene program and constitutes of CD34<sup>+</sup> and monocyte-specific genes. Comparing these data sets identified several zinc finger transcription factors (TFs) as potential MLL-AF9 co-regulators. Together, these results suggest that MLL fusions collaborate with specific subsets of TFs to deregulate the RUNX1 gene program in 11q23 AMLs.</p>',
			'date' => '2017-01-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28114278',
			'doi' => '',
			'modified' => '2017-03-23 15:13:45',
			'created' => '2017-03-23 15:13:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 172 => array(
			'id' => '3090',
			'name' => 'Arabidopsis SWI/SNF chromatin remodeling complex binds both promoters and terminators to regulate gene expression',
			'authors' => 'Archacki R. et al.',
			'description' => '<p>ATP-dependent chromatin remodeling complexes are important regulators of gene expression in Eukaryotes. In plants, SWI/SNF-type complexes have been shown critical for transcriptional control of key developmental processes, growth and stress responses. To gain insight into mechanisms underlying these roles, we performed whole genome mapping of the SWI/SNF catalytic subunit BRM in Arabidopsis thaliana, combined with transcript profiling experiments. Our data show that BRM occupies thousands of sites in Arabidopsis genome, most of which located within or close to genes. Among identified direct BRM transcriptional targets almost equal numbers were up- and downregulated upon BRM depletion, suggesting that BRM can act as both activator and repressor of gene expression. Interestingly, in addition to genes showing canonical pattern of BRM enrichment near transcription start site, many other genes showed a transcription termination site-centred BRM occupancy profile. We found that BRM-bound 3' gene regions have promoter-like features, including presence of TATA boxes and high H3K4me3 levels, and possess high antisense transcriptional activity which is subjected to both activation and repression by SWI/SNF complex. Our data suggest that binding to gene terminators and controlling transcription of non-coding RNAs is another way through which SWI/SNF complex regulates expression of its targets.</p>',
			'date' => '2016-12-19',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27994035',
			'doi' => '',
			'modified' => '2017-01-03 10:02:56',
			'created' => '2017-01-03 10:02:56',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 173 => array(
			'id' => '3096',
			'name' => 'Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals',
			'authors' => 'Schwörer S. et al.',
			'description' => '<p>The functionality of stem cells declines during ageing, and this decline contributes to ageing-associated impairments in tissue regeneration and function. Alterations in developmental pathways have been associated with declines in stem-cell function during ageing, but the nature of this process remains poorly understood. Hox genes are key regulators of stem cells and tissue patterning during embryogenesis with an unknown role in ageing. Here we show that the epigenetic stress response in muscle stem cells (also known as satellite cells) differs between aged and young mice. The alteration includes aberrant global and site-specific induction of active chromatin marks in activated satellite cells from aged mice, resulting in the specific induction of Hoxa9 but not other Hox genes. Hoxa9 in turn activates several developmental pathways and represents a decisive factor that separates satellite cell gene expression in aged mice from that in young mice. The activated pathways include most of the currently known inhibitors of satellite cell function in ageing muscle, including Wnt, TGF&beta;, JAK/STAT and senescence signalling. Inhibition of aberrant chromatin activation or deletion of Hoxa9 improves satellite cell function and muscle regeneration in aged mice, whereas overexpression of Hoxa9 mimics ageing-associated defects in satellite cells from young mice, which can be rescued by the inhibition of Hoxa9-targeted developmental pathways. Together, these data delineate an altered epigenetic stress response in activated satellite cells from aged mice, which limits satellite cell function and muscle regeneration by Hoxa9-dependent activation of developmental pathways.</p>',
			'date' => '2016-12-15',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27919074',
			'doi' => '',
			'modified' => '2017-01-03 12:28:33',
			'created' => '2017-01-03 12:28:33',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 174 => array(
			'id' => '3111',
			'name' => 'Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity',
			'authors' => 'Arts R.J. et al.',
			'description' => '<p>Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by &beta;-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases. Furthermore, fumarate itself induced an epigenetic program similar to &beta;-glucan-induced trained immunity. In line with this, inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by &beta;-glucan. Identification of the metabolic pathways leading to induction of trained immunity contributes to our understanding of innate immune memory and opens new therapeutic avenues.</p>',
			'date' => '2016-12-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27866838',
			'doi' => '',
			'modified' => '2017-01-04 11:17:08',
			'created' => '2017-01-04 11:17:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 175 => array(
			'id' => '3110',
			'name' => 'Immunometabolic Pathways in BCG-Induced Trained Immunity',
			'authors' => 'Arts R.J. et al.',
			'description' => '<p>The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity. Here, we show that BCG induction of trained immunity in monocytes is accompanied by a strong increase in glycolysis and, to a lesser extent, glutamine metabolism, both in an in-vitro model and after vaccination of mice and humans. Pharmacological and genetic modulation of rate-limiting glycolysis enzymes inhibits trained immunity, changes that are reflected by the effects on the histone marks (H3K4me3 and H3K9me3) underlying BCG-induced trained immunity. These data demonstrate that a shift of the glucose metabolism toward glycolysis is crucial for the induction of the histone modifications and functional changes underlying BCG-induced trained immunity. The identification of these pathways may be a first step toward vaccines that combine immunological and metabolic stimulation.</p>',
			'date' => '2016-12-06',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27926861',
			'doi' => '',
			'modified' => '2017-01-04 11:15:23',
			'created' => '2017-01-04 11:15:23',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 176 => array(
			'id' => '3098',
			'name' => 'TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells',
			'authors' => 'de la Rica L. et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Ten-eleven translocation (TET) enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable elements (TEs), which make up nearly half of the mouse and human genomes. Epigenetic mechanisms controlling TEs have the potential to affect their mobility and to drive the co-adoption of TEs for the benefit of the host.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">We performed a detailed investigation of the role of TET enzymes in the regulation of TEs in mouse embryonic stem cells (ESCs). We find that TET1 and TET2 bind multiple TE classes that harbour a variety of epigenetic signatures indicative of different functional roles. TETs co-bind with pluripotency factors to enhancer-like TEs that interact with highly expressed genes in ESCs whose expression is partly maintained by TET2-mediated DNA demethylation. TETs and 5-hydroxymethylcytosine (5hmC) are also strongly enriched at the 5' UTR of full-length, evolutionarily young LINE-1 elements, a pattern that is conserved in human ESCs. TETs drive LINE-1 demethylation, but surprisingly, LINE-1s are kept repressed through additional TET-dependent activities. We find that the SIN3A co-repressive complex binds to LINE-1s, ensuring their repression in a TET1-dependent manner.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">Our data implicate TET enzymes in the evolutionary dynamics of TEs, both in the context of exaptation processes and of retrotransposition control. The dual role of TET action on LINE-1s may reflect the evolutionary battle between TEs and the host.</abstracttext></p>
</div>',
			'date' => '2016-11-18',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27863519',
			'doi' => '',
			'modified' => '2017-01-03 14:23:08',
			'created' => '2017-01-03 14:23:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 177 => array(
			'id' => '3103',
			'name' => 'β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance',
			'authors' => 'Novakovic B. et al.',
			'description' => '<p>Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as lipopolysaccharide (LPS). We apply an integrated epigenomic&nbsp;approach to characterize the molecular events involved in LPS-induced tolerance in a time-dependent manner. Mechanistically, LPS-treated monocytes fail to accumulate active histone marks at promoter and enhancers of genes in the lipid metabolism and phagocytic pathways. Transcriptional inactivity in response to a second LPS exposure in tolerized macrophages is accompanied by failure to deposit active histone marks at promoters of tolerized genes. In contrast, &beta;-glucan partially reverses the LPS-induced tolerance in&nbsp;vitro. Importantly, ex&nbsp;vivo &beta;-glucan treatment of monocytes from volunteers with experimental endotoxemia re-instates their capacity for cytokine production. Tolerance is reversed at the level of distal element histone modification and transcriptional reactivation of otherwise unresponsive genes.</p>',
			'date' => '2016-11-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27863248',
			'doi' => '',
			'modified' => '2017-01-03 15:31:46',
			'created' => '2017-01-03 15:31:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 178 => array(
			'id' => '3105',
			'name' => 'EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells',
			'authors' => 'Beringer M. et al.',
			'description' => '<p>The cellular plasticity of pluripotent stem cells is thought to be sustained by genomic regions that display both active and repressive chromatin properties. These regions exhibit low levels of gene expression, yet the mechanisms controlling these levels remain unknown. Here, we describe Elongin BC as a binding factor at the promoters of bivalent sites. Biochemical and genome-wide analyses show that Elongin BC is associated with Polycomb Repressive Complex 2 (PRC2) in pluripotent stem cells. Elongin BC is recruited to chromatin by the PRC2-associated&nbsp;factor EPOP (Elongin BC and Polycomb Repressive Complex 2 Associated Protein, also termed C17orf96, esPRC2p48, E130012A19Rik), a protein expressed in the inner cell mass of the mouse blastocyst. Both EPOP and Elongin BC are required to maintain low levels of expression at PRC2 genomic targets. Our results indicate that keeping the balance between activating and repressive cues is a more general feature of chromatin in pluripotent stem cells than previously appreciated.</p>',
			'date' => '2016-11-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27863225',
			'doi' => '',
			'modified' => '2017-01-03 16:02:21',
			'created' => '2017-01-03 16:02:21',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 179 => array(
			'id' => '3087',
			'name' => 'The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs',
			'authors' => 'Mandoli A. et al.',
			'description' => '<p>The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels of histone acetylation but also at distal elements characterized by low acetylation levels and binding of the hematopoietic transcription factors LYL1 and LMO2. In contrast, ERG, FLI1, TAL1, and RUNX1 bind at all AML1-ETO-occupied regulatory regions, including those of the AML1-ETO gene itself, suggesting their involvement in regulating AML1-ETO expression levels. While expression of AML1-ETO in myeloid differentiated induced pluripotent stem cells (iPSCs) induces leukemic characteristics, overexpression increases cell death. We find that expression of wild-type transcription factors RUNX1 and ERG in AML is required to prevent this oncogene overexpression. Together our results show that the interplay of the epigenome and transcription factors prevents apoptosis in t(8;21) AML cells.</p>',
			'date' => '2016-11-15',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27851970',
			'doi' => '',
			'modified' => '2017-01-02 11:07:24',
			'created' => '2017-01-02 11:07:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 180 => array(
			'id' => '3114',
			'name' => 'Iterative Fragmentation Improves the Detection of ChIP-seq Peaks for Inactive Histone Marks',
			'authors' => 'Laczik M. et al.',
			'description' => '<p>As chromatin immunoprecipitation (ChIP) sequencing is becoming the dominant technique for studying chromatin modifications, new protocols surface to improve the method. Bioinformatics is also essential to analyze and understand the results, and precise analysis helps us to identify the effects of protocol optimizations. We applied iterative sonication - sending the fragmented DNA after ChIP through additional round(s) of shearing - to a number of samples, testing the effects on different histone marks, aiming to uncover potential benefits of inactive histone marks specifically. We developed an analysis pipeline that utilizes our unique, enrichment-type specific approach to peak calling. With the help of this pipeline, we managed to accurately describe the advantages and disadvantages of the iterative refragmentation technique, and we successfully identified possible fields for its applications, where it enhances the results greatly. In addition to the resonication protocol description, we provide guidelines for peak calling optimization and a freely implementable pipeline for data analysis.</p>',
			'date' => '2016-10-25',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27812282',
			'doi' => '',
			'modified' => '2017-01-17 16:07:44',
			'created' => '2017-01-17 16:07:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 181 => array(
			'id' => '3033',
			'name' => 'Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition',
			'authors' => 'Sciacovelli M et al.',
			'description' => '<p>Mutations of the tricarboxylic acid cycle enzyme fumarate hydratase cause hereditary leiomyomatosis and renal cell cancer<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref1" title="Tomlinson, I. P. et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat. Genet. 30, 406&ndash;410 (2002)" id="ref-link-5">1</a></sup>. Fumarate hydratase-deficient renal cancers are highly aggressive and metastasize even when small, leading to a very poor clinical outcome<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref2" title="Schmidt, L. S. &amp; Linehan, W. M. Hereditary leiomyomatosis and renal cell carcinoma. Int. J. Nephrol. Renovasc. Dis. 7, 253&ndash;260 (2014)" id="ref-link-6">2</a></sup>. Fumarate, a small molecule metabolite that accumulates in fumarate hydratase-deficient cells, plays a key role in cell transformation, making it a <i>bona fide</i> oncometabolite<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref3" title="Yang, M., Soga, T., Pollard, P. J. &amp; Adam, J. The emerging role of fumarate as an oncometabolite. Front Oncol. 2, 85 (2012)" id="ref-link-7">3</a></sup>. Fumarate has been shown to inhibit &alpha;-ketoglutarate-dependent dioxygenases that are involved in DNA and histone demethylation<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref4" title="Laukka, T. et al. Fumarate and succinate regulate expression of hypoxia-inducible genes via TET enzymes. J. Biol. Chem. 291, 4256&ndash;4265 (2016)" id="ref-link-8">4</a>, <a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref5" title="Xiao, M. et al. Inhibition of &alpha;-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev. 26, 1326&ndash;1338 (2012)" id="ref-link-9">5</a></sup>. However, the link between fumarate accumulation, epigenetic changes, and tumorigenesis is unclear. Here we show that loss of fumarate hydratase and the subsequent accumulation of fumarate in mouse and human cells elicits an epithelial-to-mesenchymal-transition (EMT), a phenotypic switch associated with cancer initiation, invasion, and metastasis<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref6" title="De Craene, B. &amp; Berx, G. Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer 13, 97&ndash;110 (2013)" id="ref-link-10">6</a></sup>. We demonstrate that fumarate inhibits Tet-mediated demethylation of a regulatory region of the antimetastatic miRNA cluster<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref6" title="De Craene, B. &amp; Berx, G. Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer 13, 97&ndash;110 (2013)" id="ref-link-11">6</a></sup> <i>mir-200ba429</i>, leading to the expression of EMT-related transcription factors and enhanced migratory properties. These epigenetic and phenotypic changes are recapitulated by the incubation of fumarate hydratase-proficient cells with cell-permeable fumarate. Loss of fumarate hydratase is associated with suppression of miR-200 and the EMT signature in renal cancer and is associated with poor clinical outcome. These results imply that loss of fumarate hydratase and fumarate accumulation contribute to the aggressive features of fumarate hydratase-deficient tumours.</p>',
			'date' => '2016-08-31',
			'pmid' => 'http://www.nature.com/nature/journal/v537/n7621/full/nature19353.html',
			'doi' => '',
			'modified' => '2016-09-23 10:44:15',
			'created' => '2016-09-23 10:44:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 182 => array(
			'id' => '3006',
			'name' => 'reChIP-seq reveals widespread bivalency of H3K4me3 and H3K27me3 in CD4(+) memory T cells',
			'authors' => 'Kinkley S et al.',
			'description' => '<p>The combinatorial action of co-localizing chromatin modifications and regulators determines chromatin structure and function. However, identifying co-localizing chromatin features in a high-throughput manner remains a technical challenge. Here we describe a novel reChIP-seq approach and tailored bioinformatic analysis tool, normR that allows for the sequential enrichment and detection of co-localizing DNA-associated proteins in an unbiased and genome-wide manner. We illustrate the utility of the reChIP-seq method and normR by identifying H3K4me3 or H3K27me3 bivalently modified nucleosomes in primary human CD4(+) memory T cells. We unravel widespread bivalency at hypomethylated CpG-islands coinciding with inactive promoters of developmental regulators. reChIP-seq additionally uncovered heterogeneous bivalency in the population, which was undetectable by intersecting H3K4me3 and H3K27me3 ChIP-seq tracks. Finally, we provide evidence that bivalency is established and stabilized by an interplay between the genome and epigenome. Our reChIP-seq approach augments conventional ChIP-seq and is broadly applicable to unravel combinatorial modes of action.</p>',
			'date' => '2016-08-17',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27530917',
			'doi' => '',
			'modified' => '2016-08-26 11:56:46',
			'created' => '2016-08-26 11:38:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 183 => array(
			'id' => '3002',
			'name' => 'Phenotypic Plasticity through Transcriptional Regulation of the Evolutionary Hotspot Gene tan in Drosophila melanogaster',
			'authors' => 'Gibert JM et al.',
			'description' => '<p>Phenotypic plasticity is the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions. Phenotypic plasticity can be adaptive. Furthermore, it is thought to facilitate evolution. Although phenotypic plasticity is a widespread phenomenon, its molecular mechanisms are only beginning to be unravelled. Environmental conditions can affect gene expression through modification of chromatin structure, mainly via histone modifications, nucleosome remodelling or DNA methylation, suggesting that phenotypic plasticity might partly be due to chromatin plasticity. As a model of phenotypic plasticity, we study abdominal pigmentation of Drosophila melanogaster females, which is temperature sensitive. Abdominal pigmentation is indeed darker in females grown at 18&deg;C than at 29&deg;C. This phenomenon is thought to be adaptive as the dark pigmentation produced at lower temperature increases body temperature. We show here that temperature modulates the expression of tan (t), a pigmentation gene involved in melanin production. t is expressed 7 times more at 18&deg;C than at 29&deg;C in female abdominal epidermis. Genetic experiments show that modulation of t expression by temperature is essential for female abdominal pigmentation plasticity. Temperature modulates the activity of an enhancer of t without modifying compaction of its chromatin or level of the active histone mark H3K27ac. By contrast, the active mark H3K4me3 on the t promoter is strongly modulated by temperature. The H3K4 methyl-transferase involved in this process is likely Trithorax, as we show that it regulates t expression and the H3K4me3 level on the t promoter and also participates in female pigmentation and its plasticity. Interestingly, t was previously shown to be involved in inter-individual variation of female abdominal pigmentation in Drosophila melanogaster, and in abdominal pigmentation divergence between Drosophila species. Sensitivity of t expression to environmental conditions might therefore give more substrate for selection, explaining why this gene has frequently been involved in evolution of pigmentation.</p>',
			'date' => '2016-08-10',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27508387',
			'doi' => '',
			'modified' => '2016-08-25 17:23:22',
			'created' => '2016-08-25 17:23:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 184 => array(
			'id' => '3023',
			'name' => 'MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis',
			'authors' => 'Wang W et al.',
			'description' => '<p>DNA double strand break (DSB) repair is critical for generation of B-cell receptors, which are pre-requisite for B-cell progenitor survival. However, the transcription factors that promote DSB repair in B cells are not known. Here we show that MEF2C enhances the expression of DNA repair and recombination factors in B-cell progenitors, promoting DSB repair, V(D)J recombination and cell survival. Although Mef2c-deficient mice maintain relatively intact peripheral B-lymphoid cellularity during homeostasis, they exhibit poor B-lymphoid recovery after sub-lethal irradiation and 5-fluorouracil injection. MEF2C binds active regulatory regions with high-chromatin accessibility in DNA repair and V(D)J genes in both mouse B-cell progenitors and human B lymphoblasts. Loss of Mef2c in pre-B cells reduces chromatin accessibility in multiple regulatory regions of the MEF2C-activated genes. MEF2C therefore protects B lymphopoiesis during stress by ensuring proper expression of genes that encode DNA repair and B-cell factors.</p>',
			'date' => '2016-08-10',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27507714',
			'doi' => '',
			'modified' => '2016-08-31 10:42:58',
			'created' => '2016-08-31 10:42:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 185 => array(
			'id' => '3004',
			'name' => 'Toxoplasma gondii TgIST co-opts host chromatin repressors dampening STAT1-dependent gene regulation and IFN-γ-mediated host defenses',
			'authors' => 'Gay G et al.',
			'description' => '<p>An early hallmark of Toxoplasma gondii infection is the rapid control of the parasite population by a potent multifaceted innate immune response that engages resident and homing immune cells along with pro- and counter-inflammatory cytokines. In this context, IFN-&gamma; activates a variety of T. gondii-targeting activities in immune and nonimmune cells but can also contribute to host immune pathology. T. gondii has evolved mechanisms to timely counteract the host IFN-&gamma; defenses by interfering with the transcription of IFN-&gamma;-stimulated genes. We now have identified TgIST (T. gondii inhibitor of STAT1 transcriptional activity) as a critical molecular switch that is secreted by intracellular parasites and traffics to the host cell nucleus where it inhibits STAT1-dependent proinflammatory gene expression. We show that TgIST not only sequesters STAT1 on dedicated loci but also promotes shaping of a nonpermissive chromatin through its capacity to recruit the nucleosome remodeling deacetylase (NuRD) transcriptional repressor. We found that during mice acute infection, TgIST-deficient parasites are rapidly eliminated by the homing Gr1<sup>+</sup> inflammatory monocytes, thus highlighting the protective role of TgIST against IFN-&gamma;-mediated killing. By uncovering TgIST functions, this study brings novel evidence on how T. gondii has devised a molecular weapon of choice to take control over a ubiquitous immune gene expression mechanism in metazoans, as a way to promote long-term parasitism.</p>',
			'date' => '2016-08-08',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27503074',
			'doi' => '',
			'modified' => '2016-08-26 11:02:25',
			'created' => '2016-08-26 11:02:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 186 => array(
			'id' => '3003',
			'name' => 'Epigenetic dynamics of monocyte-to-macrophage differentiation',
			'authors' => 'Wallner S et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Monocyte-to-macrophage differentiation involves major biochemical and structural changes. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete transcriptome and epigenome of human monocytes that were differentiated in vitro by addition of colony-stimulating factor 1 in serum-free medium.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Numerous mRNAs and miRNAs were significantly up- or down-regulated. More than 100 discrete DNA regions, most often far away from transcription start sites, were rapidly demethylated by the ten eleven translocation enzymes, became nucleosome-free and gained histone marks indicative of active enhancers. These regions were unique for macrophages and associated with genes involved in the regulation of the actin cytoskeleton, phagocytosis and innate immune response.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">In summary, we have discovered a phagocytic gene network that is repressed by DNA methylation in monocytes and rapidly de-repressed after the onset of macrophage differentiation.</abstracttext></p>
</div>',
			'date' => '2016-07-29',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27478504',
			'doi' => '10.1186/s13072-016-0079-z',
			'modified' => '2016-08-26 11:59:54',
			'created' => '2016-08-26 10:20:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 187 => array(
			'id' => '3021',
			'name' => 'Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis',
			'authors' => 'Rinaldi L et al.',
			'description' => '<p>The genome-wide localization and function of endogenous Dnmt3a and Dnmt3b in adult stem cells are unknown. Here, we show that in human epidermal stem cells, the two proteins bind in a histone H3K36me3-dependent manner to the most active enhancers and are required to produce their associated enhancer RNAs. Both proteins prefer super-enhancers associated to genes that either define the ectodermal lineage or establish the stem cell and differentiated states. However, Dnmt3a and Dnmt3b differ in their mechanisms of enhancer regulation: Dnmt3a associates with p63 to maintain high levels of DNA hydroxymethylation at the center of enhancers in a Tet2-dependent manner, whereas Dnmt3b promotes DNA methylation along the body of the enhancer. Depletion of either protein inactivates their target enhancers and profoundly affects epidermal stem cell function. Altogether, we reveal novel functions for Dnmt3a and Dnmt3b at enhancers that could contribute to their roles in disease and tumorigenesis.</p>',
			'date' => '2016-07-26',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27476967',
			'doi' => '',
			'modified' => '2016-08-31 10:22:54',
			'created' => '2016-08-31 10:22:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 188 => array(
			'id' => '2915',
			'name' => 'PAFAH1B1 and the lncRNA NONHSAT073641 maintain an angiogenic phenotype in human endothelial cells',
			'authors' => 'Josipovic I at al.',
			'description' => '<h4>AIM:</h4>
<p><abstracttext label="AIM" nlmcategory="OBJECTIVE">Platelet-activating factor acetyl hydrolase 1B1 (PAFAH1B1, also known as Lis1) is a protein essentially involved in neurogenesis and mostly studied in the nervous system. As we observed a significant expression of PAFAH1B1 in the vascular system, we hypothesized that PAFAH1B1 is important during angiogenesis of endothelial cells as well as in human vascular diseases.</abstracttext></p>
<h4>METHOD:</h4>
<p><abstracttext label="METHOD" nlmcategory="METHODS">The functional relevance of the protein in endothelial cell angiogenic function, its downstream targets and the influence of NONHSAT073641, a long non-coding RNA (lncRNA) with 92% similarity to PAFAH1B1, were studied by knockdown and overexpression in human umbilical vein endothelial cells (HUVEC).</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Knockdown of PAFAH1B1 led to impaired tube formation of HUVEC and decreased sprouting in the spheroid assay. Accordingly, the overexpression of PAFAH1B1 increased tube number, sprout length and sprout number. LncRNA NONHSAT073641 behaved similarly. Microarray analysis after PAFAH1B1 knockdown and its overexpression indicated that the protein maintains Matrix Gla Protein (MGP) expression. Chromatin immunoprecipitation experiments revealed that PAFAH1B1 is required for active histone marks and proper binding of RNA Polymerase II to the transcriptional start site of MGP. MGP itself was required for endothelial angiogenic capacity and knockdown of both, PAFAH1B1 and MGP, reduced migration. In vascular samples of patients with chronic thromboembolic pulmonary hypertension (CTEPH), PAFAH1B1 and MGP were upregulated. The function of PAFAH1B1 required the presence of the intact protein as overexpression of NONHSAT073641, which was highly upregulated during CTEPH, did not affect PAFAH1B1 target genes.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">PAFAH1B1 and NONHSAT073641 are important for endothelial angiogenic function. This article is protected by copyright. All rights reserved.</abstracttext></p>',
			'date' => '2016-04-28',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27124368',
			'doi' => ' 10.1111/apha.12700',
			'modified' => '2016-05-12 10:42:06',
			'created' => '2016-05-12 10:42:06',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 189 => array(
			'id' => '2914',
			'name' => 'Chromatin immunoprecipitation from fixed clinical tissues reveals tumor-specific enhancer profiles.',
			'authors' => 'Cejas P et al.',
			'description' => '<p>Extensive cross-linking introduced during routine tissue fixation of clinical pathology specimens severely hampers chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) analysis from archived tissue samples. This limits the ability to study the epigenomes of valuable, clinically annotated tissue resources. Here we describe fixed-tissue chromatin immunoprecipitation sequencing (FiT-seq), a method that enables reliable extraction of soluble chromatin from formalin-fixed paraffin-embedded (FFPE) tissue samples for accurate detection of histone marks. We demonstrate that FiT-seq data from FFPE specimens are concordant with ChIP-seq data from fresh-frozen samples of the same tumors. By using multiple histone marks, we generate chromatin-state maps and identify cis-regulatory elements in clinical samples from various tumor types that can readily allow us to distinguish between cancers by the tissue of origin. Tumor-specific enhancers and superenhancers that are elucidated by FiT-seq analysis correlate with known oncogenic drivers in different tissues and can assist in the understanding of how chromatin states affect gene regulation.</p>',
			'date' => '2016-04-25',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27111282',
			'doi' => '10.1038/nm.4085',
			'modified' => '2016-05-11 17:34:25',
			'created' => '2016-05-11 17:34:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 190 => array(
			'id' => '2894',
			'name' => 'Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time',
			'authors' => 'Feichtinger J, Hernández I, Fischer C, Hanscho M, Auer N, Hackl M, Jadhav V, Baumann M, Krempl PM, Schmidl C, Farlik M, Schuster M, Merkel A, Sommer A, Heath S, Rico D, Bock C, Thallinger GG, Borth N',
			'description' => '<p>The most striking characteristic of CHO cells is their adaptability, which enables efficient production of proteins as well as growth under a variety of culture conditions, but also results in genomic and phenotypic instability. To investigate the relative contribution of genomic and epigenetic modifications towards phenotype evolution, comprehensive genome and epigenome data are presented for 6 related CHO cell lines, both in response to perturbations (different culture conditions and media as well as selection of a specific phenotype with increased transient productivity) and in steady state (prolonged time in culture under constant conditions). Clear transitions were observed in DNA-methylation patterns upon each perturbation, while few changes occurred over time under constant conditions. Only minor DNA-methylation changes were observed between exponential and stationary growth phase, however, throughout a batch culture the histone modification pattern underwent continuous adaptation. Variation in genome sequence between the 6 cell lines on the level of SNPs, InDels and structural variants is high, both upon perturbation and under constant conditions over time. The here presented comprehensive resource may open the door to improved control and manipulation of gene expression during industrial bioprocesses based on epigenetic mechanisms</p>',
			'date' => '2016-04-12',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27072894',
			'doi' => '10.1002/bit.25990',
			'modified' => '2016-04-22 12:53:44',
			'created' => '2016-04-22 12:37:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 191 => array(
			'id' => '2880',
			'name' => 'GATA-1 Inhibits PU.1 Gene via DNA and Histone H3K9 Methylation of Its Distal Enhancer in Erythroleukemia',
			'authors' => 'Burda P, Vargova J, Curik N, Salek C, Papadopoulos GL, Strouboulis J, Stopka T',
			'description' => '<p>GATA-1 and PU.1 are two important hematopoietic transcription factors that mutually inhibit each other in progenitor cells to guide entrance into the erythroid or myeloid lineage, respectively. PU.1 controls its own expression during myelopoiesis by binding to the distal URE enhancer, whose deletion leads to acute myeloid leukemia (AML). We herein present evidence that GATA-1 binds to the PU.1 gene and inhibits its expression in human AML-erythroleukemias (EL). Furthermore, GATA-1 together with DNA methyl Transferase I (DNMT1) mediate repression of the PU.1 gene through the URE. Repression of the PU.1 gene involves both DNA methylation at the URE and its histone H3 lysine-K9 methylation and deacetylation as well as the H3K27 methylation at additional DNA elements and the promoter. The GATA-1-mediated inhibition of PU.1 gene transcription in human AML-EL mediated through the URE represents important mechanism that contributes to PU.1 downregulation and leukemogenesis that is sensitive to DNA demethylation therapy.</p>',
			'date' => '2016-03-24',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27010793',
			'doi' => '10.1371/journal.pone.0152234',
			'modified' => '2016-04-06 10:26:31',
			'created' => '2016-04-06 10:26:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 192 => array(
			'id' => '2886',
			'name' => 'Role of Annexin gene and its regulation during zebrafish caudal fin regeneration',
			'authors' => 'Saxena S, Purushothaman S, Meghah V, Bhatti B, Poruri A, Meena Lakshmi MG, Sarath Babu N, Murthy CL, Mandal KK, Kumar A, Idris MM',
			'description' => '<p>The molecular mechanism of epimorphic regeneration is elusive due to its complexity and limitation in mammals. Epigenetic regulatory mechanisms play a crucial role in development and regeneration. This investigation attempted to reveal the role of epigenetic regulatory mechanisms, such as histone H3 and H4 lysine acetylation and methylation during zebrafish caudal fin regeneration. It was intriguing to observe that H3K9,14 acetylation, H4K20 trimethylation, H3K4 trimethylation and H3K9 dimethylation along with their respective regulatory genes, such as <em>GCN5, SETd8b, SETD7/9</em> and <em>SUV39h1</em>, were differentially regulated in the regenerating fin at various time points of post-amputation. Annexin genes have been associated with regeneration; this study reveals the significant upregulation of <em>ANXA2a</em> and <em>ANXA2b</em> transcripts and their protein products during the regeneration process. Chromatin Immunoprecipitation (ChIP) and PCR analysis of the regulatory regions of the <em>ANXA2a</em> and <em>ANXA2b</em> genes demonstrated the ability to repress two histone methylations, H3K27me3 and H4K20me3, in transcriptional regulation during regeneration. It is hypothesized that this novel insight into the diverse epigenetic mechanisms that play a critical role during the regeneration process may help to strategize the translational efforts, in addition to identifying the molecules involved in vertebrate regeneration.</p>',
			'date' => '2016-03-12',
			'pmid' => 'http://onlinelibrary.wiley.com/doi/10.1111/wrr.12429/abstract',
			'doi' => '10.1111/wrr.12429',
			'modified' => '2016-04-08 17:24:06',
			'created' => '2016-04-08 17:24:06',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 193 => array(
			'id' => '2856',
			'name' => 'Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis',
			'authors' => 'Weigel C. et al.',
			'description' => '<p>Radiotherapy is a fundamental part of cancer treatment but its use is limited by the onset of late adverse effects in the normal tissue, especially radiation-induced fibrosis. Since the molecular causes for fibrosis are largely unknown, we analyse if epigenetic regulation might explain inter-individual differences in fibrosis risk. DNA methylation profiling of dermal fibroblasts obtained from breast cancer patients prior to irradiation identifies differences associated with fibrosis. One region is characterized as a differentially methylated enhancer of diacylglycerol kinase alpha (<i>DGKA</i>). Decreased DNA methylation at this enhancer enables recruitment of the profibrotic transcription factor early growth response 1 (EGR1) and facilitates radiation-induced <i>DGKA</i> transcription in cells from patients later developing fibrosis. Conversely, inhibition of DGKA has pronounced effects on diacylglycerol-mediated lipid homeostasis and reduces profibrotic fibroblast activation. Collectively, DGKA is an epigenetically deregulated kinase involved in radiation response and may serve as a marker and therapeutic target for personalized radiotherapy.</p>',
			'date' => '2016-03-11',
			'pmid' => 'http://www.nature.com/ncomms/2016/160311/ncomms10893/full/ncomms10893.html',
			'doi' => '10.1038/ncomms10893',
			'modified' => '2016-03-15 11:08:21',
			'created' => '2016-03-15 11:08:21',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 194 => array(
			'id' => '2970',
			'name' => 'Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development.',
			'authors' => 'Yuan S et al.',
			'description' => '<p>Although it is believed that mammalian sperm carry small noncoding RNAs (sncRNAs) into oocytes during fertilization, it remains unknown whether these sperm-borne sncRNAs truly have any function during fertilization and preimplantation embryonic development. Germline-specific Dicer and Drosha conditional knockout (cKO) mice produce gametes (i.e. sperm and oocytes) partially deficient in miRNAs and/or endo-siRNAs, thus providing a unique opportunity for testing whether normal sperm (paternal) or oocyte (maternal) miRNA and endo-siRNA contents are required for fertilization and preimplantation development. Using the outcome of intracytoplasmic sperm injection (ICSI) as a readout, we found that sperm with altered miRNA and endo-siRNA profiles could fertilize wild-type (WT) eggs, but embryos derived from these partially sncRNA-deficient sperm displayed a significant reduction in developmental potential, which could be rescued by injecting WT sperm-derived total or small RNAs into ICSI embryos. Disrupted maternal transcript turnover and failure in early zygotic gene activation appeared to associate with the aberrant miRNA profiles in Dicer and Drosha cKO spermatozoa. Overall, our data support a crucial function of paternal miRNAs and/or endo-siRNAs in the control of the transcriptomic homeostasis in fertilized eggs, zygotes and two-cell embryos. Given that supplementation of sperm RNAs enhances both the developmental potential of preimplantation embryos and the live birth rate, it might represent a novel means to improve the success rate of assisted reproductive technologies in fertility clinics.</p>',
			'date' => '2016-02-15',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26718009',
			'doi' => '10.1242/dev.131755',
			'modified' => '2016-06-29 17:11:02',
			'created' => '2016-06-29 17:11:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 195 => array(
			'id' => '2849',
			'name' => 'MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199',
			'authors' => 'Benito JM et al.',
			'description' => '<p>Targeted therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of current research. <em>Mixed Lineage Leukemia</em> (<em>MLL</em>) mutations such as the t(4;11) translocation cause aggressive leukemias that are refractory to conventional treatment. The t(4;11) translocation produces an MLL/AF4 fusion protein that activates key target genes through both epigenetic and transcriptional elongation mechanisms. In this study, we show that t(4;11) patient cells express high levels of BCL-2 and are highly sensitive to treatment with the BCL-2-specific BH3 mimetic ABT-199. We demonstrate that MLL/AF4 specifically upregulates the <em>BCL-2</em> gene but not other BCL-2 family members via DOT1L-mediated H3K79me2/3. We use this information to show that a t(4;11) cell line is sensitive to a combination of ABT-199 and DOT1L inhibitors. In addition, ABT-199 synergizes with standard induction-type therapy in a xenotransplant model, advocating for the introduction of ABT-199 into therapeutic regimens for MLL-rearranged leukemias.</p>',
			'date' => '2015-12-29',
			'pmid' => 'http://www.cell.com/cell-reports/abstract/S2211-1247%2815%2901415-1',
			'doi' => ' http://dx.doi.org/10.1016/j.celrep.2015.12.003',
			'modified' => '2016-03-11 17:31:23',
			'created' => '2016-03-11 17:11:09',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 196 => array(
			'id' => '2810',
			'name' => 'Standardizing chromatin research: a simple and universal method for ChIP-seq',
			'authors' => 'Laura Arrigoni, Andreas S. Richter, Emily Betancourt, Kerstin Bruder, Sarah Diehl, Thomas Manke and Ulrike Bönisch',
			'description' => '<p><span>Here we&nbsp;demonstrate that harmonization of ChIP-seq workflows across cell types and conditions is possible when obtaining chromatin from properly isolated nuclei. We established an ultrasound-based nuclei extraction method (Nuclei Extraction by Sonication) that is highly effective across various organisms, cell types and cell numbers. The described method has the potential to replace complex cell-type-specific, but largely ineffective, nuclei isolation protocols. This article demonstrates protocol standardization using the Bioruptor shearing systems and the IP-Star Automation System for ChIP automation.</span></p>',
			'date' => '2015-12-23',
			'pmid' => 'http://pubmed.gov/26704968',
			'doi' => '10.1093/nar/gkv1495',
			'modified' => '2016-06-09 09:47:00',
			'created' => '2016-01-10 08:32:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 197 => array(
			'id' => '2952',
			'name' => 'Dynamic changes in histone modifications precede de novo DNA methylation in oocytes',
			'authors' => 'Stewart KR et al.',
			'description' => '<p>Erasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation establishment remain poorly understood, but a number of post-translational modifications of histones are implicated in antagonizing or recruiting the de novo DNA methylation complex. In mouse oogenesis, DNA methylation establishment occurs on a largely unmethylated genome and in nondividing cells, making it a highly informative model for examining how histone modifications can shape the DNA methylome. Using a chromatin immunoprecipitation (ChIP) and genome-wide sequencing (ChIP-seq) protocol optimized for low cell numbers and novel techniques for isolating primary and growing oocytes, profiles were generated for histone modifications implicated in promoting or inhibiting DNA methylation. CGIs destined for DNA methylation show reduced protective H3K4 dimethylation (H3K4me2) and trimethylation (H3K4me3) in both primary and growing oocytes, while permissive H3K36me3 increases specifically at these CGIs in growing oocytes. Methylome profiling of oocytes deficient in H3K4 demethylase KDM1A or KDM1B indicated that removal of H3K4 methylation is necessary for proper methylation establishment at CGIs. This work represents the first systematic study performing ChIP-seq in oocytes and shows that histone remodeling in the mammalian oocyte helps direct de novo DNA methylation events.</p>',
			'date' => '2015-12-01',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26584620',
			'doi' => '10.1101/gad.271353.115',
			'modified' => '2016-06-10 16:39:45',
			'created' => '2016-06-10 16:39:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 198 => array(
			'id' => '2963',
			'name' => 'Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma',
			'authors' => 'Aldiri I et al.',
			'description' => '<p>Retinal development requires precise temporal and spatial coordination of cell cycle exit, cell fate specification, cell migration and differentiation. When this process is disrupted, retinoblastoma, a developmental tumor of the retina, can form. Epigenetic modulators are central to precisely coordinating developmental events, and many epigenetic processes have been implicated in cancer. Studying epigenetic mechanisms in development is challenging because they often regulate multiple cellular processes; therefore, elucidating the primary molecular mechanisms involved can be difficult. Here we explore the role of Brg1 (Smarca4) in retinal development and retinoblastoma in mice using molecular and cellular approaches. Brg1 was found to regulate retinal size by controlling cell cycle length, cell cycle exit and cell survival during development. Brg1 was not required for cell fate specification but was required for photoreceptor differentiation and cell adhesion/polarity programs that contribute to proper retinal lamination during development. The combination of defective cell differentiation and lamination led to retinal degeneration in Brg1-deficient retinae. Despite the hypocellularity, premature cell cycle exit, increased cell death and extended cell cycle length, retinal progenitor cells persisted in Brg1-deficient retinae, making them more susceptible to retinoblastoma. ChIP-Seq analysis suggests that Brg1 might regulate gene expression through multiple mechanisms.</p>',
			'date' => '2015-12-01',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26628093',
			'doi' => '10.1242/dev.124800',
			'modified' => '2016-06-24 09:48:45',
			'created' => '2016-06-24 09:48:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 199 => array(
			'id' => '2964',
			'name' => 'Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization',
			'authors' => 'Kuznetsova T et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">The impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from remodeling of higher order chromatin architecture by activated transcription factors to recruitment of activated transcription factors to pre-established long-range interactions.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Using circular chromosome conformation capture coupled with next generation sequencing and high-resolution chromatin interaction analysis by paired-end tag sequencing of P300, we observed agonist-induced changes in long-range chromatin interactions, and uncovered interconnected enhancer-enhancer hubs spanning up to one megabase. The vast majority of activated glucocorticoid receptor and nuclear factor kappa-b appeared to join pre-existing P300 enhancer hubs without affecting the chromatin conformation. In contrast, binding of the activated transcription factors to loci with their consensus response elements led to the increased formation of an active epigenetic state of enhancers and a significant increase in long-range interactions within pre-existing enhancer networks. De novo enhancers or ligand-responsive enhancer hubs preferentially interacted with ligand-induced genes.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">We demonstrate that, at a subset of genomic loci, ligand-mediated induction leads to active enhancer formation and an increase in long-range interactions, facilitating efficient regulation of target genes. Therefore, our data suggest an active role of signal-dependent transcription factors in chromatin and long-range interaction remodeling.</abstracttext></p>
</div>',
			'date' => '2015-12-01',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26619937',
			'doi' => '10.1186/s13059-015-0832-9',
			'modified' => '2016-06-24 10:02:16',
			'created' => '2016-06-24 10:02:16',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 200 => array(
			'id' => '2909',
			'name' => 'Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells',
			'authors' => 'Rønningen T, Shah A, Reiner AH, Collas P, Moskaug JØ',
			'description' => '<p>Cellular metabolism confers wide-spread epigenetic modifications required for regulation of transcriptional networks that determine cellular states. Mesenchymal stromal cells are responsive to metabolic cues including circulating glucose levels and modulate inflammatory responses. We show here that long term exposure of undifferentiated human adipose tissue stromal cells (ASCs) to high glucose upregulates a subset of inflammation response (IR) genes and alters their promoter histone methylation patterns in a manner consistent with transcriptional de-repression. Modeling of chromatin states from combinations of histone modifications in nearly 500 IR genes unveil three overarching chromatin configurations reflecting repressive, active, and potentially active states in promoter and enhancer elements. Accordingly, we show that adipogenic differentiation in high glucose predominantly upregulates IR genes. Our results indicate that elevated extracellular glucose levels sensitize in ASCs an IR gene expression program which is exacerbated during adipocyte differentiation. We propose that high glucose exposure conveys an epigenetic 'priming' of IR genes, favoring a transcriptional inflammatory response upon adipogenic stimulation. Chromatin alterations at IR genes by high glucose exposure may play a role in the etiology of metabolic diseases.</p>',
			'date' => '2015-11-27',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26462465',
			'doi' => '10.1016/j.bbrc.2015.10.030',
			'modified' => '2016-05-09 22:54:48',
			'created' => '2016-05-09 22:54:48',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 201 => array(
			'id' => '2957',
			'name' => 'The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth',
			'authors' => 'Palazzo E et al.',
			'description' => '<p>Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epidermal hyperplasia and squamous tumorigenesis. By integrating genetic and transcriptomic approaches, we demonstrate that DLX3 operates through a p53-regulated network. DLX3 and p53 physically interact on the p21 promoter to enhance p21 expression. Elevating DLX3 in keratinocytes produces a G1-S blockade associated with p53 signature transcriptional profiles. In contrast, DLX3 loss promotes a mitogenic phenotype associated with constitutive activation of ERK. DLX3 expression is lost in human skin cancers and is extinguished during progression of experimentally induced mouse squamous cell carcinoma (SCC). Reinstatement of DLX3 function is sufficient to attenuate the migration of SCC cells, leading to decreased wound closure. Our data establish the DLX3-p53 interplay as a major regulatory axis in epidermal differentiation and suggest that DLX3 is a modulator of skin carcinogenesis.</p>',
			'date' => '2015-11-02',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26522723',
			'doi' => '10.1038/onc.2015.380',
			'modified' => '2016-06-15 16:18:44',
			'created' => '2016-06-15 16:18:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 202 => array(
			'id' => '2962',
			'name' => 'VEGF-mediated cell survival in non-small-cell lung cancer: implications for epigenetic targeting of VEGF receptors as a therapeutic approach',
			'authors' => 'Barr MP et al.',
			'description' => '<div class="">
<h4>AIMS:</h4>
<p><abstracttext label="AIMS" nlmcategory="OBJECTIVE">To evaluate the potential therapeutic utility of histone deacetylase inhibitors (HDACi) in targeting VEGF receptors in non-small-cell lung cancer.</abstracttext></p>
<h4>MATERIALS &amp; METHODS:</h4>
<p><abstracttext label="MATERIALS &amp; METHODS" nlmcategory="METHODS">Non-small-cell lung cancer cells were screened for the VEGF receptors at the mRNA and protein levels, while cellular responses to various HDACi were examined.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Significant effects on the regulation of the VEGF receptors were observed in response to HDACi. These were associated with decreased secretion of VEGF, decreased cellular proliferation and increased apoptosis which could not be rescued by addition of exogenous recombinant VEGF. Direct remodeling of the VEGFR1 and VEGFR2 promoters was observed. In contrast, HDACi treatments resulted in significant downregulation of the Neuropilin receptors.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">Epigenetic targeting of the Neuropilin receptors may offer an effective treatment for lung cancer patients in the clinical setting.</abstracttext></p>
</div>',
			'date' => '2015-10-07',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26479311',
			'doi' => '10.2217/epi.15.51',
			'modified' => '2016-06-23 15:24:41',
			'created' => '2016-06-23 15:24:41',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 203 => array(
			'id' => '2917',
			'name' => 'Chromatin assembly factor CAF-1 represses priming of plant defence response genes',
			'authors' => 'Mozgova I et al.',
			'description' => '<p><b>Plants have evolved efficient defence systems against pathogens that often rely on specific transcriptional responses. Priming is part of the defence syndrome, by establishing a hypersensitive state of defence genes such as after a first encounter with a pathogen. Because activation of defence responses has a fitness cost, priming must be tightly controlled to prevent spurious activation of defence. However, mechanisms that repress defence gene priming are poorly understood. Here, we show that the histone chaperone CAF-1 is required to establish a repressed chromatin state at defence genes. Absence of CAF-1 results in spurious activation of a salicylic acid-dependent pathogen defence response in plants grown under non-sterile conditions. Chromatin at defence response genes in CAF-1 mutants under non-inductive (sterile) conditions is marked by low nucleosome occupancy and high H3K4me3 at transcription start sites, resembling chromatin in primed wild-type plants. We conclude that CAF-1-mediated chromatin assembly prevents the establishment of a primed state that may under standard non-sterile growth conditions result in spurious activation of SA-dependent defence responses and consequential reduction of plant vigour.</b></p>',
			'date' => '2015-09-01',
			'pmid' => 'http://www.nature.com/articles/nplants2015127',
			'doi' => '10.1038/nplants.2015.127',
			'modified' => '2016-05-13 11:13:50',
			'created' => '2016-05-13 11:13:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 204 => array(
			'id' => '2817',
			'name' => 'Spatiotemporal control of estrogen-responsive transcription in ERα-positive breast cancer cells.',
			'authors' => 'P-Y Hsu, H-K Hsu, T-H Hsiao, Z Ye, E Wang, A L Profit, I Jatoi, Y Chen, N B Kirma, V X Jin, Z D Sharp and T H-M Huang',
			'description' => '<p><span>Recruitment of transcription machinery to target promoters for aberrant gene expression has been well studied, but underlying control directed by distant-acting enhancers remains unclear in cancer development. Our previous study demonstrated that distant estrogen response elements (DEREs) located on chromosome 20q13 are frequently amplified and translocated to other chromosomes in ER&alpha;-positive breast cancer cells. In this study, we used three-dimensional interphase fluorescence in situ hybridization to decipher spatiotemporal gathering of multiple DEREs in the nucleus. Upon estrogen stimulation, scattered 20q13 DEREs were mobilized to form regulatory depots for synchronized gene expression of target loci. A chromosome conformation capture assay coupled with chromatin immunoprecipitation further uncovered that ER&alpha;-bound regulatory depots are tethered to heterochromatin protein 1 (HP1) for coordinated chromatin movement and histone modifications of target loci, resulting in transcription repression. Neutralizing HP1 function dysregulated the formation of DERE-involved regulatory depots and transcription inactivation of candidate tumor-suppressor genes. Deletion of amplified DEREs using the CRISPR/Cas9 genomic-editing system profoundly altered transcriptional profiles of proliferation-associated signaling networks, resulting in reduction of cancer cell growth. These findings reveal a formerly uncharacterized feature wherein multiple copies of the amplicon congregate as transcriptional units in the nucleus for synchronous regulation of function-related loci in tumorigenesis. Disruption of their assembly can be a new strategy for treating breast cancers and other malignancies</span></p>',
			'date' => '2015-08-24',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26300005',
			'doi' => '10.1038/onc.2015.298',
			'modified' => '2016-02-10 16:20:01',
			'created' => '2016-02-10 16:20:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 205 => array(
			'id' => '2816',
			'name' => 'Non-coding recurrent mutations in chronic lymphocytic leukaemia.',
			'authors' => 'Xose S. Puente, Silvia Beà, Rafael Valdés-Mas, Neus Villamor, Jesús Gutiérrez-Abril et al.',
			'description' => '<p><span>Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3, ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding regions, including the 3' region of NOTCH1, which cause aberrant splicing events, increase NOTCH1 activity and result in a more aggressive disease. In addition, mutations in an enhancer located on chromosome 9p13 result in reduced expression of the B-cell-specific transcription factor PAX5. The accumulative number of driver alterations (0 to &ge;4) discriminated between patients with differences in clinical behaviour. This study provides an integrated portrait of the CLL genomic landscape, identifies new recurrent driver mutations of the disease, and suggests clinical interventions that may improve the management of this neoplasia.</span></p>',
			'date' => '2015-07-22',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26200345',
			'doi' => '10.1038/nature14666',
			'modified' => '2016-02-10 16:17:29',
			'created' => '2016-02-10 16:17:29',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 206 => array(
			'id' => '2893',
			'name' => 'Allele-specific binding of ZFP57 in the epigenetic regulation of imprinted and non-imprinted monoallelic expression',
			'authors' => 'Strogantsev R, Krueger F, Yamazawa K, Shi H, Gould P, Goldman-Roberts M, McEwen K, Sun B, Pedersen R, Ferguson-Smith AC',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Selective maintenance of genomic epigenetic imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary for maintaining the DNA methylation memory at multiple imprinting control regions in early mouse embryos and embryonic stem (ES) cells. Maternal-zygotic deletion of ZFP57 in mice presents a highly penetrant phenotype with no animals surviving to birth. Additionally, several cases of human transient neonatal diabetes are associated with somatic mutations in the ZFP57 coding sequence.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Here, we comprehensively map sequence-specific ZFP57 binding sites in an allele-specific manner using hybrid ES cell lines from reciprocal crosses between C57BL/6J and Cast/EiJ mice, assigning allele specificity to approximately two-thirds of all binding sites. While half of these are biallelic and include endogenous retrovirus (ERV) targets, the rest show monoallelic binding based either on parental origin or on genetic background of the allele. Parental-origin allele-specific binding is methylation-dependent and maps only to imprinting control differentially methylated regions (DMRs) established in the germline. We identify a novel imprinted gene, Fkbp6, which has a critical function in mouse male germ cell development. Genetic background-specific sequence differences also influence ZFP57 binding, as genetic variation that disrupts the consensus binding motif and its methylation is often associated with monoallelic expression of neighboring genes.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">The work described here uncovers further roles for ZFP57-mediated regulation of genomic imprinting and identifies a novel mechanism for genetically determined monoallelic gene expression.</abstracttext></p>
</div>',
			'date' => '2015-05-30',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26025256',
			'doi' => '10.1186/s13059-015-0672-7',
			'modified' => '2016-04-14 17:20:03',
			'created' => '2016-04-14 17:20:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 207 => array(
			'id' => '2790',
			'name' => 'Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency.',
			'authors' => 'Chen H, Aksoy I, Gonnot F, Osteil P, Aubry M, Hamela C, Rognard C, Hochard A, Voisin S, Fontaine E, Mure M, Afanassieff M, Cleroux E, Guibert S, Chen J, Vallot C, Acloque H, Genthon C, Donnadieu C, De Vos J, Sanlaville D, Guérin JF, Weber M, Stanton LW, R',
			'description' => 'Leukemia inhibitory factor (LIF)/STAT3 signalling is a hallmark of naive pluripotency in rodent pluripotent stem cells (PSCs), whereas fibroblast growth factor (FGF)-2 and activin/nodal signalling is required to sustain self-renewal of human PSCs in a condition referred to as the primed state. It is unknown why LIF/STAT3 signalling alone fails to sustain pluripotency in human PSCs. Here we show that the forced expression of the hormone-dependent STAT3-ER (ER, ligand-binding domain of the human oestrogen receptor) in combination with 2i/LIF and tamoxifen allows human PSCs to escape from the primed state and enter a state characterized by the activation of STAT3 target genes and long-term self-renewal in FGF2- and feeder-free conditions. These cells acquire growth properties, a gene expression profile and an epigenetic landscape closer to those described in mouse naive PSCs. Together, these results show that temporarily increasing STAT3 activity is sufficient to reprogramme human PSCs to naive-like pluripotent cells.',
			'date' => '2015-05-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25968054',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 208 => array(
			'id' => '2611',
			'name' => 'Opposite expression of CYP51A1 and its natural antisense transcript AluCYP51A1 in adenovirus type 37 infected retinal pigmented epithelial cells.',
			'authors' => 'Pickl JM, Kamel W, Ciftci S, Punga T, Akusjärvi G',
			'description' => 'Cytochrome P450 family member CYP51A1 is a key enzyme in cholesterol biosynthesis whose deregulation is implicated in numerous diseases, including retinal degeneration. Here we describe that HAdV-37 infection leads to downregulation of CYP51A1 expression and overexpression of its antisense non-coding Alu element (AluCYP51A1) in retinal pigment epithelium (RPE) cells. This change in gene expression is associated with a reversed accumulation of a positive histone mark at the CYP51A1 and AluCYP51A1 promoters. Further, transient AluCYP51A1 RNA overexpression correlates with reduced CYP51A1 mRNA accumulation. Collectively, our data suggest that AluCYP51A1 might control CYP51A1 gene expression in HAdV-37-infected RPE cells.',
			'date' => '2015-04-20',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25907535',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 209 => array(
			'id' => '2684',
			'name' => 'A cohesin-OCT4 complex mediates Sox enhancers to prime an early embryonic lineage.',
			'authors' => 'Abboud N, Moore-Morris T, Hiriart E, Yang H, Bezerra H, Gualazzi MG, Stefanovic S, Guénantin AC, Evans SM, Pucéat M',
			'description' => 'Short- and long-scales intra- and inter-chromosomal interactions are linked to gene transcription, but the molecular events underlying these structures and how they affect cell fate decision during embryonic development are poorly understood. One of the first embryonic cell fate decisions (that is, mesendoderm determination) is driven by the POU factor OCT4, acting in concert with the high-mobility group genes Sox-2 and Sox-17. Here we report a chromatin-remodelling mechanism and enhancer function that mediate cell fate switching. OCT4 alters the higher-order chromatin structure at both Sox-2 and Sox-17 loci. OCT4 titrates out cohesin and switches the Sox-17 enhancer from a locked (within an inter-chromosomal Sox-2 enhancer/CCCTC-binding factor CTCF/cohesin loop) to an active (within an intra-chromosomal Sox-17 promoter/enhancer/cohesin loop) state. SALL4 concomitantly mobilizes the polycomb complexes at the Soxs loci. Thus, OCT4/SALL4-driven cohesin- and polycombs-mediated changes in higher-order chromatin structure mediate instruction of early cell fate in embryonic cells.',
			'date' => '2015-04-08',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25851587',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 210 => array(
			'id' => '2625',
			'name' => 'Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1.',
			'authors' => 'Tomazou EM, Sheffield NC, Schmidl C, Schuster M, Schönegger A, Datlinger P, Kubicek S, Bock C, Kovar H',
			'description' => '<p>Transcription factor fusion proteins can transform cells by inducing global changes of the transcriptome, often creating a state of oncogene addiction. Here, we investigate the role of epigenetic mechanisms in this process, focusing on Ewing sarcoma cells that are dependent on the EWS-FLI1 fusion protein. We established reference epigenome maps comprising DNA methylation, seven histone marks, open chromatin states, and RNA levels, and we analyzed the epigenome dynamics upon downregulation of the driving oncogene. Reduced EWS-FLI1 expression led to widespread epigenetic changes in&nbsp;promoters, enhancers, and super-enhancers, and we identified histone H3K27 acetylation as the most strongly affected mark. Clustering of epigenetic promoter signatures defined classes of EWS-FLI1-regulated genes that responded differently to low-dose treatment with histone deacetylase inhibitors. Furthermore, we observed strong and opposing enrichment patterns for&nbsp;E2F and AP-1 among EWS-FLI1-correlated and anticorrelated genes. Our data describe extensive genome-wide rewiring of epigenetic cell states driven by an oncogenic fusion protein.</p>',
			'date' => '2015-02-24',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25704812',
			'doi' => '',
			'modified' => '2017-02-14 12:53:04',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 211 => array(
			'id' => '2575',
			'name' => 'Embryonic stem cell differentiation requires full length Chd1.',
			'authors' => 'Piatti P, Lim CY, Nat R, Villunger A, Geley S, Shue YT, Soratroi C, Moser M, Lusser A',
			'description' => 'The modulation of chromatin dynamics by ATP-dependent chromatin remodeling factors has been recognized as an important mechanism to regulate the balancing of self-renewal and pluripotency in embryonic stem cells (ESCs). Here we have studied the effects of a partial deletion of the gene encoding the chromatin remodeling factor Chd1 that generates an N-terminally truncated version of Chd1 in mouse ESCs in vitro as well as in vivo. We found that a previously uncharacterized serine-rich region (SRR) at the N-terminus is not required for chromatin assembly activity of Chd1 but that it is subject to phosphorylation. Expression of Chd1 lacking this region in ESCs resulted in aberrant differentiation properties of these cells. The self-renewal capacity and ESC chromatin structure, however, were not affected. Notably, we found that newly established ESCs derived from Chd1(Δ2/Δ2) mutant mice exhibited similar differentiation defects as in vitro generated mutant ESCs, even though the N-terminal truncation of Chd1 was fully compatible with embryogenesis and post-natal life in the mouse. These results underscore the importance of Chd1 for the regulation of pluripotency in ESCs and provide evidence for a hitherto unrecognized critical role of the phosphorylated N-terminal SRR for full functionality of Chd1.',
			'date' => '2015-01-26',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25620209',
			'doi' => '',
			'modified' => '2015-07-24 15:39:04',
			'created' => '2015-07-24 15:39:04',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 212 => array(
			'id' => '2552',
			'name' => 'A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus.',
			'authors' => 'Lazorthes S, Vallot C, Briois S, Aguirrebengoa M, Thuret JY, Laurent GS, Rougeulle C, Kapranov P, Mann C, Trouche D, Nicolas E',
			'description' => 'Non-coding RNAs (ncRNAs) play major roles in proper chromatin organization and function. Senescence, a strong anti-proliferative process and a major anticancer barrier, is associated with dramatic chromatin reorganization in heterochromatin foci. Here we analyze strand-specific transcriptome changes during oncogene-induced human senescence. Strikingly, while differentially expressed RNAs are mostly repressed during senescence, ncRNAs belonging to the recently described vlincRNA (very long intergenic ncRNA) class are mainly activated. We show that VAD, a novel antisense vlincRNA strongly induced during senescence, is required for the maintenance of senescence features. VAD modulates chromatin structure in cis and activates gene expression in trans at the INK4 locus, which encodes cell cycle inhibitors important for senescence-associated cell proliferation arrest. Importantly, VAD inhibits the incorporation of the repressive histone variant H2A.Z at INK4 gene promoters in senescent cells. Our data underline the importance of vlincRNAs as sensors of cellular environment changes and as mediators of the correct transcriptional response.',
			'date' => '2015-01-20',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25601475',
			'doi' => '',
			'modified' => '2015-07-24 15:39:04',
			'created' => '2015-07-24 15:39:04',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 213 => array(
			'id' => '2492',
			'name' => 'Cryosectioning the intestinal crypt-villus axis: an ex vivo method to study the dynamics of epigenetic modifications from stem cells to differentiated cells',
			'authors' => 'Vincent A, Kazmierczak C, Duchêne B, Jonckheere N, Leteurtre E, Van Seuningen I',
			'description' => 'The intestinal epithelium is a particularly attractive biological adult model to study epigenetic mechanisms driving adult stem cell renewal and cell differentiation. Since epigenetic modifications are dynamic, we have developed an original ex vivo approach to study the expression and epigenetic profiles of key genes associated with either intestinal cell pluripotency or differentiation by isolating cryosections of the intestinal crypt-villus axis. Gene expression, DNA methylation and histone modifications were studied by qRT-PCR, Methylation Specific-PCR and micro-Chromatin Immunoprecipitation, respectively. Using this approach, it was possible to identify segment-specific methylation and chromatin profiles. We show that (i) expression of intestinal stem cell markers (Lgr5, Ascl2) exclusively in the crypt is associated with active histone marks, (ii) promoters of all pluripotency genes studied and transcription factors involved in intestinal cell fate (Cdx2) harbour a bivalent chromatin pattern in the crypts, (iii) expression of differentiation markers (Muc2, Sox9) along the crypt-villus axis is associated with DNA methylation. Hence, using an original model of cryosectioning along the crypt-villus axis that allows in situ detection of dynamic epigenetic modifications, we demonstrate that regulation of pluripotency and differentiation markers in healthy intestinal mucosa involves different and specific epigenetic mechanisms.',
			'date' => '2014-12-27',
			'pmid' => 'http://www.sciencedirect.com/science/article/pii/S1873506114001585',
			'doi' => '',
			'modified' => '2015-07-24 15:39:04',
			'created' => '2015-07-24 15:39:04',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 214 => array(
			'id' => '2299',
			'name' => 'Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs.',
			'authors' => 'Adoue V, Schiavi A, Light N, Almlöf JC, Lundmark P, Ge B, Kwan T, Caron M, Rönnblom L, Wang C, Chen SH, Goodall AH, Cambien F, Deloukas P, Ouwehand WH, Syvänen AC, Pastinen T',
			'description' => 'Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40-60% of these cis-rSNPs to be shared across cell types. We uncover a new class of cis-rSNPs, which disrupt footprint-derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof-of-principle for a new approach for genome-wide functional validation of transcription factor-SNP interactions. By perturbing NFκB action in lymphoblasts, we identified 489 cis-regulated transcripts with altered AE after NFκB perturbation. Altogether, we perform a comprehensive analysis of cis-variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases. ',
			'date' => '2014-10-16',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/25326100',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 215 => array(
			'id' => '2330',
			'name' => 'Obesity increases histone H3 lysine 9 and 18 acetylation at Tnfa and Ccl2 genes in mouse liver',
			'authors' => 'Mikula M, Majewska A, Ledwon JK, Dzwonek A, Ostrowski J',
			'description' => 'Obesity contributes to the development of non‑alcoholic fatty liver disease (NAFLD), which is characterized by the upregulated expression of two key inflammatory mediators: tumor necrosis factor (Tnfa) and monocyte chemotactic protein 1 (Mcp1; also known as Ccl2). However, the chromatin make-up at these genes in the liver in obese individuals has not been explored. In this study, to identify obesity-mediated epigenetic changes at Tnfa and Ccl2, we used a murine model of obesity induced by a high-fat diet (HFD) and hyperphagic (ob/ob) mice. Chromatin immunoprecipitation (ChIP) assay was used to determine the abundance of permissive histone marks, namely histone H3 lysine 9 and 18 acetylation (H3K9/K18Ac), H3 lysine 4 trimethylation (H3K4me3) and H3 lysine 36 trimethylation (H3K36me3), in conjunction with polymerase 2 RNA (Pol2) and nuclear factor (Nf)-κB recruitment in the liver. Additionally, to correlate the liver tissue‑derived ChIP measurements with a robust in vitro transcriptional response at the Tnfa and Ccl2 genes, we used lipopolysaccharide (LPS) treatment to induce an inflammatory response in Hepa1-6 cells, a cell line derived from murine hepatocytes. ChIP revealed increased H3K9/K18Ac at Tnfa and Ccl2 in the obese mice, although the differences were only statistically significant for Tnfa (p<0.05). Unexpectedly, the levels of H3K4me3 and H3K36me3 marks, as well as Pol2 and Nf-κB recruitment, did not correspond with the increased expression of these two genes in the obese mice. By contrast, the acute treatment of Hepa1-6 cells with LPS significantly increased the H3K9/K18Ac marks, as well as Pol2 and Nf-κB recruitment at both genes, while the levels of H3K4me3 and H3K36me3 marks remained unaltered. These results demonstrate that increased Tnfa and Ccl2 expression in fatty liver at the chromatin level corresponds to changes in the level of histone H3 acetylation.',
			'date' => '2014-10-03',
			'pmid' => 'http://www.spandidos-publications.com/10.3892/ijmm.2014.1958',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 216 => array(
			'id' => '2338',
			'name' => 'The specific alteration of histone methylation profiles by DZNep during early zebrafish development.',
			'authors' => 'Ostrup O, Reiner AH, Aleström P, Collas P',
			'description' => '<p>Early embryo development constitutes a unique opportunity to study acquisition of epigenetic marks, including histone methylation. This study investigates the in vivo function and specificity of 3-deazaneplanocin A (DZNep), a promising anti-cancer drug that targets polycomb complex genes. One- to two-cell stage embryos were cultured with DZNep, and subsequently evaluated at the post-mid blastula transition stage for H3K27me3, H3K4me3 and H3K9me3 occupancy and enrichment at promoters using ChIP-chip microarrays. DZNep affected promoter enrichment of H3K27me3 and H3K9me3, whereas H3K4me3 remained stable. Interestingly, DZNep induced a loss of H3K27me3 and H3K9me3 from a substantial number of promoters but did not prevent de novo acquisition of these marks on others, indicating gene-specific targeting of its action. Loss/gain of H3K27me3 on promoters did not result in changes in gene expression levels until 24h post-fertilization. In contrast, genes gaining H3K9me3 displayed strong and constant down-regulation upon DZNep treatment. H3K9me3 enrichment on these gene promoters was observed not only in the proximal area as expected, but also over the transcription start site. Altered H3K9me3 profiles were associated with severe neuronal and cranial phenotypes at day 4-5 post-fertilization. Thus, DZNep was shown to affect enrichment patterns of H3K27me3 and H3K9me3 at promoters in a gene-specific manner.</p>',
			'date' => '2014-09-28',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25260724',
			'doi' => '',
			'modified' => '2016-04-08 09:43:32',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 217 => array(
			'id' => '2228',
			'name' => 'Interrogation of allelic chromatin states in human cells by high-density ChIP-genotyping.',
			'authors' => 'Light N, Adoue V, Ge B, Chen SH, Kwan T, Pastinen T',
			'description' => 'Allele-specific (AS) assessment of chromatin has the potential to elucidate specific cis-regulatory mechanisms, which are predicted to underlie the majority of the known genetic associations to complex disease. However, development of chromatin landscapes at allelic resolution has been challenging since sites of variable signal strength require substantial read depths not commonly applied in sequencing based approaches. In this study, we addressed this by performing parallel analyses of input DNA and chromatin immunoprecipitates (ChIP) on high-density Illumina genotyping arrays. Allele-specificity for the histone modifications H3K4me1, H3K4me3, H3K27ac, H3K27me3, and H3K36me3 was assessed using ChIP samples generated from 14 lymphoblast and 6 fibroblast cell lines. AS-ChIP SNPs were combined into domains and validated using high-confidence ChIP-seq sites. We observed characteristic patterns of allelic-imbalance for each histone-modification around allele-specifically expressed transcripts. Notably, we found H3K4me1 to be significantly anti-correlated with allelic expression (AE) at transcription start sites, indicating H3K4me1 allelic imbalance as a marker of AE. We also found that allelic chromatin domains exhibit population and cell-type specificity as well as heritability within trios. Finally, we observed that a subset of allelic chromatin domains is regulated by DNase I-sensitive quantitative trait loci and that these domains are significantly enriched for genome-wide association studies hits, with autoimmune disease associated SNPs specifically enriched in lymphoblasts. This study provides the first genome-wide maps of allelic-imbalance for five histone marks. Our results provide new insights into the role of chromatin in cis-regulation and highlight the need for high-depth sequencing in ChIP-seq studies along with the need to improve allele-specificity of ChIP-enrichment.',
			'date' => '2014-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25055051',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 218 => array(
			'id' => '2298',
			'name' => 'Differences among brain tumor stem cell types and fetal neural stem cells in focal regions of histone modifications and DNA methylation, broad regions of modifications, and bivalent promoters.',
			'authors' => 'Yoo S, Bieda MC',
			'description' => 'BACKGROUND: Aberrational epigenetic marks are believed to play a major role in establishing the abnormal features of cancer cells. Rational use and development of drugs aimed at epigenetic processes requires an understanding of the range, extent, and roles of epigenetic reprogramming in cancer cells. Using ChIP-chip and MeDIP-chip approaches, we localized well-established and prevalent epigenetic marks (H3K27me3, H3K4me3, H3K9me3, DNA methylation) on a genome scale in several lines of putative glioma stem cells (brain tumor stem cells, BTSCs) and, for comparison, normal human fetal neural stem cells (fNSCs). RESULTS: We determined a substantial "core" set of promoters possessing each mark in every surveyed BTSC cell type, which largely overlapped the corresponding fNSC sets. However, there was substantial diversity among cell types in mark localization. We observed large differences among cell types in total number of H3K9me3+ positive promoters and peaks and in broad modifications (defined as >50 kb peak length) for H3K27me3 and, to a lesser extent, H3K9me3. We verified that a change in a broad modification affected gene expression of CACNG7. We detected large numbers of bivalent promoters, but most bivalent promoters did not display direct overlap of contrasting epigenetic marks, but rather occupied nearby regions of the proximal promoter. There were significant differences in the sets of promoters bearing bivalent marks in the different cell types and few consistent differences between fNSCs and BTSCs. CONCLUSIONS: Overall, our "core set" data establishes sets of potential therapeutic targets, but the diversity in sets of sites and broad modifications among cell types underscores the need to carefully consider BTSC subtype variation in epigenetic therapy. Our results point toward substantial differences among cell types in the activity of the production/maintenance systems for H3K9me3 and for broad regions of modification (H3K27me3 or H3K9me3). Finally, the unexpected diversity in bivalent promoter sets among these multipotent cells indicates that bivalent promoters may play complex roles in the overall biology of these cells. These results provide key information for forming the basis for future rational drug therapy aimed at epigenetic processes in these cells.',
			'date' => '2014-08-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25163646',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 219 => array(
			'id' => '2201',
			'name' => 'Long Noncoding RNA TARID Directs Demethylation and Activation of the Tumor Suppressor TCF21 via GADD45A.',
			'authors' => 'Arab K, Park YJ, Lindroth AM, Schäfer A, Oakes C, Weichenhan D, Lukanova A, Lundin E, Risch A, Meister M, Dienemann H, Dyckhoff G, Herold-Mende C, Grummt I, Niehrs C, Plass C',
			'description' => 'DNA methylation is a dynamic and reversible process that governs gene expression during development and disease. Several examples of active DNA demethylation have been documented, involving genome-wide and gene-specific DNA demethylation. How demethylating enzymes are targeted to specific genomic loci remains largely unknown. We show that an antisense lncRNA, termed TARID (for TCF21 antisense RNA inducing demethylation), activates TCF21 expression by inducing promoter demethylation. TARID interacts with both the TCF21 promoter and GADD45A (growth arrest and DNA-damage-inducible, alpha), a regulator of DNA demethylation. GADD45A in turn recruits thymine-DNA glycosylase for base excision repair-mediated demethylation involving oxidation of 5-methylcytosine to 5-hydroxymethylcytosine in the TCF21 promoter by ten-eleven translocation methylcytosine dioxygenase proteins. The results reveal a function of lncRNAs, serving as a genomic address label for GADD45A-mediated demethylation of specific target genes.',
			'date' => '2014-08-21',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25087872',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 220 => array(
			'id' => '2063',
			'name' => 'Identification of a large protein network involved in epigenetic transmission in replicating DNA of embryonic stem cells.',
			'authors' => 'Aranda S, Rutishauser D, Ernfors P',
			'description' => 'Pluripotency of embryonic stem cells (ESCs) is maintained by transcriptional activities and chromatin modifying complexes highly organized within the chromatin. Although much effort has been focused on identifying genome-binding sites, little is known on their dynamic association with chromatin across cell divisions. Here, we used a modified version of the iPOND (isolation of proteins at nascent DNA) technology to identify a large protein network enriched at nascent DNA in ESCs. This comprehensive and unbiased proteomic characterization in ESCs reveals that, in addition to the core replication machinery, proteins relevant for pluripotency of ESCs are present at DNA replication sites. In particular, we show that the chromatin remodeller HDAC1-NuRD complex is enriched at nascent DNA. Interestingly, an acute block of HDAC1 in ESCs leads to increased acetylation of histone H3 lysine 9 at nascent DNA together with a concomitant loss of methylation. Consistently, in contrast to what has been described in tumour cell lines, these chromatin marks were found to be stable during cell cycle progression of ESCs. Our results are therefore compatible with a rapid deacetylation-coupled methylation mechanism during the replication of DNA in ESCs that may participate in the preservation of pluripotency of ESCs during replication.',
			'date' => '2014-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24852249',
			'doi' => '',
			'modified' => '2015-07-24 15:39:02',
			'created' => '2015-07-24 15:39:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 221 => array(
			'id' => '2107',
			'name' => 'Seminoma and embryonal carcinoma footprints identified by analysis of integrated genome-wide epigenetic and expression profiles of germ cell cancer cell lines.',
			'authors' => 'van der Zwan YG, Rijlaarsdam MA, Rossello FJ, Notini AJ, de Boer S, Watkins DN, Gillis AJ, Dorssers LC, White SJ, Looijenga LH',
			'description' => 'BACKGROUND: Originating from Primordial Germ Cells/gonocytes and developing via a precursor lesion called Carcinoma In Situ (CIS), Germ Cell Cancers (GCC) are the most common cancer in young men, subdivided in seminoma (SE) and non-seminoma (NS). During physiological germ cell formation/maturation, epigenetic processes guard homeostasis by regulating the accessibility of the DNA to facilitate transcription. Epigenetic deregulation through genetic and environmental parameters (i.e. genvironment) could disrupt embryonic germ cell development, resulting in delayed or blocked maturation. This potentially facilitates the formation of CIS and progression to invasive GCC. Therefore, determining the epigenetic and functional genomic landscape in GCC cell lines could provide insight into the pathophysiology and etiology of GCC and provide guidance for targeted functional experiments. RESULTS: This study aims at identifying epigenetic footprints in SE and EC cell lines in genome-wide profiles by studying the interaction between gene expression, DNA CpG methylation and histone modifications, and their function in the pathophysiology and etiology of GCC. Two well characterized GCC-derived cell lines were compared, one representative for SE (TCam-2) and the other for EC (NCCIT). Data were acquired using the Illumina HumanHT-12-v4 (gene expression) and HumanMethylation450 BeadChip (methylation) microarrays as well as ChIP-sequencing (activating histone modifications (H3K4me3, H3K27ac)). Results indicate known germ cell markers not only to be differentiating between SE and NS at the expression level, but also in the epigenetic landscape. CONCLUSION: The overall similarity between TCam-2/NCCIT support an erased embryonic germ cell arrested in early gonadal development as common cell of origin although the exact developmental stage from which the tumor cells are derived might differ. Indeed, subtle difference in the (integrated) epigenetic and expression profiles indicate TCam-2 to exhibit a more germ cell-like profile, whereas NCCIT shows a more pluripotent phenotype. The results provide insight into the functional genome in GCC cell lines.',
			'date' => '2014-06-02',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24887064',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 222 => array(
			'id' => '2054',
			'name' => 'Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer',
			'authors' => 'Zecchini V, Madhu B, Russell R, Pértega-Gomes N, Warren A, Gaude E, Borlido J, Stark R, Ireland-Zecchini H, Rao R, Scott H, Boren J, Massie C, Asim M, Brindle K, Griffiths J, Frezza C, Neal DE, Mills IG',
			'description' => 'Tumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. Hypoxia-inducible factor 1A (HIF1A) is a major regulator of this process, but its activation under normoxic conditions, termed pseudohypoxia, is not well documented. Here, using an integrative approach combining the first genome-wide mapping of chromatin binding for an endocytic adaptor, ARRB1, both in vitro and in vivo with gene expression profiling, we demonstrate that nuclear ARRB1 contributes to this metabolic shift in prostate cancer cells via regulation of HIF1A transcriptional activity under normoxic conditions through regulation of succinate dehydrogenase A (SDHA) and fumarate hydratase (FH) expression. ARRB1-induced pseudohypoxia may facilitate adaptation of cancer cells to growth in the harsh conditions that are frequently encountered within solid tumours. Our study is the first example of an endocytic adaptor protein regulating metabolic pathways. It implicates ARRB1 as a potential tumour promoter in prostate cancer and highlights the importance of metabolic alterations in prostate cancer.',
			'date' => '2014-05-16',
			'pmid' => 'http://onlinelibrary.wiley.com/doi/10.15252/embj.201386874/full',
			'doi' => '',
			'modified' => '2015-07-24 15:39:02',
			'created' => '2015-07-24 15:39:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 223 => array(
			'id' => '1891',
			'name' => 'Stage-specific control of early B cell development by the transcription factor Ikaros.',
			'authors' => 'Schwickert TA, Tagoh H, Gültekin S, Dakic A, Axelsson E, Minnich M, Ebert A, Werner B, Roth M, Cimmino L, Dickins RA, Zuber J, Jaritz M, Busslinger M',
			'description' => 'The transcription factor Ikaros is an essential regulator of lymphopoiesis. Here we studied its B cell-specific function by conditional inactivation of the gene encoding Ikaros (Ikzf1) in pro-B cells. B cell development was arrested at an aberrant 'pro-B cell' stage characterized by increased cell adhesion and loss of signaling via the pre-B cell signaling complex (pre-BCR). Ikaros activated genes encoding signal transducers of the pre-BCR and repressed genes involved in the downregulation of pre-BCR signaling and upregulation of the integrin signaling pathway. Unexpectedly, derepression of expression of the transcription factor Aiolos did not compensate for the loss of Ikaros in pro-B cells. Ikaros induced or suppressed active chromatin at regulatory elements of activated or repressed target genes. Notably, binding of Ikaros and expression of its target genes were dynamically regulated at distinct stages of early B lymphopoiesis.',
			'date' => '2014-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24509509',
			'doi' => '',
			'modified' => '2015-07-24 15:39:02',
			'created' => '2015-07-24 15:39:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 224 => array(
			'id' => '1793',
			'name' => 'A novel microscopy-based high-throughput screening method to identify proteins that regulate global histone modification levels.',
			'authors' => 'Baas R, Lelieveld D, van Teeffelen H, Lijnzaad P, Castelijns B, van Schaik FM, Vermeulen M, Egan DA, Timmers HT, de Graaf P',
			'description' => '<p>Posttranslational modifications of histones play an important role in the regulation of gene expression and chromatin structure in eukaryotes. The balance between chromatin factors depositing (writers) and removing (erasers) histone marks regulates the steady-state levels of chromatin modifications. Here we describe a novel microscopy-based screening method to identify proteins that regulate histone modification levels in a high-throughput fashion. We named our method CROSS, for Chromatin Regulation Ontology SiRNA Screening. CROSS is based on an siRNA library targeting the expression of 529 proteins involved in chromatin regulation. As a proof of principle, we used CROSS to identify chromatin factors involved in histone H3 methylation on either lysine-4 or lysine-27. Furthermore, we show that CROSS can be used to identify chromatin factors that affect growth in cancer cell lines. Taken together, CROSS is a powerful method to identify the writers and erasers of novel and known chromatin marks and facilitates the identification of drugs targeting epigenetic modifications.</p>',
			'date' => '2014-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24334265',
			'doi' => '',
			'modified' => '2016-04-12 09:46:40',
			'created' => '2015-07-24 15:39:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 225 => array(
			'id' => '1783',
			'name' => 'Pan-histone demethylase inhibitors simultaneously targeting Jumonji C and lysine-specific demethylases display high anticancer activities.',
			'authors' => 'Rotili D, Tomassi S, Conte M, Benedetti R, Tortorici M, Ciossani G, Valente S, Marrocco B, Labella D, Novellino E, Mattevi A, Altucci L, Tumber A, Yapp C, King ON, Hopkinson RJ, Kawamura A, Schofield CJ, Mai A',
			'description' => 'In prostate cancer, two different types of histone lysine demethylases (KDM), LSD1/KDM1 and JMJD2/KDM4, are coexpressed and colocalize with the androgen receptor. We designed and synthesized hybrid LSD1/JmjC or "pan-KDM" inhibitors 1-6 by coupling the skeleton of tranylcypromine 7, a known LSD1 inhibitor, with 4-carboxy-4'-carbomethoxy-2,2'-bipyridine 8 or 5-carboxy-8-hydroxyquinoline 9, two 2-oxoglutarate competitive templates developed for JmjC inhibition. Hybrid compounds 1-6 are able to simultaneously target both KDM families and have been validated as potential antitumor agents in cells. Among them, 2 and 3 increase H3K4 and H3K9 methylation levels in cells and cause growth arrest and substantial apoptosis in LNCaP prostate and HCT116 colon cancer cells. When tested in noncancer mesenchymal progenitor (MePR) cells, 2 and 3 induced little and no apoptosis, respectively, thus showing cancer-selective inhibiting action.',
			'date' => '2014-01-09',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24325601',
			'doi' => '',
			'modified' => '2015-07-24 15:39:01',
			'created' => '2015-07-24 15:39:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 226 => array(
			'id' => '1727',
			'name' => 'Interplay between active chromatin marks and RNA-directed DNA methylation in Arabidopsis thaliana.',
			'authors' => 'Greenberg MV, Deleris A, Hale CJ, Liu A, Feng S, Jacobsen SE',
			'description' => 'DNA methylation is an epigenetic mark that is associated with transcriptional repression of transposable elements and protein-coding genes. Conversely, transcriptionally active regulatory regions are strongly correlated with histone 3 lysine 4 di- and trimethylation (H3K4m2/m3). We previously showed that Arabidopsis thaliana plants with mutations in the H3K4m2/m3 demethylase JUMONJI 14 (JMJ14) exhibit a mild reduction in RNA-directed DNA methylation (RdDM) that is associated with an increase in H3K4m2/m3 levels. To determine whether this incomplete RdDM reduction was the result of redundancy with other demethylases, we examined the genetic interaction of JMJ14 with another class of H3K4 demethylases: lysine-specific demethylase 1-like 1 and lysine-specific demethylase 1-like 2 (LDL1 and LDL2). Genome-wide DNA methylation analyses reveal that both families cooperate to maintain RdDM patterns. ChIP-seq experiments show that regions that exhibit an observable DNA methylation decrease are co-incidental with increases in H3K4m2/m3. Interestingly, the impact on DNA methylation was stronger at DNA-methylated regions adjacent to H3K4m2/m3-marked protein-coding genes, suggesting that the activity of H3K4 demethylases may be particularly crucial to prevent spreading of active epigenetic marks. Finally, RNA sequencing analyses indicate that at RdDM targets, the increase of H3K4m2/m3 is not generally associated with transcriptional de-repression. This suggests that the histone mark itself--not transcription--impacts the extent of RdDM.',
			'date' => '2013-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24244201',
			'doi' => '',
			'modified' => '2015-07-24 15:39:01',
			'created' => '2015-07-24 15:39:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 227 => array(
			'id' => '1581',
			'name' => 'A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis.',
			'authors' => 'Kollmann K, Heller G, Schneckenleithner C, Warsch W, Scheicher R, Ott RG, Schäfer M, Fajmann S, Schlederer M, Schiefer AI, Reichart U, Mayerhofer M, Hoeller C, Zöchbauer-Müller S, Kerjaschki D, Bock C, Kenner L, Hoefler G, Freissmuth M, Green AR, Moriggl ',
			'description' => 'In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185(BCR-ABL+) B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16(INK4a) and the pro-angiogenic factor VEGF-A. This function is independent of CDK6's kinase activity. High CDK6 expression thus suppresses proliferation by upregulating p16(INK4a), providing an internal safeguard. However, in the absence of p16(INK4a), CDK6 can exert its full tumor-promoting function by enhancing proliferation and stimulating angiogenesis. The finding that CDK6 connects cell-cycle progression to angiogenesis confirms CDK6's central role in hematopoietic malignancies and could underlie the selection pressure to upregulate CDK6 and silence p16(INK4a).',
			'date' => '2013-08-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23948297',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 228 => array(
			'id' => '1512',
			'name' => 'Disease-Related Growth Factor and Embryonic Signaling Pathways Modulate an Enhancer of TCF21 Expression at the 6q23.2 Coronary Heart Disease Locus.',
			'authors' => 'Miller CL, Anderson DR, Kundu RK, Raiesdana A, Nürnberg ST, Diaz R, Cheng K, Leeper NJ, Chen CH, Chang IS, Schadt EE, Hsiung CA, Assimes TL, Quertermous T',
			'description' => 'Coronary heart disease (CHD) is the leading cause of mortality in both developed and developing countries worldwide. Genome-wide association studies (GWAS) have now identified 46 independent susceptibility loci for CHD, however, the biological and disease-relevant mechanisms for these associations remain elusive. The large-scale meta-analysis of GWAS recently identified in Caucasians a CHD-associated locus at chromosome 6q23.2, a region containing the transcription factor TCF21 gene. TCF21 (Capsulin/Pod1/Epicardin) is a member of the basic-helix-loop-helix (bHLH) transcription factor family, and regulates cell fate decisions and differentiation in the developing coronary vasculature. Herein, we characterize a cis-regulatory mechanism by which the lead polymorphism rs12190287 disrupts an atypical activator protein 1 (AP-1) element, as demonstrated by allele-specific transcriptional regulation, transcription factor binding, and chromatin organization, leading to altered TCF21 expression. Further, this element is shown to mediate signaling through platelet-derived growth factor receptor beta (PDGFR-β) and Wilms tumor 1 (WT1) pathways. A second disease allele identified in East Asians also appears to disrupt an AP-1-like element. Thus, both disease-related growth factor and embryonic signaling pathways may regulate CHD risk through two independent alleles at TCF21.',
			'date' => '2013-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23874238',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 229 => array(
			'id' => '1465',
			'name' => 'Bivalent chromatin marks developmental regulatory genes in the mouse embryonic germline in vivo.',
			'authors' => 'Sachs M, Onodera C, Blaschke K, Ebata KT, Song JS, Ramalho-Santos M',
			'description' => 'Developmental regulatory genes have both activating (H3K4me3) and repressive (H3K27me3) histone modifications in embryonic stem cells (ESCs). This bivalent configuration is thought to maintain lineage commitment programs in a poised state. However, establishing physiological relevance has been complicated by the high number of cells required for chromatin immunoprecipitation (ChIP). We developed a low-cell-number chromatin immunoprecipitation (low-cell ChIP) protocol to investigate the chromatin of mouse primordial germ cells (PGCs). Genome-wide analysis of embryonic day 11.5 (E11.5) PGCs revealed H3K4me3/H3K27me3 bivalent domains highly enriched at developmental regulatory genes in a manner remarkably similar to ESCs. Developmental regulators remain bivalent and transcriptionally silent through the initiation of sexual differentiation at E13.5. We also identified >2,500 "orphan" bivalent domains that are distal to known genes and expressed in a tissue-specific manner but silent in PGCs. Our results demonstrate the existence of bivalent domains in the germline and raise the possibility that the somatic program is continuously maintained as bivalent, potentially imparting transgenerational epigenetic inheritance.',
			'date' => '2013-06-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23727241',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 230 => array(
			'id' => '1458',
			'name' => 'Integrative analysis of deep sequencing data identifies estrogen receptor early response genes and links ATAD3B to poor survival in breast cancer.',
			'authors' => 'Ovaska K, Matarese F, Grote K, Charapitsa I, Cervera A, Liu C, Reid G, Seifert M, Stunnenberg HG, Hautaniemi S',
			'description' => 'Identification of responsive genes to an extra-cellular cue enables characterization of pathophysiologically crucial biological processes. Deep sequencing technologies provide a powerful means to identify responsive genes, which creates a need for computational methods able to analyze dynamic and multi-level deep sequencing data. To answer this need we introduce here a data-driven algorithm, SPINLONG, which is designed to search for genes that match the user-defined hypotheses or models. SPINLONG is applicable to various experimental setups measuring several molecular markers in parallel. To demonstrate the SPINLONG approach, we analyzed ChIP-seq data reporting PolII, estrogen receptor α (ERα), H3K4me3 and H2A.Z occupancy at five time points in the MCF-7 breast cancer cell line after estradiol stimulus. We obtained 777 ERa early responsive genes and compared the biological functions of the genes having ERα binding within 20 kb of the transcription start site (TSS) to genes without such binding site. Our results show that the non-genomic action of ERα via the MAPK pathway, instead of direct ERa binding, may be responsible for early cell responses to ERα activation. Our results also indicate that the ERα responsive genes triggered by the genomic pathway are transcribed faster than those without ERα binding sites. The survival analysis of the 777 ERα responsive genes with 150 primary breast cancer tumors and in two independent validation cohorts indicated the ATAD3B gene, which does not have ERα binding site within 20 kb of its TSS, to be significantly associated with poor patient survival.',
			'date' => '2013-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23818839',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 231 => array(
			'id' => '1425',
			'name' => 'Expression of a large LINE-1-driven antisense RNA is linked to epigenetic silencing of the metastasis suppressor gene TFPI-2 in cancer.',
			'authors' => 'Cruickshanks HA, Vafadar-Isfahani N, Dunican DS, Lee A, Sproul D, Lund JN, Meehan RR, Tufarelli C',
			'description' => 'LINE-1 retrotransposons are abundant repetitive elements of viral origin, which in normal cells are kept quiescent through epigenetic mechanisms. Activation of LINE-1 occurs frequently in cancer and can enable LINE-1 mobilization but also has retrotransposition-independent consequences. We previously reported that in cancer, aberrantly active LINE-1 promoters can drive transcription of flanking unique sequences giving rise to LINE-1 chimeric transcripts (LCTs). Here, we show that one such LCT, LCT13, is a large transcript (>300 kb) running antisense to the metastasis-suppressor gene TFPI-2. We have modelled antisense RNA expression at TFPI-2 in transgenic mouse embryonic stem (ES) cells and demonstrate that antisense RNA induces silencing and deposition of repressive histone modifications implying a causal link. Consistent with this, LCT13 expression in breast and colon cancer cell lines is associated with silencing and repressive chromatin at TFPI-2. Furthermore, we detected LCT13 transcripts in 56% of colorectal tumours exhibiting reduced TFPI-2 expression. Our findings implicate activation of LINE-1 elements in subsequent epigenetic remodelling of surrounding genes, thus hinting a novel retrotransposition-independent role for LINE-1 elements in malignancy.',
			'date' => '2013-05-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23703216',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 232 => array(
			'id' => '1389',
			'name' => 'The developmental epigenomics toolbox: ChIP-seq and MethylCap-seq profiling of early zebrafish embryos.',
			'authors' => 'Bogdanović O, Fernández-Miñán A, Tena JJ, de la Calle-Mustienes E, Gómez-Skarmeta JL',
			'description' => 'Genome-wide profiling of DNA methylation and histone modifications answered many questions as to how the genes are regulated on a global scale and what their epigenetic makeup is. Yet, little is known about the function of these marks during early vertebrate embryogenesis. Here we provide detailed protocols for ChIP-seq and MethylCap-seq procedures applied to zebrafish (Danio rerio) embryonic material at four developmental stages. As a proof of principle, we have profiled on a global scale a number of post-translational histone modifications including H3K4me1, H3K4me3 and H3K27ac. We demonstrate that these marks are dynamic during early development and that such developmental transitions can be detected by ChIP-seq. In addition, we applied MethylCap-seq to show that developmentally-regulated DNA methylation remodeling can be detected by such a procedure. Our MethylCap-seq data concur with previous DNA methylation studies of early zebrafish development rendering this method highly suitable for the global assessment of DNA methylation in early vertebrate embryos.',
			'date' => '2013-04-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23624103',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 233 => array(
			'id' => '1285',
			'name' => 'Genome-wide analysis of LXRα activation reveals new transcriptional networks in human atherosclerotic foam cells.',
			'authors' => 'Feldmann R, Fischer C, Kodelja V, Behrens S, Haas S, Vingron M, Timmermann B, Geikowski A, Sauer S',
			'description' => 'Increased physiological levels of oxysterols are major risk factors for developing atherosclerosis and cardiovascular disease. Lipid-loaded macrophages, termed foam cells, are important during the early development of atherosclerotic plaques. To pursue the hypothesis that ligand-based modulation of the nuclear receptor LXRα is crucial for cell homeostasis during atherosclerotic processes, we analysed genome-wide the action of LXRα in foam cells and macrophages. By integrating chromatin immunoprecipitation-sequencing (ChIP-seq) and gene expression profile analyses, we generated a highly stringent set of 186 LXRα target genes. Treatment with the nanomolar-binding ligand T0901317 and subsequent auto-regulatory LXRα activation resulted in sequence-dependent sharpening of the genome-binding patterns of LXRα. LXRα-binding loci that correlated with differential gene expression revealed 32 novel target genes with potential beneficial effects, which in part explained the implications of disease-associated genetic variation data. These observations identified highly integrated LXRα ligand-dependent transcriptional networks, including the APOE/C1/C4/C2-gene cluster, which contribute to the reversal of cholesterol efflux and the dampening of inflammation processes in foam cells to prevent atherogenesis.',
			'date' => '2013-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23393188',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 234 => array(
			'id' => '1304',
			'name' => 'Regulation of transcription through acetylation of H3K122 on the lateral surface of the histone octamer.',
			'authors' => 'Tropberger P, Pott S, Keller C, Kamieniarz-Gdula K, Caron M, Richter F, Li G, Mittler G, Liu ET, Bühler M, Margueron R, Schneider R',
			'description' => 'Histone modifications are key regulators of chromatin function. However, little is known to what extent histone modifications can directly impact on chromatin. Here, we address how a modification within the globular domain of histones regulates chromatin function. We demonstrate that H3K122ac can be sufficient to stimulate transcription and that mutation of H3K122 impairs transcriptional activation, which we attribute to a direct effect of H3K122ac on histone-DNA binding. In line with this, we find that H3K122ac defines genome-wide genetic elements and chromatin features associated with active transcription. Furthermore, H3K122ac is catalyzed by the coactivators p300/CBP and can be induced by nuclear hormone receptor signaling. Collectively, this suggests that transcriptional regulators elicit their effects not only via signaling to histone tails but also via direct structural perturbation of nucleosomes by directing acetylation to their lateral surface.',
			'date' => '2013-02-14',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23415232',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 235 => array(
			'id' => '1497',
			'name' => 'Histone lysine trimethylation or acetylation can be modulated by phytoestrogen, estrogen or anti-HDAC in breast cancer cell lines.',
			'authors' => 'Dagdemir A, Durif J, Ngollo M, Bignon YJ, Bernard-Gallon D',
			'description' => '<p>AIM: The isoflavones genistein, daidzein and equol (daidzein metabolite) have been reported to interact with epigenetic modifications, specifically hypermethylation of tumor suppressor genes. The objective of this study was to analyze and understand the mechanisms by which phytoestrogens act on chromatin in breast cancer cell lines. MATERIALS &amp; METHODS: Two breast cancer cell lines, MCF-7 and MDA-MB 231, were treated with genistein (18.5 &micro;M), daidzein (78.5 &micro;M), equol (12.8 &micro;M), 17&beta;-estradiol (10 nM) and suberoylanilide hydroxamic acid (1 &micro;M) for 48 h. A control with untreated cells was performed. 17&beta;-estradiol and an anti-HDAC were used to compare their actions with phytoestrogens. The chromatin immunoprecipitation coupled with quantitative PCR was used to follow soy phytoestrogen effects on H3 and H4 histones on H3K27me3, H3K9me3, H3K4me3, H4K8ac and H3K4ac marks, and we selected six genes (EZH2, BRCA1, ER&alpha;, ER&beta;, SRC3 and P300) for analysis. RESULTS: Soy phytoestrogens induced a decrease in trimethylated marks and an increase in acetylating marks studied at six selected genes. CONCLUSION: We demonstrated that soy phytoestrogens tend to modify transcription through the demethylation and acetylation of histones in breast cancer cell lines.</p>',
			'date' => '2013-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23414320',
			'doi' => '',
			'modified' => '2016-05-03 12:17:35',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 236 => array(
			'id' => '1267',
			'name' => 'Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA.',
			'authors' => 'Fadloun A, Le Gras S, Jost B, Ziegler-Birling C, Takahashi H, Gorab E, Carninci P, Torres-Padilla ME',
			'description' => 'How a more plastic chromatin state is maintained and reversed during development is unknown. Heterochromatin-mediated silencing of repetitive elements occurs in differentiated cells. Here, we used repetitive elements, including retrotransposons, as model loci to address how and when heterochromatin forms during development. RNA sequencing throughout early mouse embryogenesis revealed that repetitive-element expression is dynamic and stage specific, with most repetitive elements becoming repressed before implantation. We show that LINE-1 and IAP retrotransposons become reactivated from both parental genomes after fertilization. Chromatin immunoprecipitation for H3K4me3 and H3K9me3 in 2- and 8-cell embryos indicates that their developmental silencing follows loss of activating marks rather than acquisition of conventional heterochromatic marks. Furthermore, short LINE-1 RNAs regulate LINE-1 transcription in vivo. Our data indicate that reprogramming after mammalian fertilization comprises a robust transcriptional activation of retrotransposons and that repetitive elements are initially regulated through RNA.',
			'date' => '2013-01-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23353788',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 237 => array(
			'id' => '1195',
			'name' => 'Ezh2 maintains a key phase of muscle satellite cell expansion but does not regulate terminal differentiation.',
			'authors' => 'Woodhouse S, Pugazhendhi D, Brien P, Pell JM.',
			'description' => 'Tissue generation and repair requires a stepwise process of cell fate restriction to ensure adult stem cells differentiate in a timely and appropriate manner. A crucial role has been implicated for Polycomb-group (PcG) proteins and the H3K27me3 repressive histone mark, in coordinating the transcriptional programmes necessary for this process, but the targets and developmental timing for this repression remain unclear. To address these questions, we generated novel genome-wide maps of H3K27me3 and H3K4me3 in freshly isolated muscle stem cells. These data, together with the analysis of two conditional Ezh2-null mouse strains, identified a critical proliferation phase in which Ezh2 activity is essential. Mice lacking Ezh2 in satellite cells exhibited decreased muscle growth, severely impaired regeneration and reduced stem cell number, due to a profound failure of the proliferative progenitor population to expand. Surprisingly, deletion of Ezh2 after the onset of terminal differentiation did not impede muscle repair or homeostasis. Using these knockout models, RNA-Seq and the ChIP-Seq datasets we show that Ezh2 does not regulate the muscle differentiation process in vivo. These results emphasise the lineage and cell type specific functions for Ezh2 and the Polycomb repressive complex 2.',
			'date' => '2012-11-30',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/23203812',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 238 => array(
			'id' => '1162',
			'name' => 'Limitations and possibilities of low cell number ChIP-seq.',
			'authors' => 'Gilfillan GD, Hughes T, Sheng Y, Hjorthaug HS, Straub T, Gervin K, Harris JR, Undlien DE, Lyle R',
			'description' => 'ABSTRACT: BACKGROUND: Chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq) offers high resolution, genome-wide analysis of DNA-protein interactions. However, current standard methods require abundant starting material in the range of 1--20 million cells per immunoprecipitation, and remain a bottleneck to the acquisition of biologically relevant epigenetic data. Using a ChIP-seq protocol optimised for low cell numbers (down to 100,000 cells / IP), we examined the performance of the ChIP-seq technique on a series of decreasing cell numbers. RESULTS: We present an enhanced native ChIP-seq method tailored to low cell numbers that represents a 200-fold reduction in input requirements over existing protocols. The protocol was tested over a range of starting cell numbers covering three orders of magnitude, enabling determination of the lower limit of the technique. At low input cell numbers, increased levels of unmapped and duplicate reads reduce the number of unique reads generated, and can drive up sequencing costs and affect sensitivity if ChIP is attempted from too few cells. CONCLUSIONS: The optimised method presented here considerably reduces the input requirements for performing native ChIP-seq. It extends the applicability of the technique to isolated primary cells and rare cell populations (e.g. biobank samples, stem cells), and in many cases will alleviate the need for cell culture and any associated alteration of epigenetic marks. However, this study highlights a challenge inherent to ChIP-seq from low cell numbers: as cell input numbers fall, levels of unmapped sequence reads and PCR-generated duplicate reads rise. We discuss a number of solutions to overcome the effects of reducing cell number that may aid further improvements to ChIP performance.',
			'date' => '2012-11-21',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23171294',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 239 => array(
			'id' => '1143',
			'name' => 'Protein Group Modification and Synergy in the SUMO Pathway as Exemplified in DNA Repair.',
			'authors' => 'Psakhye I, Jentsch S',
			'description' => 'Protein modification by SUMO affects a wide range of protein substrates. Surprisingly, although SUMO pathway mutants display strong phenotypes, the function of individual SUMO modifications is often enigmatic, and SUMOylation-defective mutants commonly lack notable phenotypes. Here, we use DNA double-strand break repair as an example and show that DNA damage triggers a SUMOylation wave, leading to simultaneous multisite modifications of several repair proteins of the same pathway. Catalyzed by a DNA-bound SUMO ligase and triggered by single-stranded DNA, SUMOylation stabilizes physical interactions between the proteins. Notably, only wholesale elimination of SUMOylation of several repair proteins significantly affects the homologous recombination pathway by considerably slowing down DNA repair. Thus, SUMO acts synergistically on several proteins, and individual modifications only add up to efficient repair. We propose that SUMOylation may thus often target a protein group rather than individual proteins, whereas localized modification enzymes and highly specific triggers ensure specificity.',
			'date' => '2012-11-09',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23122649',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 240 => array(
			'id' => '1137',
			'name' => 'IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer.',
			'authors' => 'Baird AM, Leonard J, Naicker KM, Kilmartin L, O'Byrne KJ, Gray SG',
			'description' => 'BACKGROUND: IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC). METHODS: RT-PCR and chromatin immunopreciptiation (ChIP) were used to examine the levels, epigenetic regulation and effects of various drugs (DNA methyltransferase inhibitors, Histone Deacetylase inhibitors and Gemcitabine) on IL-23 expression in NSCLC cells and macrophages. The effects of recombinant IL-23 protein on cellular proliferation were examined by MTT assay. Statistical analysis consisted of Student's t-test or one way analysis of variance (ANOVA) where groups in the experiment were three or more. RESULTS: In a cohort of primary non-small cell lung cancer (NSCLC) tumours, IL-23A expression was significantly elevated in patient tumour samples (p<0.05). IL-23A expression is epigenetically regulated through histone post-translational modifications and DNA CpG methylation. Gemcitabine, a chemotherapy drug indicated for first-line treatment of NSCLC also induced IL-23A expression. Recombinant IL-23 significantly increased cellular proliferation in NSCLC cell lines. CONCLUSIONS: These results may therefore have important implications for treating NSCLC patients with either epigenetic targeted therapies or Gemcitabine.',
			'date' => '2012-10-29',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23116756',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 241 => array(
			'id' => '1078',
			'name' => 'New partners in regulation of gene expression: the enhancer of trithorax and polycomb corto interacts with methylated ribosomal protein l12 via its chromodomain.',
			'authors' => 'Coléno-Costes A, Jang SM, de Vanssay A, Rougeot J, Bouceba T, Randsholt NB, Gibert JM, Le Crom S, Mouchel-Vielh E, Bloyer S, Peronnet F',
			'description' => 'Chromodomains are found in many regulators of chromatin structure, and most of them recognize methylated lysines on histones. Here, we investigate the role of the Drosophila melanogaster protein Corto's chromodomain. The Enhancer of Trithorax and Polycomb Corto is involved in both silencing and activation of gene expression. Over-expression of the Corto chromodomain (CortoCD) in transgenic flies shows that it is a chromatin-targeting module, critical for Corto function. Unexpectedly, mass spectrometry analysis reveals that polypeptides pulled down by CortoCD from nuclear extracts correspond to ribosomal proteins. Furthermore, real-time interaction analyses demonstrate that CortoCD binds with high affinity RPL12 tri-methylated on lysine 3. Corto and RPL12 co-localize with active epigenetic marks on polytene chromosomes, suggesting that both are involved in fine-tuning transcription of genes in open chromatin. RNA-seq based transcriptomes of wing imaginal discs over-expressing either CortoCD or RPL12 reveal that both factors deregulate large sets of common genes, which are enriched in heat-response and ribosomal protein genes, suggesting that they could be implicated in dynamic coordination of ribosome biogenesis. Chromatin immunoprecipitation experiments show that Corto and RPL12 bind hsp70 and are similarly recruited on gene body after heat shock. Hence, Corto and RPL12 could be involved together in regulation of gene transcription. We discuss whether pseudo-ribosomal complexes composed of various ribosomal proteins might participate in regulation of gene expression in connection with chromatin regulators.',
			'date' => '2012-10-11',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23071455',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 242 => array(
			'id' => '831',
			'name' => 'Extensive promoter hypermethylation and hypomethylation is associated with aberrant microRNA expression in chronic lymphocytic leukemia.',
			'authors' => 'Baer C, Claus R, Frenzel LP, Zucknick M, Park YJ, Gu L, Weichenhan D, Fischer M, Pallasch CP, Herpel E, Rehli M, Byrd JC, Wendtner CM, Plass C',
			'description' => '<p>Dysregulated microRNA (miRNA) expression contributes to the pathogenesis of hematopoietic malignancies, including chronic lymphocytic leukemia (CLL). However, an understanding of the mechanisms that cause aberrant miRNA transcriptional control is lacking. In this study, we comprehensively investigated the role and extent of miRNA epigenetic regulation in CLL. Genome-wide profiling performed on 24 CLL and 10 healthy B cell samples revealed global DNA methylation patterns upstream of miRNA sequences that distinguished malignant from healthy cells and identified putative miRNA promoters. Integration of DNA methylation and miRNA promoter data led to the identification of 128 recurrent miRNA targets for aberrant promoter DNA methylation. DNA hypomethylation accounted for over 60% of all aberrant promoter-associated DNA methylation in CLL, and promoter DNA hypomethylation was restricted to well-defined regions. Individual hyper- and hypomethylated promoters allowed discrimination of CLL samples from healthy controls. Promoter DNA methylation patterns were confirmed in an independent patient cohort, with eleven miRNAs consistently demonstrating an inverse correlation between DNA methylation status and expression level. Together, our findings characterize the role of epigenetic changes in the regulation of miRNA transcription and create a repository of disease-specific promoter regions that may provide additional insights into the pathogenesis of CLL.</p>',
			'date' => '2012-06-18',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22710432',
			'doi' => '',
			'modified' => '2016-05-03 12:14:21',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 243 => array(
			'id' => '1204',
			'name' => 'The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells.',
			'authors' => 'Karpiuk O, Najafova Z, Kramer F, Hennion M, Galonska C, König A, Snaidero N, Vogel T, Shchebet A, Begus-Nahrmann Y, Kassem M, Simons M, Shcherbata H, Beissbarth T, Johnsen SA',
			'description' => 'Extensive changes in posttranslational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly understood. We show that histone H2B monoubiquitination (H2Bub1) significantly increases during differentiation of human mesenchymal stem cells (hMSCs) and various lineage-committed precursor cells and in diverse organisms. Furthermore, the H2B ubiquitin ligase RNF40 is required for the induction of differentiation markers and transcriptional reprogramming of hMSCs. This function is dependent upon CDK9 and the WAC adaptor protein, which are required for H2B monoubiquitination. Finally, we show that RNF40 is required for the resolution of the H3K4me3/H3K27me3 bivalent poised state on lineage-specific genes during the transition from an inactive to an active chromatin conformation. Thus, these data indicate that H2Bub1 is required for maintaining multipotency of hMSCs and plays a central role in controlling stem cell differentiation.',
			'date' => '2012-06-08',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22681891',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 244 => array(
			'id' => '792',
			'name' => 'Intronic RNAs mediate EZH2 regulation of epigenetic targets.',
			'authors' => 'Guil S, Soler M, Portela A, Carrère J, Fonalleras E, Gómez A, Villanueva A, Esteller M',
			'description' => 'Epigenetic deregulation at a number of genomic loci is one of the hallmarks of cancer. A role for some RNA molecules in guiding repressive polycomb complex PRC2 to specific chromatin regions has been proposed. Here we use an in vivo cross-linking method to detect and identify direct PRC2-RNA interactions in human cancer cells, revealing a number of intronic RNA sequences capable of binding to the core component EZH2 and regulating the transcriptional output of its genomic counterpart. Overexpression of EZH2-bound intronic RNA for the H3K4 methyltransferase gene SMYD3 is concomitant with an increase in EZH2 occupancy throughout the corresponding genomic fragment and is sufficient to reduce levels of the endogenous transcript and protein, resulting in reduced growth capability in cell culture and animal models. These findings reveal the role of intronic RNAs in fine-tuning gene expression regulation at the level of transcriptional control.',
			'date' => '2012-06-03',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22659877',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 245 => array(
			'id' => '732',
			'name' => 'The transcriptional and epigenomic foundations of ground state pluripotency.',
			'authors' => 'Marks H, Kalkan T, Menafra R, Denissov S, Jones K, Hofemeister H, Nichols J, Kranz A, Francis Stewart A, Smith A, Stunnenberg HG',
			'description' => 'Mouse embryonic stem (ES) cells grown in serum exhibit greater heterogeneity in morphology and expression of pluripotency factors than ES cells cultured in defined medium with inhibitors of two kinases (Mek and GSK3), a condition known as "2i" postulated to establish a naive ground state. We show that the transcriptome and epigenome profiles of serum- and 2i-grown ES cells are distinct. 2i-treated cells exhibit lower expression of lineage-affiliated genes, reduced prevalence at promoters of the repressive histone modification H3K27me3, and fewer bivalent domains, which are thought to mark genes poised for either up- or downregulation. Nonetheless, serum- and 2i-grown ES cells have similar differentiation potential. Precocious transcription of developmental genes in 2i is restrained by RNA polymerase II promoter-proximal pausing. These findings suggest that transcriptional potentiation and a permissive chromatin context characterize the ground state and that exit from it may not require a metastable intermediate or multilineage priming.',
			'date' => '2012-04-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22541430',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 246 => array(
			'id' => '456',
			'name' => 'Control of ground-state pluripotency by allelic regulation of Nanog.',
			'authors' => 'Miyanari Y, Torres-Padilla ME',
			'description' => 'Pluripotency is established through genome-wide reprogramming during mammalian pre-implantation development, resulting in the formation of the naive epiblast. Reprogramming involves both the resetting of epigenetic marks and the activation of pluripotent-cell-specific genes such as Nanog and Oct4 (also known as Pou5f1). The tight regulation of these genes is crucial for reprogramming, but the mechanisms that regulate their expression in vivo have not been uncovered. Here we show that Nanog-but not Oct4-is monoallelically expressed in early pre-implantation embryos. Nanog then undergoes a progressive switch to biallelic expression during the transition towards ground-state pluripotency in the naive epiblast of the late blastocyst. Embryonic stem (ES) cells grown in leukaemia inhibitory factor (LIF) and serum express Nanog mainly monoallelically and show asynchronous replication of the Nanog locus, a feature of monoallelically expressed genes, but ES cells activate both alleles when cultured under 2i conditions, which mimic the pluripotent ground state in vitro. Live-cell imaging with reporter ES cells confirmed the allelic expression of Nanog and revealed allelic switching. The allelic expression of Nanog is regulated through the fibroblast growth factor-extracellular signal-regulated kinase signalling pathway, and it is accompanied by chromatin changes at the proximal promoter but occurs independently of DNA methylation. Nanog-heterozygous blastocysts have fewer inner-cell-mass derivatives and delayed primitive endoderm formation, indicating a role for the biallelic expression of Nanog in the timely maturation of the inner cell mass into a fully reprogrammed pluripotent epiblast. We suggest that the tight regulation of Nanog dose at the chromosome level is necessary for the acquisition of ground-state pluripotency during development. Our data highlight an unexpected role for allelic expression in controlling the dose of pluripotency factors in vivo, adding an extra level to the regulation of reprogramming.',
			'date' => '2012-02-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22327294',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 247 => array(
			'id' => '919',
			'name' => 'Prepatterning of developmental gene expression by modified histones before zygotic genome activation.',
			'authors' => 'Lindeman LC, Andersen IS, Reiner AH, Li N, Aanes H, Østrup O, Winata C, Mathavan S, Müller F, Aleström P, Collas P',
			'description' => 'A hallmark of anamniote vertebrate development is a window of embryonic transcription-independent cell divisions before onset of zygotic genome activation (ZGA). Chromatin determinants of ZGA are unexplored; however, marking of developmental genes by modified histones in sperm suggests a predictive role of histone marks for ZGA. In zebrafish, pre-ZGA development for ten cell cycles provides an opportunity to examine whether genomic enrichment in modified histones is present before initiation of transcription. By profiling histone H3 trimethylation on all zebrafish promoters before and after ZGA, we demonstrate here an epigenetic prepatterning of developmental gene expression. This involves pre-ZGA marking of transcriptionally inactive genes involved in homeostatic and developmental regulation by permissive H3K4me3 with or without repressive H3K9me3 or H3K27me3. Our data suggest that histone modifications are instructive for the developmental gene expression program.',
			'date' => '2011-12-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22137762',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 248 => array(
			'id' => '913',
			'name' => 'IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF.',
			'authors' => 'Baird AM, Gray SG, O'Byrne KJ',
			'description' => 'BACKGROUND: IL-20 is a pleiotrophic member of the IL-10 family and plays a role in skin biology and the development of haematopoietic cells. Recently, IL-20 has been demonstrated to have potential anti-angiogenic effects in non-small cell lung cancer (NSCLC) by down regulating COX-2. METHODS: The expression of IL-20 and its cognate receptors (IL-20RA/B and IL-22R1) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of this family was examined in normal bronchial epithelial and NSCLC cell lines. Furthermore, the effect of IL-20 on VEGF family members was examined. RESULTS: The expression of IL-20 and its receptors are frequently dysregulated in NSCLC. IL-20RB mRNA was significantly elevated in NSCLC tumours (p<0.01). Protein levels of the receptors, IL-20RB and IL-22R1, were significantly increased (p<0.01) in the tumours of NSCLC patients. IL-20 and its receptors were found to be epigenetically regulated through histone post-translational modifications and DNA CpG residue methylation. In addition, treatment with recombinant IL-20 resulted in decreased expression of the VEGF family members at the mRNA level. CONCLUSIONS: This family of genes are dysregulated in NSCLC and are subject to epigenetic regulation. Whilst the anti-angiogenic properties of IL-20 require further clarification, targeting this family via epigenetic means may be a viable therapeutic option in lung cancer treatment.',
			'date' => '2011-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21565488',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 249 => array(
			'id' => '637',
			'name' => 'H3.5 is a novel hominid-specific histone H3 variant that is specifically expressed in the seminiferous tubules of human testes.',
			'authors' => 'Schenk R, Jenke A, Zilbauer M, Wirth S, Postberg J',
			'description' => 'The incorporation of histone variants into chromatin plays an important role for the establishment of particular chromatin states. Six human histone H3 variants are known to date, not counting CenH3 variants: H3.1, H3.2, H3.3 and the testis-specific H3.1t as well as the recently described variants H3.X and H3.Y. We report the discovery of H3.5, a novel non-CenH3 histone H3 variant. H3.5 is encoded on human chromosome 12p11.21 and probably evolved in a common ancestor of all recent great apes (Hominidae) as a consequence of H3F3B gene duplication by retrotransposition. H3.5 mRNA is specifically expressed in seminiferous tubules of human testis. Interestingly, H3.5 has two exact copies of ARKST motifs adjacent to lysine-9 or lysine-27, and lysine-79 is replaced by asparagine. In the Hek293 cell line, ectopically expressed H3.5 is assembled into chromatin and targeted by PTM. H3.5 preferentially colocalizes with euchromatin, and it is associated with actively transcribed genes and can replace an essential function of RNAi-depleted H3.3 in cell growth.',
			'date' => '2011-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21274551',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 250 => array(
			'id' => '256',
			'name' => 'Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer',
			'authors' => 'O'Byrne KJ, Baird AM, Kilmartin L, Leonard J, Sacevich C, Gray SG.',
			'description' => 'Due to their inherently hypoxic environment, cancer cells often resort to glycolysis, or the anaerobic breakdown of glucose to form ATP to provide for their energy needs, known as the Warburg effect. At the same time, overexpression of the insulin receptor in non-small cell lung cancer (NSCLC) is associated with an increased risk of metastasis and decreased survival. The uptake of glucose into cells is carried out via glucose transporters or GLUTs. Of these, GLUT-4 is essential for insulin-stimulated glucose uptake. Following treatment with the epigenetic targeting agents histone deacetylase inhibitors (HDACi), GLUT-3 and GLUT-4 expression were found to be induced in NSCLC cell lines, with minimal responses in transformed normal human bronchial epithelial cells (HBECs). Similar results for GLUT-4 were observed in cells derived from liver, muscle, kidney and pre-adipocytes. Bioinformatic analysis of the promoter for GLUT-4 indicates that it may also be regulated by several chromatin binding factors or complexes including CTCF, SP1 and SMYD3. Chromatin immunoprecipitation studies demonstrate that the promoter for GLUT-4 is dynamically remodeled in response to HDACi. Overall, these results may have value within the clinical setting as (a) it may be possible to use this to enhance fluorodeoxyglucose (18F) positron emission tomography (FDG-PET) imaging sensitivity; (b) it may be possible to target NSCLC through the use of HDACi and insulin mediated uptake of the metabolic targeting drugs such as 2-deoxyglucose (2-DG); or (c) enhance or sensitize NSCLC to chemotherapy. ',
			'date' => '2011-03-25',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/24212773',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 251 => array(
			'id' => '265',
			'name' => 'Characterisation of genome-wide PLZF/RARA target genes.',
			'authors' => 'Spicuglia S, Vincent-Fabert C, Benoukraf T, Tibéri G, Saurin AJ, Zacarias-Cabeza J, Grimwade D, Mills K, Calmels B, Bertucci F, Sieweke M, Ferrier P, Duprez E',
			'description' => 'The PLZF/RARA fusion protein generated by the t(11;17)(q23;q21) translocation in acute promyelocytic leukaemia (APL) is believed to act as an oncogenic transcriptional regulator recruiting epigenetic factors to genes important for its transforming potential. However, molecular mechanisms associated with PLZF/RARA-dependent leukaemogenesis still remain unclear.We searched for specific PLZF/RARA target genes by ChIP-on-chip in the haematopoietic cell line U937 conditionally expressing PLZF/RARA. By comparing bound regions found in U937 cells expressing endogenous PLZF with PLZF/RARA-induced U937 cells, we isolated specific PLZF/RARA target gene promoters. We next analysed gene expression profiles of our identified target genes in PLZF/RARA APL patients and analysed DNA sequences and epigenetic modification at PLZF/RARA binding sites. We identify 413 specific PLZF/RARA target genes including a number encoding transcription factors involved in the regulation of haematopoiesis. Among these genes, 22 were significantly down regulated in primary PLZF/RARA APL cells. In addition, repressed PLZF/RARA target genes were associated with increased levels of H3K27me3 and decreased levels of H3K9K14ac. Finally, sequence analysis of PLZF/RARA bound sequences reveals the presence of both consensus and degenerated RAREs as well as enrichment for tissue-specific transcription factor motifs, highlighting the complexity of targeting fusion protein to chromatin. Our study suggests that PLZF/RARA directly targets genes important for haematopoietic development and supports the notion that PLZF/RARA acts mainly as an epigenetic regulator of its direct target genes.',
			'date' => '2011-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21949697',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 252 => array(
			'id' => '585',
			'name' => 'Tiling histone H3 lysine 4 and 27 methylation in zebrafish using high-density microarrays.',
			'authors' => 'Lindeman LC, Reiner AH, Mathavan S, Aleström P, Collas P',
			'description' => 'BACKGROUND: Uncovering epigenetic states by chromatin immunoprecipitation and microarray hybridization (ChIP-chip) has significantly contributed to the understanding of gene regulation at the genome-scale level. Many studies have been carried out in mice and humans; however limited high-resolution information exists to date for non-mammalian vertebrate species. PRINCIPAL FINDINGS: We report a 2.1-million feature high-resolution Nimblegen tiling microarray for ChIP-chip interrogations of epigenetic states in zebrafish (Danio rerio). The array covers 251 megabases of the genome at 92 base-pair resolution. It includes ∼15 kb of upstream regulatory sequences encompassing all RefSeq promoters, and over 5 kb in the 5' end of coding regions. We identify with high reproducibility, in a fibroblast cell line, promoters enriched in H3K4me3, H3K27me3 or co-enriched in both modifications. ChIP-qPCR and sequential ChIP experiments validate the ChIP-chip data and support the co-enrichment of trimethylated H3K4 and H3K27 on a subset of genes. H3K4me3- and/or H3K27me3-enriched genes are associated with distinct transcriptional status and are linked to distinct functional categories. CONCLUSIONS: We have designed and validated for the scientific community a comprehensive high-resolution tiling microarray for investigations of epigenetic states in zebrafish, a widely used developmental and disease model organism.',
			'date' => '2010-12-20',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21187971',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 253 => array(
			'id' => '413',
			'name' => 'Autonomous silencing of the imprinted Cdkn1c gene in stem cells',
			'authors' => 'Wood MD, Hiura H, Tunster S, Arima T, Shin J-H, Higgins M, John1 RM',
			'description' => 'Parent-of-origin specific expression of imprinted genes relies on the differential DNA methylation of specific genomic regions. Differentially methylated regions (DMRs) acquire DNA methylation either during gametogenesis (primary DMR) or after fertilization when allele-specific expression is established (secondary DMR). Little is known about the function of these secondary DMRs. We investigated the DMR spanning Cdkn1c in mouse embryonic stem cells, androgenetic stem cells and embryonic germ stem cells. In all cases, expression of Cdkn1c was appropriately repressed in in vitro differentiated cells. However, stem cells failed to de novo methylate the silenced gene even after sustained differentiation. In the absence of maintained DNA methylation (Dnmt1-/-), Cdkn1c escapes silencing demonstrating the requirement for DNA methylation in long term silencing in vivo. We propose that post-fertilization differential methylation reflects the importance of retaining single gene dosage of a subset of imprinted loci in the adult.',
			'date' => '2010-04-01',
			'pmid' => 'http://www.pubmed/20372090',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 254 => array(
			'id' => '69',
			'name' => 'The histone variant macroH2A is an epigenetic regulator of key developmental genes.',
			'authors' => 'Buschbeck M, Uribesalgo I, Wibowo I, Rué P, Martin D, Gutierrez A, Morey L, Guigó R, López-Schier H, Di Croce L',
			'description' => 'The histone variants macroH2A1 and macroH2A2 are associated with X chromosome inactivation in female mammals. However, the physiological function of macroH2A proteins on autosomes is poorly understood. Microarray-based analysis in human male pluripotent cells uncovered occupancy of both macroH2A variants at many genes encoding key regulators of development and cell fate decisions. On these genes, the presence of macroH2A1+2 is a repressive mark that overlaps locally and functionally with Polycomb repressive complex 2. We demonstrate that macroH2A1+2 contribute to the fine-tuning of temporal activation of HOXA cluster genes during neuronal differentiation. Furthermore, elimination of macroH2A2 function in zebrafish embryos produced severe but specific phenotypes. Taken together, our data demonstrate that macroH2A variants constitute an important epigenetic mark involved in the concerted regulation of gene expression programs during cellular differentiation and vertebrate development.',
			'date' => '2009-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/19734898',
			'doi' => '',
			'modified' => '2015-07-24 15:38:56',
			'created' => '2015-07-24 15:38:56',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 255 => array(
			'id' => '117',
			'name' => 'High-resolution analysis of epigenetic changes associated with X inactivation.',
			'authors' => 'Marks H, Chow JC, Denissov S, Françoijs KJ, Brockdorff N, Heard E, Stunnenberg HG',
			'description' => 'Differentiation of female murine ES cells triggers silencing of one X chromosome through X-chromosome inactivation (XCI). Immunofluorescence studies showed that soon after Xist RNA coating the inactive X (Xi) undergoes many heterochromatic changes, including the acquisition of H3K27me3. However, the mechanisms that lead to the establishment of heterochromatin remain unclear. We first analyze chromatin changes by ChIP-chip, as well as RNA expression, around the X-inactivation center (Xic) in female and male ES cells, and their day 4 and 10 differentiated derivatives. A dynamic epigenetic landscape is observed within the Xic locus. Tsix repression is accompanied by deposition of H3K27me3 at its promoter during differentiation of both female and male cells. However, only in female cells does an active epigenetic landscape emerge at the Xist locus, concomitant with high Xist expression. Several regions within and around the Xic show unsuspected chromatin changes, and we define a series of unusual loci containing highly enriched H3K27me3. Genome-wide ChIP-seq analyses show a female-specific quantitative increase of H3K27me3 across the X chromosome as XCI proceeds in differentiating female ES cells. Using female ES cells with nonrandom XCI and polymorphic X chromosomes, we demonstrate that this increase is specific to the Xi by allele-specific SNP mapping of the ChIP-seq tags. H3K27me3 becomes evenly associated with the Xi in a chromosome-wide fashion. A selective and robust increase of H3K27me3 and concomitant decrease in H3K4me3 is observed over active genes. This indicates that deposition of H3K27me3 during XCI is tightly associated with the act of silencing of individual genes across the Xi.',
			'date' => '2009-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/19581487',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 256 => array(
			'id' => '1435',
			'name' => 'H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming.',
			'authors' => 'Daujat S, Weiss T, Mohn F, Lange UC, Ziegler-Birling C, Zeissler U, Lappe M, Schübeler D, Torres-Padilla ME, Schneider R',
			'description' => 'Histone modifications are central to the regulation of all DNA-dependent processes. Lys64 of histone H3 (H3K64) lies within the globular domain at a structurally important position. We identify trimethylation of H3K64 (H3K64me3) as a modification that is enriched at pericentric heterochromatin and associated with repeat sequences and transcriptionally inactive genomic regions. We show that this new mark is dynamic during the two main epigenetic reprogramming events in mammals. In primordial germ cells, H3K64me3 is present at the time of specification, but it disappears transiently during reprogramming. In early mouse embryos, it is inherited exclusively maternally; subsequently, the modification is rapidly removed, suggesting an important role for H3K64me3 turnover in development. Taken together, our findings establish H3K64me3 as a previously uncharacterized histone modification that is preferentially localized to repressive chromatin. We hypothesize that H3K64me3 helps to 'secure' nucleosomes, and perhaps the surrounding chromatin, in an appropriately repressed state during development.',
			'date' => '2009-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/19561610',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 257 => array(
			'id' => '2600',
			'name' => 'Epigenetic-Mediated Downregulation of μ-Protocadherin in Colorectal Tumours',
			'authors' => 'Bujko M, Kober P, Statkiewicz M, Mikula M, Ligaj M, Zwierzchowski L, Ostrowski J, Siedlecki JA',
			'description' => 'Carcinogenesis involves altered cellular interaction and tissue morphology that partly arise from aberrant expression of cadherins. Mucin-like protocadherin is implicated in intercellular adhesion and its expression was found decreased in colorectal cancer (CRC). This study has compared MUPCDH (CDHR5) expression in three key types of colorectal tissue samples, for normal mucosa, adenoma, and carcinoma. A gradual decrease of mRNA levels and protein expression was observed in progressive stages of colorectal carcinogenesis which are consistent with reports of increasing MUPCDH 5′ promoter region DNA methylation. High MUPCDH methylation was also observed in HCT116 and SW480 CRC cell lines that revealed low gene expression levels compared to COLO205 and HT29 cell lines which lack DNA methylation at the MUPCDH locus. Furthermore, HCT116 and SW480 showed lower levels of RNA polymerase II and histone H3 lysine 4 trimethylation (H3K4me3) as well as higher levels of H3K27 trimethylation at the MUPCDH promoter. MUPCDH expression was however restored in HCT116 and SW480 cells in the presence of 5-Aza-2′-deoxycytidine (DNA methyltransferase inhibitor). Results indicate that μ-protocadherin downregulation occurs during early stages of tumourigenesis and progression into the adenoma-carcinoma sequence. Epigenetic mechanisms are involved in this silencing.',
			'date' => '0000-00-00',
			'pmid' => 'http://www.hindawi.com/journals/grp/2015/317093/',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 258 => array(
			'id' => '783',
			'name' => 'Analysis of active chromatin modifications in early mammalian embryos reveals uncoupling of H2A.Z acetylation and H3K36 trimethylation from embryonic genome activation',
			'authors' => 'Bošković A, Bender A, Gall L, Ziegler-Birling C, Beaujean N, Torres-Padilla ME',
			'description' => 'Early embryonic development is characterized by dramatic changes in cell potency and chromatin organization. The role of histone variants in the context of chromatin remodeling during embryogenesis remains under investigated. In particular, the nuclear distribution of the histone variant H2A.Z and its modifications have not been examined. Here we investigated the dynamics of acetylation of H2A.Z and two other active chromatin marks, H3K9ac and H3K36me3, throughout murine and bovine pre-implantation development. We show that H2A.Z distribution is dynamic during the earliest stages of mouse development, with protein levels significantly varying across stages and lowest at the 2-cell stage. When present, H2A.Z localizes preferentially to euchromatin at all stages analyzed. H2A.Z is acetylated in preimplantation blastomeres and is preferentially localized to euchromatin, in line with the known role of H2A.Zac in transcriptional activation. Interestingly, however, H2A.Zac is undetectable in mouse embryos at the 2-cell stage, the time of major embryonic genome activation (EGA). Similarly, H3K36me3 is present exclusively in the maternal chromatin immediately after fertilization but becomes undetectable in interphase nuclei at the 2-cell stage, suggesting uncoupling of these active marks with global embryonic transcription activation. In bovine embryos, which undergo EGA at the 8-cell stage, H2A.Zac can be detected in zygotes, 4-, 8- and 16-cell stage embryos as well as in blastocysts, indicating that the dynamics of H2A.Zac is not conserved in mammals. In contrast, H3K36me3 displays mostly undetectable and heterogeneous localization pattern throughout bovine pre-implantation development. Thus, our results suggest that ‘canonical’ active chromatin marks exhibit a dynamic behavior in embryonic nuclei, which is both stage- and speciesspecific. We hypothesize that chromatin of early embryonic nuclei is subject to fine-tuning through differential acquisition of histone marks, allowing for proper chromatin remodeling and developmental progression in a species-specific fashion.',
			'date' => '0000-00-00',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/22647320',
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			'description' => '<p>I have used Diagenode's antibodies for my ChIP&ndash;qPCR experiments in HK-2 cells. The antibodies performed very well in our experiments with specific signal, and good signal to noise ratio in the promoter of the gapdh gene.</p>
<center><img src="../../img/categories/antibodies/H3K4me3-hk2.png" /></center>
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong> ChIP assays were performed using human HK-2 cells, the Diagenode antibody against H3K4me3 (Cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with standard fixation and sonication protocol, using sheared chromatin from 4 million cells. A total amount of 4 ug of antibody were used per ChIP experiment, normal mouse IgG (4 &mu;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). These results are in accordance with the observation that trimethylation of K4 at histone H3 is associated with the promoters of active genes.</small></p>',
			'author' => 'Claudio Cappelli PhD. Post-Doc. Investigator, Laboratory of Molecular Pathology, Institute of Biochemestry and Microbiology, University Austral of Chile, about H3K4me3 polyclonal antibody Premium, 50 μl size.',
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<p>Diagenode provides not only very good products for research but also an excellent customer support.</p>',
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			'description' => '<p><span>I work with Diagenode&rsquo;s <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> and shear the DNA on the <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a> for the last year and I have to say that these two products saved my PhD project! Some time ago, our well-established ChIP protocol suddenly stopped to work and after long time of figuring out the reason, we invested into <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a>. </span><span>I am very satisfied from the way it works, plus it&rsquo;s super quiet! Combining the sonicator with the <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> we finally got things working.&nbsp;</span><span>I have also decided to try the <a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns">Microplex Library Prep kit</a>, which is amazing. I have been working with other kits and I find this one efficient and very easy to use. </span><span>Recently, I have tested one of the epigenetics antibody (<a href="../products/search?keyword=H3K4me3">H3K4me3</a>) and it works very well on the plant tissue, together with the ChIP-seq kit and Bioruptor. </span></p>
<p>Thanks Diagenode for saving my PhD!</p>',
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		'id' => '2173',
		'antibody_id' => '115',
		'name' => 'H3K4me3 Antibody',
		'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
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<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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$testimonials = '<blockquote><p>I have used Diagenode's antibodies for my ChIP&ndash;qPCR experiments in HK-2 cells. The antibodies performed very well in our experiments with specific signal, and good signal to noise ratio in the promoter of the gapdh gene.</p>
<center><img src="../../img/categories/antibodies/H3K4me3-hk2.png" /></center>
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong> ChIP assays were performed using human HK-2 cells, the Diagenode antibody against H3K4me3 (Cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with standard fixation and sonication protocol, using sheared chromatin from 4 million cells. A total amount of 4 ug of antibody were used per ChIP experiment, normal mouse IgG (4 &mu;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). These results are in accordance with the observation that trimethylation of K4 at histone H3 is associated with the promoters of active genes.</small></p><cite>Claudio Cappelli PhD. Post-Doc. Investigator, Laboratory of Molecular Pathology, Institute of Biochemestry and Microbiology, University Austral of Chile, about H3K4me3 polyclonal antibody Premium, 50 μl size.</cite></blockquote>
<blockquote><p>In life sciences, epigenetics is nowadays the most rapid developing field with new astonishing discoveries made every day. To keep pace with this field, we are in need of reliable tools to foster our research - tools Diagenode provides us with. From <strong>antibodies</strong> to <strong>automated solutions</strong> - all from one source and with robust support. Antibodies used in our lab: H3K27me3 polyclonal antibody &ndash; Premium, H3K4me3 polyclonal antibody &ndash; Premium, H3K9me3 polyclonal antibody &ndash; Premium, H3K4me1 polyclonal antibody &ndash; Premium, CTCF polyclonal antibody &ndash; Classic, Rabbit IgG.</p><cite>Dr. Florian Uhle, Dept. of Anesthesiology, Heidelberg University Hospital, Germany</cite></blockquote>
<blockquote><p>We use the <strong>Bioruptor</strong> sonication device and the antibody against the histone modification H3K4me3 in our lab. The Bioruptor device is used for the shearing of chromatin in ChIP-Seq experiments and for generation of protein lysates (whole cell extracts). Thanks to the Bioruptor device we achieve excellent and reproducible results in both applications. The <strong>H3K4me3 antibody</strong> is used in our ChIP-Seq experiments as well as Western Blotting. With this antibody we are able to generate highly enriched ChIP-Seq samples with extremely low background. In Western Blot we can detect one specific, strong band with the H3K4me3 antibody.</p>
<p>Diagenode provides not only very good products for research but also an excellent customer support.</p><cite>Dr Lora Dimitrova, Charité-Universitätsmedizin Berlin, Germany</cite></blockquote>
<blockquote><p><span>I work with Diagenode&rsquo;s <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> and shear the DNA on the <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a> for the last year and I have to say that these two products saved my PhD project! Some time ago, our well-established ChIP protocol suddenly stopped to work and after long time of figuring out the reason, we invested into <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a>. </span><span>I am very satisfied from the way it works, plus it&rsquo;s super quiet! Combining the sonicator with the <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> we finally got things working.&nbsp;</span><span>I have also decided to try the <a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns">Microplex Library Prep kit</a>, which is amazing. I have been working with other kits and I find this one efficient and very easy to use. </span><span>Recently, I have tested one of the epigenetics antibody (<a href="../products/search?keyword=H3K4me3">H3K4me3</a>) and it works very well on the plant tissue, together with the ChIP-seq kit and Bioruptor. </span></p>
<p>Thanks Diagenode for saving my PhD!</p><cite>Kamila Kwasniewska, Plant Developmental Genetics, Smurfit Institute, Trinity College, Dublin</cite></blockquote>
<blockquote><p>I am working with the <a href="../p/true-microchip-kit-x16-16-rxns">True MicroChIP</a> &amp; <a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns">Microplex Library Preparation</a> Kits and several histone modification antibodies like H3K27ac, H3K4me3, H3K36me3, and H3K27me3.&nbsp;I got always very good and reproducible results for my ChIP-seq experiments.</p><cite>Andrea Thiesen, ZMB, Developmental Biology, Prof. Dr. Andrea Vortkamp´s lab, University Duisburg-Essen, Germany</cite></blockquote>
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	'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
</div>
</div>
<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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	'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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</div>
<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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<p>Read more:</p>
<p><a href="https://www.diagenode.com/en/categories/cutandtag">Products for CUT&amp;Tag assay</a></p>
<p><a href="https://www.diagenode.com/en/pages/cut-and-tag">Performance of Diagenode's antibodies in CUT&amp;Tag</a></p>
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<p><a href="https://www.diagenode.com/en/categories/cutandtag">Products for CUT&amp;Tag assay</a></p>
<p><a href="https://www.diagenode.com/en/pages/cut-and-tag">Performance of Diagenode's antibodies in CUT&amp;Tag</a></p>
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<p><a href="https://www.diagenode.com/en/categories/cutandtag">Products for CUT&amp;Tag assay</a></p>
<p><a href="https://www.diagenode.com/en/pages/cut-and-tag">Performance of Diagenode's antibodies in CUT&amp;Tag</a></p>
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	'authors' => 'Bošković A, Bender A, Gall L, Ziegler-Birling C, Beaujean N, Torres-Padilla ME',
	'description' => 'Early embryonic development is characterized by dramatic changes in cell potency and chromatin organization. The role of histone variants in the context of chromatin remodeling during embryogenesis remains under investigated. In particular, the nuclear distribution of the histone variant H2A.Z and its modifications have not been examined. Here we investigated the dynamics of acetylation of H2A.Z and two other active chromatin marks, H3K9ac and H3K36me3, throughout murine and bovine pre-implantation development. We show that H2A.Z distribution is dynamic during the earliest stages of mouse development, with protein levels significantly varying across stages and lowest at the 2-cell stage. When present, H2A.Z localizes preferentially to euchromatin at all stages analyzed. H2A.Z is acetylated in preimplantation blastomeres and is preferentially localized to euchromatin, in line with the known role of H2A.Zac in transcriptional activation. Interestingly, however, H2A.Zac is undetectable in mouse embryos at the 2-cell stage, the time of major embryonic genome activation (EGA). Similarly, H3K36me3 is present exclusively in the maternal chromatin immediately after fertilization but becomes undetectable in interphase nuclei at the 2-cell stage, suggesting uncoupling of these active marks with global embryonic transcription activation. In bovine embryos, which undergo EGA at the 8-cell stage, H2A.Zac can be detected in zygotes, 4-, 8- and 16-cell stage embryos as well as in blastocysts, indicating that the dynamics of H2A.Zac is not conserved in mammals. In contrast, H3K36me3 displays mostly undetectable and heterogeneous localization pattern throughout bovine pre-implantation development. Thus, our results suggest that ‘canonical’ active chromatin marks exhibit a dynamic behavior in embryonic nuclei, which is both stage- and speciesspecific. We hypothesize that chromatin of early embryonic nuclei is subject to fine-tuning through differential acquisition of histone marks, allowing for proper chromatin remodeling and developmental progression in a species-specific fashion.',
	'date' => '0000-00-00',
	'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/22647320',
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			'antibody_id' => '115',
			'name' => 'H3K4me3 polyclonal antibody  (sample size)',
			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone H3 containing the trimethylated lysine 4 (H3K4me3), using a KLH-conjugated synthetic peptide.</span></p>
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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</div>
<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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			'description' => 'Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called “histone code”. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Methylation of histone H3K4 is associated with activation of gene transcription.',
			'clonality' => '',
			'isotype' => '',
			'lot' => 'A8034D',
			'concentration' => '1.3 &micro;g/&micro;l',
			'reactivity' => 'Human, mouse, pig, zebrafish, trout, Daphnia, Arabidopsis, rice, tomato, maize, poplar, silena latifolia, wide range expected.',
			'type' => 'Polyclonal, <strong>ChIP grade, ChIP-seq grade</strong>',
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<thead>
<tr>
<th>Applications</th>
<th>Suggested dilution</th>
<th>References</th>
</tr>
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<tbody>
<tr>
<td>ChIP/ChIP-seq<sup>*</sup></td>
<td><span style="font-family: Helvetica;">0.5 - 1&nbsp;&micro;g</span></td>
<td>Fig 1, 2</td>
</tr>
<tr>
<td>CUT&amp;Tag</td>
<td>0.5 &micro;g</td>
<td>Fig 3</td>
</tr>
<tr>
<td>ELISA</td>
<td>1:2,000</td>
<td>Fig 4</td>
</tr>
<tr>
<td>Dot Blotting</td>
<td>1:1000</td>
<td>Fig 5</td>
</tr>
<tr>
<td>Western Blotting</td>
<td>1:1,000</td>
<td>Fig 6</td>
</tr>
<tr>
<td>Immunofluorescence</td>
<td>1:200</td>
<td>Fig 7</td>
</tr>
</tbody>
</table>
<p></p>
<p><small><sup>*</sup> Please note that the optimal antibody amount per IP should be determined by the end-user. We recommend testing 0.5-5 &micro;g per IP.</small></p>',
			'storage_conditions' => 'Store at -20°C; for long storage, store at -80°C. Avoid multiple freeze-thaw cycles.',
			'storage_buffer' => 'PBS containing 0.05% azide and 0.05% ProClin 300.',
			'precautions' => 'This product is for research use only. Not for use in diagnostic or therapeutic procedures.',
			'uniprot_acc' => '',
			'slug' => '',
			'meta_keywords' => '',
			'meta_description' => '',
			'modified' => '2022-08-17 11:57:06',
			'created' => '0000-00-00 00:00:00',
			'select_label' => '115 - H3K4me3 polyclonal antibody (A8034D - 1.3 &micro;g/&micro;l - Human, mouse, pig, zebrafish, trout, Daphnia, Arabidopsis, rice, tomato, maize, poplar, silena latifolia, wide range expected. - Affinity purified polyclonal antibody. - Rabbit)'
		),
		'Slave' => array(),
		'Group' => array(
			'Group' => array(
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			),
			'Master' => array(
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			'Product' => array(
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		),
		'Related' => array(
			(int) 0 => array(
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			(int) 1 => array(
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			),
			(int) 2 => array(
				[maximum depth reached]
			),
			(int) 3 => array(
				[maximum depth reached]
			),
			(int) 4 => array(
				[maximum depth reached]
			),
			(int) 5 => array(
				[maximum depth reached]
			),
			(int) 6 => array(
				[maximum depth reached]
			),
			(int) 7 => array(
				[maximum depth reached]
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		),
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			(int) 2 => array(
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			(int) 3 => array(
				[maximum depth reached]
			),
			(int) 4 => array(
				[maximum depth reached]
			),
			(int) 5 => array(
				[maximum depth reached]
			),
			(int) 6 => array(
				[maximum depth reached]
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			(int) 7 => array(
				[maximum depth reached]
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		),
		'Category' => array(
			(int) 0 => array(
				[maximum depth reached]
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			(int) 1 => array(
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			(int) 2 => array(
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			(int) 3 => array(
				[maximum depth reached]
			),
			(int) 4 => array(
				[maximum depth reached]
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			(int) 5 => array(
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			(int) 1 => array(
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			(int) 2 => array(
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		),
		'Feature' => array(),
		'Image' => array(
			(int) 0 => array(
				[maximum depth reached]
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		),
		'Promotion' => array(),
		'Protocol' => array(),
		'Publication' => array(
			(int) 0 => array(
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			(int) 1 => array(
				[maximum depth reached]
			),
			(int) 2 => array(
				[maximum depth reached]
			),
			(int) 3 => array(
				[maximum depth reached]
			),
			(int) 4 => array(
				[maximum depth reached]
			),
			(int) 5 => array(
				[maximum depth reached]
			),
			(int) 6 => array(
				[maximum depth reached]
			),
			(int) 7 => array(
				[maximum depth reached]
			),
			(int) 8 => array(
				[maximum depth reached]
			),
			(int) 9 => array(
				[maximum depth reached]
			),
			(int) 10 => array(
				[maximum depth reached]
			),
			(int) 11 => array(
				[maximum depth reached]
			),
			(int) 12 => array(
				[maximum depth reached]
			),
			(int) 13 => array(
				[maximum depth reached]
			),
			(int) 14 => array(
				[maximum depth reached]
			),
			(int) 15 => array(
				[maximum depth reached]
			),
			(int) 16 => array(
				[maximum depth reached]
			),
			(int) 17 => array(
				[maximum depth reached]
			),
			(int) 18 => array(
				[maximum depth reached]
			),
			(int) 19 => array(
				[maximum depth reached]
			),
			(int) 20 => array(
				[maximum depth reached]
			),
			(int) 21 => array(
				[maximum depth reached]
			),
			(int) 22 => array(
				[maximum depth reached]
			),
			(int) 23 => array(
				[maximum depth reached]
			),
			(int) 24 => array(
				[maximum depth reached]
			),
			(int) 25 => array(
				[maximum depth reached]
			),
			(int) 26 => array(
				[maximum depth reached]
			),
			(int) 27 => array(
				[maximum depth reached]
			),
			(int) 28 => array(
				[maximum depth reached]
			),
			(int) 29 => array(
				[maximum depth reached]
			),
			(int) 30 => array(
				[maximum depth reached]
			),
			(int) 31 => array(
				[maximum depth reached]
			),
			(int) 32 => array(
				[maximum depth reached]
			),
			(int) 33 => array(
				[maximum depth reached]
			),
			(int) 34 => array(
				[maximum depth reached]
			),
			(int) 35 => array(
				[maximum depth reached]
			),
			(int) 36 => array(
				[maximum depth reached]
			),
			(int) 37 => array(
				[maximum depth reached]
			),
			(int) 38 => array(
				[maximum depth reached]
			),
			(int) 39 => array(
				[maximum depth reached]
			),
			(int) 40 => array(
				[maximum depth reached]
			),
			(int) 41 => array(
				[maximum depth reached]
			),
			(int) 42 => array(
				[maximum depth reached]
			),
			(int) 43 => array(
				[maximum depth reached]
			),
			(int) 44 => array(
				[maximum depth reached]
			),
			(int) 45 => array(
				[maximum depth reached]
			),
			(int) 46 => array(
				[maximum depth reached]
			),
			(int) 47 => array(
				[maximum depth reached]
			),
			(int) 48 => array(
				[maximum depth reached]
			),
			(int) 49 => array(
				[maximum depth reached]
			),
			(int) 50 => array(
				[maximum depth reached]
			),
			(int) 51 => array(
				[maximum depth reached]
			),
			(int) 52 => array(
				[maximum depth reached]
			),
			(int) 53 => array(
				[maximum depth reached]
			),
			(int) 54 => array(
				[maximum depth reached]
			),
			(int) 55 => array(
				[maximum depth reached]
			),
			(int) 56 => array(
				[maximum depth reached]
			),
			(int) 57 => array(
				[maximum depth reached]
			),
			(int) 58 => array(
				[maximum depth reached]
			),
			(int) 59 => array(
				[maximum depth reached]
			),
			(int) 60 => array(
				[maximum depth reached]
			),
			(int) 61 => array(
				[maximum depth reached]
			),
			(int) 62 => array(
				[maximum depth reached]
			),
			(int) 63 => array(
				[maximum depth reached]
			),
			(int) 64 => array(
				[maximum depth reached]
			),
			(int) 65 => array(
				[maximum depth reached]
			),
			(int) 66 => array(
				[maximum depth reached]
			),
			(int) 67 => array(
				[maximum depth reached]
			),
			(int) 68 => array(
				[maximum depth reached]
			),
			(int) 69 => array(
				[maximum depth reached]
			),
			(int) 70 => array(
				[maximum depth reached]
			),
			(int) 71 => array(
				[maximum depth reached]
			),
			(int) 72 => array(
				[maximum depth reached]
			),
			(int) 73 => array(
				[maximum depth reached]
			),
			(int) 74 => array(
				[maximum depth reached]
			),
			(int) 75 => array(
				[maximum depth reached]
			),
			(int) 76 => array(
				[maximum depth reached]
			),
			(int) 77 => array(
				[maximum depth reached]
			),
			(int) 78 => array(
				[maximum depth reached]
			),
			(int) 79 => array(
				[maximum depth reached]
			),
			(int) 80 => array(
				[maximum depth reached]
			),
			(int) 81 => array(
				[maximum depth reached]
			),
			(int) 82 => array(
				[maximum depth reached]
			),
			(int) 83 => array(
				[maximum depth reached]
			),
			(int) 84 => array(
				[maximum depth reached]
			),
			(int) 85 => array(
				[maximum depth reached]
			),
			(int) 86 => array(
				[maximum depth reached]
			),
			(int) 87 => array(
				[maximum depth reached]
			),
			(int) 88 => array(
				[maximum depth reached]
			),
			(int) 89 => array(
				[maximum depth reached]
			),
			(int) 90 => array(
				[maximum depth reached]
			),
			(int) 91 => array(
				[maximum depth reached]
			),
			(int) 92 => array(
				[maximum depth reached]
			),
			(int) 93 => array(
				[maximum depth reached]
			),
			(int) 94 => array(
				[maximum depth reached]
			),
			(int) 95 => array(
				[maximum depth reached]
			),
			(int) 96 => array(
				[maximum depth reached]
			),
			(int) 97 => array(
				[maximum depth reached]
			),
			(int) 98 => array(
				[maximum depth reached]
			),
			(int) 99 => array(
				[maximum depth reached]
			),
			(int) 100 => array(
				[maximum depth reached]
			),
			(int) 101 => array(
				[maximum depth reached]
			),
			(int) 102 => array(
				[maximum depth reached]
			),
			(int) 103 => array(
				[maximum depth reached]
			),
			(int) 104 => array(
				[maximum depth reached]
			),
			(int) 105 => array(
				[maximum depth reached]
			),
			(int) 106 => array(
				[maximum depth reached]
			),
			(int) 107 => array(
				[maximum depth reached]
			),
			(int) 108 => array(
				[maximum depth reached]
			),
			(int) 109 => array(
				[maximum depth reached]
			),
			(int) 110 => array(
				[maximum depth reached]
			),
			(int) 111 => array(
				[maximum depth reached]
			),
			(int) 112 => array(
				[maximum depth reached]
			),
			(int) 113 => array(
				[maximum depth reached]
			),
			(int) 114 => array(
				[maximum depth reached]
			),
			(int) 115 => array(
				[maximum depth reached]
			),
			(int) 116 => array(
				[maximum depth reached]
			),
			(int) 117 => array(
				[maximum depth reached]
			),
			(int) 118 => array(
				[maximum depth reached]
			),
			(int) 119 => array(
				[maximum depth reached]
			),
			(int) 120 => array(
				[maximum depth reached]
			),
			(int) 121 => array(
				[maximum depth reached]
			),
			(int) 122 => array(
				[maximum depth reached]
			),
			(int) 123 => array(
				[maximum depth reached]
			),
			(int) 124 => array(
				[maximum depth reached]
			),
			(int) 125 => array(
				[maximum depth reached]
			),
			(int) 126 => array(
				[maximum depth reached]
			),
			(int) 127 => array(
				[maximum depth reached]
			),
			(int) 128 => array(
				[maximum depth reached]
			),
			(int) 129 => array(
				[maximum depth reached]
			),
			(int) 130 => array(
				[maximum depth reached]
			),
			(int) 131 => array(
				[maximum depth reached]
			),
			(int) 132 => array(
				[maximum depth reached]
			),
			(int) 133 => array(
				[maximum depth reached]
			),
			(int) 134 => array(
				[maximum depth reached]
			),
			(int) 135 => array(
				[maximum depth reached]
			),
			(int) 136 => array(
				[maximum depth reached]
			),
			(int) 137 => array(
				[maximum depth reached]
			),
			(int) 138 => array(
				[maximum depth reached]
			),
			(int) 139 => array(
				[maximum depth reached]
			),
			(int) 140 => array(
				[maximum depth reached]
			),
			(int) 141 => array(
				[maximum depth reached]
			),
			(int) 142 => array(
				[maximum depth reached]
			),
			(int) 143 => array(
				[maximum depth reached]
			),
			(int) 144 => array(
				[maximum depth reached]
			),
			(int) 145 => array(
				[maximum depth reached]
			),
			(int) 146 => array(
				[maximum depth reached]
			),
			(int) 147 => array(
				[maximum depth reached]
			),
			(int) 148 => array(
				[maximum depth reached]
			),
			(int) 149 => array(
				[maximum depth reached]
			),
			(int) 150 => array(
				[maximum depth reached]
			),
			(int) 151 => array(
				[maximum depth reached]
			),
			(int) 152 => array(
				[maximum depth reached]
			),
			(int) 153 => array(
				[maximum depth reached]
			),
			(int) 154 => array(
				[maximum depth reached]
			),
			(int) 155 => array(
				[maximum depth reached]
			),
			(int) 156 => array(
				[maximum depth reached]
			),
			(int) 157 => array(
				[maximum depth reached]
			),
			(int) 158 => array(
				[maximum depth reached]
			),
			(int) 159 => array(
				[maximum depth reached]
			),
			(int) 160 => array(
				[maximum depth reached]
			),
			(int) 161 => array(
				[maximum depth reached]
			),
			(int) 162 => array(
				[maximum depth reached]
			),
			(int) 163 => array(
				[maximum depth reached]
			),
			(int) 164 => array(
				[maximum depth reached]
			),
			(int) 165 => array(
				[maximum depth reached]
			),
			(int) 166 => array(
				[maximum depth reached]
			),
			(int) 167 => array(
				[maximum depth reached]
			),
			(int) 168 => array(
				[maximum depth reached]
			),
			(int) 169 => array(
				[maximum depth reached]
			),
			(int) 170 => array(
				[maximum depth reached]
			),
			(int) 171 => array(
				[maximum depth reached]
			),
			(int) 172 => array(
				[maximum depth reached]
			),
			(int) 173 => array(
				[maximum depth reached]
			),
			(int) 174 => array(
				[maximum depth reached]
			),
			(int) 175 => array(
				[maximum depth reached]
			),
			(int) 176 => array(
				[maximum depth reached]
			),
			(int) 177 => array(
				[maximum depth reached]
			),
			(int) 178 => array(
				[maximum depth reached]
			),
			(int) 179 => array(
				[maximum depth reached]
			),
			(int) 180 => array(
				[maximum depth reached]
			),
			(int) 181 => array(
				[maximum depth reached]
			),
			(int) 182 => array(
				[maximum depth reached]
			),
			(int) 183 => array(
				[maximum depth reached]
			),
			(int) 184 => array(
				[maximum depth reached]
			),
			(int) 185 => array(
				[maximum depth reached]
			),
			(int) 186 => array(
				[maximum depth reached]
			),
			(int) 187 => array(
				[maximum depth reached]
			),
			(int) 188 => array(
				[maximum depth reached]
			),
			(int) 189 => array(
				[maximum depth reached]
			),
			(int) 190 => array(
				[maximum depth reached]
			),
			(int) 191 => array(
				[maximum depth reached]
			),
			(int) 192 => array(
				[maximum depth reached]
			),
			(int) 193 => array(
				[maximum depth reached]
			),
			(int) 194 => array(
				[maximum depth reached]
			),
			(int) 195 => array(
				[maximum depth reached]
			),
			(int) 196 => array(
				[maximum depth reached]
			),
			(int) 197 => array(
				[maximum depth reached]
			),
			(int) 198 => array(
				[maximum depth reached]
			),
			(int) 199 => array(
				[maximum depth reached]
			),
			(int) 200 => array(
				[maximum depth reached]
			),
			(int) 201 => array(
				[maximum depth reached]
			),
			(int) 202 => array(
				[maximum depth reached]
			),
			(int) 203 => array(
				[maximum depth reached]
			),
			(int) 204 => array(
				[maximum depth reached]
			),
			(int) 205 => array(
				[maximum depth reached]
			),
			(int) 206 => array(
				[maximum depth reached]
			),
			(int) 207 => array(
				[maximum depth reached]
			),
			(int) 208 => array(
				[maximum depth reached]
			),
			(int) 209 => array(
				[maximum depth reached]
			),
			(int) 210 => array(
				[maximum depth reached]
			),
			(int) 211 => array(
				[maximum depth reached]
			),
			(int) 212 => array(
				[maximum depth reached]
			),
			(int) 213 => array(
				[maximum depth reached]
			),
			(int) 214 => array(
				[maximum depth reached]
			),
			(int) 215 => array(
				[maximum depth reached]
			),
			(int) 216 => array(
				[maximum depth reached]
			),
			(int) 217 => array(
				[maximum depth reached]
			),
			(int) 218 => array(
				[maximum depth reached]
			),
			(int) 219 => array(
				[maximum depth reached]
			),
			(int) 220 => array(
				[maximum depth reached]
			),
			(int) 221 => array(
				[maximum depth reached]
			),
			(int) 222 => array(
				[maximum depth reached]
			),
			(int) 223 => array(
				[maximum depth reached]
			),
			(int) 224 => array(
				[maximum depth reached]
			),
			(int) 225 => array(
				[maximum depth reached]
			),
			(int) 226 => array(
				[maximum depth reached]
			),
			(int) 227 => array(
				[maximum depth reached]
			),
			(int) 228 => array(
				[maximum depth reached]
			),
			(int) 229 => array(
				[maximum depth reached]
			),
			(int) 230 => array(
				[maximum depth reached]
			),
			(int) 231 => array(
				[maximum depth reached]
			),
			(int) 232 => array(
				[maximum depth reached]
			),
			(int) 233 => array(
				[maximum depth reached]
			),
			(int) 234 => array(
				[maximum depth reached]
			),
			(int) 235 => array(
				[maximum depth reached]
			),
			(int) 236 => array(
				[maximum depth reached]
			),
			(int) 237 => array(
				[maximum depth reached]
			),
			(int) 238 => array(
				[maximum depth reached]
			),
			(int) 239 => array(
				[maximum depth reached]
			),
			(int) 240 => array(
				[maximum depth reached]
			),
			(int) 241 => array(
				[maximum depth reached]
			),
			(int) 242 => array(
				[maximum depth reached]
			),
			(int) 243 => array(
				[maximum depth reached]
			),
			(int) 244 => array(
				[maximum depth reached]
			),
			(int) 245 => array(
				[maximum depth reached]
			),
			(int) 246 => array(
				[maximum depth reached]
			),
			(int) 247 => array(
				[maximum depth reached]
			),
			(int) 248 => array(
				[maximum depth reached]
			),
			(int) 249 => array(
				[maximum depth reached]
			),
			(int) 250 => array(
				[maximum depth reached]
			),
			(int) 251 => array(
				[maximum depth reached]
			),
			(int) 252 => array(
				[maximum depth reached]
			),
			(int) 253 => array(
				[maximum depth reached]
			),
			(int) 254 => array(
				[maximum depth reached]
			),
			(int) 255 => array(
				[maximum depth reached]
			),
			(int) 256 => array(
				[maximum depth reached]
			),
			(int) 257 => array(
				[maximum depth reached]
			),
			(int) 258 => array(
				[maximum depth reached]
			)
		),
		'Testimonial' => array(
			(int) 0 => array(
				[maximum depth reached]
			),
			(int) 1 => array(
				[maximum depth reached]
			),
			(int) 2 => array(
				[maximum depth reached]
			),
			(int) 3 => array(
				[maximum depth reached]
			),
			(int) 4 => array(
				[maximum depth reached]
			)
		),
		'Area' => array(),
		'SafetySheet' => array(
			(int) 0 => array(
				[maximum depth reached]
			),
			(int) 1 => array(
				[maximum depth reached]
			),
			(int) 2 => array(
				[maximum depth reached]
			),
			(int) 3 => array(
				[maximum depth reached]
			),
			(int) 4 => array(
				[maximum depth reached]
			),
			(int) 5 => array(
				[maximum depth reached]
			),
			(int) 6 => array(
				[maximum depth reached]
			),
			(int) 7 => array(
				[maximum depth reached]
			)
		)
	),
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		'id' => '2172',
		'antibody_id' => '115',
		'name' => 'H3K4me3 polyclonal antibody  (sample size)',
		'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone H3 containing the trimethylated lysine 4 (H3K4me3), using a KLH-conjugated synthetic peptide.</span></p>
<script src="chrome-extension://hhojmcideegachlhfgfdhailpfhgknjm/web_accessible_resources/index.js"></script>',
		'label1' => 'Validation Data',
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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		'price_EUR' => '125',
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		'slug' => 'h3k4me3-polyclonal-antibody-premium-sample-size-10-ug',
		'meta_title' => 'H3K4me3 polyclonal antibody - Premium (sample size)',
		'meta_keywords' => '',
		'meta_description' => 'H3K4me3 polyclonal antibody - Premium (sample size)',
		'modified' => '2022-06-29 14:43:38',
		'created' => '2015-06-29 14:08:20',
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	'Antibody' => array(
		'host' => '*****',
		'id' => '115',
		'name' => 'H3K4me3 polyclonal antibody',
		'description' => 'Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called “histone code”. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Methylation of histone H3K4 is associated with activation of gene transcription.',
		'clonality' => '',
		'isotype' => '',
		'lot' => 'A8034D',
		'concentration' => '1.3 &micro;g/&micro;l',
		'reactivity' => 'Human, mouse, pig, zebrafish, trout, Daphnia, Arabidopsis, rice, tomato, maize, poplar, silena latifolia, wide range expected.',
		'type' => 'Polyclonal, <strong>ChIP grade, ChIP-seq grade</strong>',
		'purity' => 'Affinity purified polyclonal antibody.',
		'classification' => 'Premium',
		'application_table' => '<table>
<thead>
<tr>
<th>Applications</th>
<th>Suggested dilution</th>
<th>References</th>
</tr>
</thead>
<tbody>
<tr>
<td>ChIP/ChIP-seq<sup>*</sup></td>
<td><span style="font-family: Helvetica;">0.5 - 1&nbsp;&micro;g</span></td>
<td>Fig 1, 2</td>
</tr>
<tr>
<td>CUT&amp;Tag</td>
<td>0.5 &micro;g</td>
<td>Fig 3</td>
</tr>
<tr>
<td>ELISA</td>
<td>1:2,000</td>
<td>Fig 4</td>
</tr>
<tr>
<td>Dot Blotting</td>
<td>1:1000</td>
<td>Fig 5</td>
</tr>
<tr>
<td>Western Blotting</td>
<td>1:1,000</td>
<td>Fig 6</td>
</tr>
<tr>
<td>Immunofluorescence</td>
<td>1:200</td>
<td>Fig 7</td>
</tr>
</tbody>
</table>
<p></p>
<p><small><sup>*</sup> Please note that the optimal antibody amount per IP should be determined by the end-user. We recommend testing 0.5-5 &micro;g per IP.</small></p>',
		'storage_conditions' => 'Store at -20°C; for long storage, store at -80°C. Avoid multiple freeze-thaw cycles.',
		'storage_buffer' => 'PBS containing 0.05% azide and 0.05% ProClin 300.',
		'precautions' => 'This product is for research use only. Not for use in diagnostic or therapeutic procedures.',
		'uniprot_acc' => '',
		'slug' => '',
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		'modified' => '2022-08-17 11:57:06',
		'created' => '0000-00-00 00:00:00',
		'select_label' => '115 - H3K4me3 polyclonal antibody (A8034D - 1.3 &micro;g/&micro;l - Human, mouse, pig, zebrafish, trout, Daphnia, Arabidopsis, rice, tomato, maize, poplar, silena latifolia, wide range expected. - Affinity purified polyclonal antibody. - Rabbit)'
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			'id' => '47',
			'name' => 'C15410003',
			'product_id' => '2173',
			'modified' => '2016-02-18 20:50:17',
			'created' => '2016-02-18 20:50:17'
		),
		'Master' => array(
			'id' => '2173',
			'antibody_id' => '115',
			'name' => 'H3K4me3 Antibody',
			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
			'label1' => 'Validation data',
			'info1' => '<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
</div>
</div>
<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
</div>
</div>
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			'format' => '50 µg',
			'catalog_number' => 'C15410003',
			'old_catalog_number' => 'pAb-003-050',
			'sf_code' => 'C15410003-D001-000581',
			'type' => 'FRE',
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			'slug' => 'h3k4me3-polyclonal-antibody-premium-50-ug-50-ul',
			'meta_title' => 'H3K4me3 Antibody - ChIP-seq Grade (C15410003) | Diagenode',
			'meta_keywords' => '',
			'meta_description' => 'H3K4me3 (Histone H3 trimethylated at lysine 4) Polyclonal Antibody validated  in ChIP-seq, ChIP-qPCR, CUT&Tag, ELISA, DB, WB and IF. Specificity confirmed by Peptide array. Batch-specific data available on the website. Sample size available.',
			'modified' => '2024-11-19 16:51:19',
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	'Related' => array(
		(int) 0 => array(
			'id' => '1836',
			'antibody_id' => null,
			'name' => 'iDeal ChIP-seq kit for Histones',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/ideal-chipseq-for-histones-complete-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<p>Don&rsquo;t risk wasting your precious sequencing samples. Diagenode&rsquo;s validated <strong>iDeal ChIP-seq kit for Histones</strong> has everything you need for a successful start-to-finish <strong>ChIP of histones prior to Next-Generation Sequencing</strong>. The complete kit contains all buffers and reagents for cell lysis, chromatin shearing, immunoprecipitation and DNA purification. In addition, unlike competing solutions, the kit contains positive and negative control antibodies (H3K4me3 and IgG, respectively) as well as positive and negative control PCR primers pairs (GAPDH TSS and Myoglobin exon 2, respectively) for your convenience and a guarantee of optimal results. The kit has been validated on multiple histone marks.</p>
<p>&nbsp;The &nbsp;iDeal ChIP-seq kit for Histones<strong> </strong>is perfect for <strong>cells</strong> (<strong>100,000 cells</strong> to <strong>1,000,000 cells</strong> per IP) and has been validated for <strong>tissues</strong> (<strong>1.5 mg</strong> to <strong>5 mg</strong> of tissue per IP).</p>
<p>&nbsp;The iDeal ChIP-seq kit is the only kit on the market validated for the major sequencing systems. Our expertise in ChIP-seq tools allows reproducible and efficient results every time.</p>
<p></p>
<p>&nbsp;<strong></strong></p>
<p></p>',
			'label1' => 'Characteristics',
			'info1' => '<ul style="list-style-type: disc;">
<li>Highly <strong>optimized</strong> protocol for ChIP-seq from cells and tissues</li>
<li><strong>Validated</strong> for ChIP-seq with multiple histones marks</li>
<li>Most <strong>complete</strong> kit available (covers all steps, including the control antibodies and primers)</li>
<li>Optimized chromatin preparation in combination with the Bioruptor ensuring the best <strong>epitope integrity</strong></li>
<li>Magnetic beads make ChIP easy, fast and more <strong>reproducible</strong></li>
<li>Combination with Diagenode ChIP-seq antibodies provides high yields with excellent <strong>specificity</strong> and <strong>sensitivity</strong></li>
<li>Purified DNA suitable for any downstream application</li>
<li>Easy-to-follow protocol</li>
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<p>Note: to obtain optimal results, this kit should be used in combination with the DiaMag1.5 - magnetic rack.</p>
<h3>ChIP-seq on cells</h3>
<p><img src="https://www.diagenode.com/img/product/kits/iDeal-kit-C01010053-figure-1.jpg" alt="Figure 1A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1A. The high consistency of the iDeal ChIP-seq kit on the Ion Torrent&trade; PGM&trade; (Life Technologies) and GAIIx (Illumina<sup>&reg;</sup>)</strong><br /> ChIP was performed on sheared chromatin from 1 million HelaS3 cells using the iDeal ChIP-seq kit and 1 &micro;g of H3K4me3 positive control antibody. Two different biological samples have been analyzed using two different sequencers - GAIIx (Illumina<sup>&reg;</sup>) and PGM&trade; (Ion Torrent&trade;). The expected ChIP-seq profile for H3K4me3 on the GAPDH promoter region has been obtained.<br /> Image A shows a several hundred bp along chr12 with high similarity of read distribution despite the radically different sequencers. Image B is a close capture focusing on the GAPDH that shows that even the peak structure is similar.</p>
<p class="text-center"><strong>Perfect match between ChIP-seq data obtained with the iDeal ChIP-seq workflow and reference dataset</strong></p>
<p><img src="https://www.diagenode.com/img/product/kits/perfect-match-between-chipseq-data.png" alt="Figure 1B" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>
<p><img src="https://www.diagenode.com/img/product/kits/iDeal-kit-C01010053-figure-2.jpg" alt="Figure 2" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 2. Efficient and easy chromatin shearing using the Bioruptor<sup>&reg;</sup> and Shearing buffer iS1 from the iDeal ChIP-seq kit</strong><br /> Chromatin from 1 million of Hela cells was sheared using the Bioruptor<sup>&reg;</sup> combined with the Bioruptor<sup>&reg;</sup> Water cooler (Cat No. BioAcc-cool) during 3 rounds of 10 cycles of 30 seconds &ldquo;ON&rdquo; / 30 seconds &ldquo;OFF&rdquo; at HIGH power setting (position H). Diagenode 1.5 ml TPX tubes (Cat No. M-50001) were used for chromatin shearing. Samples were gently vortexed before and after performing each sonication round (rounds of 10 cycles), followed by a short centrifugation at 4&deg;C to recover the sample volume at the bottom of the tube. The sheared chromatin was then decross-linked as described in the kit manual and analyzed by agarose gel electrophoresis.</p>
<p><img src="https://www.diagenode.com/img/product/kits/iDeal-kit-C01010053-figure-3.jpg" alt="Figure 3" style="display: block; margin-left: auto; margin-right: auto;" width="264" height="320" /></p>
<p><strong>Figure 3. Validation of ChIP by qPCR: reliable results using Diagenode&rsquo;s ChIP-seq grade H3K4me3 antibody, isotype control and sets of validated primers</strong><br /> Specific enrichment on positive loci (GAPDH, EIF4A2, c-fos promoter regions) comparing to no enrichment on negative loci (TSH2B promoter region and Myoglobin exon 2) was detected by qPCR. Samples were prepared using the Diagenode iDeal ChIP-seq kit. Diagenode ChIP-seq grade antibody against H3K4me3 and the corresponding isotype control IgG were used for immunoprecipitation. qPCR amplification was performed with sets of validated primers.</p>
<h3>ChIP-seq on tissue</h3>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-figure-h3k4me3.jpg" alt="Figure 4A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 4A.</strong> Chromatin Immunoprecipitation has been performed using chromatin from mouse liver tissue, the iDeal ChIP-seq kit for Histones and the Diagenode ChIP-seq-grade H3K4me3 (Cat. No. C15410003) antibody. The IP'd DNA was subsequently analysed on an Illumina&reg; HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in a region surrounding the GAPDH positive control gene.</p>
<p><img src="https://www.diagenode.com/img/product/kits/match-of-the-top40-peaks-2.png" alt="Figure 4B" caption="false" style="display: block; margin-left: auto; margin-right: auto;" width="700" height="280" /></p>
<p><strong>Figure 4B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>',
			'label2' => 'Species, cell lines, tissues tested',
			'info2' => '<p>The iDeal ChIP-seq Kit for Histones is compatible with a broad variety of cell lines, tissues and species - some examples are shown below. Other species / cell lines / tissues can be used with this kit.</p>
<p><u>Cell lines:</u></p>
<p>Human: A549, A673, CD8+ T, Blood vascular endothelial cells, Lymphatic endothelial cells, fibroblasts, K562, MDA-MB231</p>
<p>Pig: Alveolar macrophages</p>
<p>Mouse: C2C12, primary HSPC, synovial fibroblasts, HeLa-S3, FACS sorted cells from embryonic kidneys, macrophages, mesodermal cells, myoblasts, NPC, salivary glands, spermatids, spermatocytes, skeletal muscle stem cells, stem cells, Th2</p>
<p>Hamster: CHO</p>
<p>Other cell lines / species: compatible, not tested</p>
<p><u>Tissues</u></p>
<p>Bee &ndash; brain</p>
<p>Daphnia &ndash; whole animal</p>
<p>Horse &ndash; brain, heart, lamina, liver, lung, skeletal muscles, ovary</p>
<p>Human &ndash; Erwing sarcoma tumor samples</p>
<p>Other tissues: compatible, not tested</p>
<p>Did you use the iDeal ChIP-seq for Histones Kit on other cell line / tissue / species? <a href="mailto:agnieszka.zelisko@diagenode.com?subject=Species, cell lines, tissues tested with the iDeal ChIP-seq Kit for TF&amp;body=Dear Customer,%0D%0A%0D%0APlease, leave below your feedback about the iDeal ChIP-seq for Transcription Factors (cell / tissue type, species, other information...).%0D%0A%0D%0AThank you for sharing with us your experience !%0D%0A%0D%0ABest regards,%0D%0A%0D%0AAgnieszka Zelisko-Schmidt, PhD">Let us know!</a></p>',
			'label3' => '  Additional solutions compatible with iDeal ChIP-seq Kit for Histones',
			'info3' => '<p><a href="../p/chromatin-shearing-optimization-kit-low-sds-100-million-cells">Chromatin EasyShear Kit - Ultra Low SDS </a>optimizes chromatin shearing, a critical step for ChIP.</p>
<p>&nbsp;The <a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq">MicroPlex Library Preparation Kit </a>provides easy and optimal &nbsp;library preparation of ChIPed samples.</p>
<p><a href="../categories/chip-seq-grade-antibodies">ChIP-seq grade anti-histone antibodies</a> provide high yields with excellent specificity and sensitivity.</p>
<p>&nbsp;Plus, for our IP-Star Automation users for automated ChIP, check out our <a href="../p/auto-ideal-chip-seq-kit-for-histones-x24-24-rxns">automated</a> version of this kit.</p>',
			'format' => '4 chrom. prep./24 IPs',
			'catalog_number' => 'C01010051',
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			'slug' => 'ideal-chip-seq-kit-x24-24-rxns',
			'meta_title' => 'iDeal ChIP-seq kit x24',
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			'meta_description' => 'iDeal ChIP-seq kit x24',
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			'name' => 'iDeal ChIP-seq kit for Transcription Factors',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/ideal-chipseq-transcription-factors-x10-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
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<div class="small-12 medium-8 large-8 columns"><br />
<p><span style="font-weight: 400;">Diagenode&rsquo;s <strong>iDeal ChIP-seq Kit for Transcription Factors</strong> is a highly validated solution for robust transcription factor and other non-histone proteins ChIP-seq results and contains everything you need for start-to-finish </span><b>ChIP </b><span style="font-weight: 400;">prior to </span><b>Next-Generation Sequencing</b><span style="font-weight: 400;">. This complete solution contains all buffers and reagents for cell lysis, chromatin shearing, immunoprecipitation, and DNA purification. In addition, unlike competing solutions, the kit contains positive and negative control antibodies (CTCF and IgG, respectively) as well as positive and negative control PCR primers pairs (H19 and Myoglobin exon 2, respectively) for your convenience and a guarantee of optimal results. <br /></span></p>
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<p><span style="font-weight: 400;">The </span><b>&nbsp;iDeal ChIP-seq kit for Transcription Factors </b><span style="font-weight: 400;">is compatible for cells or tissues:</span></p>
<table style="width: 419px; margin-left: auto; margin-right: auto;">
<tbody>
<tr>
<td style="width: 144px;"></td>
<td style="width: 267px; text-align: center;"><span style="font-weight: 400;">Amount per IP</span></td>
</tr>
<tr>
<td style="width: 144px;">Cells</td>
<td style="width: 267px; text-align: center;"><strong>4,000,000</strong></td>
</tr>
<tr>
<td style="width: 144px;">Tissues</td>
<td style="width: 267px; text-align: center;"><strong>30 mg</strong></td>
</tr>
</tbody>
</table>
<p><span style="font-weight: 400;">The iDeal ChIP-seq kit is the only kit on the market validated for major sequencing systems. Our expertise in ChIP-seq tools allows reproducible and efficient results every time. </span></p>
<p></p>
<p></p>',
			'label1' => 'Characteristics',
			'info1' => '<ul>
<li><span style="font-weight: 400;"><strong>Highly optimized protocol</strong> for ChIP-seq from cells and tissues</span></li>
<li><span style="font-weight: 400;"><strong>Validated</strong> for <strong>ChIP-seq</strong> with multiple transcription factors and non-histone targets<br /></span></li>
<li><span style="font-weight: 400;"><strong>Most complete kit</strong> available (covers all steps, including the control antibodies and primers)<br /></span></li>
<li><span style="font-weight: 400;"><strong>Magnetic beads</strong> make ChIP <strong>easy</strong>, <strong>fast</strong> and more <strong>reproducible</strong></span></li>
<li><span style="font-weight: 400;">Combination with Diagenode ChIP-seq antibodies provides <strong>high yields</strong> with excellent <strong>specificity</strong> and <strong>sensitivity</strong><br /></span></li>
<li><span style="font-weight: 400;">Purified DNA suitable for any downstream application</span></li>
<li><span style="font-weight: 400;">Easy-to-follow protocol</span></li>
</ul>
<p><span style="font-weight: 400;"></span></p>
<p>&nbsp;</p>
<h3>ChIP-seq on cells</h3>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-ctcf-diagenode.jpg" alt="CTCF Diagenode" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1.</strong> (A) Chromatin Immunoprecipitation has been performed using chromatin from HeLa cells, the iDeal ChIP-seq kit for Transcription Factors and the Diagenode ChIP-seq-grade CTCF antibody. The IP'd DNA was subsequently analysed on an Illumina<sup>&reg;</sup> HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in a region surrounding the GAPDH positive control gene.</p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-figure-b-total-diagendoe-peaks.png" alt="CTCF Diagenode" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>
<p>&nbsp;</p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-TF-chip-seq-A.png" alt="ChIP-seq figure A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-TF-chip-seq-B.png" alt="ChIP-seq figure B" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-TF-chip-seq-C.png" alt="ChIP-seq figure C" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 2.</strong> Chromatin Immunoprecipitation has been performed using chromatin from HeLa cells, the iDeal ChIP-seq kit for Transcription Factors and the Diagenode ChIP-seq-grade HDAC1 (A), LSD1 (B) and p53 antibody (C). The IP'd DNA was subsequently analysed on an Illumina<sup>&reg;</sup> Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in regions of chromosome 3 (A), chromosome 12 (B) and chromosome 6 (C) respectively.</p>
<p>&nbsp;</p>
<h3>ChIP-seq on tissue</h3>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-figure-3a.jpg" alt="ChIP-seq figure A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 3A.</strong> Chromatin Immunoprecipitation has been performed using chromatin from mouse liver tissue, the iDeal ChIP-seq kit for Transcription Factors and the Diagenode ChIP-seq-grade CTCF antibody. The IP'd DNA was subsequently analysed on an Illumina&reg; HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in a region surrounding the Vwf positive control gene.</p>
<p><img src="https://www.diagenode.com/img/product/kits/match-of-the-top40-peaks.png" alt="Match of the Top40 peaks" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 3B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>',
			'label2' => 'Species, cell lines, tissues tested',
			'info2' => '<p>The iDeal ChIP-seq Kit for Transcription Factors is compatible with a broad variety of cell lines, tissues and species - some examples are shown below. Other species / cell lines / tissues can be used with this kit.</p>
<p><span style="text-decoration: underline;">Cell lines:</span></p>
<p>Human: A549, A673, BT-549, CD4 T, HCC1806, HeLa, HepG2, HFF, HK-GFP-MR, ILC,&nbsp;K562, KYSE-180, LapC4, M14, MCF7, MDA-MB-231, MDA-MB-436, RDES, SKNO1, VCaP, U2-OS, ZR-75-1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;</p>
<p>Mouse: ESC, NPCs, BZ, GT1-7, acinar cells, HSPCs, Th2 cells, keratinocytes</p>
<p>Cattle: pbMEC, <span>MAC-T</span></p>
<p><span>Other cell lines / species: compatible, not tested</span></p>
<p><span style="text-decoration: underline;">Tissues:</span></p>
<p>Mouse: kidney, heart, brain, iris, liver, limbs from E10.5 embryos</p>
<p><span>Horse: l</span>iver, brain, heart, lung, skeletal muscle, lamina, ovary</p>
<p>Other tissues: compatible, not tested</p>
<p><span style="text-decoration: underline;">ChIP on yeast</span></p>
<p>The iDeal ChIP-seq kit for TF is compatible with yeast samples. Check out our <strong><a href="https://www.diagenode.com/files/products/kits/Application_Note-ChIP_on_Yeast.pdf">Application Note</a></strong>&nbsp;presenting an optimized detailed protocol for ChIP on yeast.</p>
<p></p>
<p>Did you use the iDeal ChIP-seq for Transcription Factors Kit on other cell line / tissue / species? <a href="mailto:agnieszka.zelisko@diagenode.com?subject=Species, cell lines, tissues tested with the iDeal ChIP-seq Kit for TF&amp;body=Dear Customer,%0D%0A%0D%0APlease, leave below your feedback about the iDeal ChIP-seq for Transcription Factors (cell / tissue type, species, other information...).%0D%0A%0D%0AThank you for sharing with us your experience !%0D%0A%0D%0ABest regards,%0D%0A%0D%0AAgnieszka Zelisko-Schmidt, PhD">Let us know!</a></p>',
			'label3' => 'Additional solutions compatible with iDeal ChIP-seq kit for Transcription Factors',
			'info3' => '<p><span style="font-weight: 400;">The</span> <a href="https://www.diagenode.com/en/p/chromatin-shearing-optimization-kit-low-sds-for-tfs-25-rxns"><span style="font-weight: 400;">Chromatin EasyShear Kit &ndash; Low SDS </span></a><span style="font-weight: 400;">is the kit compatible with the iDeal ChIP-seq kit for TF, recommended for the optimization of chromatin shearing, a critical step for ChIP.</span></p>
<p><a href="https://www.diagenode.com/en/p/chip-cross-link-gold-600-ul"><span style="font-weight: 400;">ChIP Cross-link Gold</span></a> <span style="font-weight: 400;">should be used in combination with formaldehyde when working with higher order and/or dynamic interactions, for efficient protein-protein fixation.</span></p>
<p><span style="font-weight: 400;">For library preparation of immunoprecipitated samples we recommend to use the </span><b>&nbsp;</b><a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq"><span style="font-weight: 400;">MicroPlex Library Preparation Kit</span></a><span style="font-weight: 400;"> - validated for library preparation from picogram inputs.</span></p>
<p><a href="https://www.diagenode.com/en/categories/chip-seq-grade-antibodies"><span style="font-weight: 400;">ChIP-seq grade antibodies</span></a><span style="font-weight: 400;"> provide high yields with excellent specificity and sensitivity.</span></p>
<p><span style="font-weight: 400;">Check the list of available </span><a href="https://www.diagenode.com/en/categories/primer-pairs"><span style="font-weight: 400;">Primer pairs</span></a><span style="font-weight: 400;"> designed for high specificity to specific genomic regions.</span></p>
<p><span style="font-weight: 400;">Plus, for our <a href="https://www.diagenode.com/en/categories/ip-star">IP-Star Automation</a> users for automated ChIP, check out our <a href="https://www.diagenode.com/en/p/auto-ideal-chip-seq-kit-for-transcription-factors-x24-24-rxns">automated version</a> of this kit.</span></p>',
			'format' => '4 chrom. prep./24 IPs',
			'catalog_number' => 'C01010055',
			'old_catalog_number' => '',
			'sf_code' => 'C01010055-',
			'type' => 'RFR',
			'search_order' => '04-undefined',
			'price_EUR' => '915',
			'price_USD' => '1130',
			'price_GBP' => '840',
			'price_JPY' => '143335',
			'price_CNY' => '',
			'price_AUD' => '2825',
			'country' => 'ALL',
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			'last_datasheet_update' => '0000-00-00',
			'slug' => 'ideal-chip-seq-kit-for-transcription-factors-x24-24-rxns',
			'meta_title' => 'iDeal ChIP-seq kit for Transcription Factors x24',
			'meta_keywords' => '',
			'meta_description' => 'iDeal ChIP-seq kit for Transcription Factors x24',
			'modified' => '2023-06-20 18:27:37',
			'created' => '2015-06-29 14:08:20',
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		(int) 2 => array(
			'id' => '1856',
			'antibody_id' => null,
			'name' => 'True MicroChIP-seq Kit',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/truemicrochipseq-kit-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<p>The <b>True </b><b>MicroChIP-seq</b><b> kit </b>provides a robust ChIP protocol suitable for the investigation of histone modifications within chromatin from as few as <b>10 000 cells</b>, including <b>FACS sorted cells</b>. The kit can be used for chromatin preparation for downstream ChIP-qPCR or ChIP-seq analysis. The <b>complete kit</b> contains everything you need for start-to-finish ChIP including all validated buffers and reagents for chromatin shearing, immunoprecipitation and DNA purification for exceptional <strong>ChIP-qPCR</strong> or <strong>ChIP-seq</strong> results. In addition, positive control antibodies and negative control PCR primers are included for your convenience and assurance of result sensitivity and specificity.</p>
<p>The True MicroChIP-seq kit offers unique benefits:</p>
<ul>
<li>An <b>optimized chromatin preparation </b>protocol compatible with low number of cells (<b>10.000</b>) in combination with the Bioruptor&trade; shearing device</li>
<li>Most <b>complete kit </b>available (covers all steps and includes control antibodies and primers)</li>
<li><b>Magnetic beads </b>make ChIP easy, fast, and more reproducible</li>
<li>MicroChIP DiaPure columns (included in the kit) enable the <b>maximum recovery </b>of immunoprecipitation DNA suitable for any downstream application</li>
<li><b>Excellent </b><b>ChIP</b><b>-seq </b>result when combined with <a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq">MicroPlex</a><a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq"> Library Preparation kit </a>adapted for low input</li>
</ul>
<p>For fast ChIP-seq on low input &ndash; check out Diagenode&rsquo;s <a href="https://www.diagenode.com/en/p/uchipmentation-for-histones-24-rxns">&micro;</a><a href="https://www.diagenode.com/en/p/uchipmentation-for-histones-24-rxns">ChIPmentation</a><a href="https://www.diagenode.com/en/p/uchipmentation-for-histones-24-rxns"> for histones</a>.</p>
<p><sub>The True MicroChIP-seq kit, Cat. No. C01010132 is an upgraded version of the kit True MicroChIP, Cat. No. C01010130, with the new validated protocols (e.g. FACS sorted cells) and MicroChIP DiaPure columns included in the kit.</sub></p>',
			'label1' => 'Characteristics',
			'info1' => '<ul>
<li><b>Revolutionary:</b> Only 10,000 cells needed for complete ChIP-seq procedure</li>
<li><b>Validated on</b> studies for histone marks</li>
<li><b>Automated protocol </b>for the IP-Star<sup>&reg;</sup> Compact Automated Platform available</li>
</ul>
<p></p>
<p>The True MicroChIP-seq kit protocol has been optimized for the use of 10,000 - 100,000 cells per immunoprecipitation reaction. Regarding chromatin immunoprecipitation, three protocol variants have been optimized:<br />starting with a batch, starting with an individual sample and starting with the FACS-sorted cells.</p>
<div><button id="readmorebtn" style="background-color: #b02736; color: white; border-radius: 5px; border: none; padding: 5px;">Show Workflow</button></div>
<p><br /> <img src="https://www.diagenode.com/img/product/kits/workflow-microchip.png" id="workflowchip" class="hidden" width="600px" /></p>
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<div>
<h3>High efficiency ChIP on 10,000 cells</h3>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><img src="https://www.diagenode.com/img/product/kits/true-micro-chip-histone-results.png" width="800px" /></div>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><center>
<p><small><strong>Figure 1.&nbsp;</strong>ChIP efficiency on 10,000 cells. ChIP was performed on human Hela cells using the Diagenode antibodies <a href="https://www.diagenode.com/en/p/h3k4me3-polyclonal-antibody-premium-50-ug-50-ul">H3K4me3</a> (Cat. No. C15410003), <a href="https://www.diagenode.com/en/p/h3k27ac-polyclonal-antibody-classic-50-mg-42-ml">H3K27ac</a> (C15410174), <a href="https://www.diagenode.com/en/p/h3k9me3-polyclonal-antibody-classic-50-ug">H3K9me3</a> (C15410056) and <a href="https://www.diagenode.com/en/p/h3k27me3-polyclonal-antibody-classic-50-mg-34-ml">H3K27me3</a> (C15410069). Sheared chromatin from 10,000 cells and 0.1 &micro;g (H3K27ac), 0.25 &micro;g (H3K4me3 and H3K27me3) or 0.5 &micro;g (H3K9me3) of the antibody were used per IP. Corresponding amount of IgG was used as control. Quantitative PCR was performed with primers for corresponding positive and negative loci. Figure shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
</center></div>
</div>
<div>
<h3>True MicroChIP-seq protocol in a combination with MicroPlex library preparation kit results in reliable and accurate sequencing data</h3>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><img src="https://www.diagenode.com/img/product/kits/fig2-truemicro.jpg" alt="True MicroChip results" width="800px" /></div>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><center>
<p><small><strong>Figure 2.</strong> Integrative genomics viewer (IGV) visualization of ChIP-seq experiments using 50.000 of K562 cells. ChIP has been performed accordingly to True MicroChIP protocol followed by the library preparation using MicroPlex Library Preparation Kit (C05010001). The above figure shows the peaks from ChIP-seq experiments using the following antibodies: H3K4me1 (C15410194), H3K9/14ac (C15410200), H3K27ac (C15410196) and H3K36me3 (C15410192).</small></p>
</center></div>
</div>
<div>
<h3>Successful chromatin profiling from 10.000 of FACS-sorted cells</h3>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><img src="https://www.diagenode.com/img/product/kits/fig3ab-truemicro.jpg" alt="small non coding RNA" width="800px" /></div>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><center>
<p><small><strong>Figure 3.</strong> (A) Integrative genomics viewer (IGV) visualization of ChIP-seq experiments and heatmap 3kb upstream and downstream of the TSS (B) for H3K4me3. ChIP has been performed using 10.000 of FACS-sorted cells (K562) and H3K4me3 antibody (C15410003) accordingly to True MicroChIP protocol followed by the library preparation using MicroPlex Library Preparation Kit (C05010001). Data were compared to ENCODE standards.</small></p>
</center></div>
</div>
</div>
</div>
</div>
</div>
</div>
<p>
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</p>',
			'label2' => 'Additional solutions compatible with the True MicroChIP-seq Kit',
			'info2' => '<p><span style="font-weight: 400;">The <a href="https://www.diagenode.com/en/p/chromatin-shearing-optimization-kit-high-sds-100-million-cells">Chromatin EasyShear Kit &ndash; High SDS</a></span><span style="font-weight: 400;">&nbsp;Recommended for the optimizing chromatin shearing.</span></p>
<p><a href="https://www.diagenode.com/en/categories/chip-seq-grade-antibodies"><span style="font-weight: 400;">ChIP-seq grade antibodies</span></a><span style="font-weight: 400;"> for high yields, specificity, and sensitivity.</span></p>
<p><span style="font-weight: 400;">Check the list of available </span><a href="https://www.diagenode.com/en/categories/primer-pairs"><span style="font-weight: 400;">primer pairs</span></a><span style="font-weight: 400;"> designed for high specificity to specific genomic regions.</span></p>
<p><span style="font-weight: 400;">For library preparation of immunoprecipitated samples we recommend to use the </span><b>&nbsp;</b><a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq"><span style="font-weight: 400;">MicroPlex Library Preparation Kit</span></a><span style="font-weight: 400;"> - validated for library preparation from picogram inputs.</span></p>
<p><span style="font-weight: 400;">For IP-Star Automation users, check out the </span><a href="https://www.diagenode.com/en/p/auto-true-microchip-kit-16-rxns"><span style="font-weight: 400;">automated version</span></a><span style="font-weight: 400;"> of this kit.</span></p>
<p><span style="font-weight: 400;">Application note: </span><a href="https://www.diagenode.com/files/application_notes/Diagenode_AATI_Joint.pdf"><span style="font-weight: 400;">Best Workflow Practices for ChIP-seq Analysis with Small Samples</span></a></p>
<p></p>',
			'label3' => 'Species, cell lines, tissues tested',
			'info3' => '<p>The True MicroChIP-seq kit is compatible with a broad variety of cell lines, tissues and species - some examples are shown below. Other species / cell lines / tissues can be used with this kit.</p>
<p><strong>Cell lines:</strong></p>
<p>Bovine: blastocysts,<br />Drosophila: embryos, salivary glands<br />Human: EndoC-ẞH1 cells, HeLa cells, PBMC, urothelial cells<br />Mouse: adipocytes, B cells, blastocysts, pre-B cells, BMDM cells, chondrocytes, embryonic stem cells, KH2 cells, LSK cells, macrophages, MEP cells, microglia, NK cells, oocytes, pancreatic cells, P19Cl6 cells, RPE cells,</p>
<p>Other cell lines / species: compatible, not tested</p>
<p><strong>Tissues:</strong></p>
<p>Horse: adipose tissue</p>
<p>Mice: intestine tissue</p>
<p>Other tissues: not tested</p>',
			'format' => '20 rxns',
			'catalog_number' => 'C01010132',
			'old_catalog_number' => 'C01010130',
			'sf_code' => 'C01010132-',
			'type' => 'RFR',
			'search_order' => '04-undefined',
			'price_EUR' => '625',
			'price_USD' => '680',
			'price_GBP' => '575',
			'price_JPY' => '97905',
			'price_CNY' => '',
			'price_AUD' => '1700',
			'country' => 'ALL',
			'except_countries' => 'None',
			'quote' => false,
			'in_stock' => false,
			'featured' => true,
			'no_promo' => false,
			'online' => true,
			'master' => true,
			'last_datasheet_update' => '0000-00-00',
			'slug' => 'true-microchip-kit-x16-16-rxns',
			'meta_title' => 'True MicroChIP-seq Kit | Diagenode C01010132',
			'meta_keywords' => '',
			'meta_description' => 'True MicroChIP-seq Kit provides a robust ChIP protocol suitable for the investigation of histone modifications within chromatin from as few as 10 000 cells, including FACS sorted cells. Compatible with ChIP-qPCR as well as ChIP-seq.',
			'modified' => '2023-04-20 16:06:10',
			'created' => '2015-06-29 14:08:20',
			'ProductsRelated' => array(
				[maximum depth reached]
			),
			'Image' => array(
				[maximum depth reached]
			)
		),
		(int) 3 => array(
			'id' => '1927',
			'antibody_id' => null,
			'name' => 'MicroPlex Library Preparation Kit v2 (12 indexes)',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/MicroPlex-Libary-Prep-Kit-v2-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<p><span><strong>Specifically optimized for ChIP-seq</strong></span><br /><br /><span>The MicroPlex Library Preparation&trade; kit is the only kit on the market which is validated for ChIP-seq and which allows the preparation of indexed libraries from just picogram inputs. In combination with the&nbsp;</span><a href="./true-microchip-kit-x16-16-rxns">True MicroChIP kit</a><span>, it allows for performing ChIP-seq on as few as 10,000 cells. Less input, fewer steps, fewer supplies, faster time to results!&nbsp;</span></p>
<p>The MicroPlex v2 kit (Cat. No. C05010012) contains all necessary reagents including single indexes for multiplexing up to 12 samples using single barcoding. For higher multiplexing (using dual indexes) check <a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns">MicroPlex Library Preparation Kits v3</a>.</p>',
			'label1' => 'Characteristics',
			'info1' => '<ul>
<li><strong>1 tube, 2 hours, 3 steps</strong> protocol</li>
<li><strong>Input: </strong>50 pg &ndash; 50 ng</li>
<li><strong>Reduce potential bias</strong> - few PCR amplification cycles needed</li>
<li><strong>High sensitivity ChIP-seq</strong> - low PCR duplication rate</li>
<li><strong>Great multiplexing flexibility</strong> with 12 barcodes (8 nt) included</li>
<li><strong>Validated with the <a href="https://www.diagenode.com/p/sx-8g-ip-star-compact-automated-system-1-unit" title="IP-Star Automated System">IP-Star<sup>&reg;</sup> Automated Platform</a></strong></li>
</ul>
<h3>How it works</h3>
<center><img src="https://www.diagenode.com/img/product/kits/microplex-method-overview-v2.png" /></center>
<p style="margin-bottom: 0;"><small><strong>Microplex workflow - protocol with single indexes</strong><br />An input of 50 pg to 50 ng of fragmented dsDNA is converted into sequencing-ready libraries for Illumina&reg; NGS platforms using a fast and simple 3-step protocol</small></p>
<ul class="accordion" data-accordion="" id="readmore" style="margin-left: 0;">
<li class="accordion-navigation"><a href="#first" style="background: #ffffff; padding: 0rem; margin: 0rem; color: #13b2a2;"><small>Read more about MicroPlex workflow</small></a>
<div id="first" class="content">
<p><small><strong>Step 1. Template Preparation</strong> provides efficient repair of the fragmented double-stranded DNA input.</small></p>
<p><small>In this step, the DNA is repaired and yields molecules with blunt ends.</small></p>
<p><small><strong>Step 2. Library Synthesis.</strong> enables ligation of MicroPlex patented stem- loop adapters.</small></p>
<p><small>In the next step, stem-loop adaptors with blocked 5&rsquo; ends are ligated with high efficiency to the 5&rsquo; end of the genomic DNA, leaving a nick at the 3&rsquo; end. The adaptors cannot ligate to each other and do not have single- strand tails, both of which contribute to non-specific background found with many other NGS preparations.</small></p>
<p><small><strong>Step 3. Library Amplification</strong> enables extension of the template, cleavage of the stem-loop adaptors, and amplification of the library. Illumina- compatible indexes are also introduced using a high-fidelity, highly- processive, low-bias DNA polymerase.</small></p>
<p><small>In the final step, the 3&rsquo; ends of the genomic DNA are extended to complete library synthesis and Illumina-compatible indexes are added through a high-fidelity amplification. Any remaining free adaptors are destroyed. Hands-on time and the risk of contamination are minimized by using a single tube and eliminating intermediate purifications.</small></p>
<p><small>Obtained libraries are purified, quantified and sized. The libraries pooling can be performed as well before sequencing.</small></p>
</div>
</li>
</ul>
<p></p>
<h3>Reliable detection of enrichments in ChIP-seq</h3>
<p><img src="https://www.diagenode.com/img/product/kits/microplex-library-prep-kit-figure-a.png" alt="Reliable detection of enrichments in ChIP-seq figure 1" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure A.</strong> ChIP has been peformed with H3K4me3 antibody, amplification of 17 pg of DNA ChIP'd from 10.000 cells and amplification of 35 pg of DNA ChIP'd from 100.000 cells (control experiment). The IP'd DNA was amplified and transformed into a sequencing-ready preparation for the Illumina plateform with the MicroPlex Library Preparation kit. The library was then analysed on an Illumina<sup>&reg;</sup> Genome Analyzer. Cluster generation and sequencing were performed according to the manufacturer's instructions.</p>
<p><img src="https://www.diagenode.com/img/product/kits/microplex-library-prep-kit-figure-b.png" alt="Reliable detection of enrichments in ChIP-seq figure 2" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure B.</strong> We observed a perfect match between the top 40% of True MicroChIP peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>',
			'label2' => '',
			'info2' => '',
			'label3' => '',
			'info3' => '',
			'format' => '12 rxns',
			'catalog_number' => 'C05010012',
			'old_catalog_number' => 'C05010010',
			'sf_code' => 'C05010012-',
			'type' => 'FRE',
			'search_order' => '04-undefined',
			'price_EUR' => '935',
			'price_USD' => '1215',
			'price_GBP' => '835',
			'price_JPY' => '146470',
			'price_CNY' => '',
			'price_AUD' => '3038',
			'country' => 'ALL',
			'except_countries' => 'None',
			'quote' => false,
			'in_stock' => false,
			'featured' => false,
			'no_promo' => false,
			'online' => true,
			'master' => true,
			'last_datasheet_update' => '0000-00-00',
			'slug' => 'microplex-library-preparation-kit-v2-x12-12-indices-12-rxns',
			'meta_title' => 'MicroPlex Library Preparation Kit v2 x12 (12 indices)',
			'meta_keywords' => '',
			'meta_description' => 'MicroPlex Library Preparation Kit v2 x12 (12 indices)',
			'modified' => '2023-04-20 15:01:16',
			'created' => '2015-06-29 14:08:20',
			'ProductsRelated' => array(
				[maximum depth reached]
			),
			'Image' => array(
				[maximum depth reached]
			)
		),
		(int) 4 => array(
			'id' => '2264',
			'antibody_id' => '121',
			'name' => 'H3K9me3 Antibody',
			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone<strong> H3 containing the trimethylated lysine 9</strong> (<strong>H3K9me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
			'label1' => 'Validation Data',
			'info1' => '<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig1.png" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K9me3</strong><br />ChIP assays were performed using human HeLa cells, the Diagenode antibody against H3K9me3 (cat. No. C15410193) and optimized PCR primer sets for qPCR. ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using the &ldquo;iDeal ChIP-seq&rdquo; kit (cat. No. C01010051). A titration of the antibody consisting of 0.5, 1, 2, and 5 &micro;g per ChIP experiment was analysed. IgG (1 &micro;g/IP) was used as negative IP control. QPCR was performed with primers for the heterochromatin marker Sat2 and for the ZNF510 gene, used as positive controls, and for the promoters of the active EIF4A2 and GAPDH genes, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2a.png" width="700" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2b.png" width="700" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2c.png" width="700" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2d.png" width="700" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K9me3</strong><br />ChIP was performed with 0.5 &micro;g of the Diagenode antibody against H3K9me3 (cat. No. C15410193) on sheared chromatin from 1,000,000 HeLa cells using the &ldquo;iDeal ChIP-seq&rdquo; kit as described above. The IP'd DNA was subsequently analysed on an Illumina HiSeq 2000. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 50 bp tags were aligned to the human genome using the BWA algorithm. Figure 2A shows the signal distribution along the long arm of chromosome 19 and a zoomin to an enriched region containing several ZNF repeat genes. The arrows indicate two satellite repeat regions which exhibit a stronger signal. Figures 2B, 2C and 2D show the enrichment along the ZNF510 positive control target and at the H19 and KCNQ1 imprinted genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-CT-Fig3a.png" width="700" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-CT-Fig3b.png" width="700" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K9me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 1 &micro;g of the Diagenode antibody against H3K9me3 (cat. No. C15410193) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in a genomic regions on chromosome 1 containing several ZNF repeat genes and in a genomic region surrounding the KCNQ1 imprinting control gene on chromosome 11 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-Elisa-Fig4.png" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the antibody directed against human H3K9me3 (cat. No. C15410193) in antigen coated wells. The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:87,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-DB-Fig5.png" /></center></div>
<div class="small-8 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K9me3</strong><br />A Dot Blot analysis was performed to test the cross reactivity of the Diagenode antibody against H3K9me3 (cat. No. C15410193) with peptides containing other modifications and unmodified sequences of histone H3 and H4. One hundred to 0.2 pmol of the peptide containing the respective histone modification were spotted on a membrane. The antibody was used at a dilution of 1:20,000. Figure 5 shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-WB-Fig6.png" /></center></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K9me3</strong><br />Western blot was performed on whole cell (25 &micro;g, lane 1) and histone extracts (15 &micro;g, lane 2) from HeLa cells, and on 1 &micro;g of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K9me3 (cat. No. C15410193). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-IF-Fig7.png" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K9me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K9me3 (cat. No. C15410193) and with DAPI. Cells were fixed with 4% formaldehyde for 10&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labelled with the H3K9me3 antibody (middle) diluted 1:500 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The left panel shows staining of the nuclei with DAPI. A merge of both stainings is shown on the right.</small></p>
</div>
</div>',
			'label2' => 'Target Description',
			'info2' => '<p>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called &ldquo;histone code&rdquo;. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Trimethylation of histone H3K9 is associated with inactive genomic regions, satellite repeats and ZNF gene repeats.</p>',
			'label3' => '',
			'info3' => '',
			'format' => '50 μg',
			'catalog_number' => 'C15410193',
			'old_catalog_number' => 'pAb-193-050',
			'sf_code' => 'C15410193-D001-000581',
			'type' => 'FRE',
			'search_order' => '03-Antibody',
			'price_EUR' => '480',
			'price_USD' => '470',
			'price_GBP' => '430',
			'price_JPY' => '75190',
			'price_CNY' => '0',
			'price_AUD' => '1175',
			'country' => 'ALL',
			'except_countries' => 'None',
			'quote' => false,
			'in_stock' => false,
			'featured' => false,
			'no_promo' => false,
			'online' => true,
			'master' => true,
			'last_datasheet_update' => 'December 12, 2017',
			'slug' => 'h3k9me3-polyclonal-antibody-premium-50-mg',
			'meta_title' => 'H3K9me3 Antibody - ChIP-seq Grade (C15410193) | Diagenode',
			'meta_keywords' => '',
			'meta_description' => 'H3K9me3  (Histone H3 trimethylated at lysine 9) Polyclonal Antibody validated  in ChIP-seq, ChIP-qPCR, CUT&Tag, ELISA, DB, WB and IF. Specificity confirmed by Peptide array assay. Batch-specific data available on the website. Sample size available.',
			'modified' => '2021-10-20 09:55:53',
			'created' => '2015-06-29 14:08:20',
			'ProductsRelated' => array(
				[maximum depth reached]
			),
			'Image' => array(
				[maximum depth reached]
			)
		),
		(int) 5 => array(
			'id' => '2268',
			'antibody_id' => '70',
			'name' => 'H3K27me3 Antibody',
			'description' => '<p>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 27</strong> (<strong>H3K27me3</strong>), using a KLH-conjugated synthetic peptide.</p>',
			'label1' => 'Validation Data',
			'info1' => '<div class="row">
<div class="small-6 columns">
<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig1.png" alt="H3K27me3 Antibody ChIP Grade" /></p>
<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2.png" alt="H3K27me3 Antibody for ChIP" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K27me3</strong><br />ChIP assays were performed using human HeLa cells, the Diagenode antibody against H3K27me3 (Cat. No. C15410195) and optimized PCR primer pairs for qPCR. ChIP was performed with the &ldquo;iDeal ChIP-seq&rdquo; kit (Cat. No. C01010051), using sheared chromatin from 1 million cells. The chromatin was spiked with a panel of in vitro assembled nucleosomes, each containing a specific lysine methylation. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control.</small></p>
<p><small><strong>Figure 1A.</strong> Quantitative PCR was performed with primers specific for the promoter of the active GAPDH and EIF4A2 genes, used as negative controls, and for the inactive TSH2B and MYT1 genes, used as positive controls. The graph shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
<p><small><strong>Figure 1B.</strong> Recovery of the nucleosomes carrying the H3K27me1, H3K27me2, H3K27me3, H3K4me3, H3K9me3 and H3K36me3 modifications and the unmodified H3K27 as determined by qPCR. The figure clearly shows the antibody is very specific in ChIP for the H3K27me3 modification.</small></p>
</div>
</div>
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<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2a.png" alt="H3K27me3 Antibody ChIP-seq Grade" /></p>
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<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2b.png" alt="H3K27me3 Antibody for ChIP-seq" /></p>
<p>C. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2c.png" alt="H3K27me3 Antibody for ChIP-seq assay" /></p>
<p>D. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2d.png" alt="H3K27me3 Antibody validated in ChIP-seq" /></p>
</div>
</div>
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<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K27me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLa cells using 1 &micro;g of the Diagenode antibody against H3K27me3 (Cat. No. C15410195) as described above. The IP'd DNA was subsequently analysed on an Illumina HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 50 bp tags were aligned to the human genome using the BWA algorithm. Figure 2 shows the enrichment in genomic regions of chromosome 6 and 20, surrounding the TSH2B and MYT1 positive control genes (fig 2A and 2B, respectively), and in two genomic regions of chromosome 1 and X (figure 2C and D).</small></p>
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<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-CUTTAG-Fig3A.png" /></p>
<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-CUTTAG-Fig3B.png" /></p>
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<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K27me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 1 &micro;g of the Diagenode antibody against H3K27me3 (cat. No. C15410195) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions on chromosome and 13 and 20 (figure 3A and B, respectively).</small></p>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-ELISA-Fig4.png" alt="H3K27me3 Antibody ELISA Validation " /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody directed against H3K27me3 (Cat. No. C15410195). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:3,000.</small></p>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-DB-Fig5a.png" alt="H3K27me3 Antibody Dot Blot Validation " /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K27me3</strong><br />A Dot Blot analysis was performed to test the cross reactivity of the Diagenode antibody against H3K27me3 (Cat. No. C15410195) with peptides containing other modifications of histone H3 and H4 and the unmodified H3K27 sequence. One hundred to 0.2 pmol of the peptide containing the respective histone modification were spotted on a membrane. The antibody was used at a dilution of 1:5,000. Figure 5 shows a high specificity of the antibody for the modification of interest. Please note that the antibody also recognizes the modification if S28 is phosphorylated.</small></p>
</div>
</div>
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<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-WB-Fig6.png" alt="H3K27me3 Antibody validated in Western Blot" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K27me3</strong><br />Western blot was performed on whole cell (25 &micro;g, lane 1) and histone extracts (15 &micro;g, lane 2) from HeLa cells, and on 1 &micro;g of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K27me3 (cat. No. C15410195) diluted 1:500 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
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<div class="small-12 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-IF-Fig7.png" alt="H3K27me3 Antibody validated for Immunofluorescence" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K27me3</strong><br />Human HeLa cells were stained with the Diagenode antibody against H3K27me3 (Cat. No. C15410195) and with DAPI. Cells were fixed with 4% formaldehyde for 10&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labelled with the H3K27me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The middle panel shows staining of the nuclei with DAPI. A merge of the two stainings is shown on the right.</small></p>
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			'label2' => 'Target Description',
			'info2' => '<p><small>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which alter chromatin structure to facilitate transcriptional activation, repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called &ldquo;histone code&rdquo;. Histone methylation and demethylation is regulated by histone methyl transferases and histone demethylases. Methylation of histone H3K27 is associated with inactive genomic regions.</small></p>',
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			'format' => '50 μg',
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			'sf_code' => 'C15410195-D001-000581',
			'type' => 'FRE',
			'search_order' => '03-Antibody',
			'price_EUR' => '480',
			'price_USD' => '470',
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			'slug' => 'h3k27me3-polyclonal-antibody-premium-50-mg-27-ml',
			'meta_title' => 'H3K27me3 Antibody - ChIP-seq Grade (C15410195) | Diagenode',
			'meta_keywords' => '',
			'meta_description' => 'H3K27me3 (Histone H3 trimethylated at lysine 27) Polyclonal Antibody validated  in ChIP-seq, ChIP-qPCR, CUT&Tag, ELISA, DB, WB and IF. Specificity confirmed by Peptide array assay. Batch-specific data available on the website. Sample size available.',
			'modified' => '2024-01-17 13:55:58',
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		(int) 6 => array(
			'id' => '2262',
			'antibody_id' => '74',
			'name' => 'H3K36me3 Antibody',
			'description' => '<p>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 36</strong> (<strong>H3K36me3</strong>), using a KLH-conjugated synthetic peptide.</p>',
			'label1' => 'Validation Data',
			'info1' => '<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig1.png" alt="H3K36me3 Antibody ChIP Grade" caption="false" width="432" height="674" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K36me3</strong><br /> <strong>Figure 1A</strong> ChIP assays were performed using human HeLa cells, the Diagenode antibody against H3K36me3 (Cat. No. C15410192) and optimized PCR primer pairs for qPCR. ChIP was performed with the &ldquo;Auto Histone ChIP-seq&rdquo; kit (Cat. No. C01010022) on the IP-Star automated system, using sheared chromatin from 1,000,000 cells. A titration consisting of 1, 2, 5 and 10 &micro;g of antibody per ChIP experiment was analyzed. IgG (2 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers for the coding region of the active GAPDH and ACTB genes, used as positive controls, and for the promoter and a region located 1 kb upstream of the promoter of the GAPDH gene, used as negative controls.<br /><br /> <strong>Figure 1B</strong> ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K36me3 (Cat. No. C15410192) and optimized PCR primer pairs for qPCR. ChIP was performed with the &ldquo;iDeal ChIP-seq&rdquo; kit (Cat. No. C01010051), using sheared chromatin from 100,000 cells. A titration consisting of 0.2, 0.5, 1 and 2 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers for the coding region of the active GAPDH and ACTB genes, used as positive controls, and for the coding region of the inactive MB gene and the Sat satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig2-2.jpg" alt="H3K36me3 Antibody SNAP-ChIP validation" caption="false" width="432" height="298" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 2. ChIP results obtained with the Diagenode antibody directed against H3K36me3</strong><br /> ChIP assays were performed on sheared chromatin from 1 million human HeLa cells as described above. The chromatin was spiked with a panel of in vitro assembled nucleosomes, each containing a specific lysine methylation (SNAP-ChIP K-MetStat Panel, Epicypher). A titration consisting of 0.2, 0.5, 1 and 2 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the nucleosomes carrying the H3K36me1, H3K36me2, H3K36me3, H3K4me3, H3K9me3, H3K27me3 and H4K20me3 modifications and the unmodified H3K4. The graph shows the recovery, expressed as a % of input. These results demonstrate a high specificity of the H3K36me3 antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig2.png" alt="H3K36me3 Antibody for ChIP-seq" caption="false" width="893" height="702" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. ChIP-seq results obtained with the Diagenode antibody directed against H3K36me3</strong><br /> ChIP was performed on sheared chromatin from 100,000 K562 cells with the &ldquo;iDeal ChIP-seq&rdquo; kit (Cat. No. C01010051) using 0.5 &micro;g of the Diagenode antibody against H3K36me3 (Cat. No. C15410192) as described above. The IP&rsquo;d DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer&rsquo;s instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 3 shows the H3K36me3 signal distribution along the complete sequence and a zoomin of human chromosome 12 (figure 2A and B) and in 2 genomic regions containing the GAPDH and ACTB positive control genes (figure 3C and D).</small></p>
</div>
</div>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig3.png" alt="H3K36me3 Antibody ELISA validation" caption="false" width="432" height="328" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K36me3 (Cat. No. C15410192). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:132,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns">
<p>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig4-a.png" alt="H3K36me3 Antibody Dot Blot Validation" caption="false" width="432" height="162" /></p>
<p>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig4-b.png" alt="H3K36me3 Antibody Peptide Array validation" caption="false" width="432" height="257" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K36me3</strong><br /> <strong>Figure 5A.</strong> To test the cross reactivity of the Diagenode antibody against H3K36me3 (Cat. No. C15410192), a Dot Blot analysis was performed with peptides containing other modifications or unmodified sequences of histone H3 and H4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:20,000. Figure 5A shows a high specificity of the antibody for the modification of interest. <strong>Figure 5B.</strong> The specificity of the antibody was further demonstrated by peptide array analyses on an array containing 384 peptides with different combinations of modifications from histone H3, H4, H2A and H2B. The antibody was used at a dilution of 1:10,000. Figure 5B shows the specificity factor, calculated as the ratio of the average intensity of all spots containing the mark, divided by the average intensity of all spots not containing the mark. The peptide array analysis shows a slight cross reaction with H4K20me3 that was not observed in dot blot.</small></p>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig5.png" alt="H3K36me3 Antibody for Western Blot" caption="false" width="432" height="346" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K36me3</strong><br /> Western blot was performed on whole cell (25 &micro;g, lane 1) and histone extracts (15 &micro;g, lane 2) from HeLa cells, and on 1 &micro;g of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K36me3 (Cat. No. C15410192). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is shown on the right, the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig6.png" alt="H3K36me3 Antibody for Immunofluorescence " caption="false" width="893" height="232" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K36me3</strong><br /> HeLa cells were stained with the Diagenode antibody against H3K36me3 (Cat. C15410192) and with DAPI. Cells were fixed with 4% formaldehyde for 10&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labeled with the H3K36me3 antibody (left) diluted 1:500 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The middle panel shows staining of the nuclei with DAPI. A merge of the two stainings is shown on the right.</small></p>
</div>
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			'label2' => 'Target Description',
			'info2' => '<p>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called &ldquo;histone code&rdquo;. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Trimethylation of histone H3K36 is associated with active genes.</p>',
			'label3' => '',
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			'format' => '50 μg',
			'catalog_number' => 'C15410192',
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			'sf_code' => 'C15410192-D001-000581',
			'type' => 'FRE',
			'search_order' => '03-Antibody',
			'price_EUR' => '480',
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			'slug' => 'h3k36me3-polyclonal-antibody-premium-50-mg',
			'meta_title' => 'H3K36me3 Antibody - ChIP-seq Grade (C15410192) | Diagenode',
			'meta_keywords' => '',
			'meta_description' => 'H3K36me3 (Histone H3 trimethylated at lysine 36) Polyclonal Antibody validated  in ChIP-seq, ChIP-grade, ELISA, DB, WB and IF. Specificity confirmed by Peptide array. Batch-specific data available on the website. Sample size available. ',
			'modified' => '2021-10-20 09:55:18',
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		(int) 7 => array(
			'id' => '2173',
			'antibody_id' => '115',
			'name' => 'H3K4me3 Antibody',
			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
			'label1' => 'Validation data',
			'info1' => '<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
</div>
</div>
<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
</div>
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<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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<p>Learn more about: <a href="https://www.diagenode.com/applications/western-blot">Loading control, MW marker visualization</a><em>. <br /></em></p>
<p><em></em>Check our selection of antibodies validated in Western blot.</p>',
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<p>Diagenode offers huge selection of highly sensitive antibodies validated in IF.</p>
<p><img src="https://www.diagenode.com/img/product/antibodies/C15200229-IF.jpg" alt="" height="245" width="256" /></p>
<p><sup><strong>Immunofluorescence using the Diagenode monoclonal antibody directed against CRISPR/Cas9</strong></sup></p>
<p><sup>HeLa cells transfected with a Cas9 expression vector (left) or untransfected cells (right) were fixed in methanol at -20&deg;C, permeabilized with acetone at -20&deg;C and blocked with PBS containing 2% BSA. The cells were stained with the Cas9 C-terminal antibody (Cat. No. C15200229) diluted 1:400, followed by incubation with an anti-mouse secondary antibody coupled to AF488. The bottom images show counter-staining of the nuclei with Hoechst 33342.</sup></p>
<h5><sup>Check our selection of antibodies validated in IF.</sup></h5>',
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<p>Read more:</p>
<p><a href="https://www.diagenode.com/en/categories/cutandtag">Products for CUT&amp;Tag assay</a></p>
<p><a href="https://www.diagenode.com/en/pages/cut-and-tag">Performance of Diagenode's antibodies in CUT&amp;Tag</a></p>
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<p><span style="font-weight: 400;">Diagenode provides leading solutions for epigenetic research. Because ChIP-seq is a widely-used technique, we validate our antibodies in ChIP and ChIP-seq experiments (in addition to conventional methods like Western blot, Dot blot, ELISA, and immunofluorescence) to provide the highest quality antibody. We standardize our validation and production to guarantee high product quality without technical bias. Diagenode guarantees ChIP-seq grade antibody performance under our suggested conditions.</span></p>
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<div class="small-12 medium-9 large-9 columns">
<p><strong>ChIP-seq profile</strong> of active (H3K4me3 and H3K36me3) and inactive (H3K27me3) marks using Diagenode antibodies.</p>
<img src="https://www.diagenode.com/img/categories/antibodies/chip-seq-grade-antibodies.png" /></div>
<div class="small-12 medium-3 large-3 columns">
<p><small> ChIP was performed on sheared chromatin from 100,000 K562 cells using iDeal ChIP-seq kit for Histones (cat. No. C01010051) with 1 &micro;g of the Diagenode antibodies against H3K27me3 (cat. No. C15410195) and H3K4me3 (cat. No. C15410003), and 0.5 &micro;g of the antibody against H3K36me3 (cat. No. C15410192). The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. The figure shows the signal distribution along the complete sequence of human chromosome 3, a zoomin to a 10 Mb region and a further zoomin to a 1.5 Mb region. </small></p>
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<p>Diagenode&rsquo;s highly validated antibodies:</p>
<ul>
<li>Highly sensitive and specific</li>
<li>Cost-effective (requires less antibody per reaction)</li>
<li>Batch-specific data is available on the website</li>
<li>Expert technical support</li>
<li>Sample sizes available</li>
<li>100% satisfaction guarantee</li>
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			'name' => 'Histone antibodies',
			'description' => '<p>Histones are the main protein components of chromatin involved in the compaction of DNA into nucleosomes, the basic units of chromatin. A <strong>nucleosome</strong> consists of one pair of each of the core histones (<strong>H2A</strong>, <strong>H2B</strong>, <strong>H3</strong> and <strong>H4</strong>) forming an octameric structure wrapped by 146 base pairs of DNA. The different nucleosomes are linked by the linker histone<strong> H1, </strong>allowing for further condensation of chromatin.</p>
<p>The core histones have a globular structure with large unstructured N-terminal tails protruding from the nucleosome.&nbsp; They can undergo to multiple post-translational modifications (PTM), mainly at the N-terminal tails. These <strong>post-translational modifications </strong>include&nbsp; methylation, acetylation, phosphorylation, ubiquitinylation, citrullination, sumoylation, deamination and crotonylation.&nbsp; The most well characterized PTMs are <strong>methylation,</strong> <strong>acetylation and phosphorylation</strong>. Histone methylation occurs mainly on lysine (K) residues, which can be mono-, di- or tri-methylated, and on arginines (R), which can be mono-methylated and symmetrically or asymmetrically di-methylated. Histone acetylation occurs on lysines and histone phosphorylation mainly on serines (S), threonines (T) and tyrosines (Y).</p>
<p>The PTMs of the different residues are involved in numerous processes such as DNA repair, DNA replication and chromosome condensation. They influence the chromatin organization and can be positively or negatively associated with gene expression. Trimethylation of H3K4, H3K36 and H3K79, and lysine acetylation generally result in an open chromatin configuration (figure below) and are therefore associated with <strong>euchromatin</strong> and gene activation. Trimethylation of H3K9, K3K27 and H4K20, on the other hand, is enriched in <strong>heterochromatin </strong>and associated with gene silencing. The combination of different histone modifications is called the "<strong>histone code</strong>&rdquo;, analogous to the genetic code.</p>
<p><img src="https://www.diagenode.com/img/categories/antibodies/histone-marks-illustration.png" /></p>
<p>Diagenode is proud to offer a large range of antibodies against histones and histone modifications. Our&nbsp; antibodies are highly specific and have been validated in many applications, including <strong>ChIP</strong> and <strong>ChIP-seq</strong>.</p>
<p>Diagenode&rsquo;s collection includes antibodies recognizing:</p>
<ul>
<li><strong>Histone H1 variants</strong></li>
<li><strong>Histone H2A, H2A variants and histone H2A</strong> <strong>modifications</strong> (serine phosphorylation, lysine acetylation, lysine ubiquitinylation)</li>
<li><strong>Histone H2B and H2B</strong> <strong>modifications </strong>(serine phosphorylation, lysine acetylation)</li>
<li><strong>Histone H3 and H3 modifications </strong>(lysine methylation (mono-, di- and tri-methylated), lysine acetylation, serine phosphorylation, threonine phosphorylation, arginine methylation (mono-methylated, symmetrically and asymmetrically di-methylated))</li>
<li><strong>Histone H4 and H4 modifications (</strong>lysine methylation (mono-, di- and tri-methylated), lysine acetylation, arginine methylation (mono-methylated and symmetrically di-methylated), serine phosphorylation )</li>
</ul>
<p><span style="font-weight: 400;"><strong>HDAC's HAT's, HMT's and other</strong> <strong>enzymes</strong> which modify histones can be found in the category <a href="../categories/chromatin-modifying-proteins-histone-transferase">Histone modifying enzymes</a><br /></span></p>
<p><span style="font-weight: 400;"> Diagenode&rsquo;s highly validated antibodies:</span></p>
<ul>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Highly sensitive and specific</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Cost-effective (requires less antibody per reaction)</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Batch-specific data is available on the website</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Expert technical support</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Sample sizes available</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 100% satisfaction guarantee</span></li>
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			'description' => '<h1><strong>Validated epigenetics antibodies</strong>&nbsp;&ndash; care for a sample?<br />&nbsp;</h1>
<p>Diagenode has partnered with leading epigenetics experts and numerous epigenetics consortiums to bring to you a validated and comprehensive collection of epigenetic antibodies. As an expert in epigenetics, we are committed to offering highly-specific antibodies validated for ChIP/ChIP-seq and many other applications. All batch-specific validation data is available on our website.<br /><a href="../categories/antibodies">Read about our expertise in antibody production</a>.</p>
<ul>
<li><strong>Focused</strong> -&nbsp;Diagenode's selection of antibodies is exclusively dedicated for epigenetic research. <a title="See the full collection." href="../categories/all-antibodies">See the full collection.</a></li>
<li><strong>Strict quality standards</strong>&nbsp;with rigorous QC and validation</li>
<li><strong>Classified</strong>&nbsp;based on level of validation for flexibility of application</li>
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<p>Existing sample sizes are listed below. We will soon expand our collection. &nbsp;Are you looking for a sample size of another antibody? Just <a href="mailto:agnieszka.zelisko@diagenode.com?Subject=Sample%20Size%20Request" target="_top">Contact us</a>.</p>',
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			'description' => '<p><span style="font-weight: 400;">All Diagenode&rsquo;s antibodies are listed below. Please, use our Quick search field to find the antibody of interest by target name, application, purity.</span></p>
<p><span style="font-weight: 400;">Diagenode&rsquo;s highly validated antibodies:</span></p>
<ul>
<li>Highly sensitive and specific</li>
<li>Cost-effective (requires less antibody per reaction)</li>
<li>Batch-specific data is available on the website</li>
<li>Expert technical support</li>
<li>Sample sizes available</li>
<li>100% satisfaction guarantee</li>
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			'meta_title' => 'Diagenode's selection of Antibodies is exclusively dedicated for Epigenetic Research | Diagenode',
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			'name' => 'ChIP-grade antibodies',
			'description' => '<div class="row">
<div class="small-12 columns"><center></center>
<p><br />Chromatin immunoprecipitation (<b>ChIP</b>) is a technique to study the associations of proteins with the specific genomic regions in intact cells. One of the most important steps of this protocol is the immunoprecipitation of targeted protein using the antibody specifically recognizing it. The quality of antibodies used in ChIP is essential for the success of the experiment. Diagenode offers extensively validated ChIP-grade antibodies, confirmed for their specificity, and high level of performance in ChIP. Each batch is validated, and batch-specific data are available on the website.</p>
<p></p>
</div>
</div>
<p><strong>ChIP results</strong> obtained with the antibody directed against H3K4me3 (Cat. No. <a href="../p/h3k4me3-polyclonal-antibody-premium-50-ug-50-ul">C15410003</a>).&nbsp;</p>
<div class="row">
<div class="small-12 medium-6 large-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" alt="" width="400" height="315" />&nbsp;</div>
<div class="small-12 medium-6 large-6 columns">
<p></p>
<p></p>
<p></p>
</div>
</div>
<p></p>
<p>Our aim at Diagenode is to offer the largest collection of highly specific <strong>ChIP-grade antibodies</strong>. We add new antibodies monthly. Find your ChIP-grade antibody in the list below and check more information about tested applications, extensive validation data, and product information.</p>',
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			'name' => 'Datasheet H3K4me3 C15410003',
			'description' => '<p>Datasheet description</p>',
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			'type' => 'Datasheet',
			'url' => 'files/products/antibodies/Datasheet_H3K4me3_C15410003.pdf',
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			'name' => 'Antibodies you can trust',
			'description' => '<p style="text-align: justify;"><span>Epigenetic research tools have evolved over time from endpoint PCR to qPCR to the analyses of large sets of genome-wide sequencing data. ChIP sequencing (ChIP-seq) has now become the gold standard method for chromatin studies, given the accuracy and coverage scale of the approach over other methods. Successful ChIP-seq, however, requires a higher level of experimental accuracy and consistency in all steps of ChIP than ever before. Particularly crucial is the quality of ChIP antibodies. </span></p>',
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			'type' => 'Poster',
			'url' => 'files/posters/Antibodies_you_can_trust_Poster.pdf',
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		(int) 0 => array(
			'id' => '5000',
			'name' => 'Claudin-1 as a potential marker of stress-induced premature senescence in vascular smooth muscle cells',
			'authors' => 'Agnieszka Gadecka et al.',
			'description' => '<p><span>Cellular senescence, a permanent state of cell cycle arrest, can result either from external stress and is then called stress-induced premature senescence (SIPS), or from the exhaustion of cell division potential giving rise to replicative senescence (RS). Despite numerous biomarkers distinguishing SIPS from RS remains challenging. We propose claudin-1 (CLDN1) as a potential cell-specific marker of SIPS in vascular smooth muscle cells (VSMCs). In our study, VSMCs subjected to RS or SIPS exhibited significantly higher levels of CLDN1 expression exclusively in SIPS. Moreover, nuclear accumulation of this protein was also characteristic only of prematurely senescent cells. ChIP-seq results suggest that higher CLDN1 expression in SIPS might be a result of a more open chromatin state, as evidenced by a broader H3K4me3 peak in the gene promoter region. However, the broad H3K4me3 peak and relatively high&nbsp;</span><em>CLDN1</em><span><span>&nbsp;</span>expression in RS did not translate into protein level, which implies a different regulatory mechanism in this type of senescence. Elevated CLDN1 levels were also observed in VSMCs isolated from atherosclerotic plaques, although this was highly donor dependent. These findings indicate that increased CLDN1 level in prematurely senescent cells may serve as a promising cell-specific marker of SIPS in VSMCs, both in vitro and ex vivo.</span></p>',
			'date' => '2024-11-07',
			'pmid' => 'https://www.researchsquare.com/article/rs-5192437/v1',
			'doi' => 'https://doi.org/10.21203/rs.3.rs-5192437/v1',
			'modified' => '2024-11-12 09:27:24',
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		(int) 1 => array(
			'id' => '4965',
			'name' => 'Trained immunity is regulated by T cell-induced CD40-TRAF6 signaling',
			'authors' => 'Jacobs M.M.E. et al.',
			'description' => '<p><span>Trained immunity is characterized by histone modifications and metabolic changes in innate immune cells following exposure to inflammatory signals, leading to heightened responsiveness to secondary stimuli. Although our understanding of the molecular regulation of trained immunity has increased, the role of adaptive immune cells herein remains largely unknown. Here, we show that T&nbsp;cells modulate trained immunity via cluster of differentiation 40-tissue necrosis factor receptor-associated factor 6 (CD40-TRAF6) signaling. CD40-TRAF6 inhibition modulates functional, transcriptomic, and metabolic reprogramming and modifies histone 3 lysine 4 trimethylation associated with trained immunity. Besides&nbsp;</span><i>in&nbsp;vitro</i><span><span>&nbsp;</span>studies, we reveal that single-nucleotide polymorphisms in the proximity of<span>&nbsp;</span></span><i>CD40</i><span><span>&nbsp;</span>are linked to trained immunity responses<span>&nbsp;</span></span><i>in&nbsp;vivo</i><span><span>&nbsp;</span>and that combining CD40-TRAF6 inhibition with cytotoxic T lymphocyte antigen 4-immunoglobulin (CTLA4-Ig)-mediated co-stimulatory blockade induces long-term graft acceptance in a murine heart transplantation model. Combined, our results reveal that trained immunity is modulated by CD40-TRAF6 signaling between myeloid and adaptive immune cells and that this can be leveraged for therapeutic purposes.</span></p>',
			'date' => '2024-09-24',
			'pmid' => 'https://www.cell.com/cell-reports/fulltext/S2211-1247(24)01015-5',
			'doi' => '',
			'modified' => '2024-09-02 10:23:11',
			'created' => '2024-09-02 10:23:11',
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		(int) 2 => array(
			'id' => '4958',
			'name' => 'Legionella pneumophila modulates macrophage functions through epigenetic reprogramming via the C-type lectin receptor Mincle',
			'authors' => 'Stegmann F. et al.',
			'description' => '<p><em>Legionella pneumophila</em><span><span>&nbsp;</span>is a pathogen which can lead to a severe form of pneumonia in humans known as Legionnaires disease after replication in alveolar macrophages. Viable<span>&nbsp;</span></span><em>L.&nbsp;pneumophila</em><span><span>&nbsp;</span>actively secrete effector molecules to modulate the host&rsquo;s immune response. Here, we report that<span>&nbsp;</span></span><em>L.&nbsp;pneumophila</em><span>-derived factors reprogram macrophages into a tolerogenic state, a process to which the C-type lectin receptor Mincle (CLEC4E) markedly contributes. The underlying epigenetic state is characterized by increases of the closing mark H3K9me3 and decreases of the opening mark H3K4me3, subsequently leading to the reduced secretion of the cytokines TNF, IL-6, IL-12, the production of reactive oxygen species, and cell-surface expression of MHC-II and CD80 upon re-stimulation. In summary, these findings provide important implications for our understanding of Legionellosis and the contribution of Mincle to reprogramming of macrophages by<span>&nbsp;</span></span><em>L.&nbsp;pneumophila</em><span>.</span></p>',
			'date' => '2024-09-20',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S2589004224019254#:~:text=L.,crucial%20for%20mediating%20tolerance%20induction.',
			'doi' => 'https://doi.org/10.1016/j.isci.2024.110700',
			'modified' => '2024-09-02 10:06:00',
			'created' => '2024-09-02 10:06:00',
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		(int) 3 => array(
			'id' => '4974',
			'name' => 'Systematic prioritization of functional variants and effector genes underlying colorectal cancer risk',
			'authors' => 'Law P.J. et al.',
			'description' => '<p><span>Genome-wide association studies of colorectal cancer (CRC) have identified 170 autosomal risk loci. However, for most of these, the functional variants and their target genes are unknown. Here, we perform statistical fine-mapping incorporating tissue-specific epigenetic annotations and massively parallel reporter assays to systematically prioritize functional variants for each CRC risk locus. We identify plausible causal variants for the 170 risk loci, with a single variant for 40. We link these variants to 208 target genes by analyzing colon-specific quantitative trait loci and implementing the activity-by-contact model, which integrates epigenomic features and Micro-C data, to predict enhancer&ndash;gene connections. By deciphering CRC risk loci, we identify direct links between risk variants and target genes, providing further insight into the molecular basis of CRC susceptibility and highlighting potential pharmaceutical targets for prevention and treatment.</span></p>',
			'date' => '2024-09-16',
			'pmid' => 'https://www.nature.com/articles/s41588-024-01900-w',
			'doi' => 'https://doi.org/10.1038/s41588-024-01900-w',
			'modified' => '2024-09-23 10:14:18',
			'created' => '2024-09-23 10:14:18',
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			)
		),
		(int) 4 => array(
			'id' => '4971',
			'name' => 'Bivalent chromatin accommodates survivin and BRG1/SWI complex to activate DNA damage response in CD4+ cells',
			'authors' => 'Chandrasekaran V. et al.',
			'description' => '<section aria-labelledby="Abs1" data-title="Abstract" lang="en">
<div class="c-article-section" id="Abs1-section">
<div class="c-article-section__content" id="Abs1-content">
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Background</h3>
<p>Bivalent regions of chromatin (BvCR) are characterized by trimethylated lysine 4 (H3K4me3) and lysine 27 on histone H3 (H3K27me3) deposition which aid gene expression control during cell differentiation. The role of BvCR in post-transcriptional DNA damage response remains unidentified. Oncoprotein survivin binds chromatin and mediates IFN&gamma; effects in CD4<sup>+</sup><span>&nbsp;</span>cells. In this study, we explored the role of BvCR in DNA damage response of autoimmune CD4<sup>+</sup><span>&nbsp;</span>cells in rheumatoid arthritis (RA).</p>
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Methods</h3>
<p>We performed deep sequencing of the chromatin bound to survivin, H3K4me3, H3K27me3, and H3K27ac, in human CD4<sup>+</sup><span>&nbsp;</span>cells and identified BvCR, which possessed all three histone H3 modifications. Protein partners of survivin on chromatin were predicted by integration of motif enrichment analysis, computational machine-learning, and structural modeling, and validated experimentally by mass spectrometry and peptide binding array. Survivin-dependent change in BvCR and transcription of genes controlled by the BvCR was studied in CD4<sup>+</sup><span>&nbsp;</span>cells treated with survivin inhibitor, which revealed survivin-dependent biological processes. Finally, the survivin-dependent processes were mapped to the transcriptome of CD4<sup>+</sup><span>&nbsp;</span>cells in blood and in synovial tissue of RA patients and the effect of modern immunomodulating drugs on these processes was explored.</p>
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Results</h3>
<p>We identified that BvCR dominated by H3K4me3 (H3K4me3-BvCR) accommodated survivin within<span>&nbsp;</span><i>cis</i>-regulatory elements of the genes controlling DNA damage. Inhibition of survivin or JAK-STAT signaling enhanced H3K4me3-BvCR dominance, which improved DNA damage recognition and arrested cell cycle progression in cultured CD4<sup>+</sup><span>&nbsp;</span>cells. Specifically, BvCR accommodating survivin aided sequence-specific anchoring of the BRG1/SWI chromatin-remodeling complex coordinating DNA damage response. Mapping survivin interactome to BRG1/SWI complex demonstrated interaction of survivin with the subunits anchoring the complex to chromatin. Co-expression of BRG1, survivin and IFN&gamma; in CD4<sup>+</sup><span>&nbsp;</span>cells rendered complete deregulation of DNA damage response in RA. Such cells possessed strong ability of homing to RA joints. Immunomodulating drugs inhibited the anchoring subunits of BRG1/SWI complex, which affected arthritogenic profile of CD4<sup>+</sup><span>&nbsp;</span>cells.</p>
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Conclusions</h3>
<p>BvCR execute DNA damage control to maintain genome fidelity in IFN-activated CD4<sup>+</sup><span>&nbsp;</span>cells. Survivin anchors the BRG1/SWI complex to BvCR to repress DNA damage response. These results offer a platform for therapeutic interventions targeting survivin and BRG1/SWI complex in autoimmunity.</p>
</div>
</div>
</section>
<section data-title="Background">
<div class="c-article-section" id="Sec1-section">
<h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec1"></h2>
</div>
</section>',
			'date' => '2024-09-11',
			'pmid' => 'https://biosignaling.biomedcentral.com/articles/10.1186/s12964-024-01814-4',
			'doi' => 'https://doi.org/10.1186/s12964-024-01814-4',
			'modified' => '2024-09-16 10:02:18',
			'created' => '2024-09-16 10:02:18',
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		),
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			'id' => '4951',
			'name' => 'LL37/self-DNA complexes mediate monocyte reprogramming',
			'authors' => 'Aman Damara et al.',
			'description' => '<p><span>LL37 alone and in complex with self-DNA triggers inflammatory responses in myeloid cells and plays a crucial role in the development of systemic autoimmune diseases, like psoriasis and systemic lupus erythematosus. We demonstrated that LL37/self-DNA complexes induce long-term metabolic and epigenetic changes in monocytes, enhancing their responsiveness to subsequent stimuli. Monocytes trained with LL37/self-DNA complexes and those derived from psoriatic patients exhibited heightened glycolytic and oxidative phosphorylation rates, elevated release of proinflammatory cytokines, and affected na&iuml;ve CD4</span><sup>+</sup><span><span>&nbsp;</span>T cells. Additionally, KDM6A/B, a demethylase of lysine 27 on histone 3, was upregulated in psoriatic monocytes and monocytes treated with LL37/self-DNA complexes. Inhibition of KDM6A/B reversed the trained immune phenotype by reducing proinflammatory cytokine production, metabolic activity, and the induction of IL-17-producing T cells by LL37/self-DNA-treated monocytes. Our findings highlight the role of LL37/self-DNA-induced innate immune memory in psoriasis pathogenesis, uncovering its impact on monocyte and T cell dynamics.</span></p>',
			'date' => '2024-08-01',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S1521661624003966',
			'doi' => 'https://doi.org/10.1016/j.clim.2024.110287',
			'modified' => '2024-07-04 15:53:17',
			'created' => '2024-07-04 15:53:17',
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		),
		(int) 6 => array(
			'id' => '4968',
			'name' => 'Innate immune training restores pro-reparative myeloid functions to promote remyelination in the aged central nervous system',
			'authors' => 'Tiwari V. et al.',
			'description' => '<p><span>The reduced ability of the central nervous system to regenerate with increasing age limits functional recovery following demyelinating injury. Previous work has shown that myelin debris can overwhelm the metabolic capacity of microglia, thereby impeding tissue regeneration in aging, but the underlying mechanisms are unknown. In a model of demyelination, we found that a substantial number of genes that were not effectively activated in aged myeloid cells displayed epigenetic modifications associated with restricted chromatin accessibility. Ablation of two class I histone deacetylases in microglia was sufficient to restore the capacity of aged mice to remyelinate lesioned tissue. We used Bacillus Calmette-Guerin (BCG), a live-attenuated vaccine, to train the innate immune system and detected epigenetic reprogramming of brain-resident myeloid cells and functional restoration of myelin debris clearance and lesion recovery. Our results provide insight into aging-associated decline in myeloid function and how this decay can be prevented by innate immune reprogramming.</span></p>',
			'date' => '2024-07-24',
			'pmid' => 'https://www.cell.com/immunity/fulltext/S1074-7613(24)00348-0',
			'doi' => '',
			'modified' => '2024-09-02 17:05:54',
			'created' => '2024-09-02 17:05:54',
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		),
		(int) 7 => array(
			'id' => '4954',
			'name' => 'A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment',
			'authors' => 'Perez R. F. at al. ',
			'description' => '<p><span>Aging involves the deterioration of organismal function, leading to the emergence of multiple pathologies. Environmental stimuli, including lifestyle, can influence the trajectory of this process and may be used as tools in the pursuit of healthy aging. To evaluate the role of epigenetic mechanisms in this context, we have generated bulk tissue and single cell multi-omic maps of the male mouse dorsal hippocampus in young and old animals exposed to environmental stimulation in the form of enriched environments. We present a molecular atlas of the aging process, highlighting two distinct axes, related to inflammation and to the dysregulation of mRNA metabolism, at the functional RNA and protein level. Additionally, we report the alteration of heterochromatin domains, including the loss of bivalent chromatin and the uncovering of a heterochromatin-switch phenomenon whereby constitutive heterochromatin loss is partially mitigated through gains in facultative heterochromatin. Notably, we observed the multi-omic reversal of a great number of aging-associated alterations in the context of environmental enrichment, which was particularly linked to glial and oligodendrocyte pathways. In conclusion, our work describes the epigenomic landscape of environmental stimulation in the context of aging and reveals how lifestyle intervention can lead to the multi-layered reversal of aging-associated decline.</span></p>',
			'date' => '2024-07-16',
			'pmid' => 'https://www.nature.com/articles/s41467-024-49608-z',
			'doi' => 'https://doi.org/10.1038/s41467-024-49608-z',
			'modified' => '2024-07-29 11:33:49',
			'created' => '2024-07-29 11:33:49',
			'ProductsPublication' => array(
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		(int) 8 => array(
			'id' => '4946',
			'name' => 'The landscape of RNA-chromatin interaction reveals small non-coding RNAs as essential mediators of leukemia maintenance',
			'authors' => 'Haiyang Yun et al.',
			'description' => '<p><span>RNA constitutes a large fraction of chromatin. Spatial distribution and functional relevance of most of RNA-chromatin interactions remain unknown. We established a landscape analysis of RNA-chromatin interactions in human acute myeloid leukemia (AML). In total more than 50 million interactions were captured in an AML cell line. Protein-coding mRNAs and long non-coding RNAs exhibited a substantial number of interactions with chromatin in&nbsp;</span><i>cis</i><span><span>&nbsp;</span>suggesting transcriptional activity. In contrast, small nucleolar RNAs (snoRNAs) and small nuclear RNAs (snRNAs) associated with chromatin predominantly in<span>&nbsp;</span></span><i>trans</i><span><span>&nbsp;</span>suggesting chromatin specific functions. Of note, snoRNA-chromatin interaction was associated with chromatin modifications and occurred independently of the classical snoRNA-RNP complex. Two C/D box snoRNAs, namely<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span>, displayed high frequency of<span>&nbsp;</span></span><i>trans</i><span>-association with chromatin. The transcription of<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span><span>&nbsp;</span>was increased upon leukemia transformation and enriched in leukemia stem cells, but decreased during myeloid differentiation. Suppression of<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span><span>&nbsp;</span>impaired leukemia cell proliferation and colony forming capacity in AML cell lines and primary patient samples. Notably, this effect was leukemia specific with less impact on healthy CD34+ hematopoietic stem and progenitor cells. These findings highlight the functional importance of chromatin-associated RNAs overall and in particular of<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span><span>&nbsp;</span>in maintaining leukemia propagation.</span></p>',
			'date' => '2024-06-28',
			'pmid' => 'https://www.nature.com/articles/s41375-024-02322-7',
			'doi' => 'https://doi.org/10.1038/s41375-024-02322-7',
			'modified' => '2024-07-04 14:32:41',
			'created' => '2024-07-04 14:32:41',
			'ProductsPublication' => array(
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			)
		),
		(int) 9 => array(
			'id' => '4948',
			'name' => 'Single-cell epigenomic reconstruction of developmental trajectories from pluripotency in human neural organoid systems',
			'authors' => 'Fides Zenk et al.',
			'description' => '<p><span>Cell fate progression of pluripotent progenitors is strictly regulated, resulting in high human cell diversity. Epigenetic modifications also orchestrate cell fate restriction. Unveiling the epigenetic mechanisms underlying human cell diversity has been difficult. In this study, we use human brain and retina organoid models and present single-cell profiling of H3K27ac, H3K27me3 and H3K4me3 histone modifications from progenitor to differentiated neural fates to reconstruct the epigenomic trajectories regulating cell identity acquisition. We capture transitions from pluripotency through neuroepithelium to retinal and brain region and cell type specification. Switching of repressive and activating epigenetic modifications can precede and predict cell fate decisions at each stage, providing a temporal census of gene regulatory elements and transcription factors. Removing H3K27me3 at the neuroectoderm stage disrupts fate restriction, resulting in aberrant cell identity acquisition. Our single-cell epigenome-wide map of human neural organoid development serves as a blueprint to explore human cell fate determination.</span></p>',
			'date' => '2024-06-24',
			'pmid' => 'https://www.nature.com/articles/s41593-024-01652-0',
			'doi' => 'https://doi.org/10.1038/s41593-024-01652-0',
			'modified' => '2024-07-04 14:54:14',
			'created' => '2024-07-04 14:54:14',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 10 => array(
			'id' => '4924',
			'name' => 'SURVIVIN IN SYNERGY WITH BAF/SWI COMPLEX BINDS BIVALENT CHROMATIN REGIONS AND ACTIVATES DNA DAMAGE RESPONSE IN CD4+ T CELLS',
			'authors' => 'Chandrasekaran V. et al.',
			'description' => '<p id="p-2">This study explores a regulatory role of oncoprotein survivin on the bivalent regions of chromatin (BvCR) characterized by concomitant deposition of trimethylated lysine of histone H3 at position 4 (H3K4me3) and 27 (H3K27me3).</p>
<p id="p-3">Intersect between BvCR and chromatin sequences bound to survivin demonstrated their co-localization on<span>&nbsp;</span><em>cis</em>-regulatory elements of genes which execute DNA damage control in primary human CD4<sup>+</sup><span>&nbsp;</span>cells. Survivin anchored BRG1-complex to BvCR to repress DNA damage repair genes in IFN&gamma;-stimulated CD4<sup>+</sup><span>&nbsp;</span>cells. In contrast, survivin inhibition shifted the functional balance of BvCR in favor of H3K4me3, which activated DNA damage recognition and repair. Co-expression of BRG1, survivin and IFN&gamma; in CD4<sup>+</sup><span>&nbsp;</span>cells of patients with rheumatoid arthritis identified arthritogenic BRG1<sup>hi</sup><span>&nbsp;</span>cells abundant in autoimmune synovia. Immunomodulating drugs inhibited the subunits anchoring BRG1-complex to BvCR, which changed the arthritogenic profile.</p>
<p id="p-4">Together, this study demonstrates the function of BvCR in DNA damage control of CD4<sup>+</sup><span>&nbsp;</span>cells offering an epigenetic platform for survivin and BRG1-complex targeting interventions to combat autoimmunity.</p>
<div id="sec-1" class="subsection">
<p id="p-5"><strong>Summary</strong><span>&nbsp;</span>This study shows that bivalent chromatin regions accommodate survivin which represses DNA repair enzymes in IFN&gamma;-stimulated CD4<sup>+</sup><span>&nbsp;</span>T cells. Survivin anchors BAF/SWI complex to these regions and supports autoimmune profile of T cells, providing novel targets for therapeutic intervention.</p>
</div>',
			'date' => '2024-03-10',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/2024.03.05.583464v1',
			'doi' => 'https://doi.org/10.1101/2024.03.05.583464',
			'modified' => '2024-03-13 17:07:31',
			'created' => '2024-03-13 17:07:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 11 => array(
			'id' => '4911',
			'name' => 'Multiomics uncovers the epigenomic and transcriptomic response to viral and bacterial stimulation in turbot',
			'authors' => 'Aramburu O. et al.',
			'description' => '<p><span>Uncovering the epigenomic regulation of immune responses is essential for a comprehensive understanding of host defence mechanisms but remains poorly described in farmed fish. Here, we report the first annotation of the innate immune regulatory response in the genome of turbot (</span><em>Scophthalmus maximus</em><span>), a farmed flatfish. We integrated RNA-Seq with ATAC-Seq and ChIP-Seq (histone marks H3K4me3, H3K27ac and H3K27me3) using samples from head kidney. Sampling was performed 24 hours post-stimulation with viral (poly I:C) and bacterial (inactivate<span>&nbsp;</span></span><em>Vibrio anguillarum</em><span>) mimics<span>&nbsp;</span></span><em>in vivo</em><span><span>&nbsp;</span>and<span>&nbsp;</span></span><em>in vitro</em><span><span>&nbsp;</span>(primary leukocyte cultures). Among the 8,797 differentially expressed genes (DEGs), we observed enrichment of transcriptional activation pathways in response to<span>&nbsp;</span></span><em>Vibrio</em><span><span>&nbsp;</span>and immune response pathways - including interferon stimulated genes - for poly I:C. Meanwhile, metabolic and cell cycle were downregulated by both mimics. We identified notable differences in chromatin accessibility (20,617<span>&nbsp;</span></span><em>in vitro</em><span>, 59,892<span>&nbsp;</span></span><em>in vivo</em><span>) and H3K4me3 bound regions (11,454<span>&nbsp;</span></span><em>in vitro</em><span>, 10,275<span>&nbsp;</span></span><em>in viv</em><span>o) - i.e. marking active promoters - between stimulations and controls. Overlaps of DEGs with promoters showing differential accessibility or histone mark binding revealed a significant coupling of the transcriptome and chromatin state. DEGs with activation marks in their promoters were enriched for similar functions to the global DEG set, but not in all cases, suggesting key regulatory genes were in poised or bivalent states. Active promoters and putative enhancers were differentially enriched in transcription factor binding motifs, many of them common to viral and bacterial responses. Finally, an in-depth analysis of immune response changes in chromatin state surrounding key DEGs encoding transcription factors was performed. This comprehensive multi-omics investigation provides an improved understanding of the epigenomic basis for the turbot immune responses and provides novel functional genomic information that can be leveraged in selective breeding towards enhanced disease resistance.</span></p>',
			'date' => '2024-02-15',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/2024.02.15.580452v1',
			'doi' => 'https://doi.org/10.1101/2024.02.15.580452',
			'modified' => '2024-02-22 11:41:27',
			'created' => '2024-02-22 11:41:27',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 12 => array(
			'id' => '4842',
			'name' => 'Alterations in the hepatocyte epigenetic landscape in steatosis.',
			'authors' => 'Maji  Ranjan K. et al.',
			'description' => '<p>Fatty liver disease or the accumulation of fat in the liver, has been reported to affect the global population. This comes with an increased risk for the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Yet, little is known about the effects of a diet containing high fat and alcohol towards epigenetic aging, with respect to changes in transcriptional and epigenomic profiles. In this study, we took up a multi-omics approach and integrated gene expression, methylation signals, and chromatin signals to study the epigenomic effects of a high-fat and alcohol-containing diet on mouse hepatocytes. We identified four relevant gene network clusters that were associated with relevant pathways that promote steatosis. Using a machine learning approach, we predict specific transcription factors that might be responsible to modulate the functionally relevant clusters. Finally, we discover four additional CpG loci and validate aging-related differential CpG methylation. Differential CpG methylation linked to aging showed minimal overlap with altered methylation in steatosis.</p>',
			'date' => '2023-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37415213',
			'doi' => '10.1186/s13072-023-00504-8',
			'modified' => '2023-08-01 14:08:16',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 13 => array(
			'id' => '4859',
			'name' => 'Sexual differentiation in human malaria parasites is regulated bycompetition between phospholipid metabolism and histone methylation.',
			'authors' => 'Harris  C. T. et al.',
			'description' => '<p>For Plasmodium falciparum, the most widespread and virulent malaria parasite that infects humans, persistence depends on continuous asexual replication in red blood cells, while transmission to their mosquito vector requires asexual blood-stage parasites to differentiate into non-replicating gametocytes. This decision is controlled by stochastic derepression of a heterochromatin-silenced locus encoding AP2-G, the master transcription factor of sexual differentiation. The frequency of ap2-g derepression was shown to be responsive to extracellular phospholipid precursors but the mechanism linking these metabolites to epigenetic regulation of ap2-g was unknown. Through a combination of molecular genetics, metabolomics and chromatin profiling, we show that this response is mediated by metabolic competition for the methyl donor S-adenosylmethionine between histone methyltransferases and phosphoethanolamine methyltransferase, a critical enzyme in the parasite's pathway for de novo phosphatidylcholine synthesis. When phosphatidylcholine precursors are scarce, increased consumption of SAM for de novo phosphatidylcholine synthesis impairs maintenance of the histone methylation responsible for silencing ap2-g, increasing the frequency of derepression and sexual differentiation. This provides a key mechanistic link that explains how LysoPC and choline availability can alter the chromatin status of the ap2-g locus controlling sexual differentiation.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37277533',
			'doi' => '10.1038/s41564-023-01396-w',
			'modified' => '2023-08-01 14:48:21',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 14 => array(
			'id' => '4862',
			'name' => 'Mutant FUS induces chromatin reorganization in the hippocampus andalters memory processes.',
			'authors' => 'Tzeplaeff  L. et al.',
			'description' => '<p>Cytoplasmic mislocalization of the nuclear Fused in Sarcoma (FUS) protein is associated to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cytoplasmic FUS accumulation is recapitulated in the frontal cortex and spinal cord of heterozygous Fus mice. Yet, the mechanisms linking FUS mislocalization to hippocampal function and memory formation are still not characterized. Herein, we show that in these mice, the hippocampus paradoxically displays nuclear FUS accumulation. Multi-omic analyses showed that FUS binds to a set of genes characterized by the presence of an ETS/ELK-binding motifs, and involved in RNA metabolism, transcription, ribosome/mitochondria and chromatin organization. Importantly, hippocampal nuclei showed a decompaction of the neuronal chromatin at highly expressed genes and an inappropriate transcriptomic response was observed after spatial training of Fus mice. Furthermore, these mice lacked precision in a hippocampal-dependent spatial memory task and displayed decreased dendritic spine density. These studies shows that mutated FUS affects epigenetic regulation of the chromatin landscape in hippocampal neurons, which could participate in FTD/ALS pathogenic events. These data call for further investigation in the neurological phenotype of FUS-related diseases and open therapeutic strategies towards epigenetic drugs.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37327984',
			'doi' => '10.1016/j.pneurobio.2023.102483',
			'modified' => '2023-08-01 14:55:49',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 15 => array(
			'id' => '4820',
			'name' => 'The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cellfate.',
			'authors' => 'Lackner  A. et al.',
			'description' => '<p><span>Placental development relies on coordinated cell fate decisions governed by signalling inputs. However, little is known about how signalling cues are transformed into repressive mechanisms triggering lineage-specific transcriptional signatures. Here, we demonstrate that upon inhibition of the Fgf/Erk pathway in mouse trophoblast stem cells (TSCs), the Ets2 repressor factor (Erf) interacts with the Nuclear Receptor Co-Repressor Complex 1 and 2 (NCoR1/2) and recruits it to key trophoblast genes. Genetic ablation of Erf or Tbl1x (a component of the NCoR1/2 complex) abrogates the Erf/NCoR1/2 interaction. This leads to mis-expression of Erf/NCoR1/2 target genes, resulting in a TSC differentiation defect. Mechanistically, Erf regulates expression of these genes by recruiting the NCoR1/2 complex and decommissioning their H3K27ac-dependent enhancers. Our findings uncover how the Fgf/Erf/NCoR1/2 repressive axis governs cell fate and placental development, providing a paradigm for Fgf-mediated transcriptional control.</span></p>',
			'date' => '2023-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37137875',
			'doi' => '10.1038/s41467-023-38101-8',
			'modified' => '2023-06-19 10:10:38',
			'created' => '2023-06-13 21:11:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 16 => array(
			'id' => '4778',
			'name' => 'Comprehensive epigenomic profiling reveals the extent of disease-specificchromatin states and informs target discovery in ankylosing spondylitis',
			'authors' => 'Brown  A.C. et al.',
			'description' => '<p>Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterized by enthesitis of the spine and sacroiliac joints. Genome-wide association studies (GWASs) have revealed more than 100 genetic associations whose functional effects remain largely unresolved. Here, we present a comprehensive transcriptomic and epigenomic map of disease-relevant blood immune cell subsets from AS patients and healthy controls.We find that, while CD14+ monocytes and CD4+ and CD8+ T cells show disease-specific differences at the RNA level, epigenomic differences are only apparent upon multi-omics integration. The latter reveals enrichment at disease-associated loci in monocytes. We link putative functional SNPs to genes using high-resolution Capture-C at 10 loci, including PTGER4 and ETS1, and show how disease-specific functional genomic data can be integrated with GWASs to enhance therapeutic target discovery. This study combines epigenetic and transcriptional analysis with GWASs to identify disease-relevant cell types and gene regulation of likely pathogenic relevance and prioritize drug targets.</p>',
			'date' => '2023-04-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.xgen.2023.100306',
			'doi' => '10.1016/j.xgen.2023.100306',
			'modified' => '2023-06-13 09:14:26',
			'created' => '2023-05-05 12:34:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 17 => array(
			'id' => '4763',
			'name' => 'Chromatin profiling identifies transcriptional readthrough as a conservedmechanism for piRNA biogenesis in mosquitoes.',
			'authors' => 'Qu  J. et al.',
			'description' => '<p>The piRNA pathway in mosquitoes differs substantially from other model organisms, with an expanded PIWI gene family and functions in antiviral defense. Here, we define core piRNA clusters as genomic loci that show ubiquitous piRNA expression in both somatic and germline tissues. These core piRNA clusters are enriched for non-retroviral endogenous viral elements (nrEVEs) in antisense orientation and depend on key biogenesis factors, Veneno, Tejas, Yb, and Shutdown. Combined transcriptome and chromatin state analyses identify transcriptional readthrough as a conserved mechanism for cluster-derived piRNA biogenesis in the vector mosquitoes Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and Anopheles gambiae. Comparative analyses between the two Aedes species suggest that piRNA clusters function as traps for nrEVEs, allowing adaptation to environmental challenges such as virus infection. Our systematic transcriptome and chromatin state analyses lay the foundation for studies of gene regulation, genome evolution, and piRNA function in these important vector species.</p>',
			'date' => '2023-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36930642',
			'doi' => '10.1016/j.celrep.2023.112257',
			'modified' => '2023-04-17 09:12:37',
			'created' => '2023-04-14 13:41:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 18 => array(
			'id' => '4765',
			'name' => 'Epigenetic dosage identifies two major and functionally distinct beta cells ubtypes.',
			'authors' => 'Dror  E.et al.',
			'description' => '<p>The mechanisms that specify and stabilize cell subtypes remain poorly understood. Here, we identify two major subtypes of pancreatic &Icirc;&sup2; cells based on histone mark heterogeneity (beta HI and beta LO). Beta HI cells exhibit 4-fold higher levels of H3K27me3, distinct chromatin organization and compaction, and a specific transcriptional pattern. B<span>eta HI and beta LO</span> cells also differ in size, morphology, cytosolic and nuclear ultrastructure, epigenomes, cell surface marker expression, and function, and can be FACS separated into CD24 and CD24 fractions. Functionally, &Icirc;&sup2; cells have increased mitochondrial mass, activity, and insulin secretion in vivo and ex vivo. Partial loss of function indicates that H3K27me3 dosage regulates <span>beta HI/beta LO&nbsp;</span>ratio in vivo, suggesting that control of <span>beta HI&nbsp;</span>cell subtype identity and ratio is at least partially uncoupled. Both subtypes are conserved in humans, with <span>beta HI</span> cells enriched in humans with type 2 diabetes. Thus, epigenetic dosage is a novel regulator of cell subtype specification and identifies two functionally distinct&nbsp;beta cell subtypes.</p>',
			'date' => '2023-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36948185',
			'doi' => '10.1016/j.cmet.2023.03.008',
			'modified' => '2023-04-17 09:26:02',
			'created' => '2023-04-14 13:41:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 19 => array(
			'id' => '4667',
			'name' => 'Detailed molecular and epigenetic characterization of the Pig IPECJ2and Chicken SL-29 cell lines',
			'authors' => 'de Vos  J. et al.',
			'description' => '<p>The pig IPECJ2 and chicken SL-29 cell lines are of interest because of their untransformed nature and wide use in functional studies. Molecular characterization of these cell lines is important to gain insight into possible molecular aberrations. The aims of this paper are providing a molecular and epigenetic characterization of the IPEC-J2 and SL-29 cell lines and providing a cell-line reference for the FAANG community, and future biomedical research. Whole genome sequencing , gene expression, DNA methylation , chromatin accessibility and ChIP-seq of four histone marks (H3K4me1, H3K4me3, H3K27ac, H3K27me3) and an insulator (CTCF) are used to achieve these aims. Heteroploidy (aneuploidy) of various chromosomes was observed from whole genome sequencing analysis in both cell lines. Furthermore, higher gene expression for genes located on chromosomes with aneuploidy in comparison to diploid chromosomes was observed. Regulatory complexity of gene expression, DNA methylation and chromatin accessibility was investigated through an integrative approach.</p>',
			'date' => '2023-02-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.isci.2023.106252',
			'doi' => '10.1016/j.isci.2023.106252',
			'modified' => '2023-04-07 16:52:26',
			'created' => '2023-02-28 12:19:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 20 => array(
			'id' => '4669',
			'name' => 'Histone remodeling reflects conserved mechanisms of bovine and humanpreimplantation development.',
			'authors' => 'Zhou  C. et al.',
			'description' => '<p>How histone modifications regulate changes in gene expression during preimplantation development in any species remains poorly understood. Using CUT\&amp;Tag to overcome limiting amounts of biological material, we profiled two activating (H3K4me3 and H3K27ac) and two repressive (H3K9me3 and H3K27me3) marks in bovine oocytes, 2-, 4-, and 8-cell embryos, morula, blastocysts, inner cell mass, and trophectoderm. In oocytes, broad bivalent domains mark developmental genes, and prior to embryonic genome activation (EGA), H3K9me3 and H3K27me3 co-occupy gene bodies, suggesting a global mechanism for transcription repression. During EGA, chromatin accessibility is established before canonical H3K4me3 and H3K27ac signatures. Embryonic transcription is required for this remodeling, indicating that maternally provided products alone are insufficient for reprogramming. Last, H3K27me3 plays a major role in restriction of cellular potency, as blastocyst lineages are defined by differential polycomb repression and transcription factor activity. Notably, inferred regulators of EGA and blastocyst formation strongly resemble those described in humans, as opposed to mice. These similarities suggest that cattle are a better model than rodents to investigate the molecular basis of human preimplantation development.</p>',
			'date' => '2023-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36779365',
			'doi' => '10.15252/embr.202255726',
			'modified' => '2023-04-14 09:34:12',
			'created' => '2023-02-28 12:19:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 21 => array(
			'id' => '4605',
			'name' => 'Gene Regulatory Interactions at Lamina-Associated Domains',
			'authors' => 'Madsen-Østerbye  J. et al.',
			'description' => '<p>The nuclear lamina provides a repressive chromatin environment at the nuclear periphery. However, whereas most genes in lamina-associated domains (LADs) are inactive, over ten percent reside in local euchromatic contexts and are expressed. How these genes are regulated and whether they are able to interact with regulatory elements remain unclear. Here, we integrate publicly available enhancer-capture Hi-C data with our own chromatin state and transcriptomic datasets to show that inferred enhancers of active genes in LADs are able to form connections with other enhancers within LADs and outside LADs. Fluorescence in situ hybridization analyses show proximity changes between differentially expressed genes in LADs and distant enhancers upon the induction of adipogenic differentiation. We also provide evidence of involvement of lamin A/C, but not lamin B1, in repressing genes at the border of an in-LAD active region within a topological domain. Our data favor a model where the spatial topology of chromatin at the nuclear lamina is compatible with gene expression in this dynamic nuclear compartment.</p>',
			'date' => '2023-01-01',
			'pmid' => 'https://doi.org/10.3390%2Fgenes14020334',
			'doi' => '10.3390/genes14020334',
			'modified' => '2023-04-04 08:57:32',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 22 => array(
			'id' => '4802',
			'name' => 'Analyzing the Genome-Wide Distribution of Histone Marks byCUT\&Tag in Drosophila Embryos.',
			'authors' => 'Zenk  F. et al.',
			'description' => '<p><span>CUT&amp;Tag is a method to map the genome-wide distribution of histone modifications and some chromatin-associated proteins. CUT&amp;Tag relies on antibody-targeted chromatin tagmentation and can easily be scaled up or automatized. This protocol provides clear experimental guidelines and helpful considerations when planning and executing CUT&amp;Tag experiments.</span></p>',
			'date' => '2023-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37212984',
			'doi' => '10.1007/978-1-0716-3143-0_1',
			'modified' => '2023-06-15 08:43:40',
			'created' => '2023-06-13 21:11:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 23 => array(
			'id' => '4545',
			'name' => 'Histone Deacetylases 1 and 2 target gene regulatory networks of nephronprogenitors to control nephrogenesis.',
			'authors' => 'Liu  Hongbing et al.',
			'description' => '<p>Our studies demonstrated the critical role of Histone deacetylases (HDACs) in the regulation of nephrogenesis. To better understand the key pathways regulated by HDAC1/2 in early nephrogenesis, we performed chromatin immunoprecipitation sequencing (ChIP-Seq) of Hdac1/2 on isolated nephron progenitor cells (NPCs) from mouse E16.5 kidneys. Our analysis revealed that 11802 (40.4\%) of Hdac1 peaks overlap with Hdac2 peaks, further demonstrates the redundant role of Hdac1 and Hdac2 during nephrogenesis. Common Hdac1/2 peaks are densely concentrated close to the transcriptional start site (TSS). GREAT Gene Ontology analysis of overlapping Hdac1/2 peaks reveals that Hdac1/2 are associated with metanephric nephron morphogenesis, chromatin assembly or disassembly, as well as other DNA checkpoints. Pathway analysis shows that negative regulation of Wnt signaling pathway is one of Hdac1/2's most significant function in NPCs. Known motif analysis indicated that Hdac1 is enriched in motifs for Six2, Hox family, and Tcf family members, which are essential for self-renewal and differentiation of nephron progenitors. Interestingly, we found the enrichment of HDAC1/2 at the enhancer and promoter regions of actively transcribed genes, especially those concerned with NPC self-renewal. HDAC1/2 simultaneously activate or repress the expression of different genes to maintain the cellular state of nephron progenitors. We used the Integrative Genomics Viewer to visualize these target genes associated with each function and found that Hdac1/2 co-bound to the enhancers or/and promoters of genes associated with nephron morphogenesis, differentiation, and cell cycle control. Taken together, our ChIP-Seq analysis demonstrates that Hdac1/2 directly regulate the molecular cascades essential for nephrogenesis.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36356658',
			'doi' => '10.1016/j.bcp.2022.115341',
			'modified' => '2022-11-24 10:24:07',
			'created' => '2022-11-24 08:49:52',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 24 => array(
			'id' => '4658',
			'name' => 'Balance between autophagy and cell death is maintained byPolycomb-mediated regulation during stem cell differentiation.',
			'authors' => 'Puri  Deepika et al.',
			'description' => '<p>Autophagy is a conserved cytoprotective process, aberrations in which lead to numerous degenerative disorders. While the cytoplasmic components of autophagy have been extensively studied, the epigenetic regulation of autophagy genes, especially in stem cells, is less understood. Deciphering the epigenetic regulation of autophagy genes becomes increasingly relevant given the therapeutic benefits of small-molecule epigenetic inhibitors in novel treatment modalities. We observe that, during retinoic acid-mediated differentiation of mouse embryonic stem cells (mESCs), autophagy is induced, and identify the Polycomb group histone methyl transferase EZH2 as a regulator of this process. In mESCs, EZH2 represses several autophagy genes, including the autophagy regulator DNA damage-regulated autophagy modulator protein 1 (Dram1). EZH2 facilitates the formation of a bivalent chromatin domain at the Dram1 promoter, allowing gene expression and autophagy induction during differentiation while retaining the repressive H3K27me3 mark. EZH2 inhibition leads to loss of the bivalent domain, with consequent "hyper-expression" of Dram1, accompanied by extensive cell death. This study shows that Polycomb group proteins help maintain a balance between autophagy and cell death during stem cell differentiation, in part by regulating the expression of the Dram1 gene.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36380631',
			'doi' => '10.1111/febs.16656',
			'modified' => '2023-03-07 08:59:36',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 25 => array(
			'id' => '4788',
			'name' => 'Dietary methionine starvation impairs acute myeloid leukemia progression.',
			'authors' => 'Cunningham  A. et al.',
			'description' => '<p>Targeting altered tumor cell metabolism might provide an attractive opportunity for patients with acute myeloid leukemia (AML). An amino acid dropout screen on primary leukemic stem cells and progenitor populations revealed a number of amino acid dependencies, of which methionine was one of the strongest. By using various metabolite rescue experiments, nuclear magnetic resonance-based metabolite quantifications and 13C-tracing, polysomal profiling, and chromatin immunoprecipitation sequencing, we identified that methionine is used predominantly for protein translation and to provide methyl groups to histones via S-adenosylmethionine for epigenetic marking. H3K36me3 was consistently the most heavily impacted mark following loss of methionine. Methionine depletion also reduced total RNA levels, enhanced apoptosis, and induced a cell cycle block. Reactive oxygen species levels were not increased following methionine depletion, and replacement of methionine with glutathione or N-acetylcysteine could not rescue phenotypes, excluding a role for methionine in controlling redox balance control in AML. Although considered to be an essential amino acid, methionine can be recycled from homocysteine. We uncovered that this is primarily performed by the enzyme methionine synthase and only when methionine availability becomes limiting. In&Acirc;&nbsp;vivo, dietary methionine starvation was not only tolerated by mice, but also significantly delayed both cell line and patient-derived AML progression. Finally, we show that inhibition of the H3K36-specific methyltransferase SETD2 phenocopies much of the cytotoxic effects of methionine depletion, providing a more targeted therapeutic approach. In conclusion, we show that methionine depletion is a vulnerability in AML that can be exploited therapeutically, and we provide mechanistic insight into how cells metabolize and recycle methionine.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://doi.org/10.33612%2Fdiss.205032978',
			'doi' => '10.1182/blood.2022017575',
			'modified' => '2023-06-12 09:01:21',
			'created' => '2023-05-05 12:34:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 26 => array(
			'id' => '4499',
			'name' => 'Trained Immunity Provides Long-Term Protection againstBacterial Infections in Channel Catfish.',
			'authors' => 'Petrie-Hanson  L. et al.',
			'description' => '<p>Beta glucan exposure induced trained immunity in channel catfish that conferred long-term protection against and infections one month post exposure. Flow cytometric analyses demonstrated that isolated macrophages and neutrophils phagocytosed higher amounts of and . Beta glucan induced changes in the distribution of histone modifications in the monomethylation and trimethylation of H3K4 and modifications in the acetylation and trimethylation of H3K27. KEGG pathway analyses revealed that these modifications affected expressions of genes controlling phagocytosis, phagosome functions and enhanced immune cell signaling. These analyses correlate the histone modifications with gene functions and to the observed enhanced phagocytosis and to the increased survival following bacterial challenge in channel catfish. These data suggest the chromatin reconfiguration that directs trained immunity as demonstrated in mammals also occurs in channel catfish. Understanding the mechanisms underlying trained immunity can help us design prophylactic and non-antibiotic based therapies and develop broad-based vaccines to limit bacterial disease outbreaks in catfish production.</p>',
			'date' => '2022-10-01',
			'pmid' => 'https://doi.org/10.3390%2Fpathogens11101140',
			'doi' => '10.3390/pathogens11101140',
			'modified' => '2022-11-21 10:31:12',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 27 => array(
			'id' => '4451',
			'name' => 'bESCs from cloned embryos do not retain transcriptomic or epigenetic memory from somatic donor cells.',
			'authors' => 'Navarro  M. et al.',
			'description' => '<p>Embryonic stem cells (ESC) indefinitely maintain the pluripotent state of the blastocyst epiblast. Stem cells are invaluable for studying development and lineage commitment, and in livestock they constitute a useful tool for genomic improvement and in vitro breeding programs. Although these cells have been recently derived from bovine blastocysts, a detailed characterization of their molecular state is still lacking. Here, we apply cutting-edge technologies to analyze the transcriptomic and epigenomic landscape of bovine ESC (bESC) obtained from in vitro fertilized (IVF) and somatic cell nuclear transfer (SCNT) embryos. Bovine ESC were efficiently derived from SCNT and IVF embryos and expressed pluripotency markers while retaining genome stability. Transcriptome analysis revealed that only 46 genes were differentially expressed between IVF- and SCNT-derived bESC, which did not reflect significant deviation in cellular function. Interrogating the histone marks H3K4me3, H3K9me3 and H3K27me3 with CUT\&amp;Tag, we found that the epigenomes of both bESC groups were virtually indistinguishable. Minor epigenetic differences were randomly distributed throughout the genome and were not associated with differentially expressed or developmentally important genes. Finally, categorization of genomic regions according to their combined histone mark signal demonstrated that all bESC shared the same epigenomic signatures, especially at promoters. Overall, we conclude that bESC derived from SCNT and IVF are transcriptomically and epigenetically analogous, allowing for the production of an unlimited source of pluripotent cells from high genetic merit organisms without resorting to genome editing techniques.</p>',
			'date' => '2022-08-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/35951478/',
			'doi' => '10.1530/REP-22-0063',
			'modified' => '2022-10-21 09:31:32',
			'created' => '2022-09-28 09:53:13',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 28 => array(
			'id' => '4416',
			'name' => 'Large-scale manipulation of promoter DNA methylation revealscontext-specific transcriptional responses and stability.',
			'authors' => 'de Mendoza  A. et al. ',
			'description' => '<p>BACKGROUND: Cytosine DNA methylation is widely described as a transcriptional repressive mark with the capacity to silence promoters. Epigenome engineering techniques enable direct testing of the effect of induced DNA methylation on endogenous promoters; however, the downstream effects have not yet been comprehensively assessed. RESULTS: Here, we simultaneously induce methylation at thousands of promoters in human cells using an engineered zinc finger-DNMT3A fusion protein, enabling us to test the effect of forced DNA methylation upon transcription, chromatin accessibility, histone modifications, and DNA methylation persistence after the removal of the fusion protein. We find that transcriptional responses to DNA methylation are highly context-specific, including lack of repression, as well as cases of increased gene expression, which appears to be driven by the eviction of methyl-sensitive transcriptional repressors. Furthermore, we find that some regulatory networks can override DNA methylation and that promoter methylation can cause alternative promoter usage. DNA methylation deposited at promoter and distal regulatory regions is rapidly erased after removal of the zinc finger-DNMT3A fusion protein, in a process combining passive and TET-mediated demethylation. Finally, we demonstrate that induced DNA methylation can exist simultaneously on promoter nucleosomes that possess the active histone modification H3K4me3, or DNA bound by the initiated form of RNA polymerase II. CONCLUSIONS: These findings have important implications for epigenome engineering and demonstrate that the response of promoters to DNA methylation is more complex than previously appreciated.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35883107',
			'doi' => '10.1186/s13059-022-02728-5',
			'modified' => '2022-09-15 09:01:24',
			'created' => '2022-09-08 16:32:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 29 => array(
			'id' => '4417',
			'name' => 'HOTAIR interacts with PRC2 complex regulating the regional preadipocytetranscriptome and human fat distribution.',
			'authors' => 'Kuo  Feng-Chih et al.',
			'description' => '<p>Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA HOTAIR (HOX transcript antisense RNA) is exclusively expressed in gluteofemoral AT, where it is essential for adipocyte development. We find that HOTAIR interacts with polycomb repressive complex 2 (PRC2) and we identify core HOTAIR-PRC2 target genes involved in adipocyte lineage determination. Repression of target genes coincides with PRC2 promoter occupancy and H3K27 trimethylation. HOTAIR is also involved in modifying the gluteal adipocyte transcriptome through alternative splicing. Gluteal-specific expression of HOTAIR is maintained by defined regions of open chromatin across the HOTAIR promoter. HOTAIR expression levels can be modified by hormonal (estrogen, glucocorticoids) and genetic variation (rs1443512 is a HOTAIR eQTL associated with reduced gynoid fat mass). These data identify HOTAIR as a dynamic regulator of the gluteal adipocyte transcriptome and epigenome with functional importance for human regional AT development.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35905723',
			'doi' => '10.1016/j.celrep.2022.111136',
			'modified' => '2022-09-27 14:41:23',
			'created' => '2022-09-08 16:32:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 30 => array(
			'id' => '4458',
			'name' => 'Epiblast inducers capture mouse trophectoderm stem cells in vitro andpattern blastoids for implantation in utero.',
			'authors' => 'Seong  Jinwoo et al.',
			'description' => '<p>The embryo instructs the allocation of cell states to spatially regulate functions. In the blastocyst, patterning of trophoblast (TR) cells ensures successful implantation and placental development. Here, we defined an optimal set of molecules secreted by the epiblast (inducers) that captures in&nbsp;vitro stable, highly self-renewing mouse trophectoderm stem cells (TESCs) resembling the blastocyst stage. When exposed to suboptimal inducers, these stem cells fluctuate to form interconvertible subpopulations with reduced self-renewal and facilitated differentiation, resembling peri-implantation cells, known as TR stem cells (TSCs). TESCs have enhanced capacity to form blastoids that implant more efficiently in utero due to inducers maintaining not only local TR proliferation and self-renewal, but also WNT6/7B secretion that stimulates uterine decidualization. Overall, the epiblast maintains sustained growth and decidualization potential of abutting TR cells, while, as known, distancing imposed by the blastocyst cavity differentiates TR cells for uterus adhesion, thus patterning the essential functions of implantation.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35803228',
			'doi' => '10.1016/j.stem.2022.06.002',
			'modified' => '2022-10-21 09:44:00',
			'created' => '2022-09-28 09:53:13',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 31 => array(
			'id' => '4386',
			'name' => 'Epigenomic analysis reveals a dynamic and context-specific macrophageenhancer landscape associated with innate immune activation and tolerance.',
			'authors' => 'Zhang  P. et al.',
			'description' => '<p>BACKGROUND: Chromatin states and enhancers associate gene expression, cell identity and disease. Here, we systematically delineate the acute innate immune response to endotoxin in terms of human macrophage enhancer activity and contrast with endotoxin tolerance, profiling the coding and non-coding transcriptome, chromatin accessibility and epigenetic modifications. RESULTS: We describe the spectrum of enhancers under acute and tolerance conditions and the regulatory networks between these enhancers and biological processes including gene expression, splicing regulation, transcription factor binding and enhancer RNA signatures. We demonstrate that the vast majority of differentially regulated enhancers on acute stimulation are subject to tolerance and that expression quantitative trait loci, disease-risk variants and eRNAs are enriched in these regulatory regions and related to context-specific gene expression. We find enrichment for context-specific eQTL involving endotoxin response and specific infections and delineate specific differential regions informative for GWAS variants in inflammatory bowel disease and multiple sclerosis, together with a context-specific enhancer involving a bacterial infection eQTL for KLF4. We show enrichment in differential enhancers for tolerance involving transcription factors NF&kappa;B-p65, STATs and IRFs and prioritize putative causal genes directly linking genetic variants and disease risk enhancers. We further delineate similarities and differences in epigenetic landscape between stem cell-derived macrophages and primary cells and characterize the context-specific enhancer activities for key innate immune response genes KLF4, SLAMF1 and IL2RA. CONCLUSIONS: Our study demonstrates the importance of context-specific macrophage enhancers in gene regulation and utility for interpreting disease associations, providing a roadmap to link genetic variants with molecular and cellular functions.</p>',
			'date' => '2022-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35751107',
			'doi' => '10.1186/s13059-022-02702-1',
			'modified' => '2022-08-11 14:07:03',
			'created' => '2022-08-11 12:14:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 32 => array(
			'id' => '4221',
			'name' => 'Epigenetic Mechanisms Mediating Cell State Transitions in Chondrocytes',
			'authors' => 'Wuelling M. et al.',
			'description' => '<p><span>Epigenetic modifications play critical roles in regulating cell lineage differentiation, but the epigenetic mechanisms guiding specific differentiation steps within a cell lineage have rarely been investigated. To decipher such mechanisms, we used the defined transition from proliferating (PC) into hypertrophic chondrocytes (HC) during endochondral ossification as a model. We established a map of activating and repressive histone modifications for each cell type. ChromHMM state transition analysis and Pareto-based integration of differential levels of mRNA and epigenetic marks revealed that differentiation-associated gene repression is initiated by the addition of H3K27me3 to promoters still carrying substantial levels of activating marks. Moreover, the integrative analysis identified genes specifically expressed in cells undergoing the transition into hypertrophy. Investigation of enhancer profiles detected surprising differences in enhancer number, location, and transcription factor binding sites between the two closely related cell types. Furthermore, cell type-specific upregulation of gene expression was associated with increased numbers of H3K27ac peaks. Pathway analysis identified PC-specific enhancers associated with chondrogenic genes, whereas HC-specific enhancers mainly control metabolic pathways linking epigenetic signature to biological functions. Since HC-specific enhancers show a higher conservation in postnatal tissues, the switch to metabolic pathways seems to be a hallmark of differentiated tissues. Surprisingly, the analysis of H3K27ac levels at super-enhancers revealed a rapid adaption of H3K27ac occupancy to changes in gene expression, supporting the importance of enhancer modulation for acute alterations in gene expression. &copy; 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).</span></p>',
			'date' => '2022-05-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/33534175/',
			'doi' => '10.1002/jbmr.4263',
			'modified' => '2022-04-25 11:46:32',
			'created' => '2022-04-21 12:00:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 33 => array(
			'id' => '4446',
			'name' => 'Variation in PU.1 binding and chromatin looping at neutrophil enhancersinfluences autoimmune disease susceptibility',
			'authors' => 'Watt  S. et al. ',
			'description' => '<p>Neutrophils play fundamental roles in innate inflammatory response, shape adaptive immunity1, and have been identified as a potentially causal cell type underpinning genetic associations with immune system traits and diseases2,3 The majority of these variants are non-coding and the underlying mechanisms are not fully understood. Here, we profiled the binding of one of the principal myeloid transcriptional regulators, PU.1, in primary neutrophils across nearly a hundred volunteers, and elucidate the coordinated genetic effects of PU.1 binding variation, local chromatin state, promoter-enhancer interactions and gene expression. We show that PU.1 binding and the associated chain of molecular changes underlie genetically-driven differences in cell count and autoimmune disease susceptibility. Our results advance interpretation for genetic loci associated with neutrophil biology and immune disease.</p>',
			'date' => '2022-05-01',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/620260v1.abstract',
			'doi' => '10.1101/620260',
			'modified' => '2022-10-14 16:39:03',
			'created' => '2022-09-28 09:53:13',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 34 => array(
			'id' => '4402',
			'name' => 'The CpG Island-Binding Protein SAMD1 Contributes to anUnfavorable Gene Signature in HepG2 Hepatocellular CarcinomaCells.',
			'authors' => 'Simon  C. et al.',
			'description' => '<p>The unmethylated CpG island-binding protein SAMD1 is upregulated in many human cancer types, but its cancer-related role has not yet been investigated. Here, we used the hepatocellular carcinoma cell line HepG2 as a cancer model and investigated the cellular and transcriptional roles of SAMD1 using ChIP-Seq and RNA-Seq. SAMD1 targets several thousand gene promoters, where it acts predominantly as a transcriptional repressor. HepG2 cells with SAMD1 deletion showed slightly reduced proliferation, but strongly impaired clonogenicity. This phenotype was accompanied by the decreased expression of pro-proliferative genes, including MYC target genes. Consistently, we observed a decrease in the active H3K4me2 histone mark at most promoters, irrespective of SAMD1 binding. Conversely, we noticed an increase in interferon response pathways and a gain of H3K4me2 at a subset of enhancers that were enriched for IFN-stimulated response elements (ISREs). We identified key transcription factor genes, such as , , and , that were directly repressed by SAMD1. Moreover, SAMD1 deletion also led to the derepression of the PI3K-inhibitor , contributing to diminished mTOR signaling and ribosome biogenesis pathways. Our work suggests that SAMD1 is involved in establishing a pro-proliferative setting in hepatocellular carcinoma cells. Inhibiting SAMD1's function in liver cancer cells may therefore lead to a more favorable gene signature.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35453756',
			'doi' => '10.3390/biology11040557',
			'modified' => '2022-08-11 14:45:43',
			'created' => '2022-08-11 12:14:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 35 => array(
			'id' => '4524',
			'name' => 'Local euchromatin enrichment in lamina-associated domains anticipatestheir repositioning in the adipogenic lineage.',
			'authors' => 'Madsen-Østerbye  J. et al.',
			'description' => '<p>BACKGROUND: Interactions of chromatin with the nuclear lamina via lamina-associated domains (LADs) confer structural stability to the genome. The dynamics of positioning of LADs during differentiation, and how LADs impinge on developmental gene expression, remains, however, elusive. RESULTS: We examined changes in the association of lamin B1 with the genome in the first 72 h of differentiation of adipose stem cells into adipocytes. We demonstrate a repositioning of entire stand-alone LADs and of LAD edges as a prominent nuclear structural feature of early adipogenesis. Whereas adipogenic genes are released from LADs, LADs sequester downregulated or repressed genes irrelevant for the adipose lineage. However, LAD repositioning only partly concurs with gene expression changes. Differentially expressed genes in LADs, including LADs conserved throughout differentiation, reside in local euchromatic and lamin-depleted sub-domains. In these sub-domains, pre-differentiation histone modification profiles correlate with the LAD versus inter-LAD outcome of these genes during adipogenic commitment. Lastly, we link differentially expressed genes in LADs to short-range enhancers which overall co-partition with these genes in LADs versus inter-LADs during differentiation. CONCLUSIONS: We conclude that LADs are predictable structural features of adipose nuclear architecture that restrain non-adipogenic genes in a repressive environment.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35410387',
			'doi' => '10.1186/s13059-022-02662-6',
			'modified' => '2022-11-24 09:08:01',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 36 => array(
			'id' => '4528',
			'name' => 'ZWC complex-mediated SPT5 phosphorylation suppresses divergentantisense RNA transcription at active gene promoters.',
			'authors' => 'Park  K. et al.',
			'description' => '<p>The human genome encodes large numbers of non-coding RNAs, including divergent antisense transcripts at transcription start sites (TSSs). However, molecular mechanisms by which divergent antisense transcription is regulated have not been detailed. Here, we report a novel ZWC complex composed of ZC3H4, WDR82&nbsp;and CK2 that suppresses divergent antisense transcription. The ZWC complex preferentially localizes at TSSs of active genes through direct interactions of ZC3H4 and WDR82 subunits with the S5p RNAPII C-terminal domain. ZC3H4 depletion leads to increased divergent antisense transcription, especially at genes that naturally produce divergent antisense transcripts. We further demonstrate that the ZWC complex phosphorylates the previously uncharacterized N-terminal acidic domain of SPT5, a subunit of the transcription-elongation factor DSIF, and that this phosphorylation is responsible for suppressing divergent antisense transcription. Our study provides evidence that the newly identified ZWC-DSIF axis regulates the direction of transcription during the transition from early to productive elongation.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35325203',
			'doi' => '10.1093/nar/gkac193',
			'modified' => '2022-11-24 09:24:05',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 37 => array(
			'id' => '4857',
			'name' => 'Broad domains of histone marks in the highly compact  macronucleargenome.',
			'authors' => 'Drews  F. et al.',
			'description' => '<p>The unicellular ciliate contains a large vegetative macronucleus with several unusual characteristics, including an extremely high coding density and high polyploidy. As macronculear chromatin is devoid of heterochromatin, our study characterizes the functional epigenomic organization necessary for gene regulation and proper Pol II activity. Histone marks (H3K4me3, H3K9ac, H3K27me3) reveal no narrow peaks but broad domains along gene bodies, whereas intergenic regions are devoid of nucleosomes. Our data implicate H3K4me3 levels inside ORFs to be the main factor associated with gene expression, and H3K27me3 appears in association with H3K4me3 in plastic genes. Silent and lowly expressed genes show low nucleosome occupancy, suggesting that gene inactivation does not involve increased nucleosome occupancy and chromatin condensation. Because of a high occupancy of Pol II along highly expressed ORFs, transcriptional elongation appears to be quite different from that of other species. This is supported by missing heptameric repeats in the C-terminal domain of Pol II and a divergent elongation system. Our data imply that unoccupied DNA is the default state, whereas gene activation requires nucleosome recruitment together with broad domains of H3K4me3. In summary, gene activation and silencing in run counter to the current understanding of chromatin biology.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35264449',
			'doi' => '10.1101/gr.276126.121',
			'modified' => '2023-08-01 14:45:37',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 38 => array(
			'id' => '4367',
			'name' => 'Cell-type specific transcriptional networks in root xylem adjacent celllayers',
			'authors' => 'Asensi Fabado  Maria Amparo et al.',
			'description' => '<p>Transport of water, ions and signals from roots to leaves via the xylem vessels is essential for plant life and needs to be tightly regulated. The final composition of the transpiration stream before passage into the shoots is controlled by the xylem-adjacent cell layers, namely xylem parenchyma and pericycle, in the upper part of the root. To unravel regulatory networks in this strategically important location, we generated Arabidopsis lines expressing a nuclear tag under the control of the HKT1 promoter. HKT1 retrieves sodium from the xylem to prevent toxic levels in the shoot, and this function depends on its specific expression in upper root xylem-adjacent tissues. Based on FACS RNA-sequencing and INTACT ChIP-sequencing, we identified the gene repertoire that is preferentially expressed in the tagged cell types and discovered transcription factors experiencing cell-type specific loss of H3K27me3 demethylation. For one of these, ZAT6, we show that H3K27me3-demethylase REF6 is required for de-repression. Analysis of zat6 mutants revealed that ZAT6 activates a suite of cell-type specific downstream genes and restricts Na+ accumulation in the shoots. The combined Files open novel opportunities for &lsquo;bottom-up&rsquo; causal dissection of cell-type specific regulatory networks that control root-to-shoot communication under environmental challenge.</p>',
			'date' => '2022-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2022.02.04.479129',
			'doi' => '10.1101/2022.02.04.479129',
			'modified' => '2022-08-04 16:17:32',
			'created' => '2022-08-04 14:55:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 39 => array(
			'id' => '4214',
			'name' => 'Comprehensive characterization of the epigenetic landscape in Multiple Myeloma',
			'authors' => 'Elina Alaterre et al.',
			'description' => '<p>Background: Human multiple myeloma (MM) cell lines (HMCLs) have been widely used to understand the<br />molecular processes that drive MM biology. Epigenetic modifications are involved in MM development,<br />progression, and drug resistance. A comprehensive characterization of the epigenetic landscape of MM would<br />advance our understanding of MM pathophysiology and may attempt to identify new therapeutic targets.<br />Methods: We performed chromatin immunoprecipitation sequencing to analyze histone mark changes<br />(H3K4me1, H3K4me3, H3K9me3, H3K27ac, H3K27me3 and H3K36me3) on 16 HMCLs.<br />Results: Differential analysis of histone modification profiles highlighted links between histone modifications<br />and cytogenetic abnormalities or recurrent mutations. Using histone modifications associated to enhancer<br />regions, we identified super-enhancers (SE) associated with genes involved in MM biology. We also identified<br />promoters of genes enriched in H3K9me3 and H3K27me3 repressive marks associated to potential tumor<br />suppressor functions. The prognostic value of genes associated with repressive domains and SE was used to<br />build two distinct scores identifying high-risk MM patients in two independent cohorts (CoMMpass cohort; n =<br />674 and Montpellier cohort; n = 69). Finally, we explored H3K4me3 marks comparing drug-resistant and<br />-sensitive HMCLs to identify regions involved in drug resistance. From these data, we developed epigenetic<br />biomarkers based on the H3K4me3 modification predicting MM cell response to lenalidomide and histone<br />deacetylase inhibitors (HDACi).<br />Conclusions: The epigenetic landscape of MM cells represents a unique resource for future biological studies.<br />Furthermore, risk-scores based on SE and repressive regions together with epigenetic biomarkers of drug<br />response could represent new tools for precision medicine in MM.</p>',
			'date' => '2022-01-16',
			'pmid' => 'https://www.thno.org/v12p1715',
			'doi' => '10.7150/thno.54453',
			'modified' => '2022-01-27 13:17:28',
			'created' => '2022-01-27 13:14:17',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 40 => array(
			'id' => '4225',
			'name' => 'Comprehensive characterization of the epigenetic landscape in Multiple
Myeloma',
			'authors' => 'Alaterre, Elina and Ovejero, Sara and Herviou, Laurie and de
Boussac, Hugues and Papadopoulos, Giorgio and Kulis, Marta and
Boireau, Stéphanie and Robert, Nicolas and Requirand, Guilhem
and Bruyer, Angélique and Cartron, Guillaume and Vincent,
Laure and M',
			'description' => 'Background: Human multiple myeloma (MM) cell lines (HMCLs) have
been widely used to understand the molecular processes that drive MM
biology. Epigenetic modifications are involved in MM development,
progression, and drug resistance. A comprehensive characterization of the
epigenetic landscape of MM would advance our understanding of MM
pathophysiology and may attempt to identify new therapeutic
targets.

Methods: We performed chromatin immunoprecipitation
sequencing to analyze histone mark changes (H3K4me1, H3K4me3,
H3K9me3, H3K27ac, H3K27me3 and H3K36me3) on 16
HMCLs.

Results: Differential analysis of histone modification
profiles highlighted links between histone modifications and cytogenetic
abnormalities or recurrent mutations. Using histone modifications
associated to enhancer regions, we identified super-enhancers (SE)
associated with genes involved in MM biology. We also identified
promoters of genes enriched in H3K9me3 and H3K27me3 repressive
marks associated to potential tumor suppressor functions. The prognostic
value of genes associated with repressive domains and SE was used to
build two distinct scores identifying high-risk MM patients in two
independent cohorts (CoMMpass cohort; n = 674 and Montpellier cohort;
n = 69). Finally, we explored H3K4me3 marks comparing drug-resistant
and -sensitive HMCLs to identify regions involved in drug resistance.
From these data, we developed epigenetic biomarkers based on the
H3K4me3 modification predicting MM cell response to lenalidomide and
histone deacetylase inhibitors (HDACi).

Conclusions: The epigenetic
landscape of MM cells represents a unique resource for future biological
studies. Furthermore, risk-scores based on SE and repressive regions
together with epigenetic biomarkers of drug response could represent new
tools for precision medicine in MM.',
			'date' => '2022-01-01',
			'pmid' => 'https://www.thno.org/v12p1715.htm',
			'doi' => '10.7150/thno.54453',
			'modified' => '2022-05-19 10:41:50',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 41 => array(
			'id' => '4326',
			'name' => 'Loss of KMT2C reprograms the epigenomic landscape in hPSCsresulting in NODAL overexpression and a failure of hemogenic endotheliumspecification.',
			'authors' => 'Maurya Shailendra et al.',
			'description' => '<p>Germline or somatic variation in the family of KMT2 lysine methyltransferases have been associated with a variety of congenital disorders and cancers. Notably, -fusions are prevalent in 70\% of infant leukaemias but fail to phenocopy short latency leukaemogenesis in mammalian models, suggesting additional factors are necessary for transformation. Given the lack of additional somatic mutation, the role of epigenetic regulation in cell specification, and our prior results of germline variation in infant leukaemia patients, we hypothesized that germline dysfunction of KMT2C altered haematopoietic specification. In isogenic KO hPSCs, we found genome-wide differences in histone modifications at active and poised enhancers, leading to gene expression profiles akin to mesendoderm rather than mesoderm highlighted by a significant increase in NODAL expression and WNT inhibition, ultimately resulting in a lack of hemogenic endothelium specification. These unbiased multi-omic results provide new evidence for germline mechanisms increasing risk of early leukaemogenesis.</p>',
			'date' => '2022-01-01',
			'pmid' => 'https://doi.org/10.1080%2F15592294.2021.1954780',
			'doi' => '10.1080/15592294.2021.1954780',
			'modified' => '2022-06-20 09:27:45',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 42 => array(
			'id' => '4238',
			'name' => 'The long noncoding RNA H19 regulates tumor plasticity inneuroendocrine prostate cancer',
			'authors' => 'Singh N. et al.',
			'description' => '<p>Neuroendocrine (NE) prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (PCa) arising either de novo or from transdifferentiated prostate adenocarcinoma following androgen deprivation therapy (ADT). Extensive computational analysis has identified a high degree of association between the long noncoding RNA (lncRNA) H19 and NEPC, with the longest isoform highly expressed in NEPC. H19 regulates PCa lineage plasticity by driving a bidirectional cell identity of NE phenotype (H19 overexpression) or luminal phenotype (H19 knockdown). It contributes to treatment resistance, with the knockdown of H19 re-sensitizing PCa to ADT. It is also essential for the proliferation and invasion of NEPC. H19 levels are negatively regulated by androgen signaling via androgen receptor (AR). When androgen is absent SOX2 levels increase, driving H19 transcription and facilitating transdifferentiation. H19 facilitates the PRC2 complex in regulating methylation changes at H3K27me3/H3K4me3 histone sites of AR-driven and NEPC-related genes. Additionally, this lncRNA induces alterations in genome-wide DNA methylation on CpG sites, further regulating genes associated with the NEPC phenotype. Our clinical data identify H19 as a candidate diagnostic marker and predictive marker of NEPC with elevated H19 levels associated with an increased probability of biochemical recurrence and metastatic disease in patients receiving ADT. Here we report H19 as an early upstream regulator of cell fate, plasticity, and treatment resistance in NEPC that can reverse/transform cells to a treatable form of PCa once therapeutically deactivated.</p>',
			'date' => '2021-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34934057',
			'doi' => '10.1038/s41467-021-26901-9',
			'modified' => '2022-05-19 17:06:50',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 43 => array(
			'id' => '4239',
			'name' => 'Epromoters function as a hub to recruit key transcription factorsrequired for the inflammatory response',
			'authors' => 'Santiago-Algarra D. et al. ',
			'description' => '<p>Gene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. Our previous results demonstrated that a subset of gene promoters, termed Epromoters, work as bona fide enhancers and regulate distal gene expression. Here, we hypothesized that Epromoters play a key role in the coordination of rapid gene induction during the inflammatory response. Using a high-throughput reporter assay we explored the function of Epromoters in response to type I interferon. We find that clusters of IFNa-induced genes are frequently associated with Epromoters and that these regulatory elements preferentially recruit the STAT1/2 and IRF transcription factors and distally regulate the activation of interferon-response genes. Consistently, we identified and validated the involvement of Epromoter-containing clusters in the regulation of LPS-stimulated macrophages. Our findings suggest that Epromoters function as a local hub recruiting the key TFs required for coordinated regulation of gene clusters during the inflammatory response.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34795220',
			'doi' => '10.1038/s41467-021-26861-0',
			'modified' => '2022-05-19 17:10:30',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 44 => array(
			'id' => '4251',
			'name' => 'Comparing the epigenetic landscape in myonuclei purified with a PCM1antibody from a fast/glycolytic and a slow/oxidative muscle.',
			'authors' => 'Bengtsen Mads et al.',
			'description' => '<p>Muscle cells have different phenotypes adapted to different usage, and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of the epigenetic landscape by ChIP-Seq in two muscle extremes, the fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where up to 60\% of the nuclei can be of a different origin. Since cellular homogeneity is critical in epigenome-wide association studies we developed a new method for purifying skeletal muscle nuclei from whole tissue, based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labelling and a magnetic-assisted sorting approach, we were able to sort out myonuclei with 95\% purity in muscles from mice, rats and humans. The sorting eliminated influence from the other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the differences in the functional properties of the two muscles, and revealed distinct regulatory programs involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles were also regulated by different sets of transcription factors; e.g. in soleus, binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SIX1 binding sites were found to be overrepresented. In addition, more novel transcription factors for muscle regulation such as members of the MAF family, ZFX and ZBTB14 were identified.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/34752468/',
			'doi' => '10.1371/journal.pgen.1009907',
			'modified' => '2022-05-20 09:39:35',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 45 => array(
			'id' => '4241',
			'name' => 'Rhesus macaques self-curing from a schistosome infection can displaycomplete immunity to challenge',
			'authors' => 'Amaral MS et al.  ',
			'description' => '<p>The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict \&gt;200 million people worldwide. By monitoring bloodstream levels of parasite-gut-derived antigen, we show that from week 10 onwards an established infection with Schistosoma mansoni is cleared in an exponential manner, eliciting resistance to reinfection. Secondary challenge at week 42 demonstrates that protection is strong in all animals and complete in some. Antibody profiles suggest that antigens mediating protection are the released products of developing schistosomula. In culture they are killed by addition of rhesus plasma, collected from week 8 post-infection onwards, and even more efficiently with post-challenge plasma. Furthermore, cultured schistosomula lose chromatin activating marks at the transcription start site of genes related to worm development and show decreased expression of genes related to lysosomes and lytic vacuoles involved with autophagy. Overall, our results indicate that enhanced antibody responses against the challenge migrating larvae mediate the naturally acquired protective immunity and will inform the route to an effective vaccine.</p>',
			'date' => '2021-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34702841',
			'doi' => '10.1038/s41467-021-26497-0',
			'modified' => '2022-05-19 17:15:53',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 46 => array(
			'id' => '4268',
			'name' => 'p300 suppresses the transition of myelodysplastic syndromes to acutemyeloid leukemia',
			'authors' => 'Man Na et al.',
			'description' => '<p>Myelodysplastic syndromes (MDS) are hematopoietic stem and progenitor cell (HSPC) malignancies characterized by ineffective hematopoiesis and an increased risk of leukemia transformation. Epigenetic regulators are recurrently mutated in MDS, directly implicating epigenetic dysregulation in MDS pathogenesis. Here, we identified a tumor suppressor role of the acetyltransferase p300 in clinically relevant MDS models driven by mutations in the epigenetic regulators TET2, ASXL1, and SRSF2. The loss of p300 enhanced the proliferation and self-renewal capacity of Tet2-deficient HSPCs, resulting in an increased HSPC pool and leukemogenicity in primary and transplantation mouse models. Mechanistically, the loss of p300 in Tet2-deficient HSPCs altered enhancer accessibility and the expression of genes associated with differentiation, proliferation, and leukemia development. Particularly, p300 loss led to an increased expression of Myb, and the depletion of Myb attenuated the proliferation of HSPCs and improved the survival of leukemia-bearing mice. Additionally, we show that chemical inhibition of p300 acetyltransferase activity phenocopied Ep300 deletion in Tet2-deficient HSPCs, whereas activation of p300 activity with a small molecule impaired the self-renewal and leukemogenicity of Tet2-deficient cells. This suggests a potential therapeutic application of p300 activators in the treatment of MDS with TET2 inactivating mutations.</p>',
			'date' => '2021-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34622806',
			'doi' => '10.1172/jci.insight.138478',
			'modified' => '2022-05-23 09:44:16',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 47 => array(
			'id' => '4231',
			'name' => 'Differential contribution to gene expression prediction of histonemodifications at enhancers or promoters.',
			'authors' => 'González-Ramírez M. et al.',
			'description' => '<p>The ChIP-seq signal of histone modifications at promoters is a good predictor of gene expression in different cellular contexts, but whether this is also true at enhancers is not clear. To address this issue, we develop quantitative models to characterize the relationship of gene expression with histone modifications at enhancers or promoters. We use embryonic stem cells (ESCs), which contain a full spectrum of active and repressed (poised) enhancers, to train predictive models. As many poised enhancers in ESCs switch towards an active state during differentiation, predictive models can also be trained on poised enhancers throughout differentiation and in development. Remarkably, we determine that histone modifications at enhancers, as well as promoters, are predictive of gene expression in ESCs and throughout differentiation and development. Importantly, we demonstrate that their contribution to the predictive models varies depending on their location in enhancers or promoters. Moreover, we use a local regression (LOESS) to normalize sequencing data from different sources, which allows us to apply predictive models trained in a specific cellular context to a different one. We conclude that the relationship between gene expression and histone modifications at enhancers is universal and different from promoters. Our study provides new insight into how histone modifications relate to gene expression based on their location in enhancers or promoters.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/34473698/',
			'doi' => '10.1371/journal.pcbi.1009368',
			'modified' => '2022-05-19 16:50:59',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 48 => array(
			'id' => '4294',
			'name' => 'DOT1L O-GlcNAcylation promotes its protein stability andMLL-fusion leukemia cell proliferation.',
			'authors' => 'Song Tanjing et al.',
			'description' => '<p>Histone lysine methylation functions at the interface of the extracellular environment and intracellular gene expression. DOT1L is a versatile histone H3K79 methyltransferase with a prominent role in MLL-fusion leukemia, yet little is known about how DOT1L responds to extracellular stimuli. Here, we report that DOT1L protein stability is regulated by the extracellular glucose level through the hexosamine biosynthetic pathway (HBP). Mechanistically, DOT1L is O-GlcNAcylated at evolutionarily conserved S1511 in its C terminus. We identify UBE3C as a DOT1L E3 ubiquitin ligase promoting DOT1L degradation whose interaction with DOT1L is susceptible to O-GlcNAcylation. Consequently, HBP enhances H3K79 methylation and expression of critical DOT1L target genes such as HOXA9/MEIS1, promoting cell proliferation in MLL-fusion leukemia. Inhibiting HBP or O-GlcNAc transferase (OGT) increases cellular sensitivity to DOT1L inhibitor. Overall, our work uncovers O-GlcNAcylation and UBE3C as critical determinants of DOT1L protein abundance, revealing a mechanism by which glucose metabolism affects malignancy progression through histone methylation.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34551297',
			'doi' => '10.1016/j.celrep.2021.109739',
			'modified' => '2022-05-24 09:20:37',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 49 => array(
			'id' => '4297',
			'name' => 'INTS11 regulates hematopoiesis by promoting PRC2 function.',
			'authors' => 'Zhang Peng et al.',
			'description' => '<p>INTS11, the catalytic subunit of the Integrator (INT) complex, is crucial for the biogenesis of small nuclear RNAs and enhancer RNAs. However, the role of INTS11 in hematopoietic stem and progenitor cell (HSPC) biology is unknown. Here, we report that INTS11 is required for normal hematopoiesis and hematopoietic-specific genetic deletion of leads to cell cycle arrest and impairment of fetal and adult HSPCs. We identified a novel INTS11-interacting protein complex, Polycomb repressive complex 2 (PRC2), that maintains HSPC functions. Loss of INTS11 destabilizes the PRC2 complex, decreases the level of histone H3 lysine 27 trimethylation (H3K27me3), and derepresses PRC2 target genes. Reexpression of INTS11 or PRC2 proteins in -deficient HSPCs restores the levels of PRC2 and H3K27me3 as well as HSPC functions. Collectively, our data demonstrate that INTS11 is an essential regulator of HSPC homeostasis through the INTS11-PRC2 axis.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34516911',
			'doi' => '10.1126/sciadv.abh1684',
			'modified' => '2022-05-30 09:31:00',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 50 => array(
			'id' => '4282',
			'name' => 'Enhanced targeted DNA methylation of the CMV and endogenous promoterswith dCas9-DNMT3A3L entails distinct subsequent histonemodification changes in CHO cells.',
			'authors' => 'Marx Nicolas et al. ',
			'description' => '<p>With the emergence of new CRISPR/dCas9 tools that enable site specific modulation of DNA methylation and histone modifications, more detailed investigations of the contribution of epigenetic regulation to the precise phenotype of cells in culture, including recombinant production subclones, is now possible. These also allow a wide range of applications in metabolic engineering once the impact of such epigenetic modifications on the chromatin state is available. In this study, enhanced DNA methylation tools were targeted to a recombinant viral promoter (CMV), an endogenous promoter that is silenced in its native state in CHO cells, but had been reactivated previously (&beta;-galactoside &alpha;-2,6-sialyltransferase 1) and an active endogenous promoter (&alpha;-1,6-fucosyltransferase), respectively. Comparative ChIP-analysis of histone modifications revealed a general loss of active promoter histone marks and the acquisition of distinct repressive heterochromatin marks after targeted methylation. On the other hand, targeted demethylation resulted in autologous acquisition of active promoter histone marks and loss of repressive heterochromatin marks. These data suggest that DNA methylation directs the removal or deposition of specific histone marks associated with either active, poised or silenced chromatin. Moreover, we show that de novo methylation of the CMV promoter results in reduced transgene expression in CHO cells. Although targeted DNA methylation is not efficient, the transgene is repressed, thus offering an explanation for seemingly conflicting reports about the source of CMV promoter instability in CHO cells. Importantly, modulation of epigenetic marks enables to nudge the cell into a specific gene expression pattern or phenotype, which is stabilized in the cell by autologous addition of further epigenetic marks. Such engineering strategies have the added advantage of being reversible and potentially tunable to not only turn on or off a targeted gene, but also to achieve the setting of a desirable expression level.</p>',
			'date' => '2021-07-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.ymben.2021.04.014',
			'doi' => '10.1016/j.ymben.2021.04.014',
			'modified' => '2022-05-23 10:09:24',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 51 => array(
			'id' => '4118',
			'name' => 'ChIP-seq protocol for sperm cells and embryos to assess environmentalimpacts and epigenetic inheritance',
			'authors' => 'Lismer, Ariane and Lambrot, Romain and Lafleur, Christine and Dumeaux,Vanessa and Kimmins, Sarah',
			'description' => '<p>In the field of epigenetic inheritance, delineating molecular mechanisms implicated in the transfer of paternal environmental conditions to descendants has been elusive. This protocol details how to track sperm chromatin intergenerationally. We describe mouse model design to probe chromatin states in single mouse sperm and techniques to assess pre-implantation embryo chromatin and gene expression. We place emphasis on how to obtain high-quality and quantifiable data sets in sperm and embryos, as well as highlight the limitations of working with low input.</p>',
			'date' => '2021-06-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.xpro.2021.100602',
			'doi' => '10.1016/j.xpro.2021.100602',
			'modified' => '2021-12-06 17:59:57',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 52 => array(
			'id' => '4318',
			'name' => 'E2F6 initiates stable epigenetic silencing of germline genes duringembryonic development',
			'authors' => 'Dahlet T. et al.',
			'description' => '<p>In mouse development, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes; however, the molecular mechanisms of this specificity remain unclear. Here, we demonstrate that the transcription factor E2F6, a member of the polycomb repressive complex 1.6 (PRC1.6), is critical to target and initiate epigenetic silencing at germline genes in early embryogenesis. Genome-wide, E2F6 binds preferentially to CpG islands in embryonic cells. E2F6 cooperates with MGA to silence a subgroup of germline genes in mouse embryonic stem cells and in embryos, a function that critically depends on the E2F6 marked box domain. Inactivation of E2f6 leads to a failure to deposit CpG island DNA methylation at these genes during implantation. Furthermore, E2F6 is required to initiate epigenetic silencing in early embryonic cells but becomes dispensable for the maintenance in differentiated cells. Our findings elucidate the mechanisms of epigenetic targeting of germline genes and provide a paradigm for how transient repression signals by DNA-binding factors in early embryonic cells are translated into long-term epigenetic silencing during mouse development.</p>',
			'date' => '2021-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34117224',
			'doi' => '10.1038/s41467-021-23596-w',
			'modified' => '2022-08-02 16:53:03',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 53 => array(
			'id' => '4349',
			'name' => 'Lasp1 regulates adherens junction dynamics and fibroblast transformationin destructive arthritis',
			'authors' => 'Beckmann D. et al.',
			'description' => '<p>The LIM and SH3 domain protein 1 (Lasp1) was originally cloned from metastatic breast cancer and characterised as an adaptor molecule associated with tumourigenesis and cancer cell invasion. However, the regulation of Lasp1 and its function in the aggressive transformation of cells is unclear. Here we use integrative epigenomic profiling of invasive fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and from mouse models of the disease, to identify Lasp1 as an epigenomically co-modified region in chronic inflammatory arthritis and a functionally important binding partner of the Cadherin-11/&beta;-Catenin complex in zipper-like cell-to-cell contacts. In vitro, loss or blocking of Lasp1 alters pathological tissue formation, migratory behaviour and platelet-derived growth factor response of arthritic FLS. In arthritic human TNF transgenic mice, deletion of Lasp1 reduces arthritic joint destruction. Therefore, we show a function of Lasp1 in cellular junction formation and inflammatory tissue remodelling and identify Lasp1 as a potential target for treating inflammatory joint disorders associated with aggressive cellular transformation.</p>',
			'date' => '2021-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34131132',
			'doi' => '10.1038/s41467-021-23706-8',
			'modified' => '2022-08-03 17:02:30',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 54 => array(
			'id' => '4143',
			'name' => 'Placental uptake and metabolism of 25(OH)Vitamin D determines itsactivity within the fetoplacental unit',
			'authors' => 'Ashley, B. et al.',
			'description' => '<p>Pregnancy 25-hydroxyvitamin D (25(OH)D) concentrations are associated with maternal and fetal health outcomes, but the underlying mechanisms have not been elucidated. Using physiological human placental perfusion approaches and intact villous explants we demonstrate a role for the placenta in regulating the relationships between maternal 25(OH)D concentrations and fetal physiology. Here, we demonstrate active placental uptake of 25(OH)D3 by endocytosis and placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the fetal and maternal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than solely the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer, including transcriptional activation and inflammatory responses. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta; with widespread effects on the placenta itself. These data show complex and synergistic interplay between vitamin D and the placenta, and inform possible interventions to optimise placental function to better support fetal growth and the maternal adaptations to pregnancy.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.03.01.431439',
			'doi' => '10.1101/2021.03.01.431439',
			'modified' => '2021-12-13 09:29:25',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 55 => array(
			'id' => '4160',
			'name' => 'Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.',
			'authors' => 'Pettinato, Anthony M. et al. ',
			'description' => '<p>Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization by unclear mechanisms. To study this process, we engineer a human cardiomyocyte model to track replication and polyploidization using fluorescently tagged cyclin B1 and cardiac troponin T. Using time-lapse imaging, in&nbsp;vitro cardiomyocyte replication patterns recapitulate the progressive mononuclear polyploidization and replicative arrest observed in&nbsp;vivo. Single-cell transcriptomics and chromatin state analyses reveal that polyploidization is preceded by sarcomere assembly, enhanced oxidative metabolism, a DNA damage response, and p53 activation. CRISPR knockout screening reveals p53 as a driver of cell-cycle arrest and polyploidization. Inhibiting sarcomere function, or scavenging ROS, inhibits cell-cycle arrest and polyploidization. Finally, we show that cardiomyocyte engraftment in infarcted rat hearts is enhanced 4-fold by the increased proliferation of troponin-knockout cardiomyocytes. Thus, the sarcomere inhibits cell division through a DNA damage response that can be targeted to improve cardiomyocyte replacement strategies.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33951429',
			'doi' => '10.1016/j.celrep.2021.109088',
			'modified' => '2021-12-16 10:58:59',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 56 => array(
			'id' => '4343',
			'name' => 'The SAM domain-containing protein 1 (SAMD1) acts as a repressivechromatin regulator at unmethylated CpG islands',
			'authors' => 'Stielow B. et al. ',
			'description' => '<p>CpG islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here, we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 has an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. The absence of SAMD1 impairs ES cell differentiation processes, leading to misregulation of key biological pathways. Together, our work establishes SAMD1 as a newly identified chromatin regulator acting at unmethylated CGIs.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33980486',
			'doi' => '10.1126/sciadv.abf2229',
			'modified' => '2022-08-03 16:34:24',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 57 => array(
			'id' => '4350',
			'name' => 'Simplification of culture conditions and feeder-free expansion of bovineembryonic stem cells',
			'authors' => 'Soto D. A. et al. ',
			'description' => '<p>Bovine embryonic stem cells (bESCs) extend the lifespan of the transient pluripotent bovine inner cell mass in vitro. After years of research, derivation of stable bESCs was only recently reported. Although successful, bESC culture relies on complex culture conditions that require a custom-made base medium and mouse embryonic fibroblasts (MEF) feeders, limiting the widespread use of bESCs. We report here simplified bESC culture conditions based on replacing custom base medium with a commercially available alternative and eliminating the need for MEF feeders by using a chemically-defined substrate. bESC lines were cultured and derived using a base medium consisting of N2B27 supplements and 1\% BSA (NBFR-bESCs). Newly derived bESC lines were easy to establish, simple to propagate and stable after long-term culture. These cells expressed pluripotency markers and actively proliferated for more than 35 passages while maintaining normal karyotype and the ability to differentiate into derivatives of all three germ lineages in embryoid bodies and teratomas. In addition, NBFR-bESCs grew for multiple passages in a feeder-free culture system based on vitronectin and Activin A medium supplementation while maintaining pluripotency. Simplified conditions will facilitate the use of bESCs for gene editing applications and pluripotency and lineage commitment studies.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34040070',
			'doi' => '10.1038/s41598-021-90422-0',
			'modified' => '2022-08-03 16:38:27',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 58 => array(
			'id' => '4161',
			'name' => 'The anti-inflammatory cytokine interleukin-37 is an inhibitor of trainedimmunity.',
			'authors' => 'Cavalli, Giulio and Tengesdal, Isak W and Gresnigt, Mark and Nemkov, Travisand Arts, Rob J W and Domínguez-Andrés, Jorge and Molteni, Raffaella andStefanoni, Davide and Cantoni, Eleonora and Cassina, Laura and Giugliano,Silvia and Schraa, Kiki and Mill',
			'description' => '<p>Trained immunity (TI) is a de facto innate immune memory program induced in monocytes/macrophages by exposure to pathogens or vaccines, which evolved as protection against infections. TI is characterized by immunometabolic changes and histone post-translational modifications, which enhance production of pro-inflammatory cytokines. As aberrant activation of TI is implicated in inflammatory diseases, tight regulation is critical; however, the mechanisms responsible for this modulation remain elusive. Interleukin-37 (IL-37) is an anti-inflammatory cytokine that curbs inflammation and modulates metabolic pathways. In this study, we show that administration of recombinant IL-37 abrogates the protective effects of TI in&nbsp;vivo, as revealed by reduced host pro-inflammatory responses and survival to disseminated candidiasis. Mechanistically, IL-37 reverses the immunometabolic changes and histone post-translational modifications characteristic of TI in monocytes, thus suppressing cytokine production in response to infection. IL-37 thereby emerges as an inhibitor of TI and as a potential therapeutic target in immune-mediated pathologies.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33826894',
			'doi' => '10.1016/j.celrep.2021.108955',
			'modified' => '2021-12-21 15:16:27',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 59 => array(
			'id' => '4178',
			'name' => 'Comparative analysis of histone H3K4me3 modifications between blastocystsand somatic tissues in cattle.',
			'authors' => 'Ishibashi, Mao et al.',
			'description' => '<p>Epigenetic changes induced in the early developmental stages by the surrounding environment can have not only short-term but also long-term consequences throughout life. This concept constitutes the "Developmental Origins of Health and Disease" (DOHaD) hypothesis and encompasses the possibility of controlling livestock health and diseases by epigenetic regulation during early development. As a preliminary step for examining changes of epigenetic modifications in early embryos and their long-lasting effects in fully differentiated somatic tissues, we aimed to obtain high-throughput genome-wide histone H3 lysine 4 trimethylation (H3K4me3) profiles of bovine blastocysts and to compare these data with those from adult somatic tissues in order to extract common and typical features between these tissues in terms of H3K4me3 modifications. Bovine blastocysts were produced in vitro and subjected to chromatin immunoprecipitation-sequencing analysis of H3K4me3. Comparative analysis of the blastocyst-derived H3K4me3 profile with publicly available data from adult liver and muscle tissues revealed that the blastocyst profile could be used as a "sieve" to extract somatic tissue-specific modifications in genes closely related to tissue-specific functions. Furthermore, principal component analysis of the level of common modifications between blastocysts and somatic tissues in meat production-related and imprinted genes well characterized inter- and intra-tissue differences. The results of this study produced a referential genome-wide H3K4me3 profile of bovine blastocysts within the limits of their in vitro source and revealed its common and typical features in relation to the profiles of adult tissues.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33859293',
			'doi' => '10.1038/s41598-021-87683-0',
			'modified' => '2021-12-21 16:40:41',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 60 => array(
			'id' => '4181',
			'name' => 'Genetic perturbation of PU.1 binding and chromatin looping at neutrophilenhancers associates with autoimmune disease.',
			'authors' => 'Watt, Stephen et al.',
			'description' => '<p>Neutrophils play fundamental roles in innate immune response, shape adaptive immunity, and are a potentially causal cell type underpinning genetic associations with immune system traits and diseases. Here, we profile the binding of myeloid master regulator PU.1 in primary neutrophils across nearly a hundred volunteers. We show that variants associated with differential PU.1 binding underlie genetically-driven differences in cell count and susceptibility to autoimmune and inflammatory diseases. We integrate these results with other multi-individual genomic readouts, revealing coordinated effects of PU.1 binding variants on the local chromatin state, enhancer-promoter contacts and downstream gene expression, and providing a functional interpretation for 27 genes underlying immune traits. Collectively, these results demonstrate the functional role of PU.1 and its target enhancers in neutrophil transcriptional control and immune disease susceptibility.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33863903',
			'doi' => '10.1038/s41467-021-22548-8',
			'modified' => '2021-12-21 16:50:30',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 61 => array(
			'id' => '4138',
			'name' => 'Loss of SETD1B results in the redistribution of genomic H3K4me3 in theoocyte',
			'authors' => 'Hanna, C. W. et al. ',
			'description' => '<p>Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransferases SETD1B and MLL2 are essential for oogenesis. We investigated changes in H3K4me3 in Setd1b conditional knockout (cKO) GV oocytes using ultra-low input ChIP-seq, in conjunction with DNA methylation and gene expression analysis. Setd1b cKO oocytes showed a redistribution of H3K4me3, with a marked loss at active gene promoters associated with downregulated gene expression. Remarkably, many regions gained H3K4me3 in Setd1b cKOs, in particular those that were DNA hypomethylated, transcriptionally inactive and CpGrich - hallmarks of MLL2 targets. Thus, loss of SETD1B appears to enable enhanced MLL2 activity. Our work reveals two distinct, complementary mechanisms of genomic targeting of H3K4me3 in oogenesis, with SETD1B linked to gene expression in the oogenic program and MLL2 to CpG content.</p>',
			'date' => '2021-03-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.03.11.434836',
			'doi' => '10.1101/2021.03.11.434836',
			'modified' => '2021-12-13 09:15:06',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 62 => array(
			'id' => '4162',
			'name' => 'Epigenomic tensor predicts disease subtypes and reveals constrained tumorevolution.',
			'authors' => 'Leistico, Jacob R et al.',
			'description' => '<p>Understanding the epigenomic evolution and specificity of disease subtypes from complex patient data remains a major biomedical problem. We here present DeCET (decomposition and classification of epigenomic tensors), an integrative computational approach for simultaneously analyzing hierarchical heterogeneous data, to identify robust epigenomic differences among tissue types, differentiation states, and disease subtypes. Applying DeCET to our own data from 21 uterine benign tumor (leiomyoma) patients identifies distinct epigenomic features discriminating normal myometrium and leiomyoma subtypes. Leiomyomas possess preponderant alterations in distal enhancers and long-range histone modifications confined to chromatin contact domains that constrain the evolution of pathological epigenomes. Moreover, we demonstrate the power and advantage of DeCET on multiple publicly available epigenomic datasets representing different cancers and cellular states. Epigenomic features extracted by DeCET can thus help improve our understanding of disease states, cellular development, and differentiation, thereby facilitating future therapeutic, diagnostic, and prognostic strategies.</p>',
			'date' => '2021-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33789109',
			'doi' => '10.1016/j.celrep.2021.108927',
			'modified' => '2021-12-21 15:19:13',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 63 => array(
			'id' => '4196',
			'name' => 'Functional annotations of three domestic animal genomes provide vitalresources for comparative and agricultural research.',
			'authors' => 'Kern C. et al.',
			'description' => '<p>Gene regulatory elements are central drivers of phenotypic variation and thus of critical importance towards understanding the genetics of complex traits. The Functional Annotation of Animal Genomes consortium was formed to collaboratively annotate the functional elements in animal genomes, starting with domesticated animals. Here we present an expansive collection of datasets from eight diverse tissues in three important agricultural species: chicken (Gallus gallus), pig (Sus scrofa), and cattle (Bos taurus). Comparative analysis of these datasets and those from the human and mouse Encyclopedia of DNA Elements projects reveal that a core set of regulatory elements are functionally conserved independent of divergence between species, and that tissue-specific transcription factor occupancy at regulatory elements and their predicted target genes are also conserved. These datasets represent a unique opportunity for the emerging field of comparative epigenomics, as well as the agricultural research community, including species that are globally important food resources.</p>',
			'date' => '2021-03-01',
			'pmid' => 'https://doi.org/10.1038%2Fs41467-021-22100-8',
			'doi' => '10.1038/s41467-021-22100-8',
			'modified' => '2022-01-06 14:30:41',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 64 => array(
			'id' => '4127',
			'name' => 'The histone modification H3K4me3 is altered at the  locus in Alzheimer'sdisease brain.',
			'authors' => 'Smith, Adam et al.',
			'description' => '<p>Several epigenome-wide association studies of DNA methylation have highlighted altered DNA methylation in the gene in Alzheimer's disease (AD) brain samples. However, no study has specifically examined histone modifications in the disease. We use chromatin immunoprecipitation-qPCR to quantify tri-methylation at histone 3 lysine 4 (H3K4me3) and 27 (H3K27me3) in the gene in entorhinal cortex from donors with high (n&nbsp;=&nbsp;59) or low (n&nbsp;=&nbsp;29) Alzheimer's disease&nbsp;pathology. We demonstrate decreased levels of H3K4me3, a marker of active gene transcription, with no change in H3K27me3, a marker of inactive genes. H3K4me3 is negatively correlated with DNA methylation in specific regions of the gene. Our study suggests that the gene shows altered epigenetic marks indicative of reduced gene activation in Alzheimer's disease.</p>',
			'date' => '2021-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33815817',
			'doi' => '10.2144/fsoa-2020-0161',
			'modified' => '2021-12-07 10:16:08',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 65 => array(
			'id' => '4146',
			'name' => 'The G2-phase enriched lncRNA SNHG26 is necessary for proper cell cycleprogression and proliferation',
			'authors' => 'Samdal, H. et al.',
			'description' => '<p>Long noncoding RNAs (lncRNAs) are involved in the regulation of cell cycle, although only a few have been functionally characterized. By combining RNA sequencing and ChIP sequencing of cell cycle synchronized HaCaT cells we have previously identified lncRNAs highly enriched for cell cycle functions. Based on a cyclic expression profile and an overall high correlation to histone 3 lysine 4 trimethylation (H3K4me3) and RNA polymerase II (Pol II) signals, the lncRNA SNHG26 was identified as a top candidate. In the present study we report that downregulation of SNHG26 affects mitochondrial stress, proliferation, cell cycle phase distribution, and gene expression in cis- and in trans, and that this effect is reversed by upregulation of SNHG26. We also find that the effect on cell cycle phase distribution is cell type specific and stable over time. Results indicate an oncogenic role of SNHG26, possibly by affecting cell cycle progression through the regulation of downstream MYC-responsive genes.</p>',
			'date' => '2021-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.02.22.432245',
			'doi' => '10.1101/2021.02.22.432245',
			'modified' => '2021-12-14 09:21:27',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 66 => array(
			'id' => '4151',
			'name' => 'The epigenetic landscape in purified myonuclei from fast and slow muscles',
			'authors' => 'Bengtsen, M. et al.',
			'description' => '<p>Muscle cells have different phenotypes adapted to different usage and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of chromatin environment by ChIP-Seq in two muscle extremes, the almost completely fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where less than 60\% of the nuclei are inside muscle fibers. Since cellular homogeneity is critical in epigenome-wide association studies we devised a new method for purifying skeletal muscle nuclei from whole tissue based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labeling and a magnetic-assisted sorting approach we were able to sort out myonuclei with 95\% purity. The sorting eliminated influence from other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the functional properties of the two muscles each with a distinct regulatory program involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles are also regulated by different sets of transcription factors; e.g. in soleus binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SOX1 binding sites were found to be overrepresented. In addition, novel factors for muscle regulation such as MAF, ZFX and ZBTB14 were identified.</p>',
			'date' => '2021-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.02.04.429545',
			'doi' => '10.1101/2021.02.04.429545',
			'modified' => '2021-12-14 09:40:02',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 67 => array(
			'id' => '4198',
			'name' => 'WAPL maintains a cohesin loading cycle to preserve cell-type-specificdistal gene regulation.',
			'authors' => 'Liu N. Q.et al.',
			'description' => '<p>The cohesin complex has an essential role in maintaining genome organization. However, its role in gene regulation remains largely unresolved. Here we report that the cohesin release factor WAPL creates a pool of free cohesin, in a process known as cohesin turnover, which reloads it to cell-type-specific binding sites. Paradoxically, stabilization of cohesin binding, following WAPL ablation, results in depletion of cohesin from these cell-type-specific regions, loss of gene expression and differentiation. Chromosome conformation capture experiments show that cohesin turnover is important for maintaining promoter-enhancer loops. Binding of cohesin to cell-type-specific sites is dependent on the pioneer transcription factors OCT4 (POU5F1) and SOX2, but not NANOG. We show the importance of cohesin turnover in controlling transcription and propose that a cycle of cohesin loading and off-loading, instead of static cohesin binding, mediates promoter and enhancer interactions critical for gene regulation.</p>',
			'date' => '2020-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33318687',
			'doi' => '10.1038/s41588-020-00744-4',
			'modified' => '2022-01-06 14:38:26',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 68 => array(
			'id' => '4061',
			'name' => 'Dissecting Herpes Simplex Virus 1-Induced Host Shutoff at the RNA Level.',
			'authors' => 'Friedel, Caroline C and Whisnant, Adam W and Djakovic, Lara and Rutkowski,Andrzej J and Friedl, Marie-Sophie and Kluge, Michael and Williamson, JamesC and Sai, Somesh and Vidal, Ramon Oliveira and Sauer, Sascha and Hennig,Thomas and Grothey, Arnhild an',
			'description' => '<p>Herpes simplex virus 1 (HSV-1) induces a profound host shut-off during lytic infection. The virion host shut-off () protein plays a key role in this process by efficiently cleaving host and viral mRNAs. Furthermore, the onset of viral DNA replication is accompanied by a rapid decline in host transcriptional activity. To dissect relative contributions of both mechanisms and elucidate gene-specific host transcriptional responses throughout the first 8h of lytic HSV-1 infection, we employed RNA-seq of total, newly transcribed (4sU-labelled) and chromatin-associated RNA in wild-type (WT) and &Delta; infection of primary human fibroblasts. Following virus entry, v activity rapidly plateaued at an elimination rate of around 30\% of cellular mRNAs per hour until 8h p.i. In parallel, host transcriptional activity dropped to 10-20\%. While the combined effects of both phenomena dominated infection-induced changes in total RNA, extensive gene-specific transcriptional regulation was observable in chromatin-associated RNA and was surprisingly concordant between WT and &Delta; infection. Both induced strong transcriptional up-regulation of a small subset of genes that were poorly expressed prior to infection but already primed by H3K4me3 histone marks at their promoters. Most interestingly, analysis of chromatin-associated RNA revealed -nuclease-activity-dependent transcriptional down-regulation of at least 150 cellular genes, in particular of many integrin adhesome and extracellular matrix components. This was accompanied by a -dependent reduction in protein levels by 8h p.i. for many of these genes. In summary, our study provides a comprehensive picture of the molecular mechanisms that govern cellular RNA metabolism during the first 8h of lytic HSV-1 infection. The HSV-1 virion host shut-off () protein efficiently cleaves both host and viral mRNAs in a translation-dependent manner. In this study, we model and quantify changes in activity as well as virus-induced global loss of host transcriptional activity during productive HSV-1 infection. In general, HSV-1-induced alterations in total RNA levels were dominated by these two global effects. In contrast, chromatin-associated RNA depicted gene-specific transcriptional changes. This revealed highly concordant transcriptional changes in WT and infection, confirmed DUX4 as a key transcriptional regulator in HSV-1 infection and depicted -dependent, transcriptional down-regulation of the integrin adhesome and extracellular matrix components. The latter explained seemingly gene-specific effects previously attributed to -mediated mRNA degradation and resulted in a concordant loss in protein levels by 8h p.i. for many of the respective genes.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33148793',
			'doi' => '10.1128/JVI.01399-20',
			'modified' => '2021-02-19 17:31:53',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 69 => array(
			'id' => '4069',
			'name' => 'Increased H3K4me3 methylation and decreased miR-7113-5p expression lead toenhanced Wnt/β-catenin signaling in immune cells from PTSD patientsleading to inflammatory phenotype.',
			'authors' => 'Bam, Marpe and Yang, Xiaoming and Busbee, Brandon P and Aiello, Allison Eand Uddin, Monica and Ginsberg, Jay P and Galea, Sandro and Nagarkatti,Prakash S and Nagarkatti, Mitzi',
			'description' => '<p>BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric disorder accompanied by chronic peripheral inflammation. What triggers inflammation in PTSD is currently unclear. In the present study, we identified potential defects in signaling pathways in peripheral blood mononuclear cells (PBMCs) from individuals with PTSD. METHODS: RNAseq (5 samples each for controls and PTSD), ChIPseq (5 samples each) and miRNA array (6 samples each) were used in combination with bioinformatics tools to identify dysregulated genes in PBMCs. Real time qRT-PCR (24 samples each) and in vitro assays were employed to validate our primary findings and hypothesis. RESULTS: By RNA-seq analysis of PBMCs, we found that Wnt signaling pathway was upregulated in PTSD when compared to normal controls. Specifically, we found increased expression of WNT10B in the PTSD group when compared to controls. Our findings were confirmed using NCBI's GEO database involving a larger sample size. Additionally, in vitro activation studies revealed that activated but not na&iuml;ve PBMCs from control individuals expressed more IFN&gamma; in the presence of recombinant WNT10B suggesting that Wnt signaling played a crucial role in exacerbating inflammation. Next, we investigated the mechanism of induction of WNT10B and found that increased expression of WNT10B may result from epigenetic modulation involving downregulation of hsa-miR-7113-5p which targeted WNT10B. Furthermore, we also observed that WNT10B overexpression was linked to higher expression of H3K4me3 histone modification around the promotor of WNT10B. Additionally, knockdown of histone demethylase specific to H3K4me3, using siRNA, led to increased expression of WNT10B providing conclusive evidence that H3K4me3 indeed controlled WNT10B expression. CONCLUSIONS: In summary, our data demonstrate for the first time that Wnt signaling pathway is upregulated in PBMCs of PTSD patients resulting from epigenetic changes involving microRNA dysregulation and histone modifications, which in turn may promote the inflammatory phenotype in such cells.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33189141',
			'doi' => '10.1186/s10020-020-00238-3',
			'modified' => '2021-02-19 17:54:52',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 70 => array(
			'id' => '4084',
			'name' => 'BCG Vaccination Induces Long-Term Functional Reprogramming of HumanNeutrophils.',
			'authors' => 'Moorlag, Simone J C F M and Rodriguez-Rosales, Yessica Alina and Gillard,Joshua and Fanucchi, Stephanie and Theunissen, Kate and Novakovic, Borisand de Bont, Cynthia M and Negishi, Yutaka and Fok, Ezio T and Kalafati,Lydia and Verginis, Panayotis and M',
			'description' => '<p>The tuberculosis vaccine bacillus Calmette-Gu&eacute;rin (BCG) protects against some heterologous infections, probably via induction of non-specific innate immune memory in monocytes and natural killer (NK) cells, a process known as trained immunity. Recent studies have revealed that the induction of trained immunity is associated with a bias toward granulopoiesis in bone marrow hematopoietic progenitor cells, but it is unknown whether BCG vaccination also leads to functional reprogramming of mature neutrophils. Here, we show that BCG vaccination of healthy humans induces long-lasting changes in neutrophil phenotype, characterized by increased expression of activation markers and antimicrobial function. The enhanced function of human neutrophils persists for at least 3&nbsp;months after vaccination and is associated with genome-wide epigenetic modifications in trimethylation at histone 3 lysine 4. Functional reprogramming of neutrophils by the induction of trained immunity might offer novel therapeutic strategies in clinical conditions that could benefit from modulation of neutrophil effector function.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33207187',
			'doi' => '10.1016/j.celrep.2020.108387',
			'modified' => '2021-03-15 17:07:29',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 71 => array(
			'id' => '4095',
			'name' => 'ZNF354C is a transcriptional repressor that inhibits endothelialangiogenic sprouting.',
			'authors' => 'Oo, James A and Irmer, Barnabas and Günther, Stefan and Warwick, Timothyand Pálfi, Katalin and Izquierdo Ponce, Judit and Teichmann, Tom andPflüger-Müller, Beatrice and Gilsbach, Ralf and Brandes, Ralf P andLeisegang, Matthias S',
			'description' => '<p>Zinc finger proteins (ZNF) are a large group of transcription factors with diverse functions. We recently discovered that endothelial cells harbour a specific mechanism to limit the action of ZNF354C, whose function in endothelial cells is unknown. Given that ZNF354C&nbsp;has so far only been studied in bone and tumour, its function was determined in endothelial cells. ZNF354C is expressed in vascular cells and localises to the nucleus and cytoplasm. Overexpression of ZNF354C in human endothelial cells results in a marked inhibition of endothelial sprouting. RNA-sequencing of human microvascular endothelial cells with and without overexpression of ZNF354C revealed that the protein is a potent transcriptional repressor. ZNF354C contains an active KRAB domain which mediates this suppression as shown by mutagenesis analysis. ZNF354C interacts with dsDNA, TRIM28 and histones, as observed by proximity ligation and immunoprecipitation. Moreover, chromatin immunoprecipitation revealed that the ZNF binds to specific endothelial-relevant target-gene promoters. ZNF354C suppresses these genes as shown by CRISPR/Cas knockout and RNAi. Inhibition of endothelial sprouting by ZNF354C is dependent on the amino acids DV and MLE of the KRAB domain. These results demonstrate that ZNF354C is a repressive transcription factor which acts through a KRAB domain to inhibit endothelial angiogenic sprouting.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33154469',
			'doi' => '10.1038/s41598-020-76193-0',
			'modified' => '2021-03-17 17:19:53',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 72 => array(
			'id' => '4197',
			'name' => 'Derivation of Intermediate Pluripotent Stem Cells Amenable to PrimordialGerm Cell Specification.',
			'authors' => 'Yu L. et al.',
			'description' => '<p>Dynamic pluripotent stem cell (PSC) states are in&nbsp;vitro adaptations of pluripotency continuum in&nbsp;vivo. Previous studies have generated a number of PSCs with distinct properties. To date, however, no known PSCs have demonstrated dual competency for chimera formation and direct responsiveness to primordial germ cell (PGC) specification, a unique functional feature of formative pluripotency. Here, by modulating fibroblast growth factor (FGF), transforming growth factor &beta; (TGF-&beta;), and WNT pathways, we derived PSCs from mice, horses, and humans (designated as XPSCs) that are permissive for direct PGC-like cell induction in&nbsp;vitro and are capable of contributing to intra- or inter-species chimeras in&nbsp;vivo. XPSCs represent a pluripotency state between naive and primed pluripotency and harbor molecular, cellular, and phenotypic features characteristic of formative pluripotency. XPSCs open new avenues for studying mammalian pluripotency and dissecting the molecular mechanisms governing PGC specification. Our method may be broadly applicable for the derivation of analogous stem cells from other mammalian species.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33271070',
			'doi' => '10.1016/j.stem.2020.11.003',
			'modified' => '2022-01-06 14:35:44',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 73 => array(
			'id' => '4201',
			'name' => 'The epigenetic regulator RINF (CXXC5) maintains SMAD7 expression in human immature erythroid cells and sustains red blood cellsexpansion.',
			'authors' => 'Astori A. et al.',
			'description' => '<p>The gene CXXC5, encoding a Retinoid-Inducible Nuclear Factor (RINF), is located within a region at 5q31.2 commonly deleted in myelodysplastic syndrome (MDS) and adult acute myeloid leukemia (AML). RINF may act as an epigenetic regulator and has been proposed as a tumor suppressor in hematopoietic malignancies. However, functional studies in normal hematopoiesis are lacking, and its mechanism of action is unknow. Here, we evaluated the consequences of RINF silencing on cytokineinduced erythroid differentiation of human primary CD34+ progenitors. We found that RINF is expressed in immature erythroid cells and that RINF-knockdown accelerated erythropoietin-driven maturation, leading to a significant reduction (~45\%) in the number of red blood cells (RBCs), without affecting cell viability. The phenotype induced by RINF-silencing was TGF&beta;-dependent and mediated by SMAD7, a TGF&beta;- signaling inhibitor. RINF upregulates SMAD7 expression by direct binding to its promoter and we found a close correlation between RINF and SMAD7 mRNA levels both in CD34+ cells isolated from bone marrow of healthy donors and MDS patients with del(5q). Importantly, RINF knockdown attenuated SMAD7 expression in primary cells and ectopic SMAD7 expression was sufficient to prevent the RINF knockdowndependent erythroid phenotype. Finally, RINF silencing affects 5&rsquo;-hydroxymethylation of human erythroblasts, in agreement with its recently described role as a Tet2- anchoring platform in mouse. Altogether, our data bring insight into how the epigenetic factor RINF, as a transcriptional regulator of SMAD7, may fine-tune cell sensitivity to TGF&beta; superfamily cytokines and thus play an important role in both normal and pathological erythropoiesis.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33241676',
			'doi' => '10.3324/haematol.2020.263558',
			'modified' => '2022-01-06 14:46:32',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 74 => array(
			'id' => '4052',
			'name' => 'StE(z)2, a Polycomb group methyltransferase and deposition of H3K27me3 andH3K4me3 regulate the expression of tuberization genes in potato.',
			'authors' => 'Kumar, Amit and Kondhare, Kirtikumar R and Malankar, Nilam N and Banerjee,Anjan K',
			'description' => '<p>Polycomb Repressive Complex (PRC) group proteins regulate various developmental processes in plants by repressing the target genes via H3K27 trimethylation, whereas their function is antagonized by Trithorax group proteins-mediated H3K4 trimethylation. Tuberization in potato is widely studied, but the role of histone modifications in this process is unknown. Recently, we showed that overexpression of StMSI1 (a PRC2 member) alters the expression of tuberization genes in potato. As MSI1 lacks histone-modification activity, we hypothesized that this altered expression could be caused by another PRC2 member, StE(z)2 (a potential H3K27 methyltransferase in potato). Here, we demonstrate that short-day photoperiod influences StE(z)2 expression in leaf and stolon. Moreover, StE(z)2 overexpression alters plant architecture and reduces tuber yield, whereas its knockdown enhanced the yield. ChIP-sequencing using short-day induced stolons revealed that several tuberization and phytohormone-related genes, such as StBEL5/11/29, StSWEET11B, StGA2OX1 and StPIN1 carry H3K4me3 or H3K27me3 marks and/or are StE(z)2 targets. Interestingly, we noticed that another important tuberization gene, StSP6A is targeted by StE(z)2 in leaves and had increased deposition of H3K27me3 under non-induced (long-day) conditions compared to SD. Overall, we show that StE(z)2 and deposition of H3K27me3 and/or H3K4me3 marks could regulate the expression of key tuberization genes in potato.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33048134',
			'doi' => '10.1093/jxb/eraa468',
			'modified' => '2021-02-19 14:55:34',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 75 => array(
			'id' => '4053',
			'name' => 'Priming for enhanced ARGONAUTE2 activation accompanies induced resistanceto cucumber mosaic virus in Arabidopsis thaliana.',
			'authors' => 'Ando, Sugihiro and Jaskiewicz, Michal and Mochizuki, Sei and Koseki, Saekoand Miyashita, Shuhei and Takahashi, Hideki and Conrath, Uwe',
			'description' => '<p>Systemic acquired resistance (SAR) is a broad-spectrum disease resistance response that can be induced upon infection from pathogens or by chemical treatment, such as with benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH). SAR involves priming for more robust activation of defence genes upon pathogen attack. Whether priming for SAR would involve components of RNA silencing remained unknown. Here, we show that upon leaf infiltration of water, BTH-primed Arabidopsis thaliana plants accumulate higher amounts of mRNA of ARGONAUTE (AGO)2 and AGO3, key components of RNA silencing. The enhanced AGO2 expression is associated with prior-to-activation trimethylation of lysine 4 in histone H3 and acetylation of histone H3 in the AGO2 promoter and with induced resistance to the yellow strain of cucumber mosaic virus (CMV[Y]). The results suggest that priming A.&nbsp;thaliana for enhanced defence involves modification of histones in the AGO2 promoter that condition AGO2 for enhanced activation, associated with resistance to CMV(Y). Consistently, the fold-reduction in CMV(Y) coat protein accumulation by BTH pretreatment was lower in ago2 than in wild type, pointing to reduced capacity of ago2 to activate BTH-induced CMV(Y) resistance. A role of AGO2 in pathogen-induced SAR is suggested by the enhanced activation of AGO2 after infiltrating systemic leaves of plants expressing a localized hypersensitive response upon CMV(Y) infection. In addition, local inoculation of SAR-inducing Pseudomonas syringae pv. maculicola causes systemic priming for enhanced AGO2 expression. Together our results indicate that defence priming targets the AGO2 component of RNA silencing whose enhanced expression is likely to contribute to SAR.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33073913',
			'doi' => '10.1111/mpp.13005',
			'modified' => '2021-02-19 14:57:21',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 76 => array(
			'id' => '4062',
			'name' => 'Digging Deeper into Breast Cancer Epigenetics: Insights from ChemicalInhibition of Histone Acetyltransferase TIP60 .',
			'authors' => 'Idrissou, Mouhamed and Lebert, Andre and Boisnier, Tiphanie and Sanchez,Anna and Houfaf Khoufaf, Fatma Zohra and Penault-Llorca, Frédérique andBignon, Yves-Jean and Bernard-Gallon, Dominique',
			'description' => '<p>Breast cancer is often sporadic due to several factors. Among them, the deregulation of epigenetic proteins may be involved. TIP60 or KAT5 is an acetyltransferase that regulates gene transcription through the chromatin structure. This pleiotropic protein acts in several cellular pathways by acetylating proteins. RNA and protein expressions of TIP60 were shown to decrease in some breast cancer subtypes, particularly in triple-negative breast cancer (TNBC), where a low expression of TIP60 was exhibited compared with luminal subtypes. In this study, the inhibition of the residual activity of TIP60 in breast cancer cell lines was investigated by using two chemical inhibitors, TH1834 and NU9056, first on the acetylation of the specific target, lysine 4 of histone 3 (H3K4) by immunoblotting, and second, by chromatin immunoprecipitation (ChIP)-qPCR (-quantitative Polymerase Chain Reaction). Subsequently, significant decreases or a trend toward decrease of H3K4ac in the different chromatin compartments were observed. In addition, the expression of 48 human nuclear receptors was studied with TaqMan Low-Density Array in these breast cancer cell lines treated with TIP60 inhibitors. The statistical analysis allowed us to comprehensively characterize the androgen receptor and receptors in TNBC cell lines after TH1834 or NU9056 treatment. The understanding of the residual activity of TIP60 in the evolution of breast cancer might be a major asset in the fight against this disease, and could allow TIP60 to be used as a biomarker or therapeutic target for breast cancer progression in the future.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32960142',
			'doi' => '10.1089/omi.2020.0104',
			'modified' => '2021-02-19 17:39:52',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 77 => array(
			'id' => '4073',
			'name' => 'NSD1-deposited H3K36me2 directs de novo methylation in the mouse malegermline and counteracts Polycomb-associated silencing.',
			'authors' => 'Shirane, Kenjiro and Miura, Fumihito and Ito, Takashi and Lorincz, MatthewC',
			'description' => '<p>De novo DNA methylation (DNAme) in mammalian germ cells is dependent on DNMT3A and DNMT3L. However, oocytes and spermatozoa show distinct patterns of DNAme. In mouse oocytes, de novo DNAme requires the lysine methyltransferase (KMTase) SETD2, which deposits H3K36me3. We show here that SETD2 is dispensable for de novo DNAme in the male germline. Instead, the lysine methyltransferase NSD1, which broadly deposits H3K36me2 in euchromatic regions, plays a critical role in de novo DNAme in prospermatogonia, including at imprinted genes. However, males deficient in germline NSD1 show a more severe defect in spermatogenesis than Dnmt3l males. Notably, unlike DNMT3L, NSD1 safeguards a subset of genes against H3K27me3-associated transcriptional silencing. In contrast, H3K36me2 in oocytes is predominantly dependent on SETD2 and coincides with H3K36me3. Furthermore, females with NSD1-deficient oocytes are fertile. Thus, the sexually dimorphic pattern of DNAme in mature mouse gametes is orchestrated by distinct profiles of H3K36 methylation.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32929285',
			'doi' => '10.1038/s41588-020-0689-z',
			'modified' => '2021-02-19 18:02:40',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 78 => array(
			'id' => '4078',
			'name' => 'Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth andPotentiates Checkpoint Inhibition.',
			'authors' => 'Priem, Bram and van Leent, Mandy M T and Teunissen, Abraham J P and Sofias,Alexandros Marios and Mourits, Vera P and Willemsen, Lisa and Klein, Emma Dand Oosterwijk, Roderick S and Meerwaldt, Anu E and Munitz, Jazz andPrévot, Geoffrey and Vera Verschuu',
			'description' => '<p>Trained immunity, a functional state of myeloid cells, has been proposed as a compelling immune-oncological target. Its efficient induction requires direct engagement of myeloid progenitors in the bone marrow. For this purpose, we developed a bone marrow-avid nanobiologic platform designed specifically to induce trained immunity. We established the potent anti-tumor capabilities of our lead candidate MTP-HDL in a B16F10 mouse melanoma model. These anti-tumor effects result from trained immunity-induced myelopoiesis caused by epigenetic rewiring of multipotent progenitors in the bone marrow, which overcomes the immunosuppressive tumor microenvironment. Furthermore, MTP-HDL nanotherapy potentiates checkpoint inhibition in this melanoma model refractory to anti-PD-1 and anti-CTLA-4 therapy. Finally, we determined MTP-HDL's favorable biodistribution and safety profile in non-human primates. In conclusion, we show that rationally designed nanobiologics can promote trained immunity and elicit a durable anti-tumor response either as a monotherapy or in combination with checkpoint inhibitor drugs.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33125893',
			'doi' => '10.1016/j.cell.2020.09.059',
			'modified' => '2021-03-15 16:51:03',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 79 => array(
			'id' => '4092',
			'name' => 'Formation of the CenH3-Deficient Holocentromere in Lepidoptera AvoidsActive Chromatin.',
			'authors' => 'Senaratne, Aruni P and Muller, Héloïse and Fryer, Kelsey A and Kawamoto,Munetaka and Katsuma, Susumu and Drinnenberg, Ines A',
			'description' => '<p>Despite the essentiality for faithful chromosome segregation, centromere architectures are diverse among eukaryotes and embody two main configurations: mono- and holocentromeres, referring, respectively, to localized or unrestricted distribution of centromeric activity. Of the two, some holocentromeres offer the curious condition of having arisen independently in multiple insects, most of which have lost the otherwise essential centromere-specifying factor CenH3 (first described as CENP-A in humans). The loss of CenH3 raises intuitive questions about how holocentromeres are organized and regulated in CenH3-lacking insects. Here, we report the first chromatin-level description of CenH3-deficient holocentromeres by leveraging recently identified centromere components and genomics approaches to map and characterize the holocentromeres of the silk moth Bombyx mori, a representative lepidopteran insect lacking CenH3. This uncovered a robust correlation between the distribution of centromere sites and regions of low chromatin activity along B.&nbsp;mori chromosomes. Transcriptional perturbation experiments recapitulated the exclusion of B.&nbsp;mori centromeres from active chromatin. Based on reciprocal centromere occupancy patterns observed along differentially expressed orthologous genes of Lepidoptera, we further found that holocentromere formation in a manner that is recessive to chromatin dynamics is evolutionarily conserved. Our results help us discuss the plasticity of centromeres in the context of a role for the chromosome-wide chromatin landscape in conferring centromere identity rather than the presence of CenH3. Given the co-occurrence of CenH3 loss and holocentricity in insects, we further propose that the evolutionary establishment of holocentromeres in insects was facilitated through the loss of a CenH3-specified centromere.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33125865',
			'doi' => '10.1016/j.cub.2020.09.078',
			'modified' => '2021-03-17 17:13:50',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 80 => array(
			'id' => '4091',
			'name' => 'Epigenetic regulation of the lineage specificity of primary human dermallymphatic and blood vascular endothelial cells.',
			'authors' => 'Tacconi, Carlotta and He, Yuliang and Ducoli, Luca and Detmar, Michael',
			'description' => '<p>Lymphatic and blood vascular endothelial cells (ECs) share several molecular and developmental features. However, these two cell types possess distinct phenotypic signatures, reflecting their different biological functions. Despite significant advances in elucidating how the specification of lymphatic and blood vascular ECs is regulated at the transcriptional level during development, the key molecular mechanisms governing their lineage identity under physiological or pathological conditions remain poorly understood. To explore the epigenomic signatures in the maintenance of EC lineage specificity, we compared the transcriptomic landscapes, histone composition (H3K4me3 and H3K27me3) and DNA methylomes of cultured matched human primary dermal lymphatic and blood vascular ECs. Our findings reveal that blood vascular lineage genes manifest a more 'repressed' histone composition in lymphatic ECs, whereas DNA methylation at promoters is less linked to the differential transcriptomes of lymphatic versus blood vascular ECs. Meta-analyses identified two transcriptional regulators, BCL6 and MEF2C, which potentially govern endothelial lineage specificity. Notably, the blood vascular endothelial lineage markers CD34, ESAM and FLT1 and the lymphatic endothelial lineage markers PROX1, PDPN and FLT4 exhibited highly differential epigenetic profiles and responded in distinct manners to epigenetic drug treatments. The perturbation of histone and DNA methylation selectively promoted the expression of blood vascular endothelial markers in lymphatic endothelial cells, but not vice versa. Overall, our study reveals that the fine regulation of lymphatic and blood vascular endothelial transcriptomes is maintained via several epigenetic mechanisms, which are crucial to the maintenance of endothelial cell identity.</p>',
			'date' => '2020-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32918672',
			'doi' => '10.1007/s10456-020-09743-9',
			'modified' => '2021-03-17 17:09:36',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 81 => array(
			'id' => '3978',
			'name' => 'OxLDL-mediated immunologic memory in endothelial cells.',
			'authors' => 'Sohrabi Y, Lagache SMM, Voges VC, Semo D, Sonntag G, Hanemann I, Kahles F, Waltenberger J, Findeisen HM',
			'description' => '<p>Trained innate immunity describes the metabolic reprogramming and long-term proinflammatory activation of innate immune cells in response to different pathogen or damage associated molecular patterns, such as oxidized low-density lipoprotein (oxLDL). Here, we have investigated whether the regulatory networks of trained innate immunity also control endothelial cell activation following oxLDL treatment. Human aortic endothelial cells (HAECs) were primed with oxLDL for 24 h. After a resting time of 4 days, cells were restimulated with the TLR2-agonist PAM3cys4. OxLDL priming induced a proinflammatory memory with increased production of inflammatory cytokines such as IL-6, IL-8 and MCP-1 in response to PAM3cys4 restimulation. This memory formation was dependent on TLR2 activation. Furthermore, oxLDL priming of HAECs caused characteristic metabolic and epigenetic reprogramming, including activated mTOR-HIF1&alpha;-signaling with increases in glucose consumption and lactate production, as well as epigenetic modifications in inflammatory gene promoters. Inhibition of mTOR-HIF1&alpha;-signaling or histone methyltransferases blocked the observed phenotype. Furthermore, primed HAECs showed epigenetic activation of ICAM-1 and increased ICAM-1 expression in a HIF1&alpha;-dependent manner. Accordingly, live cell imaging revealed increased monocyte adhesion and transmigration following oxLDL priming. In summary, we demonstrate that oxLDL-mediated endothelial cell activation represents an immunologic event, which triggers metabolic and epigenetic reprogramming. Molecular mechanisms regulating trained innate immunity in innate immune cells also regulate this sustained proinflammatory phenotype in HAECs with enhanced atheroprone cell functions. Further research is necessary to elucidate the detailed metabolic regulation and the functional relevance for atherosclerosis formation in vivo.</p>',
			'date' => '2020-07-26',
			'pmid' => 'http://www.pubmed.gov/32726647',
			'doi' => '10.1016/j.yjmcc.2020.07.006',
			'modified' => '2020-08-10 13:08:21',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 82 => array(
			'id' => '3997',
			'name' => 'The Human Integrator Complex Facilitates Transcriptional Elongation by Endonucleolytic Cleavage of Nascent Transcripts.',
			'authors' => 'Beckedorff F, Blumenthal E, daSilva LF, Aoi Y, Cingaram PR, Yue J, Zhang A, Dokaneheifard S, Valencia MG, Gaidosh G, Shilatifard A, Shiekhattar R',
			'description' => '<p>Transcription by RNA polymerase II (RNAPII) is pervasive in the human genome. However, the mechanisms controlling transcription at promoters and enhancers remain enigmatic. Here, we demonstrate that Integrator subunit 11 (INTS11), the catalytic subunit of the Integrator complex, regulates transcription at these loci through its endonuclease activity. Promoters of genes require INTS11 to cleave nascent transcripts associated with paused RNAPII and induce their premature termination in the proximity of the&nbsp;+1 nucleosome. The turnover of RNAPII permits the subsequent recruitment of an elongation-competent RNAPII complex, leading to productive elongation. In contrast, enhancers require INTS11 catalysis not to evict paused RNAPII but rather to terminate enhancer RNA transcription beyond the&nbsp;+1 nucleosome. These findings are supported by the differential occupancy of negative elongation factor (NELF), SPT5, and tyrosine-1-phosphorylated RNAPII. This study elucidates the role of Integrator in mediating transcriptional elongation at human promoters through the endonucleolytic cleavage of nascent transcripts and the dynamic turnover of RNAPII.</p>',
			'date' => '2020-07-21',
			'pmid' => 'http://www.pubmed.gov/32697989',
			'doi' => '10.1016/j.celrep.2020.107917',
			'modified' => '2020-09-01 14:44:33',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 83 => array(
			'id' => '3996',
			'name' => 'Prostate cancer reactivates developmental epigenomic programs during metastatic progression.',
			'authors' => 'Pomerantz MM, Qiu X, Zhu Y, Takeda DY, Pan W, Baca SC, Gusev A, Korthauer KD, Severson TM, Ha G, Viswanathan SR, Seo JH, Nguyen HM, Zhang B, Pasaniuc B, Giambartolomei C, Alaiwi SA, Bell CA, O'Connor EP, Chabot MS, Stillman DR, Lis R, Font-Tello A, Li L, ',
			'description' => '<p>Epigenetic processes govern prostate cancer (PCa) biology, as evidenced by the dependency of PCa cells on the androgen receptor (AR), a prostate master transcription factor. We generated 268 epigenomic datasets spanning two state transitions-from normal prostate epithelium to localized PCa to metastases-in specimens derived from human tissue. We discovered that reprogrammed AR sites in metastatic PCa are not created de novo; rather, they are prepopulated by the transcription factors FOXA1 and HOXB13 in normal prostate epithelium. Reprogrammed regulatory elements commissioned in metastatic disease hijack latent developmental programs, accessing sites that are implicated in prostate organogenesis. Analysis of reactivated regulatory elements enabled the identification and functional validation of previously unknown metastasis-specific enhancers at HOXB13, FOXA1 and NKX3-1. Finally, we observed that prostate lineage-specific regulatory elements were strongly associated with PCa risk heritability and somatic mutation density. Examining prostate biology through an epigenomic lens is fundamental for understanding the mechanisms underlying tumor progression.</p>',
			'date' => '2020-07-20',
			'pmid' => 'http://www.pubmed.gov/32690948',
			'doi' => '10.1038/s41588-020-0664-8',
			'modified' => '2020-09-01 14:45:54',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 84 => array(
			'id' => '3987',
			'name' => 'The hypomethylation of imprinted genes in IVF/ICSI placenta samples is associated with concomitant changes in histone modifications.',
			'authors' => 'Choux C, Petazzi P, Sanchez-Delgado M, Hernandez Mora JR, Monteagudo A, Sagot P, Monk D, Fauque P',
			'description' => '<p>Although more and more children are born by Assisted Reproductive Technologies (ART), ART safety has not fully been demonstrated. Notably, ART could disturb the delicate step of implantation, and trigger placenta-related adverse outcomes with potential long-term effects, through disrupted epigenetic regulation. We have previously demonstrated that placental DNA methylation was significantly lower after IVF/ICSI than following natural conception at two differentially methylated regions (DMRs) associated with imprinted genes (IGs): and . As histone modifications are critical for placental physiology, the aim of this study was to profile permissive and repressive histone marks in placenta biopsies to reveal a better understanding of the epigenetic changes in the context of ART. Utilizing chromatin immunoprecipitation (ChIP) coupled with quantitative PCR, permissive (H3K4me3, H3K4me2, and H3K9ac) and repressive (H3K9me3 and H3K9me2) post-translational histone modifications were quantified. The analyses revealed a significantly higher quantity of H3K4me2 precipitation in the IVF/ICSI group than in the natural conception group for and DMRs (P&nbsp;=&nbsp;0.016 and 0.003, respectively). Conversely, the quantity of both repressive marks at and DMRs was significantly lower in the IVF/ICSI group than in the natural conception group (P&nbsp;=&nbsp;0.011 and 0.027 for ; and P&nbsp;=&nbsp;0.010 and 0.035 for ). These novel findings highlight that DNA hypomethylation at imprinted DMRs following ART is linked with increased permissive/decreased repressive histone marks, altogether promoting a more permissive chromatin conformation. This concomitant change in epigenetic state at IGs at birth might be an important developmental event because of ART manipulations.</p>',
			'date' => '2020-06-23',
			'pmid' => 'http://www.pubmed.gov/32573317',
			'doi' => '10.1080/15592294.2020.1783168',
			'modified' => '2020-09-01 15:10:37',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 85 => array(
			'id' => '3986',
			'name' => 'Epigenetic priming by Dppa2 and 4 in pluripotency facilitates multi-lineage commitment.',
			'authors' => 'Eckersley-Maslin MA, Parry A, Blotenburg M, Krueger C, Ito Y, Franklin VNR, Narita M, D'Santos CS, Reik W',
			'description' => '<p>How the epigenetic landscape is established in development is still being elucidated. Here, we uncover developmental pluripotency associated 2 and 4 (DPPA2/4) as epigenetic priming factors that establish a permissive epigenetic landscape at a subset of developmentally important bivalent promoters characterized by low expression and poised RNA-polymerase. Differentiation assays reveal that Dppa2/4 double knockout mouse embryonic stem cells fail to exit pluripotency and differentiate efficiently. DPPA2/4 bind both H3K4me3-marked and bivalent gene promoters and associate with COMPASS- and Polycomb-bound chromatin. Comparing knockout and inducible knockdown systems, we find that acute depletion of DPPA2/4 results in rapid loss of H3K4me3 from key bivalent genes, while H3K27me3 is initially more stable but lost following extended culture. Consequently, upon DPPA2/4 depletion, these promoters gain DNA methylation and are unable to be activated upon differentiation. Our findings uncover a novel epigenetic priming mechanism at developmental promoters, poising them for future lineage-specific activation.</p>',
			'date' => '2020-06-22',
			'pmid' => 'http://www.pubmed.gov/32572255',
			'doi' => '10.1038/s41594-020-0443-3',
			'modified' => '2020-09-01 15:12:03',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 86 => array(
			'id' => '3982',
			'name' => 'Genomic deregulation of PRMT5 supports growth and stress tolerance in chronic lymphocytic leukemia.',
			'authors' => 'Schnormeier AK, Pommerenke C, Kaufmann M, Drexler HG, Koeppel M',
			'description' => '<p>Patients suffering from chronic lymphocytic leukemia (CLL) display highly diverse clinical courses ranging from indolent cases to aggressive disease, with genetic and epigenetic features resembling this diversity. Here, we developed a comprehensive approach combining a variety of molecular and clinical data to pinpoint translocation events disrupting long-range chromatin interactions and causing cancer-relevant transcriptional deregulation. Thereby, we discovered a B cell specific cis-regulatory element restricting the expression of genes in the associated locus, including PRMT5 and DAD1, two factors with oncogenic potential. Experimental PRMT5 inhibition identified transcriptional programs similar to those in patients with differences in PRMT5 abundance, especially MYC-driven and stress response pathways. In turn, such inhibition impairs factors involved in DNA repair, sensitizing cells for apoptosis. Moreover, we show that artificial deletion of the regulatory element from its endogenous context resulted in upregulation of corresponding genes, including PRMT5. Furthermore, such disruption renders PRMT5 transcription vulnerable to additional stimuli and subsequently alters the expression of downstream PRMT5 targets. These studies provide a mechanism of PRMT5 deregulation in CLL and the molecular dependencies identified might have therapeutic implementations.</p>',
			'date' => '2020-06-17',
			'pmid' => 'http://www.pubmed.gov/32555249',
			'doi' => '10.1038/s41598-020-66224-1',
			'modified' => '2020-09-01 15:17:40',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 87 => array(
			'id' => '4360',
			'name' => 'The hypomethylation of imprinted genes in IVF/ICSI placenta samplesis associated with concomitant changes in histone modifications.',
			'authors' => 'Choux C. et al. ',
			'description' => '<p>Although more and more children are born by Assisted Reproductive Technologies (ART), ART safety has not fully been demonstrated. Notably, ART could disturb the delicate step of implantation, and trigger placenta-related adverse outcomes with potential long-term effects, through disrupted epigenetic regulation. We have previously demonstrated that placental DNA methylation was significantly lower after IVF/ICSI than following natural conception at two differentially methylated regions (DMRs) associated with imprinted genes (IGs): and . As histone modifications are critical for placental physiology, the aim of this study was to profile permissive and repressive histone marks in placenta biopsies to reveal a better understanding of the epigenetic changes in the context of ART. Utilizing chromatin immunoprecipitation (ChIP) coupled with quantitative PCR, permissive (H3K4me3, H3K4me2, and H3K9ac) and repressive (H3K9me3 and H3K9me2) post-translational histone modifications were quantified. The analyses revealed a significantly higher quantity of H3K4me2 precipitation in the IVF/ICSI group than in the natural conception group for and DMRs (P = 0.016 and 0.003, respectively). Conversely, the quantity of both repressive marks at and DMRs was significantly lower in the IVF/ICSI group than in the natural conception group (P = 0.011 and 0.027 for ; and P = 0.010 and 0.035 for ). These novel findings highlight that DNA hypomethylation at imprinted DMRs following ART is linked with increased permissive/decreased repressive histone marks, altogether promoting a more permissive chromatin conformation. This concomitant change in epigenetic state at IGs at birth might be an important developmental event because of ART manipulations.</p>',
			'date' => '2020-06-01',
			'pmid' => 'http://www.pubmed.gov/32573317',
			'doi' => '10.1080/15592294.2020.1783168',
			'modified' => '2022-08-03 17:14:32',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 88 => array(
			'id' => '4005',
			'name' => 'Measuring Histone Modifications in the Human Parasite Schistosoma mansoni ',
			'authors' => 'de Carvalho Augusto R, Roquis D, Al Picard M, Chaparro C, Cosseau C, Grunau C.',
			'description' => '<p>DNA-binding proteins play critical roles in many major processes such as development and sexual biology of Schistosoma mansoni and are important for the pathogenesis of schistosomiasis. Chromatin immunoprecipitation (ChIP) experiments followed by sequencing (ChIP-seq) are useful to characterize the association of genomic regions with posttranslational chemical modifications of histone proteins. Challenges in the standard ChIP protocol have motivated recent enhancements in this approach, such as reducing the number of cells required and increasing the resolution. In this chapter, we describe the latest advances made by our group in the ChIP methods to improve the standard ChIP protocol to reduce the number of input cells required and to increase the resolution and robustness of ChIP in S. mansoni.</p>',
			'date' => '2020-05-26',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/32451999/',
			'doi' => '10.1007/978-1-0716-0635-3_9 ',
			'modified' => '2020-09-11 15:31:21',
			'created' => '2020-09-11 15:25:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 89 => array(
			'id' => '3965',
			'name' => 'Histone post-translational modifications in Silene latifolia X and Y chromosomes suggest a mammal-like dosage compensation system',
			'authors' => 'Luis Rodríguez Lorenzo José, Hubinský Marcel, Vyskot Boris, Hobza Roman',
			'description' => '<p>Silene latifolia is a model organism to study evolutionary young heteromorphic sex chromosome evolution in plants. Previous research indicates a Y-allele gene degeneration and a dosage compensation system already operating. Here, we propose an epigenetic approach based on analysis of several histone post-translational modifications (PTMs) to find the first epigenetic hints of the X:Y sex chromosome system regulation in S. latifolia. Through chromatin immunoprecipitation we interrogated six genes from X and Y alleles. Several histone PTMS linked to DNA methylation and transcriptional repression (H3K27me3, H3K23me, H3K9me2 and H3K9me3) and to transcriptional activation (H3K4me3 and H4K5, 8, 12, 16ac) were used. DNA enrichment (Immunoprecipitated DNA/input DNA) was analyzed and showed three main results: i) promoters of the Y allele are associated with heterochromatin marks, ii) promoters of the X allele in males are associated with activation of transcription marks and finally, iii) promoters of X alleles in females are associated with active and repressive marks. Our finding indicates a transcription activation of X allele and transcription repression of Y allele in males. In females we found a possible differential regulation (up X1, down X2) of each female X allele. These results agree with the mammal-like epigenetic dosage compensation regulation.</p>',
			'date' => '2020-05-24',
			'pmid' => 'https://www.sciencedirect.com/science/article/abs/pii/S0168945220301333',
			'doi' => '10.1016/j.plantsci.2020.110528',
			'modified' => '2020-08-12 09:42:21',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 90 => array(
			'id' => '3952',
			'name' => 'TET3 controls the expression of the H3K27me3 demethylase Kdm6b during neural commitment.',
			'authors' => 'Montibus B, Cercy J, Bouschet T, Charras A, Maupetit-Méhouas S, Nury D, Gonthier-Guéret C, Chauveau S, Allegre N, Chariau C, Hong CC, Vaillant I, Marques CJ, Court F, Arnaud P',
			'description' => '<p>The acquisition of cell identity is associated with developmentally regulated changes in the cellular histone methylation signatures. For instance, commitment to neural differentiation relies on the tightly controlled gain or loss of H3K27me3, a hallmark of polycomb-mediated transcriptional gene silencing, at specific gene sets. The KDM6B demethylase, which removes H3K27me3 marks at defined promoters and enhancers, is a key factor in neurogenesis. Therefore, to better understand the epigenetic regulation of neural fate acquisition, it is important to determine how Kdm6b expression is regulated. Here, we investigated the molecular mechanisms involved in the induction of Kdm6b expression upon neural commitment of mouse embryonic stem cells. We found that the increase in Kdm6b expression is linked to a rearrangement between two 3D configurations defined by the promoter contact with two different regions in the Kdm6b locus. This is associated with changes in 5-hydroxymethylcytosine (5hmC) levels at these two regions, and requires a functional ten-eleven-translocation (TET) 3 protein. Altogether, our data support a model whereby Kdm6b induction upon neural commitment relies on an intronic enhancer the activity of which is defined by its TET3-mediated 5-hmC level. This original observation reveals an unexpected interplay between the 5-hmC and H3K27me3 pathways during neural lineage commitment in mammals. It also questions to which extent KDM6B-mediated changes in H3K27me3 level account for the TET-mediated effects on gene expression.</p>',
			'date' => '2020-05-14',
			'pmid' => 'http://www.pubmed.gov/32405722',
			'doi' => '10.1007/s00018-020-03541-8',
			'modified' => '2020-08-17 09:53:08',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 91 => array(
			'id' => '3951',
			'name' => 'In vitro capture and characterization of embryonic rosette-stage pluripotency between naive and primed states.',
			'authors' => 'Neagu A, van Genderen E, Escudero I, Verwegen L, Kurek D, Lehmann J, Stel J, Dirks RAM, van Mierlo G, Maas A, Eleveld C, Ge Y, den Dekker AT, Brouwer RWW, van IJcken WFJ, Modic M, Drukker M, Jansen JH, Rivron NC, Baart EB, Marks H, Ten Berge D',
			'description' => '<p>Following implantation, the naive pluripotent epiblast of the mouse blastocyst generates a rosette, undergoes lumenogenesis and forms the primed pluripotent egg cylinder, which is able to generate the embryonic tissues. How pluripotency progression and morphogenesis are linked and whether intermediate pluripotent states exist remain controversial. We identify here a rosette pluripotent state defined by the co-expression of naive factors with the transcription factor OTX2. Downregulation of blastocyst WNT signals drives the transition into rosette pluripotency by inducing OTX2. The rosette then activates MEK signals that induce lumenogenesis and drive progression to primed pluripotency. Consequently, combined WNT and MEK inhibition supports rosette-like stem cells, a self-renewing naive-primed intermediate. Rosette-like stem cells erase constitutive heterochromatin marks and display a primed chromatin landscape, with bivalently marked primed pluripotency genes. Nonetheless, WNT induces reversion to naive pluripotency. The rosette is therefore a reversible pluripotent intermediate whereby control over both pluripotency progression and morphogenesis pivots from WNT to MEK signals.</p>',
			'date' => '2020-05-01',
			'pmid' => 'http://www.pubmed.gov/32367046',
			'doi' => '10.1038/s41556-020-0508-x',
			'modified' => '2020-08-17 09:55:37',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 92 => array(
			'id' => '3929',
			'name' => 'The TGF-β profibrotic cascade targets ecto-5'-nucleotidase gene in proximal tubule epithelial cells and is a traceable marker of progressive diabetic kidney disease.',
			'authors' => 'Cappelli C, Tellez A, Jara C, Alarcón S, Torres A, Mendoza P, Podestá L, Flores C, Quezada C, Oyarzún C, Martín RS',
			'description' => '<p>Progressive diabetic nephropathy (DN) and loss of renal function correlate with kidney fibrosis. Crosstalk between TGF-&beta; and adenosinergic signaling contributes to the phenotypic transition of cells and to renal fibrosis in DN models. We evaluated the role of TGF-&beta; on NT5E gene expression coding for the ecto-5`-nucleotidase CD73, the limiting enzyme in extracellular adenosine production. We showed that high d-glucose may predispose HK-2 cells towards active transcription of the proximal promoter region of the NT5E gene while additional TGF-&beta; results in full activation. The epigenetic landscape of the NT5E gene promoter was modified by concurrent TGF-&beta; with occupancy by the p300 co-activator and the phosphorylated forms of the Smad2/3 complex and RNA Pol II. Transcriptional induction at NT5E in response to TGF-&beta; was earlier compared to the classic responsiveness genes PAI-1 and Fn1. CD73 levels and AMPase activity were concomitantly increased by TGF-&beta; in HK-2 cells. Interestingly, we found increased CD73 content in urinary extracellular vesicles only in diabetic patients with renal repercussions. Further, CD73-mediated AMPase activity was increased in the urinary sediment of DN patients. We conclude that the NT5E gene is a target of the profibrotic TGF-&beta; cascade and is a traceable marker of progressive DN.</p>',
			'date' => '2020-04-11',
			'pmid' => 'http://www.pubmed.gov/32289379',
			'doi' => '10.1016/j.bbadis.2020.165796',
			'modified' => '2020-08-17 10:46:30',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 93 => array(
			'id' => '3889',
			'name' => 'LXR Activation Induces a Proinflammatory Trained Innate Immunity-Phenotype in Human Monocytes',
			'authors' => 'Sohrabi Yahya, Sonntag Glenn V. H., Braun Laura C., Lagache Sina M. M., Liebmann Marie, Klotz Luisa, Godfrey Rinesh, Kahles Florian, Waltenberger Johannes, Findeisen Hannes M.',
			'description' => '<p>The concept of trained innate immunity describes a long-term proinflammatory memory in innate immune cells. Trained innate immunity is regulated through reprogramming of cellular metabolic pathways including cholesterol and fatty acid synthesis. Here, we have analyzed the role of Liver X Receptor (LXR), a key regulator of cholesterol and fatty acid homeostasis, in trained innate immunity.</p>',
			'date' => '2020-03-10',
			'pmid' => 'https://www.frontiersin.org/articles/10.3389/fimmu.2020.00353/full',
			'doi' => '10.3389/ﬁmmu.2020.00353',
			'modified' => '2020-03-20 17:19:37',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 94 => array(
			'id' => '3884',
			'name' => 'A MORC-driven transcriptional switch controls Toxoplasma developmental trajectories and sexual commitment.',
			'authors' => 'Farhat DC, Swale C, Dard C, Cannella D, Ortet P, Barakat M, Sindikubwabo F, Belmudes L, De Bock PJ, Couté Y, Bougdour A, Hakimi MA',
			'description' => '<p>Toxoplasma gondii has a complex life cycle that is typified by asexual development that takes place in vertebrates, and sexual reproduction, which occurs exclusively in felids and is therefore less studied. The developmental transitions rely on changes in the patterns of gene expression, and recent studies have assigned roles for chromatin shapers, including histone modifications, in establishing specific epigenetic programs for each given stage. Here, we identified the T. gondii microrchidia (MORC) protein as an upstream transcriptional repressor of sexual commitment. MORC, in a complex with Apetala 2 (AP2) transcription factors, was shown to recruit the histone deacetylase HDAC3, thereby impeding the accessibility of chromatin at the genes that are exclusively expressed during sexual stages. We found that MORC-depleted cells underwent marked transcriptional changes, resulting in the expression of a specific repertoire of genes, and revealing a shift from asexual proliferation to sexual differentiation. MORC acts as a master regulator that directs the hierarchical expression of secondary AP2 transcription factors, and these transcription factors potentially contribute to the unidirectionality of the life cycle. Thus, MORC plays a cardinal role in the T. gondii life cycle, and its conditional depletion offers a method to study the sexual development of the parasite in vitro, and is proposed as an alternative to the requirement of T. gondii infections in cats.</p>',
			'date' => '2020-02-24',
			'pmid' => 'http://www.pubmed.gov/32094587',
			'doi' => '10.1038/s41564-020-0674-4',
			'modified' => '2020-03-20 17:27:25',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 95 => array(
			'id' => '3874',
			'name' => 'Recombination may occur in the absence of transcription in the immunoglobulin heavy chain recombination centre.',
			'authors' => 'Oudinet C, Braikia FZ, Dauba A, Khamlichi AA',
			'description' => '<p>Developing B cells undergo V(D)J recombination to generate a vast repertoire of Ig molecules. V(D)J recombination is initiated by the RAG1/RAG2 complex in recombination centres (RCs), where gene segments become accessible to the complex. Whether transcription is the causal factor of accessibility or whether it is a side product of other processes that generate accessibility remains a controversial issue. At the IgH locus, V(D)J recombination is controlled by E&mu; enhancer, which directs the transcriptional, epigenetic and recombinational events in the IgH RC. Deletion of E&mu; enhancer affects both transcription and recombination, making it difficult to conclude if E&mu; controls the two processes through the same or different mechanisms. By using a mouse line carrying a CpG-rich sequence upstream of E&mu; enhancer and analyzing transcription and recombination at the single-cell level, we found that recombination could occur in the RC in the absence of detectable transcription, suggesting that E&mu; controls transcription and recombination through distinct mechanisms. Moreover, while the normally E&mu;-dependent transcription and demethylating activities were impaired, recruitment of chromatin remodeling complexes was unaffected. RAG1 was efficiently recruited, thus compensating for the defective transcription-associated recruitment of RAG2, and providing a mechanistic basis for RAG1/RAG2 assembly to initiate V(D)J recombination.</p>',
			'date' => '2020-02-22',
			'pmid' => 'http://www.pubmed.gov/32086526',
			'doi' => '10.1093/nar/gkaa108',
			'modified' => '2020-03-20 17:40:41',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 96 => array(
			'id' => '3873',
			'name' => 'Inhibition of methyltransferase activity of enhancer of zeste 2 leads to enhanced lipid accumulation and altered chromatin status in zebrafish.',
			'authors' => 'den Broeder MJ, Ballangby J, Kamminga LM, Aleström P, Legler J, Lindeman LC, Kamstra JH',
			'description' => '<p>BACKGROUND: Recent studies indicate that exposure to environmental chemicals may increase susceptibility to developing metabolic diseases. This susceptibility may in part be caused by changes to the epigenetic landscape which consequently affect gene expression and lead to changes in lipid metabolism. The epigenetic modifier enhancer of zeste 2 (Ezh2) is a histone H3K27 methyltransferase implicated to play a role in lipid metabolism and adipogenesis. In this study, we used the zebrafish (Danio rerio) to investigate the role of Ezh2 on lipid metabolism and chromatin status following developmental exposure to the Ezh1/2 inhibitor PF-06726304 acetate. We used the environmental chemical tributyltin (TBT) as a positive control, as this chemical is known to act on lipid metabolism via EZH-mediated pathways in mammals. RESULTS: Zebrafish embryos (0-5&nbsp;days post-fertilization, dpf) exposed to non-toxic concentrations of PF-06726304 acetate (5&nbsp;&mu;M) and TBT (1&nbsp;nM) exhibited increased lipid accumulation. Changes in chromatin were analyzed by the assay for transposase-accessible chromatin sequencing (ATAC-seq) at 50% epiboly (5.5 hpf). We observed 349 altered chromatin regions, predominantly located at H3K27me3 loci and mostly more open chromatin in the exposed samples. Genes associated to these loci were linked to metabolic pathways. In addition, a selection of genes involved in lipid homeostasis, adipogenesis and genes specifically targeted by PF-06726304 acetate via altered chromatin accessibility were differentially expressed after TBT and PF-06726304 acetate exposure at 5 dpf, but not at 50% epiboly stage. One gene, cebpa, did not show a change in chromatin, but did show a change in gene expression at 5 dpf. Interestingly, underlying H3K27me3 marks were significantly decreased at this locus at 50% epiboly. CONCLUSIONS: Here, we show for the first time the applicability of ATAC-seq as a tool to investigate toxicological responses in zebrafish. Our analysis indicates that Ezh2 inhibition leads to a partial primed state of chromatin linked to metabolic pathways which results in gene expression changes later in development, leading to enhanced lipid accumulation. Although ATAC-seq seems promising, our in-depth assessment of the cebpa locus indicates that we need to consider underlying epigenetic marks as well.</p>',
			'date' => '2020-02-12',
			'pmid' => 'http://www.pubmed.gov/32051014',
			'doi' => '10.1186/s13072-020-0329-y',
			'modified' => '2020-03-20 17:42:02',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 97 => array(
			'id' => '3883',
			'name' => 'Targeting Macrophage Histone H3 Modification as a Leishmania Strategy to Dampen the NF-κB/NLRP3-Mediated Inflammatory Response.',
			'authors' => 'Lecoeur H, Prina E, Rosazza T, Kokou K, N'Diaye P, Aulner N, Varet H, Bussotti G, Xing Y, Milon G, Weil R, Meng G, Späth GF',
			'description' => '<p>Aberrant macrophage activation during intracellular infection generates immunopathologies that can cause severe human morbidity. A better understanding of immune subversion strategies and macrophage phenotypic and functional responses is necessary to design host-directed intervention strategies. Here, we uncover a fine-tuned transcriptional response that is induced in primary and lesional macrophages infected by the parasite Leishmania amazonensis and dampens NF-&kappa;B and NLRP3 inflammasome activation. Subversion is amastigote-specific and characterized by a decreased expression of activating and increased expression of de-activating components of these pro-inflammatory pathways, thus revealing a regulatory dichotomy that abrogates the anti-microbial response. Changes in transcript abundance correlate with histone H3K9/14 hypoacetylation and H3K4 hypo-trimethylation in infected primary and lesional macrophages at promoters of NF-&kappa;B-related, pro-inflammatory genes. Our results reveal a Leishmania immune subversion strategy targeting host cell epigenetic regulation to establish conditions beneficial for parasite survival and open avenues for host-directed, anti-microbial drug discovery.</p>',
			'date' => '2020-02-11',
			'pmid' => 'http://www.pubmed.gov/32049017',
			'doi' => '10.1016/j.celrep.2020.01.030',
			'modified' => '2020-03-20 17:29:47',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 98 => array(
			'id' => '3868',
			'name' => 'Replicational Dilution of H3K27me3 in Mammalian Cells and the Role of Poised Promoters.',
			'authors' => 'Jadhav U, Manieri E, Nalapareddy K, Madha S, Chakrabarti S, Wucherpfennig K, Barefoot M, Shivdasani RA',
			'description' => '<p>Polycomb repressive complex 2 (PRC2) places H3K27me3 at developmental genes and is causally implicated in keeping bivalent genes silent. It is unclear if that silence requires minimum H3K27me3 levels and how the mark transmits faithfully across mammalian somatic cell generations. Mouse intestinal cells lacking EZH2 methyltransferase reduce H3K27me3 proportionately at all PRC2 target sites, but &sim;40% uniform residual levels keep target genes inactive. These genes, derepressed in PRC2-null villus cells, remain silent in intestinal stem cells (ISCs). Quantitative chromatin immunoprecipitation and computational modeling indicate that because unmodified histones dilute H3K27me3 by 50% each time DNA replicates, PRC2-deficient ISCs initially retain sufficient H3K27me3 to avoid gene derepression. EZH2 mutant human lymphoma cells also require multiple divisions before H3K27me3 dilution relieves gene silencing. In both cell types, promoters with high basal H3K4me2/3 activate in spite of some residual H3K27me3, compared to less-poised promoters. These findings have implications for PRC2 inhibition in cancer therapy.</p>',
			'date' => '2020-01-29',
			'pmid' => 'http://www.pubmed.gov/32027840',
			'doi' => '10.1016/j.molcel.2020.01.017',
			'modified' => '2020-03-20 17:46:30',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 99 => array(
			'id' => '3848',
			'name' => 'A comprehensive epigenomic analysis of phenotypically distinguishable, genetically identical female and male Daphnia pulex.',
			'authors' => 'Kvist J, Athanàsio CG, Pfrender ME, Brown JB, Colbourne JK, Mirbahai L',
			'description' => '<p>BACKGROUND: Daphnia species reproduce by cyclic parthenogenesis involving both sexual and asexual reproduction. The sex of the offspring is environmentally determined and mediated via endocrine signalling by the mother. Interestingly, male and female Daphnia can be genetically identical, yet display large differences in behaviour, morphology, lifespan and metabolic activity. Our goal was to integrate multiple omics datasets, including gene expression, splicing, histone modification and DNA methylation data generated from genetically identical female and male Daphnia pulex under controlled laboratory settings with the aim of achieving a better understanding of the underlying epigenetic factors that may contribute to the phenotypic differences observed between the two genders. RESULTS: In this study we demonstrate that gene expression level is positively correlated with increased DNA methylation, and histone H3 trimethylation at lysine&thinsp;4 (H3K4me3) at predicted promoter regions. Conversely, elevated histone H3 trimethylation at lysine&thinsp;27 (H3K27me3), distributed across the entire transcript length, is negatively correlated with gene expression level. Interestingly, male Daphnia are dominated with epigenetic modifications that globally promote elevated gene expression, while female Daphnia are dominated with epigenetic modifications that reduce gene expression globally. For examples, CpG methylation (positively correlated with gene expression level) is significantly higher in almost all differentially methylated sites in male compared to female Daphnia. Furthermore, H3K4me3 modifications are higher in male compared to female Daphnia in more than 3/4 of the differentially regulated promoters. On the other hand, H3K27me3 is higher in female compared to male Daphnia in more than 5/6 of differentially modified sites. However, both sexes demonstrate roughly equal number of genes that are up-regulated in one gender compared to the other sex. Since, gene expression analyses typically assume that most genes are expressed at equal level among samples and different conditions, and thus cannot detect global changes affecting most genes. CONCLUSIONS: The epigenetic differences between male and female in Daphnia pulex are vast and dominated by changes that promote elevated gene expression in male Daphnia. Furthermore, the differences observed in both gene expression changes and epigenetic modifications between the genders relate to pathways that are physiologically relevant to the observed phenotypic differences.</p>',
			'date' => '2020-01-06',
			'pmid' => 'http://www.pubmed.gov/31906859',
			'doi' => '10.1186/s12864-019-6415-5',
			'modified' => '2020-02-20 11:34:47',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 100 => array(
			'id' => '3802',
			'name' => 'Analysis of Histone Modifications in Rodent Pancreatic Islets by Native Chromatin Immunoprecipitation.',
			'authors' => 'Sandovici I, Nicholas LM, O'Neill LP',
			'description' => '<p>The islets of Langerhans are clusters of cells dispersed throughout the pancreas that produce several hormones essential for controlling a variety of metabolic processes, including glucose homeostasis and lipid metabolism. Studying the transcriptional control of pancreatic islet cells has important implications for understanding the mechanisms that control their normal development, as well as the pathogenesis of metabolic diseases such as diabetes. Histones represent the main protein components of the chromatin and undergo diverse covalent modifications that are very important for gene regulation. Here we describe the isolation of pancreatic islets from rodents and subsequently outline the methods used to immunoprecipitate and analyze the native chromatin obtained from these cells.</p>',
			'date' => '2020-01-01',
			'pmid' => 'http://www.pubmed.gov/31586329',
			'doi' => '10.1007/978-1-4939-9882-1',
			'modified' => '2019-12-05 11:28:01',
			'created' => '2019-12-02 15:25:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 101 => array(
			'id' => '4096',
			'name' => 'Changes in H3K27ac at Gene Regulatory Regions in Porcine AlveolarMacrophages Following LPS or PolyIC Exposure.',
			'authors' => 'Herrera-Uribe, Juber and Liu, Haibo and Byrne, Kristen A and Bond, Zahra Fand Loving, Crystal L and Tuggle, Christopher K',
			'description' => '<p>Changes in chromatin structure, especially in histone modifications (HMs), linked with chromatin accessibility for transcription machinery, are considered to play significant roles in transcriptional regulation. Alveolar macrophages (AM) are important immune cells for protection against pulmonary pathogens, and must readily respond to bacteria and viruses that enter the airways. Mechanism(s) controlling AM innate response to different pathogen-associated molecular patterns (PAMPs) are not well defined in pigs. By combining RNA sequencing (RNA-seq) with chromatin immunoprecipitation and sequencing (ChIP-seq) for four histone marks (H3K4me3, H3K4me1, H3K27ac and H3K27me3), we established a chromatin state map for AM stimulated with two different PAMPs, lipopolysaccharide (LPS) and Poly(I:C), and investigated the potential effect of identified histone modifications on transcription factor binding motif (TFBM) prediction and RNA abundance changes in these AM. The integrative analysis suggests that the differential gene expression between non-stimulated and stimulated AM is significantly associated with changes in the H3K27ac level at active regulatory regions. Although global changes in chromatin states were minor after stimulation, we detected chromatin state changes for differentially expressed genes involved in the TLR4, TLR3 and RIG-I signaling pathways. We found that regions marked by H3K27ac genome-wide were enriched for TFBMs of TF that are involved in the inflammatory response. We further documented that TF whose expression was induced by these stimuli had TFBMs enriched within H3K27ac-marked regions whose chromatin state changed by these same stimuli. Given that the dramatic transcriptomic changes and minor chromatin state changes occurred in response to both stimuli, we conclude that regulatory elements (i.e. active promoters) that contain transcription factor binding motifs were already active/poised in AM for immediate inflammatory response to PAMPs. In summary, our data provides the first chromatin state map of porcine AM in response to bacterial and viral PAMPs, contributing to the Functional Annotation of Animal Genomes (FAANG) project, and demonstrates the role of HMs, especially H3K27ac, in regulating transcription in AM in response to LPS and Poly(I:C).</p>',
			'date' => '2020-01-01',
			'pmid' => 'https://www.frontiersin.org/articles/10.3389/fgene.2020.00817/full',
			'doi' => '10.3389/fgene.2020.00817',
			'modified' => '2021-03-17 17:22:56',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 102 => array(
			'id' => '3839',
			'name' => 'Functionally Annotating Regulatory Elements in the Equine Genome Using Histone Mark ChIP-Seq.',
			'authors' => 'Kingsley NB, Kern C, Creppe C, Hales EN, Zhou H, Kalbfleisch TS, MacLeod JN, Petersen JL, Finno CJ, Bellone RR',
			'description' => '<p>One of the primary aims of the Functional Annotation of ANimal Genomes (FAANG) initiative is to characterize tissue-specific regulation within animal genomes. To this end, we used chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to map four histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me3) in eight prioritized tissues collected as part of the FAANG equine biobank from two thoroughbred mares. Data were generated according to optimized experimental parameters developed during quality control testing. To ensure that we obtained sufficient ChIP and successful peak-calling, data and peak-calls were assessed using six quality metrics, replicate comparisons, and site-specific evaluations. Tissue specificity was explored by identifying binding motifs within unique active regions, and motifs were further characterized by gene ontology (GO) and protein-protein interaction analyses. The histone marks identified in this study represent some of the first resources for tissue-specific regulation within the equine genome. As such, these publicly available annotation data can be used to advance equine studies investigating health, performance, reproduction, and other traits of economic interest in the horse.</p>',
			'date' => '2019-12-18',
			'pmid' => 'http://www.pubmed.gov/31861495',
			'doi' => '10.3390/genes11010003',
			'modified' => '2020-02-20 11:20:25',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 103 => array(
			'id' => '3837',
			'name' => 'H3K4me1 Supports Memory-like NK Cells Induced by Systemic Inflammation.',
			'authors' => 'Rasid O, Chevalier C, Camarasa TM, Fitting C, Cavaillon JM, Hamon MA',
			'description' => '<p>Natural killer (NK) cells are unique players in innate immunity and, as such, an attractive target for immunotherapy. NK cells display immune memory properties in certain models, but the long-term status of NK cells following systemic inflammation is unknown. Here we show that following LPS-induced endotoxemia in mice, NK cells acquire cell-intrinsic memory-like properties, showing increased production of IFN&gamma; upon specific secondary stimulation. The NK cell memory response is detectable for at least 9&nbsp;weeks and contributes to protection from E.&nbsp;coli infection upon adoptive transfer. Importantly, we reveal a mechanism essential for NK cell memory, whereby an H3K4me1-marked latent enhancer is uncovered at the ifng locus. Chemical inhibition of histone methyltransferase activity erases the enhancer and abolishes NK cell memory. Thus, NK cell memory develops after endotoxemia in a histone methylation-dependent manner, ensuring a heightened response to secondary stimulation.</p>',
			'date' => '2019-12-17',
			'pmid' => 'http://www.pubmed.gov/31851924',
			'doi' => '10.1016/j.celrep.2019.11.043',
			'modified' => '2020-02-20 11:24:10',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 104 => array(
			'id' => '3830',
			'name' => 'Trained immunity modulates inflammation-induced fibrosis.',
			'authors' => 'Jeljeli M, Riccio LGC, Doridot L, Chêne C, Nicco C, Chouzenoux S, Deletang Q, Allanore Y, Kavian N, Batteux F',
			'description' => '<p>Chronic inflammation and fibrosis can result from inappropriately activated immune responses that are mediated by macrophages. Macrophages can acquire memory-like characteristics in response to antigen exposure. Here, we show the effect of BCG or low-dose LPS stimulation on macrophage phenotype, cytokine production, chromatin and metabolic modifications. Low-dose LPS training alleviates fibrosis and inflammation in a mouse model of systemic sclerosis (SSc), whereas BCG-training exacerbates disease in this model. Adoptive transfer of low-dose LPS-trained or BCG-trained macrophages also has beneficial or harmful effects, respectively. Furthermore, coculture with low-dose LPS trained macrophages reduces the fibro-inflammatory profile of fibroblasts from mice and patients with SSc, indicating that trained immunity might be a phenomenon that can be targeted to treat SSc and other autoimmune and inflammatory fibrotic disorders.</p>',
			'date' => '2019-12-11',
			'pmid' => 'http://www.pubmed.gov/31827093',
			'doi' => '10.1038/s41467-019-13636-x',
			'modified' => '2020-02-25 13:32:01',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 105 => array(
			'id' => '3826',
			'name' => 'MicroRNA-708 is a novel regulator of the Hoxa9 program in myeloid cells.',
			'authors' => 'Schneider E, Pochert N, Ruess C, MacPhee L, Escano L, Miller C, Krowiorz K, Delsing Malmberg E, Heravi-Moussavi A, Lorzadeh A, Ashouri A, Grasedieck S, Sperb N, Kumar Kopparapu P, Iben S, Staffas A, Xiang P, Rösler R, Kanduri M, Larsson E, Fogelstrand L, ',
			'description' => '<p>MicroRNAs (miRNAs) are commonly deregulated in acute myeloid leukemia (AML), affecting critical genes not only through direct targeting, but also through modulation of downstream effectors. Homeobox (Hox) genes balance self-renewal, proliferation, cell death, and differentiation in many tissues and aberrant Hox gene expression can create a predisposition to leukemogenesis in hematopoietic cells. However, possible linkages between the regulatory pathways of Hox genes and miRNAs are not yet fully resolved. We identified miR-708 to be upregulated in Hoxa9/Meis1 AML inducing cell lines as well as in AML patients. We further showed Meis1 directly targeting miR-708 and modulating its expression through epigenetic transcriptional regulation. CRISPR/Cas9 mediated knockout of miR-708 in Hoxa9/Meis1 cells delayed disease onset in vivo, demonstrating for the first time a pro-leukemic contribution of miR-708 in this context. Overexpression of miR-708 however strongly impeded Hoxa9 mediated transformation and homing capacity in vivo through modulation of adhesion factors and induction of myeloid differentiation. Taken together, we reveal miR-708, a putative tumor suppressor miRNA and direct target of Meis1, as a potent antagonist of the Hoxa9 phenotype but an effector of transformation in Hoxa9/Meis1. This unexpected finding highlights the yet unexplored role of miRNAs as indirect regulators of the Hox program during normal and aberrant hematopoiesis.</p>',
			'date' => '2019-11-25',
			'pmid' => 'http://www.pubmed.gov/31768018',
			'doi' => '10.1038/s41375-019-0651-1',
			'modified' => '2020-02-25 13:36:10',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 106 => array(
			'id' => '3807',
			'name' => 'Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.',
			'authors' => 'Aloia L, McKie MA, Vernaz G, Cordero-Espinoza L, Aleksieva N, van den Ameele J, Antonica F, Font-Cunill B, Raven A, Aiese Cigliano R, Belenguer G, Mort RL, Brand AH, Zernicka-Goetz M, Forbes SJ, Miska EA, Huch M',
			'description' => '<p>Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal cells. However, the molecular mechanisms by which adult ductal-committed cells acquire cellular plasticity, initiate organoids and regenerate the damaged tissue remain largely unknown. Here, we describe that ductal cells undergo a transient, genome-wide, remodelling of their transcriptome and epigenome during organoid initiation and in vivo following tissue damage. TET1-mediated hydroxymethylation licences differentiated ductal cells to initiate organoids and activate the regenerative programme through the transcriptional regulation of stem-cell genes and regenerative pathways including the YAP-Hippo signalling. Our results argue in favour of the remodelling of genomic methylome/hydroxymethylome landscapes as a general mechanism by which differentiated cells exit a committed state in response to tissue damage.</p>',
			'date' => '2019-11-04',
			'pmid' => 'http://www.pubmed.gov/31685987',
			'doi' => '10.1038/s41556-019-0402-6',
			'modified' => '2019-12-05 11:19:34',
			'created' => '2019-12-02 15:25:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 107 => array(
			'id' => '3824',
			'name' => 'Transcriptional alterations in glioma result primarily from DNA methylation-independent mechanisms.',
			'authors' => 'Court F, Le Boiteux E, Fogli A, Müller-Barthélémy M, Vaurs-Barrière C, Chautard E, Pereira B, Biau J, Kemeny JL, Khalil T, Karayan-Tapon L, Verrelle P, Arnaud P',
			'description' => '<p>In cancer cells, aberrant DNA methylation is commonly associated with transcriptional alterations, including silencing of tumor suppressor genes. However, multiple epigenetic mechanisms, including polycomb repressive marks, contribute to gene deregulation in cancer. To dissect the relative contribution of DNA methylation-dependent and -independent mechanisms to transcriptional alterations at CpG island/promoter-associated genes in cancer, we studied 70 samples of adult glioma, a widespread type of brain tumor, classified according to their isocitrate dehydrogenase () mutation status. We found that most transcriptional alterations in tumor samples were DNA methylation-independent. Instead, altered histone H3 trimethylation at lysine 27 (H3K27me3) was the predominant molecular defect at deregulated genes. Our results also suggest that the presence of a bivalent chromatin signature at CpG island promoters in stem cells predisposes not only to hypermethylation, as widely documented, but more generally to all types of transcriptional alterations in transformed cells. In addition, the gene expression strength in healthy brain cells influences the choice between DNA methylation- and H3K27me3-associated silencing in glioma. Highly expressed genes were more likely to be repressed by H3K27me3 than by DNA methylation. Our findings support a model in which altered H3K27me3 dynamics, more specifically defects in the interplay between polycomb protein complexes and the brain-specific transcriptional machinery, is the main cause of transcriptional alteration in glioma cells. Our study provides the first comprehensive description of epigenetic changes in glioma and their relative contribution to transcriptional changes. It may be useful for the design of drugs targeting cancer-related epigenetic defects.</p>',
			'date' => '2019-10-01',
			'pmid' => 'http://www.pubmed.gov/31533980',
			'doi' => '10.1101/gr.249219.119.',
			'modified' => '2020-02-25 13:41:40',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 108 => array(
			'id' => '3781',
			'name' => 'Functional analyses of a low-penetrance risk variant rs6702619/1p21.2 associating with colorectal cancer in Polish population.',
			'authors' => 'Statkiewicz M, Maryan N, Kulecka M, Kuklinska U, Ostrowski J, Mikula M',
			'description' => '<p>Several studies employed the genome-wide association (GWA) analysis of single-nucleotide polymorphisms (SNPs) to identify susceptibility regions in colorectal cancer (CRC). However, the functional studies exploring the role of associating SNPs with cancer biology are limited. Herein, using chromatin immunoprecipitation assay (ChIP), reporter assay and chromosome conformation capture sequencing (3C-Seq) augmented with publically available genomic and epigenomic databases we aimed to define the function of rs6702619/1p21.2 region associated with CRC in the Polish population. Using ChIP we confirmed that rs6702619 region is occupied by a CTCF, a master regulator of long-range genomic interactions, and is decorated with enhancer-like histone modifications. The enhancer blocking assay revealed that rs6702619 region acts as an insulator with activity dependent on the SNP genotype. Finally, a 3C-Seq survey indicated more than a hundred loci in the rs6702619 locus interactome, including GNAS gene that is frequently amplified in CRC. Taken together, we showed that the CRC-associated rs6702619 region has in vitro and in vivo properties of an insulator that demonstrates long-range physical interactions with CRC-relevant loci.</p>',
			'date' => '2019-09-17',
			'pmid' => 'http://www.pubmed.gov/31531420',
			'doi' => '10.1093/nar/gkm875.',
			'modified' => '2019-10-02 16:51:42',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 109 => array(
			'id' => '3776',
			'name' => 'β-Glucan-Induced Trained Immunity Protects against Leishmania braziliensis Infection: a Crucial Role for IL-32.',
			'authors' => 'Dos Santos JC, Barroso de Figueiredo AM, Teodoro Silva MV, Cirovic B, de Bree LCJ, Damen MSMA, Moorlag SJCFM, Gomes RS, Helsen MM, Oosting M, Keating ST, Schlitzer A, Netea MG, Ribeiro-Dias F, Joosten LAB',
			'description' => '<p>American tegumentary leishmaniasis is a vector-borne parasitic disease caused by Leishmania protozoans. Innate immune cells undergo long-term functional reprogramming in response to infection or Bacillus Calmette-Gu&eacute;rin (BCG) vaccination via a process called trained immunity, conferring non-specific protection from secondary infections. Here, we demonstrate that monocytes trained with the fungal cell wall component &beta;-glucan confer enhanced protection against infections caused by Leishmania braziliensis through the enhanced production of proinflammatory cytokines. Mechanistically, this augmented immunological response is dependent on increased expression of interleukin 32 (IL-32). Studies performed using a humanized IL-32 transgenic mouse highlight the clinical implications of these findings in&nbsp;vivo. This study represents a definitive characterization of the role of IL-32&gamma; in the trained phenotype induced by &beta;-glucan or BCG, the results of which improve our understanding of the molecular mechanisms governing trained immunity and Leishmania infection control.</p>',
			'date' => '2019-09-03',
			'pmid' => 'http://www.pubmed.gov/31484076',
			'doi' => '10.1016/j.celrep.2019.08.004',
			'modified' => '2019-10-02 17:00:49',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 110 => array(
			'id' => '3774',
			'name' => 'Reactivation of super-enhancers by KLF4 in human Head and Neck Squamous Cell Carcinoma.',
			'authors' => 'Tsompana M, Gluck C, Sethi I, Joshi I, Bard J, Nowak NJ, Sinha S, Buck MJ',
			'description' => '<p>Head and neck squamous cell carcinoma (HNSCC) is a disease of significant morbidity and mortality and rarely diagnosed in early stages. Despite extensive genetic and genomic characterization, targeted therapeutics and diagnostic markers of HNSCC are lacking due to the inherent heterogeneity and complexity of the disease. Herein, we have generated the global histone mark based epigenomic and transcriptomic cartogram of SCC25, a representative cell type of mesenchymal HNSCC and its normal oral keratinocyte counterpart. Examination of genomic regions marked by differential chromatin states and associated with misregulated gene expression led us to identify SCC25 enriched regulatory sequences and transcription factors (TF) motifs. These findings were further strengthened by ATAC-seq based open chromatin and TF footprint analysis which unearthed Kr&uuml;ppel-like Factor 4 (KLF4) as a potential key regulator of the SCC25 cistrome. We reaffirm the results obtained from in silico and chromatin studies in SCC25 by ChIP-seq of KLF4 and identify &Delta;Np63 as a co-oncogenic driver of the cancer-specific gene expression milieu. Taken together, our results lead us to propose a model where elevated KLF4 levels sustains the oncogenic state of HNSCC by reactivating repressed chromatin domains at key downstream genes, often by targeting super-enhancers.</p>',
			'date' => '2019-09-02',
			'pmid' => 'http://www.pubmed.gov/31477832',
			'doi' => '10.1038/s41388-019-0990-4',
			'modified' => '2019-10-02 17:05:36',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 111 => array(
			'id' => '3777',
			'name' => 'Nucleome Dynamics during Retinal Development.',
			'authors' => 'Norrie JL, Lupo MS, Xu B, Al Diri I, Valentine M, Putnam D, Griffiths L, Zhang J, Johnson D, Easton J, Shao Y, Honnell V, Frase S, Miller S, Stewart V, Zhou X, Chen X, Dyer MA',
			'description' => '<p>More than 8,000 genes are turned on or off as progenitor cells produce the 7 classes of retinal cell types during development. Thousands of enhancers are also active in the developing retinae, many having features of cell- and developmental stage-specific activity. We studied dynamic changes in the 3D chromatin landscape important for precisely orchestrated changes in gene expression during retinal development by ultra-deep in situ Hi-C analysis on murine retinae. We identified developmental-stage-specific changes in chromatin compartments and enhancer-promoter interactions. We developed a machine learning-based algorithm to map euchromatin and heterochromatin domains genome-wide and overlaid it with chromatin compartments identified by Hi-C. Single-cell ATAC-seq and RNA-seq were integrated with our Hi-C and previous ChIP-seq data to identify cell- and developmental-stage-specific super-enhancers (SEs). We identified a bipolar neuron-specific core regulatory circuit SE upstream of Vsx2, whose deletion in mice led to the loss of bipolar neurons.</p>',
			'date' => '2019-08-21',
			'pmid' => 'http://www.pubmed.gov/31493975',
			'doi' => '10.1016/j.neuron.2019.08.002',
			'modified' => '2019-10-02 16:58:50',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 112 => array(
			'id' => '3742',
			'name' => 'Development and epigenetic plasticity of murine Müller glia.',
			'authors' => 'Dvoriantchikova G, Seemungal RJ, Ivanov D',
			'description' => '<p>The ability to regenerate the entire retina and restore lost sight after injury is found in some species and relies mostly on the epigenetic plasticity of M&uuml;ller glia. To understand the role of mammalian M&uuml;ller glia as a source of progenitors for retinal regeneration, we investigated changes in gene expression during differentiation of retinal progenitor cells (RPCs) into M&uuml;ller glia. We also analyzed the global epigenetic profile of adult M&uuml;ller glia. We observed significant changes in gene expression during differentiation of RPCs into M&uuml;ller glia in only a small group of genes. We found a high similarity between RPCs and M&uuml;ller glia on the transcriptomic and epigenomic levels. Our findings also indicate that M&uuml;ller glia are epigenetically very close to late-born retinal neurons, but not early-born retinal neurons. Importantly, we found that key genes required for phototransduction were highly methylated. Thus, our data suggest that M&uuml;ller glia are epigenetically very similar to late RPCs. Meanwhile, obstacles for regeneration of the entire mammalian retina from M&uuml;ller glia may consist of repressive chromatin and highly methylated DNA in the promoter regions of many genes required for the development of early-born retinal neurons. In addition, DNA demethylation may be required for proper reprogramming and differentiation of M&uuml;ller glia into rod photoreceptors.</p>
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<div id="ConnectiveDocSignExtentionInstalled" data-extension-version="1.0.4"></div>',
			'date' => '2019-07-02',
			'pmid' => 'http://www.pubmed.gov/31276697',
			'doi' => '10.1016/j.bbamcr.2019.06.019',
			'modified' => '2019-08-13 10:50:24',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 113 => array(
			'id' => '3754',
			'name' => 'The alarmin S100A9 hampers osteoclast differentiation from human circulating precursors by reducing the expression of RANK.',
			'authors' => 'Di Ceglie I, Blom AB, Davar R, Logie C, Martens JHA, Habibi E, Böttcher LM, Roth J, Vogl T, Goodyear CS, van der Kraan PM, van Lent PL, van den Bosch MH',
			'description' => '<p>The alarmin S100A8/A9 is implicated in sterile inflammation-induced bone resorption and has been shown to increase the bone-resorptive capacity of mature osteoclasts. Here, we investigated the effects of S100A9 on osteoclast differentiation from human CD14 circulating precursors. Hereto, human CD14 monocytes were isolated and differentiated toward osteoclasts with M-CSF and receptor activator of NF-&kappa;B (RANK) ligand (RANKL) in the presence or absence of S100A9. Tartrate-resistant acid phosphatase staining showed that exposure to S100A9 during monocyte-to-osteoclast differentiation strongly decreased the numbers of multinucleated osteoclasts. This was underlined by a decreased resorption of a hydroxyapatite-like coating. The thus differentiated cells showed a high mRNA and protein production of proinflammatory factors after 16 h of exposure. In contrast, at d 4, the cells showed a decreased production of the osteoclast-promoting protein TNF-&alpha;. Interestingly, S100A9 exposure during the first 16 h of culture only was sufficient to reduce osteoclastogenesis. Using fluorescently labeled RANKL, we showed that, within this time frame, S100A9 inhibited the M-CSF-mediated induction of RANK. Chromatin immunoprecipitation showed that this was associated with changes in various histone marks at the epigenetic level. This S100A9-induced reduction in RANK was in part recovered by blocking TNF-&alpha; but not IL-1. Together, our data show that S100A9 impedes monocyte-to-osteoclast differentiation, probably a reduction in RANK expression.-Di Ceglie, I., Blom, A. B., Davar, R., Logie, C., Martens, J. H. A., Habibi, E., B&ouml;ttcher, L.-M., Roth, J., Vogl, T., Goodyear, C. S., van der Kraan, P. M., van Lent, P. L., van den Bosch, M. H. The alarmin S100A9 hampers osteoclast differentiation from human circulating precursors by reducing the expression of RANK.</p>',
			'date' => '2019-06-14',
			'pmid' => 'http://www.pubmed.gov/31199668',
			'doi' => '10.1096/fj.201802691RR',
			'modified' => '2019-10-03 12:20:02',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 114 => array(
			'id' => '3737',
			'name' => 'Probing the Tumor Suppressor Function of BAP1 in CRISPR-Engineered Human Liver Organoids.',
			'authors' => 'Artegiani B, van Voorthuijsen L, Lindeboom RGH, Seinstra D, Heo I, Tapia P, López-Iglesias C, Postrach D, Dayton T, Oka R, Hu H, van Boxtel R, van Es JH, Offerhaus J, Peters PJ, van Rheenen J, Vermeulen M, Clevers H',
			'description' => '<p>The deubiquitinating enzyme BAP1 is a tumor suppressor, among others involved in cholangiocarcinoma. BAP1 has many proposed molecular targets, while its Drosophila homolog is known to deubiquitinate histone H2AK119. We introduce BAP1 loss-of-function by CRISPR/Cas9 in normal human cholangiocyte organoids. We find that BAP1 controls&nbsp;the expression of junctional and cytoskeleton components by regulating chromatin accessibility. Consequently, we observe loss of multiple epithelial characteristics while motility increases. Importantly, restoring the catalytic activity of BAP1 in the nucleus rescues these cellular and molecular changes. We engineer human liver organoids to combine four common cholangiocarcinoma mutations (TP53, PTEN, SMAD4, and NF1). In this genetic background, BAP1 loss results in acquisition of malignant features upon xenotransplantation. Thus, control of epithelial identity through the regulation of chromatin accessibility appears to be a key aspect of BAP1's tumor suppressor function. Organoid technology combined with CRISPR/Cas9 provides an experimental platform for mechanistic studies of cancer gene function in a human context.</p>',
			'date' => '2019-06-06',
			'pmid' => 'http://www.pubmed.gov/31130514',
			'doi' => '10.1016/j.stem.2019.04.017',
			'modified' => '2019-08-06 16:58:50',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 115 => array(
			'id' => '3713',
			'name' => 'Complementary Activity of ETV5, RBPJ, and TCF3 Drives Formative Transition from Naive Pluripotency.',
			'authors' => 'Kalkan T, Bornelöv S, Mulas C, Diamanti E, Lohoff T, Ralser M, Middelkamp S, Lombard P, Nichols J, Smith A',
			'description' => '<p>The gene regulatory network (GRN) of naive mouse embryonic stem cells (ESCs) must be reconfigured to enable lineage commitment. TCF3 sanctions rewiring by suppressing components of the ESC transcription factor circuitry. However, TCF3 depletion only delays and does not prevent transition to formative pluripotency. Here, we delineate additional contributions of the ETS-family transcription factor ETV5 and the repressor RBPJ. In response to ERK signaling, ETV5 switches activity from supporting self-renewal and undergoes genome relocation linked to commissioning of enhancers activated in formative epiblast. Independent upregulation of RBPJ prevents re-expression of potent naive factors, TBX3 and NANOG, to secure exit from the naive state. Triple deletion of Etv5, Rbpj, and Tcf3 disables ESCs, such that they remain largely undifferentiated and locked in self-renewal, even in the presence of differentiation stimuli. Thus, genetic elimination of three complementary drivers of network transition stalls developmental progression, emulating environmental insulation by small-molecule inhibitors.</p>',
			'date' => '2019-05-02',
			'pmid' => 'http://www.pubmed.gov/31031137',
			'doi' => '10.1016/j.stem.2019.03.017',
			'modified' => '2019-07-05 14:28:38',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 116 => array(
			'id' => '3692',
			'name' => 'PML modulates H3.3 targeting to telomeric and centromeric repeats in mouse fibroblasts.',
			'authors' => 'Spirkoski J, Shah A, Reiner AH, Collas P, Delbarre E',
			'description' => '<p>Targeted deposition of histone variant H3.3 into chromatin is paramount for proper regulation of chromatin integrity, particularly in heterochromatic regions including repeats. We have recently shown that the promyelocytic leukemia (PML) protein prevents H3.3 from being deposited in large heterochromatic PML-associated domains (PADs). However, to what extent PML modulates H3.3 loading on chromatin in other areas of the genome remains unexplored. Here, we examined the impact of PML on targeting of H3.3 to genes and repeat regions that reside outside PADs. We show that loss of PML increases H3.3 deposition in subtelomeric, telomeric, pericentric and centromeric repeats in mouse embryonic fibroblasts, while other repeat classes are not affected. Expression of major satellite, minor satellite and telomeric non-coding transcripts is altered in Pml-null cells. In particular, telomeric Terra transcripts are strongly upregulated, in concordance with a marked reduction in H4K20me3 at these sites. Lastly, for most genes H3.3 enrichment or gene expression outcomes are independent of PML. Our data argue towards the importance of a PML-H3.3 axis in preserving a heterochromatin state at centromeres and telomeres.</p>',
			'date' => '2019-04-16',
			'pmid' => 'http://www.pubmed.gov/30850162',
			'doi' => '10.1016/j.bbrc.2019.02.087',
			'modified' => '2019-06-28 13:50:40',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 117 => array(
			'id' => '3711',
			'name' => 'Long intergenic non-coding RNAs regulate human lung fibroblast function: Implications for idiopathic pulmonary fibrosis.',
			'authors' => 'Hadjicharalambous MR, Roux BT, Csomor E, Feghali-Bostwick CA, Murray LA, Clarke DL, Lindsay MA',
			'description' => '<p>Phenotypic changes in lung fibroblasts are believed to contribute to the development of Idiopathic Pulmonary Fibrosis (IPF), a progressive and fatal lung disease. Long intergenic non-coding RNAs (lincRNAs) have been identified as novel regulators of gene expression and protein activity. In non-stimulated cells, we observed reduced proliferation and inflammation but no difference in the fibrotic response of IPF fibroblasts. These functional changes in non-stimulated cells were associated with changes in the expression of the histone marks, H3K4me1, H3K4me3 and H3K27ac indicating a possible involvement of epigenetics. Following activation with TGF-&beta;1 and IL-1&beta;, we demonstrated an increased fibrotic but reduced inflammatory response in IPF fibroblasts. There was no significant difference in proliferation following PDGF exposure. The lincRNAs, LINC00960 and LINC01140 were upregulated in IPF fibroblasts. Knockdown studies showed that LINC00960 and LINC01140 were positive regulators of proliferation in both control and IPF fibroblasts but had no effect upon the fibrotic response. Knockdown of LINC01140 but not LINC00960 increased the inflammatory response, which was greater in IPF compared to control fibroblasts. Overall, these studies demonstrate for the first time that lincRNAs are important regulators of proliferation and inflammation in human lung fibroblasts and that these might mediate the reduced inflammatory response observed in IPF-derived fibroblasts.</p>',
			'date' => '2019-04-15',
			'pmid' => 'http://www.pubmed.gov/30988425',
			'doi' => '10.1038/s41598-019-42292-w',
			'modified' => '2019-07-05 14:31:28',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 118 => array(
			'id' => '3702',
			'name' => 'Identification of ADGRE5 as discriminating MYC target between Burkitt lymphoma and diffuse large B-cell lymphoma.',
			'authors' => 'Kleo K, Dimitrova L, Oker E, Tomaszewski N, Berg E, Taruttis F, Engelmann JC, Schwarzfischer P, Reinders J, Spang R, Gronwald W, Oefner PJ, Hummel M',
			'description' => '<p>BACKGROUND: MYC is a heterogeneously expressed transcription factor that plays a multifunctional role in many biological processes such as cell proliferation and differentiation. It is also associated with many types of cancer including the malignant lymphomas. There are two types of aggressive B-cell lymphoma, namely Burkitt lymphoma (BL) and a subgroup of diffuse large cell lymphoma (DLBCL), which both carry MYC translocations and overexpress MYC but both differ significantly in their clinical outcome. In DLBCL, MYC translocations are associated with an aggressive behavior and poor outcome, whereas MYC-positive BL show a superior outcome. METHODS: To shed light on this phenomenon, we investigated the different modes of actions of MYC in aggressive B-cell lymphoma cell lines subdivided into three groups: (i) MYC-positive BL, (ii) DLBCL with MYC translocation (DLBCLpos) and (iii) DLBCL without MYC translocation (DLBCLneg) for control. In order to identify genome-wide MYC-DNA binding sites a chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) was performed. In addition, ChIP-Seq for H3K4me3 was used for determination of genomic regions accessible for transcriptional activity. These data were supplemented with gene expression data derived from RNA-Seq. RESULTS: Bioinformatics integration of all data sets revealed different MYC-binding patterns and transcriptional profiles in MYC-positive BL and DLBCL cell lines indicating different functional roles of MYC for gene regulation in aggressive B-cell lymphomas. Based on this multi-omics analysis we identified ADGRE5 (alias CD97) - a member of the EGF-TM7 subfamily of adhesion G protein-coupled receptors - as a MYC target gene, which is specifically expressed in BL but not in DLBCL regardless of MYC translocation. CONCLUSION: Our study describes a diverse genome-wide MYC-DNA binding pattern in BL and DLBCL cell lines with and without MYC translocations. Furthermore, we identified ADREG5 as a MYC target gene able to discriminate between BL and DLBCL irrespectively of the presence of MYC breaks in DLBCL. Since ADGRE5 plays an important role in tumor cell formation, metastasis and invasion, it might also be instrumental to better understand the different pathobiology of BL and DLBCL and help to explain discrepant clinical characteristics of BL and DLBCL.</p>',
			'date' => '2019-04-05',
			'pmid' => 'http://www.pubmed.gov/30953469',
			'doi' => '10.1186/s12885-019-5537-0',
			'modified' => '2019-07-05 14:41:38',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 119 => array(
			'id' => '3732',
			'name' => 'Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis.',
			'authors' => 'Mallaney C, Ostrander EL, Celik H, Kramer AC, Martens A, Kothari A, Koh WK, Haussler E, Iwamori N, Gontarz P, Zhang B, Challen GA',
			'description' => '<p>The histone demethylase KDM6B (JMJD3) is upregulated in blood disorders, suggesting that it may have important pathogenic functions. Here we examined the function of Kdm6b in hematopoietic stem cells (HSC) to evaluate its potential as a therapeutic target. Loss of Kdm6b lead to depletion of phenotypic and functional HSCs in adult mice, and Kdm6b is necessary for HSC self-renewal in response to inflammatory and proliferative stress. Loss of Kdm6b leads to a pro-differentiation poised state in HSCs due to the increased expression of the AP-1 transcription factor complex (Fos and Jun) and immediate early response (IER) genes. These gene expression changes occurred independently of chromatin modifications. Targeting AP-1 restored function of Kdm6b-deficient HSCs, suggesting that Kdm6b regulates this complex during HSC stress response. We also show Kdm6b supports developmental context-dependent leukemogenesis for T-cell acute lymphoblastic leukemia (T-ALL) and M5 acute myeloid leukemia (AML). Kdm6b is required for effective fetal-derived T-ALL and adult-derived AML, but not vice versa. These studies identify a crucial role for Kdm6b in regulating HSC self-renewal in different contexts, and highlight the potential of KDM6B as a therapeutic target in different hematopoietic malignancies.</p>',
			'date' => '2019-04-01',
			'pmid' => 'http://www.pubmed.gov/30936419',
			'doi' => '10.1038/s41375-019-0462-4',
			'modified' => '2019-08-07 09:14:05',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 120 => array(
			'id' => '3700',
			'name' => 'A critical regulator of Bcl2 revealed by systematic transcript discovery of lncRNAs associated with T-cell differentiation.',
			'authors' => 'Saadi W, Kermezli Y, Dao LTM, Mathieu E, Santiago-Algarra D, Manosalva I, Torres M, Belhocine M, Pradel L, Loriod B, Aribi M, Puthier D, Spicuglia S',
			'description' => '<p>Normal T-cell differentiation requires a complex regulatory network which supports a series of maturation steps, including lineage commitment, T-cell receptor (TCR) gene rearrangement, and thymic positive and negative selection. However, the underlying molecular mechanisms are difficult to assess due to limited T-cell models. Here we explore the use of the pro-T-cell line P5424 to study early T-cell differentiation. Stimulation of P5424 cells by the calcium ionophore ionomycin together with PMA resulted in gene regulation of T-cell differentiation and activation markers, partially mimicking the CD4CD8 double negative (DN) to double positive (DP) transition and some aspects of subsequent T-cell maturation and activation. Global analysis of gene expression, along with kinetic experiments, revealed a significant association between the dynamic expression of coding genes and neighbor lncRNAs including many newly-discovered transcripts, thus suggesting potential co-regulation. CRISPR/Cas9-mediated genetic deletion of Robnr, an inducible lncRNA located downstream of the anti-apoptotic gene Bcl2, demonstrated a critical role of the Robnr locus in the induction of Bcl2. Thus, the pro-T-cell line P5424 is a powerful model system to characterize regulatory networks involved in early T-cell differentiation and maturation.</p>',
			'date' => '2019-03-18',
			'pmid' => 'http://www.pubmed.gov/30886319',
			'doi' => '10.1038/s41598-019-41247-5',
			'modified' => '2019-07-05 14:43:51',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 121 => array(
			'id' => '3571',
			'name' => 'The role of TCF3 as potential master regulator in blastemal Wilms tumors.',
			'authors' => 'Kehl T, Schneider L, Kattler K, Stöckel D, Wegert J, Gerstner N, Ludwig N, Distler U, Tenzer S, Gessler M, Walter J, Keller A, Graf N, Meese E, Lenhof HP',
			'description' => '<p>Wilms tumors are the most common type of pediatric kidney tumors. While the overall prognosis for patients is favorable, especially tumors that exhibit a blastemal subtype after preoperative chemotherapy have a poor prognosis. For an improved risk assessment and therapy stratification, it is essential to identify the driving factors that are distinctive for this aggressive subtype. In our study, we compared gene expression profiles of 33 tumor biopsies (17 blastemal and 16 other tumors) after neoadjuvant chemotherapy. The analysis of this dataset using the Regulator Gene Association Enrichment algorithm successfully identified several biomarkers and associated molecular mechanisms that distinguish between blastemal and nonblastemal Wilms tumors. Specifically, regulators involved in embryonic development and epigenetic processes like chromatin remodeling and histone modification play an essential role in blastemal tumors. In this context, we especially identified TCF3 as the central regulatory element. Furthermore, the comparison of ChIP-Seq data of Wilms tumor cell cultures from a blastemal mouse xenograft and a stromal tumor provided further evidence that the chromatin states of blastemal cells share characteristics with embryonic stem cells that are not present in the stromal tumor cell line. These stem-cell like characteristics could potentially add to the increased malignancy and chemoresistance of the blastemal subtype. Along with TCF3, we detected several additional biomarkers that are distinctive for blastemal Wilms tumors after neoadjuvant chemotherapy and that may provide leads for new therapeutic regimens.</p>',
			'date' => '2019-03-15',
			'pmid' => 'http://www.pubmed.gov/30155889',
			'doi' => '10.1002/ijc.31834',
			'modified' => '2019-03-21 17:10:17',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 122 => array(
			'id' => '3611',
			'name' => 'Extensive Recovery of Embryonic Enhancer and Gene Memory Stored in Hypomethylated Enhancer DNA.',
			'authors' => 'Jadhav U, Cavazza A, Banerjee KK, Xie H, O'Neill NK, Saenz-Vash V, Herbert Z, Madha S, Orkin SH, Zhai H, Shivdasani RA',
			'description' => '<p>Developing and adult tissues use different cis-regulatory elements. Although DNA at some decommissioned embryonic enhancers is hypomethylated in adult cells, it is unknown whether this putative epigenetic memory is complete and recoverable. We find that, in adult mouse cells, hypomethylated CpG dinucleotides preserve a nearly complete archive of tissue-specific developmental enhancers. Sites that carry the active histone mark H3K4me1, and are therefore considered "primed," are mainly cis elements that act late in organogenesis. In contrast, sites decommissioned early in development retain hypomethylated DNA as a singular property. In adult intestinal and blood cells, sustained absence of polycomb repressive complex 2 indirectly reactivates most-and only-hypomethylated developmental enhancers. Embryonic and fetal transcriptional programs re-emerge as a result, in reverse chronology to cis element inactivation during development. Thus, hypomethylated DNA in adult cells preserves a "fossil record" of tissue-specific developmental enhancers, stably marking decommissioned sites and enabling recovery of this epigenetic memory.</p>',
			'date' => '2019-03-15',
			'pmid' => 'http://www.pubmed.gov/30905509',
			'doi' => '10.1016/j.molcel.2019.02.024',
			'modified' => '2019-04-17 14:46:15',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 123 => array(
			'id' => '3569',
			'name' => 'The epigenetic basis for the impaired ability of adult murine retinal pigment epithelium cells to regenerate retinal tissue.',
			'authors' => 'Dvoriantchikova G, Seemungal RJ, Ivanov D',
			'description' => '<p>The epigenetic plasticity of amphibian retinal pigment epithelium (RPE) allows them to regenerate the entire retina, a trait known to be absent in mammals. In this study, we investigated the epigenetic plasticity of adult murine RPE to identify possible mechanisms that prevent mammalian RPE from regenerating retinal tissue. RPE were analyzed using microarray, ChIP-seq, and whole-genome bisulfite sequencing approaches. We found that the majority of key genes required for progenitor phenotypes were in a permissive chromatin state and unmethylated in RPE. We observed that the majority of non-photoreceptor genes had promoters in a repressive chromatin state, but these promoters were in unmethylated or low-methylated regions. Meanwhile, the majority of promoters for photoreceptor genes were found in a permissive chromatin state, but were highly-methylated. Methylome states of photoreceptor-related genes in adult RPE and embryonic retina (which mostly contain progenitors) were very similar. However, promoters of these genes were demethylated and activated during retinal development. Our data suggest that, epigenetically, adult murine RPE cells are a progenitor-like cell type. Most likely two mechanisms prevent adult RPE from reprogramming and differentiating into retinal neurons: 1) repressive chromatin in the promoter regions of non-photoreceptor retinal neuron genes; 2) highly-methylated promoters of photoreceptor-related genes.</p>',
			'date' => '2019-03-07',
			'pmid' => 'http://www.pubmed.gov/30846751',
			'doi' => '10.1038/s41598-019-40262-w',
			'modified' => '2019-05-09 17:33:09',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 124 => array(
			'id' => '3671',
			'name' => 'Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes.',
			'authors' => 'Yi G, Wierenga ATJ, Petraglia F, Narang P, Janssen-Megens EM, Mandoli A, Merkel A, Berentsen K, Kim B, Matarese F, Singh AA, Habibi E, Prange KHM, Mulder AB, Jansen JH, Clarke L, Heath S, van der Reijden BA, Flicek P, Yaspo ML, Gut I, Bock C, Schuringa JJ',
			'description' => '<p>Global investigation of histone marks in acute myeloid leukemia (AML) remains limited. Analyses of 38 AML samples through integrated transcriptional and chromatin mark analysis exposes 2 major subtypes. One subtype is dominated by patients with&nbsp;NPM1 mutations or MLL-fusion genes, shows activation of the regulatory pathways involving HOX-family genes as targets, and displays high self-renewal capacity and stemness. The second subtype is enriched for RUNX1 or spliceosome mutations, suggesting potential interplay between the 2 aberrations, and mainly depends on IRF family regulators. Cellular consequences in prognosis predict a relatively worse outcome for the first subtype. Our integrated profiling establishes a rich resource to probe AML subtypes on the basis of expression and chromatin data.</p>',
			'date' => '2019-01-22',
			'pmid' => 'http://www.pubmed.gov/30673601',
			'doi' => '10.1016/j.celrep.2018.12.098',
			'modified' => '2019-07-01 11:30:31',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 125 => array(
			'id' => '3629',
			'name' => 'Comprehensive Analysis of Chromatin States in Atypical Teratoid/Rhabdoid Tumor Identifies Diverging Roles for SWI/SNF and Polycomb in Gene Regulation.',
			'authors' => 'Erkek S, Johann PD, Finetti MA, Drosos Y, Chou HC, Zapatka M, Sturm D, Jones DTW, Korshunov A, Rhyzova M, Wolf S, Mallm JP, Beck K, Witt O, Kulozik AE, Frühwald MC, Northcott PA, Korbel JO, Lichter P, Eils R, Gajjar A, Roberts CWM, Williamson D, Hasselbla',
			'description' => '<p>Biallelic inactivation of SMARCB1, encoding a member of the SWI/SNF chromatin remodeling complex, is the hallmark genetic aberration of atypical teratoid rhabdoid tumors (ATRT). Here, we report how loss of SMARCB1 affects the epigenome in these tumors. Using chromatin immunoprecipitation sequencing (ChIP-seq) on primary tumors for a series of active and repressive histone marks, we identified the chromatin states differentially represented in ATRTs compared with other brain tumors and non-neoplastic brain. Re-expression of SMARCB1 in ATRT cell lines enabled confirmation of our genome-wide findings for the chromatin states. Additional generation of ChIP-seq data for SWI/SNF and Polycomb group proteins and the transcriptional repressor protein REST determined differential dependencies of SWI/SNF and Polycomb complexes in regulation of diverse gene sets in ATRTs.</p>',
			'date' => '2019-01-14',
			'pmid' => 'http://www.pubmed.gov/30595504',
			'doi' => '10.1016/j.ccell.2018.11.014',
			'modified' => '2019-05-08 12:27:57',
			'created' => '2019-04-25 11:11:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 126 => array(
			'id' => '3658',
			'name' => 'The Wnt-Driven Mll1 Epigenome Regulates Salivary Gland and Head and Neck Cancer.',
			'authors' => 'Zhu Q, Fang L, Heuberger J, Kranz A, Schipper J, Scheckenbach K, Vidal RO, Sunaga-Franze DY, Müller M, Wulf-Goldenberg A, Sauer S, Birchmeier W',
			'description' => '<p>We identified a regulatory system that acts downstream of Wnt/&beta;-catenin signaling in salivary gland and head and neck carcinomas. We show in a mouse tumor model of K14-Cre-induced Wnt/&beta;-catenin gain-of-function and Bmpr1a loss-of-function mutations that tumor-propagating cells exhibit increased Mll1 activity and genome-wide increased H3K4 tri-methylation at promoters. Null mutations of Mll1 in tumor mice and in xenotransplanted human head and neck tumors resulted in loss of self-renewal of tumor-propagating cells and in block of tumor formation but did not alter normal tissue homeostasis. CRISPR/Cas9 mutagenesis and pharmacological interference of Mll1 at sequences that inhibit essential protein-protein interactions or the SET enzyme active site also blocked the self-renewal of mouse and human tumor-propagating cells. Our work provides strong genetic evidence for a crucial role of Mll1 in solid tumors. Moreover, inhibitors targeting specific Mll1 interactions might offer additional directions for therapies to treat these aggressive tumors.</p>',
			'date' => '2019-01-08',
			'pmid' => 'http://www.pubmed.gov/30625324',
			'doi' => '10.1016/j.celrep.2018.12.059',
			'modified' => '2019-06-07 09:00:14',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 127 => array(
			'id' => '3686',
			'name' => 'Gamma radiation induces locus specific changes to histone modification enrichment in zebrafish and Atlantic salmon.',
			'authors' => 'Lindeman LC, Kamstra JH, Ballangby J, Hurem S, Martín LM, Brede DA, Teien HC, Oughton DH, Salbu B, Lyche JL, Aleström P',
			'description' => '<p>Ionizing radiation is a recognized genotoxic agent, however, little is known about the role of the functional form of DNA in these processes. Post translational modifications on histone proteins control the organization of chromatin and hence control transcriptional responses that ultimately affect the phenotype. The purpose of this study was to investigate effects on chromatin caused by ionizing radiation in fish. Direct exposure of zebrafish (Danio rerio) embryos to gamma radiation (10.9 mGy/h for 3h) induced hyper-enrichment of H3K4me3 at the genes hnf4a, gmnn and vegfab. A similar relative hyper-enrichment was seen at the hnf4a loci of irradiated Atlantic salmon (Salmo salar) embryos (30 mGy/h for 10 days). At the selected genes in ovaries of adult zebrafish irradiated during gametogenesis (8.7 and 53 mGy/h for 27 days), a reduced enrichment of H3K4me3 was observed, which was correlated with reduced levels of histone H3 was observed. F1 embryos of the exposed parents showed hyper-methylation of H3K4me3, H3K9me3 and H3K27me3 on the same three loci, while these differences were almost negligible in F2 embryos. Our results from three selected loci suggest that ionizing radiation can affect chromatin structure and organization, and that these changes can be detected in F1 offspring, but not in subsequent generations.</p>',
			'date' => '2019-01-01',
			'pmid' => 'http://www.pubmed.gov/30759148',
			'doi' => '10.1371/journal.pone.0212123',
			'modified' => '2019-06-28 13:57:39',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 128 => array(
			'id' => '3607',
			'name' => 'Mutant p63 Affects Epidermal Cell Identity through Rewiring the Enhancer Landscape.',
			'authors' => 'Qu J, Tanis SEJ, Smits JPH, Kouwenhoven EN, Oti M, van den Bogaard EH, Logie C, Stunnenberg HG, van Bokhoven H, Mulder KW, Zhou H',
			'description' => '<p>Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Mutations in the p63 DNA-binding domain are associated with ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome. However, the underlying molecular mechanism of these mutations remains unclear. Here, we characterized the transcriptome and epigenome of p63 mutant keratinocytes derived from EEC patients. The transcriptome of p63 mutant keratinocytes deviated from the normal epidermal cell identity. Epigenomic analyses showed an altered enhancer landscape in p63 mutant keratinocytes contributed by loss of p63-bound active enhancers and unexpected gain of enhancers. The gained enhancers were frequently bound by deregulated transcription factors such as RUNX1. Reversing RUNX1 overexpression partially rescued deregulated gene expression and the altered enhancer landscape. Our findings identify a disease mechanism whereby mutant p63 rewires the enhancer landscape and affects epidermal cell identity, consolidating the pivotal role of p63 in controlling the enhancer landscape of epidermal keratinocytes.</p>',
			'date' => '2018-12-18',
			'pmid' => 'http://www.pubmed.gov/30566872',
			'doi' => '10.1016/j.celrep.2018.11.039',
			'modified' => '2019-04-17 14:51:18',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 129 => array(
			'id' => '3509',
			'name' => 'Promoter bivalency favors an open chromatin architecture in embryonic stem cells.',
			'authors' => 'Mas G, Blanco E, Ballaré C, Sansó M, Spill YG, Hu D, Aoi Y, Le Dily F, Shilatifard A, Marti-Renom MA, Di Croce L',
			'description' => '<p>In embryonic stem cells (ESCs), developmental gene promoters are characterized by their bivalent chromatin state, with simultaneous modification by MLL2 and Polycomb complexes. Although essential for embryogenesis, bivalency is functionally not well understood. Here, we show that MLL2 plays a central role in ESC genome organization. We generate a catalog of bona fide bivalent genes in ESCs and demonstrate that loss of MLL2 leads to increased Polycomb occupancy. Consequently, promoters lose accessibility, long-range interactions are redistributed, and ESCs fail to differentiate. We pose that bivalency balances accessibility and long-range connectivity of promoters, allowing developmental gene expression to be properly modulated.</p>',
			'date' => '2018-10-17',
			'pmid' => 'http://www.pubmed.gov/30224650',
			'doi' => '10.1038/s41588-018-0218-5',
			'modified' => '2019-02-27 15:45:37',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 130 => array(
			'id' => '3552',
			'name' => 'PRC2 targeting is a therapeutic strategy for EZ score defined high-risk multiple myeloma patients and overcome resistance to IMiDs.',
			'authors' => 'Herviou L, Kassambara A, Boireau S, Robert N, Requirand G, Müller-Tidow C, Vincent L, Seckinger A, Goldschmidt H, Cartron G, Hose D, Cavalli G, Moreaux J',
			'description' => '<p>BACKGROUND: Multiple myeloma (MM) is a malignant plasma cell disease with a poor survival, characterized by the accumulation of myeloma cells (MMCs) within the bone marrow. Epigenetic modifications in MM are associated not only with cancer development and progression, but also with drug resistance. METHODS: We identified a significant upregulation of the polycomb repressive complex 2 (PRC2) core genes in MM cells in association with proliferation. We used EPZ-6438, a specific small molecule inhibitor of EZH2 methyltransferase activity, to evaluate its effects on MM cells phenotype and gene expression prolile. RESULTS: PRC2 targeting results in growth inhibition due to cell cycle arrest and apoptosis together with polycomb, DNA methylation, TP53, and RB1 target genes induction. Resistance to EZH2 inhibitor is mediated by DNA methylation of PRC2 target genes. We also demonstrate a synergistic effect of EPZ-6438 and lenalidomide, a conventional drug used for MM treatment, activating B cell transcription factors and tumor suppressor gene expression in concert with MYC repression. We establish a gene expression-based EZ score allowing to identify poor prognosis patients that could benefit from EZH2 inhibitor treatment. CONCLUSIONS: These data suggest that PRC2 targeting in association with IMiDs could have a therapeutic interest in MM patients characterized by high EZ score values, reactivating B cell transcription factors, and tumor suppressor genes.</p>',
			'date' => '2018-10-03',
			'pmid' => 'http://www.pubmed.org/30285865',
			'doi' => '10.1186/s13148-018-0554-4',
			'modified' => '2019-03-21 16:45:55',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 131 => array(
			'id' => '3396',
			'name' => 'The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity',
			'authors' => 'Domínguez-Andrés Jorge, Novakovic Boris, Li Yang, Scicluna Brendon P., Gresnigt Mark S., Arts Rob J.W., Oosting Marije, Moorlag Simone J.C.F.M., Groh Laszlo A., Zwaag Jelle, Koch Rebecca M., ter Horst Rob, Joosten Leo A.B., Wijmenga Cisca, Michelucci Ales',
			'description' => '<p>Sepsis involves simultaneous hyperactivation of the immune system and immune paralysis, leading to both organ dysfunction and increased susceptibility to secondary infections. Acute activation of myeloid cells induced itaconate synthesis, which subsequently mediated innate immune tolerance in human monocytes. In contrast, induction of trained immunity by b-glucan counteracted tolerance induced in a model of human endotoxemia by inhibiting the expression of immune-responsive gene 1 (IRG1), the enzyme that controls itaconate synthesis. b-Glucan also increased the expression of succinate dehydrogenase (SDH), contributing to the integrity of the TCA cycle and leading to an enhanced innate immune response after secondary stimulation. The role of itaconate was further validated by IRG1 and SDH polymorphisms that modulate induction of tolerance and trained immunity in human monocytes. These data demonstrate the importance of the IRG1-itaconateSDH axis in the development of immune tolerance and training and highlight the potential of b-glucaninduced trained immunity to revert immunoparalysis.</p>',
			'date' => '2018-10-01',
			'pmid' => 'http://www.pubmed.gov/30293776',
			'doi' => '10.1016/j.cmet.2018.09.003',
			'modified' => '2018-11-22 15:18:30',
			'created' => '2018-11-08 12:59:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 132 => array(
			'id' => '3566',
			'name' => 'Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes.',
			'authors' => 'Ferguson GB, Van Handel B, Bay M, Fiziev P, Org T, Lee S, Shkhyan R, Banks NW, Scheinberg M, Wu L, Saitta B, Elphingstone J, Larson AN, Riester SM, Pyle AD, Bernthal NM, Mikkola HK, Ernst J, van Wijnen AJ, Bonaguidi M, Evseenko D',
			'description' => '<p>Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application of cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differentiation. Network analysis delineated five tissue-specific gene modules; these modules and chromatin state analysis defined broad similarities in gene expression during cartilage specification and maturation in vitro and in vivo, including early expression and progressive silencing of muscle- and bone-specific genes. Finally, ontogenetic analysis of freshly isolated and pluripotent stem cell-derived articular chondrocytes identified that integrin alpha 4 defines 2 subsets of functionally and molecularly distinct chondrocytes characterized by their gene expression, osteochondral potential in vitro and proliferative signature in vivo. These analyses provide new insight into human musculoskeletal development and provide an essential comparative resource for disease modeling and regenerative medicine.</p>',
			'date' => '2018-09-07',
			'pmid' => 'http://www.pubmed.gov/30194383',
			'doi' => '10.1038/s41467-018-05573-y',
			'modified' => '2019-03-25 11:14:45',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 133 => array(
			'id' => '3596',
			'name' => 'RNA Sequencing and Pathway Analysis Identify Important Pathways Involved in Hypertrichosis and Intellectual Disability in Patients with Wiedemann-Steiner Syndrome.',
			'authors' => 'Mietton L, Lebrun N, Giurgea I, Goldenberg A, Saintpierre B, Hamroune J, Afenjar A, Billuart P, Bienvenu T',
			'description' => '<p>A growing number of histone modifiers are involved in human neurodevelopmental disorders, suggesting that proper regulation of chromatin state is essential for the development of the central nervous system. Among them, heterozygous de novo variants in KMT2A, a gene coding for histone methyltransferase, have been associated with Wiedemann-Steiner syndrome (WSS), a rare developmental disorder mainly characterized by intellectual disability (ID) and hypertrichosis. As KMT2A is known to regulate the expression of multiple target genes through methylation of lysine 4 of histone 3 (H3K4me), we sought to investigate the transcriptomic consequences of KMT2A variants involved in WSS. Using fibroblasts from four WSS patients harboring loss-of-function KMT2A variants, we performed RNA sequencing and identified a number of genes for which transcription was altered in KMT2A-mutated cells compared to the control ones. Strikingly, analysis of the pathways and biological functions significantly deregulated between patients with WSS and healthy individuals revealed a number of processes predicted to be altered that are relevant for hypertrichosis and intellectual disability, the cardinal signs of this disease.</p>',
			'date' => '2018-09-01',
			'pmid' => 'http://www.pubmed.gov/30014449',
			'doi' => '10.1007/s12017-018-8502-1',
			'modified' => '2019-04-17 15:10:22',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 134 => array(
			'id' => '3564',
			'name' => 'Atopic asthma after rhinovirus-induced wheezing is associated with DNA methylation change in the SMAD3 gene promoter.',
			'authors' => 'Lund RJ, Osmala M, Malonzo M, Lukkarinen M, Leino A, Salmi J, Vuorikoski S, Turunen R, Vuorinen T, Akdis C, Lähdesmäki H, Lahesmaa R, Jartti T',
			'description' => '<p>Children with rhinovirus-induced severe early wheezing have an increased risk of developing asthma later in life. The exact molecular mechanisms for this association are still mostly unknown. To identify potential changes in the transcriptional and epigenetic regulation in rhinovirus-associated atopic or nonatopic asthma, we analyzed a cohort of 5-year-old children (n&nbsp;=&nbsp;45) according to the virus etiology of the first severe wheezing episode at the mean age of 13&nbsp;months and to 5-year asthma outcome. The development of atopic asthma in children with early rhinovirus-induced wheezing was associated with DNA methylation changes at several genomic sites in chromosomal regions previously linked to asthma. The strongest changes in atopic asthma were detected in the promoter region of SMAD3 gene at chr 15q22.33 and introns of DDO/METTL24 genes at 6q21. These changes were validated to be present also at the average age of 8&nbsp;years.</p>',
			'date' => '2018-08-01',
			'pmid' => 'http://www.pubmed.gov/29729188',
			'doi' => '10.1111/all.13473',
			'modified' => '2019-03-25 11:19:56',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 135 => array(
			'id' => '3515',
			'name' => 'Integrative multi-omics analysis of intestinal organoid differentiation',
			'authors' => 'Rik GH Lindeboom, Lisa van Voorthuijsen1, Koen C Oost, Maria J Rodríguez-Colman, Maria V Luna-Velez, Cristina Furlan, Floriane Baraille, Pascal WTC Jansen, Agnès Ribeiro, Boudewijn MT Burgering, Hugo J Snippert, & Michiel Vermeulen',
			'description' => '<p>Intestinal organoids accurately recapitulate epithelial homeostasis in vivo, thereby representing a powerful in vitro system to investigate lineage specification and cellular differentiation. Here, we applied a multi-omics framework on stem cell-enriched and stem cell-depleted mouse intestinal organoids to obtain a holistic view of the molecular mechanisms that drive differential gene expression during adult intestinal stem cell differentiation. Our data revealed a global rewiring of the transcriptome and proteome between intestinal stem cells and enterocytes, with the majority of dynamic protein expression being transcription-driven. Integrating absolute mRNA and protein copy numbers revealed post-transcriptional regulation of gene expression. Probing the epigenetic landscape identified a large number of cell-type-specific regulatory elements, which revealed Hnf4g as a major driver of enterocyte differentiation. In summary, by applying an integrative systems biology approach, we uncovered multiple layers of gene expression regulation, which contribute to lineage specification and plasticity of the mouse small intestinal epithelium.</p>',
			'date' => '2018-06-26',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/29945941/',
			'doi' => '10.15252/msb.20188227',
			'modified' => '2022-05-18 18:45:53',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 136 => array(
			'id' => '3423',
			'name' => 'The Polycomb-Dependent Epigenome Controls β Cell Dysfunction, Dedifferentiation, and Diabetes.',
			'authors' => 'Lu TT, Heyne S, Dror E, Casas E, Leonhardt L, Boenke T, Yang CH, Sagar , Arrigoni L, Dalgaard K, Teperino R, Enders L, Selvaraj M, Ruf M, Raja SJ, Xie H, Boenisch U, Orkin SH, Lynn FC, Hoffman BG, Grün D, Vavouri T, Lempradl AM, Pospisilik JA',
			'description' => '<p>To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single-cell transcriptomics to mine for evidence of chromatin dysregulation in type 2 diabetes. We find two chromatin-state signatures that track &beta; cell dysfunction in mice and humans: ectopic activation of bivalent Polycomb-silenced domains and loss of expression at an epigenomically unique class of lineage-defining genes. &beta; cell-specific Polycomb (Eed/PRC2) loss of function in mice triggers diabetes-mimicking transcriptional signatures and highly penetrant, hyperglycemia-independent dedifferentiation, indicating that PRC2 dysregulation contributes to disease. The work provides novel resources for exploring &beta;&nbsp;cell transcriptional regulation and identifies PRC2 as necessary for long-term maintenance of &beta; cell identity. Importantly, the data suggest a two-hit (chromatin and hyperglycemia) model for loss of &beta;&nbsp;cell identity in diabetes.</p>',
			'date' => '2018-06-05',
			'pmid' => 'http://www.pubmed.gov/29754954',
			'doi' => '10.1016/j.cmet.2018.04.013',
			'modified' => '2018-12-31 11:43:24',
			'created' => '2018-12-04 09:51:07',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 137 => array(
			'id' => '3380',
			'name' => 'The reference epigenome and regulatory chromatin landscape of chronic lymphocytic leukemia',
			'authors' => 'Beekman R. et al.',
			'description' => '<p>Chronic lymphocytic leukemia (CLL) is a frequent hematological neoplasm in which underlying epigenetic alterations are only partially understood. Here, we analyze the reference epigenome of seven primary CLLs and the regulatory chromatin landscape of 107 primary cases in the context of normal B cell differentiation. We identify that the CLL chromatin landscape is largely influenced by distinct dynamics during normal B cell maturation. Beyond this, we define extensive catalogues of regulatory elements de novo reprogrammed in CLL as a whole and in its major clinico-biological subtypes classified by IGHV somatic hypermutation levels. We uncover that IGHV-unmutated CLLs harbor more active and open chromatin than IGHV-mutated cases. Furthermore, we show that de novo active regions in CLL are enriched for NFAT, FOX and TCF/LEF transcription factor family binding sites. Although most genetic alterations are not associated with consistent epigenetic profiles, CLLs with MYD88 mutations and trisomy 12 show distinct chromatin configurations. Furthermore, we observe that non-coding mutations in IGHV-mutated CLLs are enriched in H3K27ac-associated regulatory elements outside accessible chromatin. Overall, this study provides an integrative portrait of the CLL epigenome, identifies extensive networks of altered regulatory elements and sheds light on the relationship between the genetic and epigenetic architecture of the disease.</p>',
			'date' => '2018-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29785028',
			'doi' => '',
			'modified' => '2018-07-27 17:10:43',
			'created' => '2018-07-27 17:10:43',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 138 => array(
			'id' => '3469',
			'name' => 'Increased H3K9 methylation and impaired expression of Protocadherins are associated with the cognitive dysfunctions of the Kleefstra syndrome.',
			'authors' => 'Iacono G, Dubos A, Méziane H, Benevento M, Habibi E, Mandoli A, Riet F, Selloum M, Feil R, Zhou H, Kleefstra T, Kasri NN, van Bokhoven H, Herault Y, Stunnenberg HG',
			'description' => '<p>Kleefstra syndrome, a disease with intellectual disability, autism spectrum disorders and other developmental defects is caused in humans by haploinsufficiency of EHMT1. Although EHMT1 and its paralog EHMT2 were shown to be histone methyltransferases responsible for deposition of the di-methylated H3K9 (H3K9me2), the exact nature of epigenetic dysfunctions in Kleefstra syndrome remains unknown. Here, we found that the epigenome of Ehmt1+/- adult mouse brain displays a marked increase of H3K9me2/3 which correlates with impaired expression of protocadherins, master regulators of neuronal diversity. Increased H3K9me3 was present already at birth, indicating that aberrant methylation patterns are established during embryogenesis. Interestingly, we found that Ehmt2+/- mice do not present neither the marked increase of H3K9me2/3 nor the cognitive deficits found in Ehmt1+/- mice, indicating an evolutionary diversification of functions. Our finding of increased H3K9me3 in Ehmt1+/- mice is the first one supporting the notion that EHMT1 can quench the deposition of tri-methylation by other Histone methyltransferases, ultimately leading to impaired neurocognitive functioning. Our insights into the epigenetic pathophysiology of Kleefstra syndrome may offer guidance for future developments of therapeutic strategies for this disease.</p>',
			'date' => '2018-06-01',
			'pmid' => 'http://www.pubmed.gov/29554304',
			'doi' => '10.1093/nar/gky196',
			'modified' => '2019-02-15 21:04:02',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 139 => array(
			'id' => '3478',
			'name' => 'Pro-inflammatory cytokines activate hypoxia-inducible factor 3α via epigenetic changes in mesenchymal stromal/stem cells.',
			'authors' => 'Cuomo F, Coppola A, Botti C, Maione C, Forte A, Scisciola L, Liguori G, Caiafa I, Ursini MV, Galderisi U, Cipollaro M, Altucci L, Cobellis G',
			'description' => '<p>Human mesenchymal stromal/stem cells (hMSCs) emerged as a promising therapeutic tool for ischemic disorders, due to their ability to regenerate damaged tissues, promote angiogenesis and reduce inflammation, leading to encouraging, but still limited results. The outcomes in clinical trials exploring hMSC therapy are influenced by low cell retention and survival in affected tissues, partially influenced by lesion's microenvironment, where low oxygen conditions (i.e. hypoxia) and inflammation coexist. Hypoxia and inflammation are pathophysiological stresses, sharing common activators, such as hypoxia-inducible factors (HIFs) and NF-&kappa;B. HIF1&alpha; and HIF2&alpha; respond essentially to hypoxia, activating pathways involved in tissue repair. Little is known about the regulation of HIF3&alpha;. Here we investigated the role of HIF3&alpha; in vitro and in vivo. Human MSCs expressed HIF3&alpha;, differentially regulated by pro-inflammatory cytokines in an oxygen-independent manner, a novel and still uncharacterized mechanism, where NF-&kappa;B is critical for its expression. We investigated if epigenetic modifications are involved in HIF3&alpha; expression by methylation-specific PCR and histone modifications. Robust hypermethylation of histone H3 was observed across HIF3A locus driven by pro-inflammatory cytokines. Experiments in a murine model of arteriotomy highlighted the activation of Hif3&alpha; expression in infiltrated inflammatory cells, suggesting a new role for Hif3&alpha; in inflammation in vivo.</p>',
			'date' => '2018-04-11',
			'pmid' => 'http://www.pubmed.gov/29643458',
			'doi' => '10.1038/s41598-018-24221-5',
			'modified' => '2019-02-15 20:21:28',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 140 => array(
			'id' => '3463',
			'name' => 'Epigenetic modifiers promote mitochondrial biogenesis and oxidative metabolism leading to enhanced differentiation of neuroprogenitor cells.',
			'authors' => 'Martine Uittenbogaard, Christine A. Brantner, Anne Chiaramello1',
			'description' => '<p>During neural development, epigenetic modulation of chromatin acetylation is part of a dynamic, sequential and critical process to steer the fate of multipotent neural progenitors toward a specific lineage. Pan-HDAC inhibitors (HDCis) trigger neuronal differentiation by generating an "acetylation" signature and promoting the expression of neurogenic bHLH transcription factors. Our studies and others have revealed a link between neuronal differentiation and increase of mitochondrial mass. However, the neuronal regulation of mitochondrial biogenesis has remained largely unexplored. Here, we show that the HDACi, sodium butyrate (NaBt), promotes mitochondrial biogenesis via the NRF-1/Tfam axis in embryonic hippocampal progenitor cells and neuroprogenitor-like PC12-NeuroD6 cells, thereby enhancing their neuronal differentiation competency. Increased mitochondrial DNA replication by several pan-HDACis indicates a common mechanism by which they regulate mitochondrial biogenesis. NaBt also induces coordinates mitochondrial ultrastructural changes and enhanced OXPHOS metabolism, thereby increasing key mitochondrial bioenergetics parameters in neural progenitor cells. NaBt also endows the neuronal cells with increased mitochondrial spare capacity to confer resistance to oxidative stress associated with neuronal differentiation. We demonstrate that mitochondrial biogenesis is under HDAC-mediated epigenetic regulation, the timing of which is consistent with its integrative role during neuronal differentiation. Thus, our findings add a new facet to our mechanistic understanding of how pan-HDACis induce differentiation of neuronal progenitor cells. Our results reveal the concept that epigenetic modulation of the mitochondrial pool prior to neurotrophic signaling dictates the efficiency of initiation of neuronal differentiation during the transition from progenitor to differentiating neuronal cells. The histone acetyltransferase CREB-binding protein plays a key role in regulating the mitochondrial biomass. By ChIP-seq analysis, we show that NaBt confers an H3K27ac epigenetic signature in several interconnected nodes of nuclear genes vital for neuronal differentiation and mitochondrial reprogramming. Collectively, our study reports a novel developmental epigenetic layer that couples mitochondrial biogenesis to neuronal differentiation.</p>',
			'date' => '2018-03-02',
			'pmid' => 'http://www.pubmed.gov/29500414',
			'doi' => '10.1038/s41419-018-0396-1',
			'modified' => '2019-02-15 21:21:45',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 141 => array(
			'id' => '3361',
			'name' => 'Micro-ribonucleic acid-155 is a direct target of Meis1, but not a driver in acute myeloid leukemia',
			'authors' => 'Schneider E. et al.',
			'description' => '<p>Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute myeloid leukemia. The additional overexpression of miR-155 accelerated the formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells <i>in vivo</i> However, in the absence or following the removal of miR-155, leukemia onset and progression were unaffected. Although miR-155 accelerated growth and homing in addition to impairing differentiation, our data underscore the pathophysiological relevance of miR-155 as an accelerator rather than a driver of leukemogenesis. This further highlights the complexity of the oncogenic program of Meis1 to compensate for the loss of a potent oncogene such as miR-155. These findings are highly relevant to current and developing approaches for targeting miR-155 in acute myeloid leukemia.</p>',
			'date' => '2018-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29217774',
			'doi' => '',
			'modified' => '2018-04-06 15:39:36',
			'created' => '2018-04-06 15:39:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 142 => array(
			'id' => '3446',
			'name' => 'Metabolic Induction of Trained Immunity through the Mevalonate Pathway.',
			'authors' => 'Bekkering S, Arts RJW, Novakovic B, Kourtzelis I, van der Heijden CDCC, Li Y, Popa CD, Ter Horst R, van Tuijl J, Netea-Maier RT, van de Veerdonk FL, Chavakis T, Joosten LAB, van der Meer JWM, Stunnenberg H, Riksen NP, Netea MG',
			'description' => '<p>Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that activation of the cholesterol synthesis pathway, but not the synthesis of cholesterol itself, is essential for training of myeloid cells. Rather, the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways. Statins, which block mevalonate generation, prevent trained immunity induction. Furthermore, monocytes of patients with hyper immunoglobulin D syndrome (HIDS), who are mevalonate kinase deficient and accumulate mevalonate, have a constitutive trained immunity phenotype at both immunological and epigenetic levels, which could explain the attacks of sterile inflammation that these patients experience. Unraveling the role of mevalonate in trained immunity contributes to our understanding of the pathophysiology of HIDS and identifies novel therapeutic targets for clinical conditions with excessive activation of trained immunity.</p>',
			'date' => '2018-01-11',
			'pmid' => 'http://www.pubmed.gov/29328908',
			'doi' => '10.1016/j.cell.2017.11.025',
			'modified' => '2019-02-15 21:37:39',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 143 => array(
			'id' => '3408',
			'name' => 'BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity.',
			'authors' => 'Arts RJW, Moorlag SJCFM, Novakovic B, Li Y, Wang SY, Oosting M, Kumar V, Xavier RJ, Wijmenga C, Joosten LAB, Reusken CBEM, Benn CS, Aaby P, Koopmans MP, Stunnenberg HG, van Crevel R, Netea MG',
			'description' => '<p>The tuberculosis vaccine bacillus Calmette-Gu&eacute;rin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was accompanied by functional changes indicative of trained immunity. Reduction of viremia was highly correlated with the upregulation of IL-1&beta;, a heterologous cytokine associated with the induction of trained immunity, but not with&nbsp;the specific IFN&gamma; response. The importance of IL-1&beta; for the induction of trained immunity was validated through genetic, epigenetic, and immunological studies. In conclusion, BCG induces epigenetic reprogramming in human monocytes in&nbsp;vivo, followed by functional reprogramming and protection against non-related viral infections, with a key role for IL-1&beta; as a mediator of trained immunity responses.</p>',
			'date' => '2018-01-10',
			'pmid' => 'http://www.pubmed.gov/29324233',
			'doi' => '10.1016/j.chom.2017.12.010',
			'modified' => '2018-11-22 15:15:09',
			'created' => '2018-11-08 12:59:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 144 => array(
			'id' => '3440',
			'name' => 'Senescence-associated reprogramming promotes cancer stemness.',
			'authors' => 'Milanovic M, Fan DNY, Belenki D, Däbritz JHM, Zhao Z, Yu Y, Dörr JR, Dimitrova L, Lenze D, Monteiro Barbosa IA, Mendoza-Parra MA, Kanashova T, Metzner M, Pardon K, Reimann M, Trumpp A, Dörken B, Zuber J, Gronemeyer H, Hummel M, Dittmar G, Lee S, Schmitt C',
			'description' => '<p>Cellular senescence is a stress-responsive cell-cycle arrest program that terminates the further expansion of (pre-)malignant cells. Key signalling components of the senescence machinery, such as p16, p21 and p53, as well as trimethylation of lysine 9 at histone H3 (H3K9me3), also operate as critical regulators of stem-cell functions (which are collectively termed 'stemness'). In cancer cells, a gain of stemness may have profound implications for tumour aggressiveness and clinical outcome. Here we investigated whether chemotherapy-induced senescence could change stem-cell-related properties of malignant cells. Gene expression and functional analyses comparing senescent and non-senescent B-cell lymphomas from E&mu;-Myc transgenic mice revealed substantial upregulation of an adult tissue stem-cell signature, activated Wnt signalling, and distinct stem-cell markers in senescence. Using genetically switchable models of senescence targeting H3K9me3 or p53 to mimic spontaneous escape from the arrested condition, we found that cells released from senescence re-entered the cell cycle with strongly enhanced and Wnt-dependent clonogenic growth potential compared to virtually identical populations that had been equally exposed to chemotherapy but had never been senescent. In vivo, these previously senescent cells presented with a much higher tumour initiation potential. Notably, the temporary enforcement of senescence in p53-regulatable models of acute lymphoblastic leukaemia and acute myeloid leukaemia was found to reprogram non-stem bulk leukaemia cells into self-renewing, leukaemia-initiating stem cells. Our data, which are further supported by consistent results in human cancer cell lines and primary samples of human haematological malignancies, reveal that senescence-associated stemness is an unexpected, cell-autonomous feature that exerts its detrimental, highly aggressive growth potential upon escape from cell-cycle blockade, and is enriched in relapse tumours. These findings have profound implications for cancer therapy, and provide new mechanistic insights into the plasticity of cancer cells.</p>',
			'date' => '2018-01-04',
			'pmid' => 'http://www.pubmed.org/29258294',
			'doi' => '10.1038/nature25167',
			'modified' => '2019-02-15 21:39:11',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 145 => array(
			'id' => '3385',
			'name' => 'MLL2 conveys transcription-independent H3K4 trimethylation in oocytes',
			'authors' => 'Hanna C.W. et al.',
			'description' => '<p>Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyte provides an attractive system to investigate these mechanisms, because extensive H3K4me3 acquisition occurs in nondividing cells. We developed low-input chromatin immunoprecipitation to interrogate H3K4me3, H3K27ac and H3K27me3 marks throughout oogenesis. In nongrowing oocytes, H3K4me3 was restricted to active promoters, but as oogenesis progressed, H3K4me3 accumulated in a transcription-independent manner and was targeted to intergenic regions, putative enhancers and silent H3K27me3-marked promoters. Ablation of the H3K4 methyltransferase&nbsp;gene Mll2 resulted in loss of transcription-independent H3K4 trimethylation but had limited effects on transcription-coupled H3K4 trimethylation or gene expression. Deletion of Dnmt3a and Dnmt3b showed that DNA methylation protects regions from acquiring H3K4me3. Our findings reveal two independent mechanisms of targeting H3K4me3 to genomic elements, with MLL2 recruited to unmethylated CpG-rich regions independently of transcription.</p>',
			'date' => '2018-01-02',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29323282',
			'doi' => '',
			'modified' => '2018-08-07 10:26:20',
			'created' => '2018-08-07 10:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 146 => array(
			'id' => '3330',
			'name' => 'The histone code reader Spin1 controls skeletal muscle development',
			'authors' => 'Greschik H. et al.',
			'description' => '<p>While several studies correlated increased expression of the histone code reader Spin1 with tumor formation or growth, little is known about physiological functions of the protein. We generated Spin1<sup>M5</sup> mice with ablation of Spin1 in myoblast precursors using the Myf5-Cre deleter strain. Most Spin1<sup>M5</sup> mice die shortly after birth displaying severe sarcomere disorganization and necrosis. Surviving Spin1<sup>M5</sup> mice are growth-retarded and exhibit the most prominent defects in soleus, tibialis anterior, and diaphragm muscle. Transcriptome analyses of limb muscle at embryonic day (E) 15.5, E16.5, and at three weeks of age provided evidence for aberrant fetal myogenesis and identified deregulated skeletal muscle (SkM) functional networks. Determination of genome-wide chromatin occupancy in primary myoblast revealed direct Spin1 target genes and suggested that deregulated basic helix-loop-helix transcription factor networks account for developmental defects in Spin1<sup>M5</sup> fetuses. Furthermore, correlating histological and transcriptome analyses, we show that aberrant expression of titin-associated proteins, abnormal glycogen metabolism, and neuromuscular junction defects contribute to SkM pathology in Spin1<sup>M5</sup> mice. Together, we describe the first example of a histone code reader controlling SkM development in mice, which hints at Spin1 as a potential player in human SkM disease.</p>',
			'date' => '2017-11-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29168801',
			'doi' => '',
			'modified' => '2018-02-07 10:20:01',
			'created' => '2018-02-07 10:20:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 147 => array(
			'id' => '3322',
			'name' => 'In Situ Fixation Redefines Quiescence and Early Activation of Skeletal Muscle Stem Cells',
			'authors' => 'Machado L. et al.',
			'description' => '<div class="abstract">
<h2 class="sectionTitle" tabindex="0">Summary</h2>
<div class="content">
<p>State of the art techniques have been developed to isolate and analyze cells from various tissues, aiming to capture their <em>in&nbsp;vivo</em> state. However, the majority of cell isolation protocols involve lengthy mechanical and enzymatic dissociation steps followed by flow cytometry, exposing cells to stress and disrupting their physiological niche. Focusing on adult skeletal muscle stem cells, we have developed a protocol that circumvents the impact of isolation procedures and captures cells in their native quiescent state. We show that current isolation protocols induce major transcriptional changes accompanied by specific histone modifications while having negligible effects on DNA methylation. In addition to proposing a protocol to avoid isolation-induced artifacts, our study reveals previously undetected quiescence and early activation genes of potential biological interest.</p>
</div>
</div>',
			'date' => '2017-11-14',
			'pmid' => 'http://www.cell.com/cell-reports/abstract/S2211-1247(17)31543-7',
			'doi' => '',
			'modified' => '2022-05-19 16:11:43',
			'created' => '2018-02-02 16:36:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 148 => array(
			'id' => '3309',
			'name' => 'GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency',
			'authors' => 'Krendl C. et al.',
			'description' => '<p>To elucidate the molecular basis of BMP4-induced differentiation of human pluripotent stem cells (PSCs) toward progeny with trophectoderm characteristics, we produced transcriptome, epigenome H3K4me3, H3K27me3, and CpG methylation maps of trophoblast progenitors, purified using the surface marker APA. We combined them with the temporally resolved transcriptome of the preprogenitor phase and of single APA+ cells. This revealed a circuit of bivalent TFAP2A, TFAP2C, GATA2, and GATA3 transcription factors, coined collectively the "trophectoderm four" (TEtra), which are also present in human trophectoderm in vivo. At the onset of differentiation, the TEtra factors occupy multiple sites in epigenetically inactive placental genes and in <i>OCT4</i> Functional manipulation of <i>GATA3</i> and <i>TFAP2A</i> indicated that they directly couple trophoblast-specific gene induction with suppression of pluripotency. In accordance, knocking down <i>GATA3</i> in primate embryos resulted in a failure to form trophectoderm. The discovery of the TEtra circuit indicates how trophectoderm commitment is regulated in human embryogenesis.</p>',
			'date' => '2017-11-07',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29078328',
			'doi' => '',
			'modified' => '2018-01-04 10:23:33',
			'created' => '2018-01-04 10:23:33',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 149 => array(
			'id' => '3302',
			'name' => 'The mixed lineage leukemia 4 (MLL4) methyltransferase complex is involved in transforming growth factor beta (TGF-β)-activated gene transcription.',
			'authors' => 'Baas R. et al.',
			'description' => '<p>Sma and Mad related (SMAD)-mediated Transforming Growth Factor &beta; (TGF-&beta;) and Bone Morphogenetic Protein (BMP) signaling is required for various cellular processes. The activated heterotrimeric SMAD protein complexes associate with nuclear proteins such as the histone acetyltransferases p300, PCAF and the Mixed Lineage Leukemia 4 (MLL4) subunit Pax Transactivation domain-Interacting Protein (PTIP) to regulate gene transcription. We investigated the functional role of PTIP and PTIP Interacting protein 1 (PA1) in relation to TGF-&beta;-activated SMAD signaling. We immunoprecipitated PTIP and PA1 with all SMAD family members to identify the TGF-&beta; and not BMP-specific SMADs as interacting proteins. Gene silencing experiments of MLL4 and the subunits PA1 and PTIP confirm TGF-&beta;-specific genes to be regulated by the MLL4 complex, which links TGF-&beta; signaling to transcription regulation by the MLL4 methyltransferase complex.</p>',
			'date' => '2017-10-04',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28976802',
			'doi' => '',
			'modified' => '2017-12-05 10:50:08',
			'created' => '2017-12-05 10:50:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 150 => array(
			'id' => '3296',
			'name' => 'Predicting stimulation-dependent enhancer-promoter interactions from ChIP-Seq time course data',
			'authors' => 'Dzida T. et al.',
			'description' => '<p>We have developed a machine learning approach to predict stimulation-dependent enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ER&alpha;), RNA polymerase (Pol II) and histone marks H2AZ and H3K4me3 were measured over time using ChIP-Seq experiments in MCF7 cells stimulated with estrogen. A Bayesian classifier was developed which uses the correlation of temporal binding patterns at enhancers and promoters and genomic proximity as features to predict interactions. This method was trained using experimentally determined interactions from the same system and was shown to achieve much higher precision than predictions based on the genomic proximity of nearest ER&alpha;&nbsp;binding. We use the method to identify a genome-wide confident set of ER&alpha;&nbsp;target genes and their regulatory enhancers genome-wide. Validation with publicly available GRO-Seq data demonstrates that our predicted targets are much more likely to show early nascent transcription than predictions based on genomic ER&alpha;&nbsp;binding proximity alone.</p>',
			'date' => '2017-09-28',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28970965',
			'doi' => '',
			'modified' => '2017-12-04 11:06:11',
			'created' => '2017-12-04 11:06:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 151 => array(
			'id' => '3303',
			'name' => 'Genetic Predisposition to Multiple Myeloma at 5q15 Is Mediated by an ELL2 Enhancer Polymorphism',
			'authors' => 'Li N. et al.',
			'description' => '<p>Multiple myeloma (MM) is a malignancy of plasma cells. Genome-wide association studies have shown that variation at 5q15 influences MM risk. Here, we have sought to decipher the causal variant at 5q15 and the mechanism by which it influences tumorigenesis. We show that rs6877329&nbsp;G &gt; C resides in a predicted enhancer element that physically interacts with the transcription start site of ELL2. The rs6877329-C risk allele is associated with reduced enhancer activity and lowered ELL2 expression. Since ELL2 is critical to the B cell differentiation process, reduced ELL2 expression is consistent with inherited genetic variation contributing to arrest of plasma cell development, facilitating MM clonal expansion. These data provide evidence for a biological mechanism underlying a hereditary risk of MM at 5q15.</p>',
			'date' => '2017-09-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28903037',
			'doi' => '',
			'modified' => '2018-01-02 17:58:38',
			'created' => '2018-01-02 17:58:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 152 => array(
			'id' => '3298',
			'name' => 'Chromosome contacts in activated T cells identify autoimmune disease candidate genes',
			'authors' => 'Burren OS et al.',
			'description' => '<div class="abstr">
<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Autoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4<sup>+</sup> T cells. Linking such regulatory regions to gene promoters in disease-relevant cell contexts facilitates identification of candidate disease genes.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Within 4&nbsp;h, activation of CD4<sup>+</sup> T cells invokes changes in histone modifications and enhancer RNA transcription that correspond to altered expression of the interacting genes identified by promoter capture Hi-C. By integrating promoter capture Hi-C data with genetic associations for five autoimmune diseases, we prioritised 245 candidate genes with a median distance from peak signal to prioritised gene of 153&nbsp;kb. Just under half (108/245) prioritised genes related to activation-sensitive interactions. This included IL2RA, where allele-specific expression analyses were consistent with its interaction-mediated regulation, illustrating the utility of the approach.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">Our systematic experimental framework offers an alternative approach to candidate causal gene identification for variants with cell state-specific functional effects, with achievable sample sizes.</abstracttext></p>
</div>
</div>',
			'date' => '2017-09-04',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28870212',
			'doi' => '',
			'modified' => '2017-12-04 11:25:15',
			'created' => '2017-12-04 11:25:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 153 => array(
			'id' => '3262',
			'name' => 'A lncRNA fine tunes the dynamics of a cell state transition involving Lin28, let-7 and de novo DNA methylation',
			'authors' => 'Li M.A. et al.',
			'description' => '<p>Execution of pluripotency requires progression from the na&iuml;ve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) <em>linc1281,</em> hereafter <em>Ephemeron</em> (<em>Eprn</em>), that modulates the dynamics of exit from na&iuml;ve pluripotency. <em>Eprn</em> deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression. In the absence of <em>Eprn</em>, <em>Lin28a</em> expression is reduced which results in persistence of <em>let-7 microRNAs, and</em> the up-regulation of de novo methyltransferases Dnmt3a/b is delayed. <em>Dnmt3a/b</em> deletion retards ES cell transition, correlating with delayed <em>Nanog</em> promoter methylation and phenocopying loss of <em>Eprn</em> or <em>Lin28a</em>. The connection from lncRNA to miRNA and DNA methylation facilitates the acute extinction of na&iuml;ve pluripotency, a pre-requisite for rapid progression from preimplantation epiblast to gastrulation in rodents. <em>Eprn</em> illustrates how lncRNAs may introduce species-specific network modulations.</p>',
			'date' => '2017-08-18',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562443/',
			'doi' => '',
			'modified' => '2017-10-09 15:55:39',
			'created' => '2017-10-09 15:55:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 154 => array(
			'id' => '3240',
			'name' => 'Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation',
			'authors' => 'Pünzeler S. et al.',
			'description' => '<p>Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine the comprehensive interactome of H2A.Z and identify PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A is a functionally uncharacterized, vertebrate-specific protein that binds very tightly to chromatin through a concerted multivalent binding mode. Two internal protein regions mediate H2A.Z-specificity and nucleosome interaction, whereas the PWWP domain exhibits direct DNA binding. Genome-wide mapping reveals that PWWP2A binds selectively to H2A.Z-containing nucleosomes with strong preference for promoters of highly transcribed genes. In human cells, its depletion affects gene expression and impairs proliferation via a mitotic delay. While PWWP2A does not influence H2A.Z occupancy, the C-terminal tail of H2A.Z is one important mediator to recruit PWWP2A to chromatin. Knockdown of PWWP2A in <i>Xenopus</i> results in severe cranial facial defects, arising from neural crest cell differentiation and migration problems. Thus, PWWP2A is a novel H2A.Z-specific multivalent chromatin binder providing a surprising link between H2A.Z, chromosome segregation, and organ development.</p>',
			'date' => '2017-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28645917',
			'doi' => '',
			'modified' => '2017-08-29 09:45:44',
			'created' => '2017-08-29 09:45:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 155 => array(
			'id' => '3270',
			'name' => 'Mouse models of 17q21.31 microdeletion and microduplication syndromes highlight the importance of Kansl1 for cognition',
			'authors' => 'Arbogast T. et al.',
			'description' => '<p>Koolen-de Vries syndrome (KdVS) is a multi-system disorder characterized by intellectual disability, friendly behavior, and congenital malformations. The syndrome is caused either by microdeletions in the 17q21.31 chromosomal region or by variants in the KANSL1 gene. The reciprocal 17q21.31 microduplication syndrome is associated with psychomotor delay, and reduced social interaction. To investigate the pathophysiology of 17q21.31 microdeletion and microduplication syndromes, we generated three mouse models: 1) the deletion (Del/+); or 2) the reciprocal duplication (Dup/+) of the 17q21.31 syntenic region; and 3) a heterozygous Kansl1 (Kans1+/-) model. We found altered weight, general activity, social behaviors, object recognition, and fear conditioning memory associated with craniofacial and brain structural changes observed in both Del/+ and Dup/+ animals. By investigating hippocampus function, we showed synaptic transmission defects in Del/+ and Dup/+ mice. Mutant mice with a heterozygous loss-of-function mutation in Kansl1 displayed similar behavioral and anatomical phenotypes compared to Del/+ mice with the exception of sociability phenotypes. Genes controlling chromatin organization, synaptic transmission and neurogenesis were upregulated in the hippocampus of Del/+ and Kansl1+/- animals. Our results demonstrate the implication of KANSL1 in the manifestation of KdVS phenotypes and extend substantially our knowledge about biological processes affected by these mutations. Clear differences in social behavior and gene expression profiles between Del/+ and Kansl1+/- mice suggested potential roles of other genes affected by the 17q21.31 deletion. Together, these novel mouse models provide new genetic tools valuable for the development of therapeutic approaches.</p>',
			'date' => '2017-07-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28704368',
			'doi' => '',
			'modified' => '2017-10-10 17:25:37',
			'created' => '2017-10-10 17:25:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 156 => array(
			'id' => '3339',
			'name' => 'Platelet function is modified by common sequence variation in megakaryocyte super enhancers',
			'authors' => 'Petersen R. et al.',
			'description' => '<p>Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quantitative traits using cell type-matched epigenomic data and promoter long-range interactions. We identify potential regulatory functions for 423 of 565 (75%) non-coding variants associated with platelet traits and we demonstrate, through <em>ex vivo</em> and proof of principle genome editing validation, that variants in super enhancers play an important role in controlling archetypical platelet functions.</p>',
			'date' => '2017-07-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511350/#S1',
			'doi' => '',
			'modified' => '2018-02-15 10:25:39',
			'created' => '2018-02-15 10:25:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 157 => array(
			'id' => '3234',
			'name' => 'Chromatin Immunoprecipitation (ChIP) in Mouse T-cell Lines',
			'authors' => 'Giaimo B.D. et al.',
			'description' => '<p>Signaling pathways regulate gene expression programs via the modulation of the chromatin structure at different levels, such as by post-translational modifications (PTMs) of histone tails, the exchange of canonical histones with histone variants, and nucleosome eviction. Such regulation requires the binding of signal-sensitive transcription factors (TFs) that recruit chromatin-modifying enzymes at regulatory elements defined as enhancers. Understanding how signaling cascades regulate enhancer activity requires a comprehensive analysis of the binding of TFs, chromatin modifying enzymes, and the occupancy of specific histone marks and histone variants. Chromatin immunoprecipitation (ChIP) assays utilize highly specific antibodies to immunoprecipitate specific protein/DNA complexes. The subsequent analysis of the purified DNA allows for the identification the region occupied by the protein recognized by the antibody. This work describes a protocol to efficiently perform ChIP of histone proteins in a mature mouse T-cell line. The presented protocol allows for the performance of ChIP assays in a reasonable timeframe and with high reproducibility.</p>',
			'date' => '2017-06-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28654055',
			'doi' => '',
			'modified' => '2017-08-24 10:13:18',
			'created' => '2017-08-24 10:13:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 158 => array(
			'id' => '3222',
			'name' => 'DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats',
			'authors' => 'Brocks D. et al.',
			'description' => '<p>Several mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known about their genome-wide transcriptional and epigenomic consequences. By mapping global transcription start site (TSS) and chromatin dynamics, we observed the cryptic transcription of thousands of treatment-induced non-annotated TSSs (TINATs) following DNMTi and HDACi treatment. The resulting transcripts frequently splice into protein-coding exons and encode truncated or chimeric ORFs translated into products with predicted abnormal or immunogenic functions. TINAT transcription after DNMTi treatment coincided with DNA hypomethylation and gain of classical promoter histone marks, while HDACi specifically induced a subset of TINATs in association with H2AK9ac, H3K14ac, and H3K23ac. Despite this mechanistic difference, both inhibitors convergently induced transcription from identical sites, as we found TINATs to be encoded in solitary long terminal repeats of the ERV9/LTR12 family, which are epigenetically repressed in virtually all normal cells.</p>',
			'date' => '2017-06-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28604729',
			'doi' => '',
			'modified' => '2017-08-18 14:14:48',
			'created' => '2017-08-18 14:14:48',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 159 => array(
			'id' => '3241',
			'name' => 'Evolutionary re-wiring of p63 and the epigenomic regulatory landscape in keratinocytes and its potential implications on species-specific gene expression and phenotypes',
			'authors' => 'Sethi I. et al.',
			'description' => '<p>Although epidermal keratinocyte development and differentiation proceeds in similar fashion between humans and mice, evolutionary pressures have also wrought significant species-specific physiological differences. These differences between species could arise in part, by the rewiring of regulatory network due to changes in the global targets of lineage-specific transcriptional master regulators such as p63. Here we have performed a systematic and comparative analysis of the p63 target gene network within the integrated framework of the transcriptomic and epigenomic landscape of mouse and human keratinocytes. We determined that there exists a core set of &sim;1600 genomic regions distributed among enhancers and super-enhancers, which are conserved and occupied by p63 in keratinocytes from both species. Notably, these DNA segments are typified by consensus p63 binding motifs under purifying selection and are associated with genes involved in key keratinocyte and skin-centric biological processes. However, the majority of the p63-bound mouse target regions consist of either murine-specific DNA elements that are not alignable to the human genome or exhibit no p63 binding in the orthologous syntenic regions, typifying an occupancy lost subset. Our results suggest that these evolutionarily divergent regions have undergone significant turnover of p63 binding sites and are associated with an underlying inactive and inaccessible chromatin state, indicative of their selective functional activity in the transcriptional regulatory network in mouse but not human. Furthermore, we demonstrate that this selective targeting of genes by p63 correlates with subtle, but measurable transcriptional differences in mouse and human keratinocytes that converges on major metabolic processes, which often exhibit species-specific trends. Collectively our study offers possible molecular explanation for the observable phenotypic differences between the mouse and human skin and broadly informs on the prevailing principles that govern the tug-of-war between evolutionary forces of rigidity and plasticity over transcriptional regulatory programs.</p>',
			'date' => '2017-05-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28505376',
			'doi' => '',
			'modified' => '2017-08-29 12:01:20',
			'created' => '2017-08-29 12:01:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 160 => array(
			'id' => '3201',
			'name' => 'RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA(+) and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells.',
			'authors' => 'Lund R.J. et al.',
			'description' => '<p>POLR3G is expressed at high levels in human pluripotent stem cells (hPSCs) and is required for maintenance of stem cell state through mechanisms not known in detail. To explore how POLR3G regulates stem cell state, we carried out deep-sequencing analysis&nbsp;of polyA<sup>+</sup> and smallRNA transcriptomes present in hPSCs and regulated in POLR3G-dependent manner. Our data reveal that&nbsp;POLR3G regulates a specific subset of the hPSC transcriptome, including multiple transcript types, such as protein-coding genes,&nbsp;long intervening non-coding RNAs, microRNAs and small nucleolar RNAs, and affects RNA splicing. The primary function of POLR3G is in the maintenance rather than repression of transcription. The majority of POLR3G polyA<sup>+</sup> transcriptome is regulated&nbsp;during differentiation, and the key pluripotency factors bind to the promoters of at least 30% of the POLR3G-regulated transcripts. Among the direct targets of POLR3G, POLG is potentially important in sustaining stem cell status in a POLR3G-dependent manner.</p>',
			'date' => '2017-05-09',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28494942',
			'doi' => '',
			'modified' => '2017-07-03 10:04:16',
			'created' => '2017-07-03 10:04:16',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 161 => array(
			'id' => '3211',
			'name' => 'The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis.',
			'authors' => 'Aldiri I. et al.',
			'description' => '<p>In the developing retina, multipotent neural progenitors undergo unidirectional differentiation in a precise spatiotemporal order. Here we profile the epigenetic and transcriptional changes that occur during retinogenesis in mice and humans. Although some progenitor genes and cell cycle genes were epigenetically silenced during retinogenesis, the most dramatic change was derepression of cell-type-specific differentiation programs. We identified developmental-stage-specific super-enhancers and showed that most epigenetic changes are conserved in humans and mice. To determine how the epigenome changes during tumorigenesis and reprogramming, we performed integrated epigenetic analysis of murine and human retinoblastomas and induced pluripotent stem cells (iPSCs) derived from murine rod photoreceptors. The retinoblastoma epigenome mapped to the developmental stage when retinal progenitors switch from neurogenic to terminal patterns of cell division. The epigenome of retinoblastomas was more similar to that of the normal retina than that of retina-derived iPSCs, and we identified retina-specific epigenetic memory.</p>',
			'date' => '2017-05-03',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28472656',
			'doi' => '',
			'modified' => '2017-07-07 17:04:39',
			'created' => '2017-07-07 17:04:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 162 => array(
			'id' => '3187',
			'name' => 'Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions',
			'authors' => 'Frank-Bertoncelj M, Trenkmann M, Klein K, Karouzakis E, Rehrauer H, Bratus A, Kolling C, Armaka M, Filer A, Michel BA, Gay RE, Buckley CD, Kollias G, Gay S, Ospelt C',
			'description' => '<p>A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNF, creating a unique microenvironment in each joint. These findings indicate that local stroma might control positional disease patterns not only in arthritis but in any disease with a prominent stromal component.</p>',
			'date' => '2017-03-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28332497',
			'doi' => '',
			'modified' => '2017-05-24 17:07:07',
			'created' => '2017-05-24 17:07:07',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 163 => array(
			'id' => '3159',
			'name' => 'Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells',
			'authors' => 'Tumber A. et al.',
			'description' => '<p>Methylation of lysine residues on histone tail is a dynamic epigenetic modification that plays a key role in chromatin structure and gene regulation. Members of the KDM5 (also known as JARID1) sub-family are 2-oxoglutarate (2-OG) and Fe<sup>2+</sup>-dependent oxygenases acting as histone 3 lysine 4 trimethyl (H3K4me3) demethylases, regulating proliferation, stem cell self-renewal, and differentiation. Here we present the characterization of KDOAM-25, an inhibitor of KDM5 enzymes. KDOAM-25 shows biochemical half maximal inhibitory concentration values of&nbsp;&lt;100&nbsp;nM for KDM5A-D in&nbsp;vitro, high selectivity toward other 2-OG oxygenases sub-families, and no off-target activity on a panel of 55 receptors and enzymes. In human cell assay systems, KDOAM-25 has a half maximal effective concentration of &sim;50&nbsp;&mu;M and good selectivity toward other demethylases. KDM5B is overexpressed in multiple myeloma and negatively correlated with the overall survival. Multiple myeloma MM1S cells treated with KDOAM-25 show increased global H3K4 methylation at transcriptional start sites and impaired proliferation.</p>',
			'date' => '2017-03-16',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28262558',
			'doi' => '',
			'modified' => '2017-04-12 14:51:37',
			'created' => '2017-04-12 14:51:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 164 => array(
			'id' => '3172',
			'name' => 'Decoupling of DNA methylation and activity of intergenic LINE-1 promoters in colorectal cancer',
			'authors' => 'Vafadar-Isfahani N. et al.',
			'description' => '<p>Hypomethylation of LINE-1 repeats in cancer has been proposed as the main mechanism behind their activation; this assumption, however, was based on findings from early studies that were biased toward young and transpositionally active elements. Here, we investigate the relationship between methylation of 2 intergenic, transpositionally inactive LINE-1 elements and expression of the LINE-1 chimeric transcript (LCT) 13 and LCT14 driven by their antisense promoters (L1-ASP). Our data from DNA modification, expression, and 5'RACE analyses suggest that colorectal cancer methylation in the regions analyzed is not always associated with LCT repression. Consistent with this, in HCT116 colorectal cancer cells lacking DNA methyltransferases DNMT1 or DNMT3B, LCT13 expression decreases, while cells lacking both DNMTs or treated with the DNMT inhibitor 5-azacytidine (5-aza) show no change in LCT13 expression. Interestingly, levels of the H4K20me3 histone modification are inversely associated with LCT13 and LCT14 expression. Moreover, at these LINE-1s, H4K20me3 levels rather than DNA methylation seem to be good predictor of their sensitivity to 5-aza treatment. Therefore, by studying individual LINE-1 promoters we have shown that in some cases these promoters can be active without losing methylation; in addition, we provide evidence that other factors (e.g., H4K20me3 levels) play prominent roles in their regulation.</p>',
			'date' => '2017-03-16',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28300471',
			'doi' => '',
			'modified' => '2017-05-10 16:26:24',
			'created' => '2017-05-10 16:26:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 165 => array(
			'id' => '3165',
			'name' => 'Assessing histone demethylase inhibitors in cells: lessons learned',
			'authors' => 'Hatch S.B. et al.',
			'description' => '<div xmlns="http://www.w3.org/1999/xhtml" class="AbstractSection" id="ASec1">
<h3 xmlns="" class="Heading">Background</h3>
<p id="Par1" class="Para">Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The first KDM inhibitors for KDM1 have entered clinical trials, and efforts are ongoing to develop potent, selective and cell-active &lsquo;probe&rsquo; molecules for this target class. Robust cellular assays to assess the specific engagement of KDM inhibitors in cells as well as their cellular selectivity are a prerequisite for the development of high-quality inhibitors. Here we describe the use of a high-content cellular immunofluorescence assay as a method for demonstrating target engagement in cells.</p>
</div>
<div xmlns="http://www.w3.org/1999/xhtml" class="AbstractSection" id="ASec2">
<h3 xmlns="" class="Heading">Results</h3>
<p id="Par2" class="Para">A panel of assays for the Jumonji C subfamily of KDMs was developed to encompass all major branches of the JmjC phylogenetic tree. These assays compare compound activity against wild-type KDM proteins to a catalytically inactive version of the KDM, in which residues involved in the active-site iron coordination are mutated to inactivate the enzyme activity. These mutants are critical for assessing the specific effect of KDM inhibitors and for revealing indirect effects on histone methylation status. The reported assays make use of ectopically expressed demethylases, and we demonstrate their use to profile several recently identified classes of KDM inhibitors and their structurally matched inactive controls. The generated data correlate well with assay results assessing endogenous KDM inhibition and confirm the selectivity observed in biochemical assays with isolated enzymes. We find that both cellular permeability and competition with 2-oxoglutarate affect the translation of biochemical activity to cellular inhibition.</p>
</div>
<div xmlns="http://www.w3.org/1999/xhtml" class="AbstractSection" id="ASec3">
<h3 xmlns="" class="Heading">Conclusions</h3>
<p id="Par3" class="Para">High-content-based immunofluorescence assays have been established for eight KDM members of the 2-oxoglutarate-dependent oxygenases covering all major branches of the JmjC-KDM phylogenetic tree. The usage of both full-length, wild-type and catalytically inactive mutant ectopically expressed protein, as well as structure-matched inactive control compounds, allowed for detection of nonspecific effects causing changes in histone methylation as a result of compound toxicity. The developed assays offer a histone lysine demethylase family-wide tool for assessing KDM inhibitors for cell activity and on-target efficacy. In addition, the presented data may inform further studies to assess the cell-based activity of histone lysine methylation inhibitors.</p>
</div>',
			'date' => '2017-03-01',
			'pmid' => 'https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-017-0116-6',
			'doi' => '',
			'modified' => '2017-05-09 10:02:47',
			'created' => '2017-05-09 10:02:47',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 166 => array(
			'id' => '3149',
			'name' => 'RNF40 regulates gene expression in an epigenetic context-dependent manner',
			'authors' => 'Xie W. et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlates with increased gene expression. In contrast, depletion of the H2B ubiquitin ligases RNF20 or RNF40 alters the expression of only a subset of genes.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Using conditional Rnf40 knockout mouse embryo fibroblasts, we show that genes occupied by low to moderate amounts of H2Bub1 are selectively regulated in response to Rnf40 deletion, whereas genes marked by high levels of H2Bub1 are mostly unaffected by Rnf40 loss. Furthermore, we find that decreased expression of RNF40-dependent genes is highly associated with widespread narrowing of H3K4me3 peaks. H2Bub1 promotes the broadening of H3K4me3 to increase transcriptional elongation, which together lead to increased tissue-specific gene transcription. Notably, genes upregulated following Rnf40 deletion, including Foxl2, are enriched for H3K27me3, which is decreased following Rnf40 deletion due to decreased expression of the Ezh2 gene. As a consequence, increased expression of some RNF40-"suppressed" genes is associated with enhancer activation via FOXL2.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">Together these findings reveal the complexity and context-dependency whereby one histone modification can have divergent effects on gene transcription. Furthermore, we show that these effects are dependent upon the activity of other epigenetic regulatory proteins and histone modifications.</abstracttext></p>
</div>',
			'date' => '2017-02-16',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28209164',
			'doi' => '',
			'modified' => '2017-03-24 17:22:20',
			'created' => '2017-03-24 17:22:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 167 => array(
			'id' => '3140',
			'name' => 'Menin regulates Inhbb expression through an Akt/Ezh2-mediated H3K27 histone modification',
			'authors' => 'Gherardi S. et al.',
			'description' => '<p>Although Men1 is a well-known tumour suppressor gene, little is known about the functions of Menin, the protein it encodes for. Since few years, numerous publications support a major role of Menin in the control of epigenetics gene regulation. While Menin interaction with MLL complex favours transcriptional activation of target genes through H3K4me3 marks, Menin also represses gene expression via mechanisms involving the Polycomb repressing complex (PRC). Interestingly, Ezh2, the PRC-methyltransferase that catalyses H3K27me3 repressive marks and Menin have been shown to co-occupy a large number of promoters. However, lack of binding between Menin and Ezh2 suggests that another member of the PRC complex is mediating this indirect interaction. Having found that ActivinB - a TGF&beta; superfamily member encoded by the Inhbb gene - is upregulated in insulinoma tumours caused by Men1 invalidation, we hypothesize that Menin could directly participate in the epigenetic-repression of Inhbb gene expression. Using Animal model and cell lines, we report that loss of Menin is directly associated with ActivinB-induced expression both in vivo and in vitro. Our work further reveals that ActivinB expression is mediated through a direct modulation of H3K27me3 marks on the Inhbb locus in Menin-KO cell lines. More importantly, we show that Menin binds on the promoter of Inhbb gene where it favours the recruitment of Ezh2 via an indirect mechanism involving Akt-phosphorylation. Our data suggests therefore that Menin could take an important part to the Ezh2-epigenetic repressive landscape in many cells and tissues through its capacity to modulate Akt phosphorylation.</p>',
			'date' => '2017-02-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28215965',
			'doi' => '',
			'modified' => '2017-03-22 12:07:48',
			'created' => '2017-03-22 12:07:48',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 168 => array(
			'id' => '3139',
			'name' => 'A novel DLX3-PKC integrated signaling network drives keratinocyte differentiation',
			'authors' => 'Palazzo E. et al.',
			'description' => '<p>Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regulate cell cycle-related signaling and that this mechanism is functionally involved in cutaneous squamous cell carcinoma development. Here we show that DLX3 expression and its downstream signaling depend on protein kinase C &alpha; (PKC&alpha;) activity in skin. We found that following 12-O-tetradecanoyl-phorbol-13-acetate (TPA) topical treatment, DLX3 expression is significantly upregulated in the epidermis and keratinocytes from mice overexpressing PKC&alpha; by transgenic targeting (K5-PKC&alpha;), resulting in cell cycle block and terminal differentiation. Epidermis lacking DLX3 (DLX3cKO), which is linked to the development of a DLX3-dependent epidermal hyperplasia with hyperkeratosis and dermal leukocyte recruitment, displays enhanced PKC&alpha; activation, suggesting a feedback regulation of DLX3 and PKC&alpha;. Of particular significance, transcriptional activation of epidermal barrier, antimicrobial peptide and cytokine genes is significantly increased in DLX3cKO skin and further increased by TPA-dependent PKC activation. Furthermore, when inhibiting PKC activity, we show that epidermal thickness, keratinocyte proliferation and inflammatory cell infiltration are reduced and the PKC-DLX3-dependent gene expression signature is normalized. Independently of PKC, DLX3 expression specifically modulates regulatory networks such as Wnt signaling, phosphatase activity and cell adhesion. Chromatin immunoprecipitation sequencing analysis of primary suprabasal keratinocytes showed binding of DLX3 to the proximal promoter regions of genes associated with cell cycle regulation, and of structural proteins and transcription factors involved in epidermal differentiation. These results indicate that Dlx3 potentially regulates a set of crucial genes necessary during the epidermal differentiation process. Altogether, we demonstrate the existence of a robust DLX3-PKC&alpha; signaling pathway in keratinocytes that is crucial to epidermal differentiation control and cutaneous homeostasis.</p>',
			'date' => '2017-02-10',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28186503',
			'doi' => '',
			'modified' => '2017-03-22 12:00:37',
			'created' => '2017-03-22 12:00:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 169 => array(
			'id' => '3100',
			'name' => 'Muscle catabolic capacities and global hepatic epigenome are modified in juvenile rainbow trout fed different vitamin levels at first feeding',
			'authors' => 'Panserat S. et al.',
			'description' => '<p>Based on the concept of nutritional programming in mammals, we tested whether a short term hyper or hypo vitamin stimulus during first-feeding could induce long-lasting changes in nutrient metabolism in rainbow trout. Trout alevins received during the 4 first weeks of exogenous feeding a diet either without supplemental vitamins (NOSUP), a diet supplemented with a vitamin premix to satisfy the minimal requirement in all the vitamins (NRC) or a diet with a vitamin premix corresponding to an optimal vitamin nutrition (OVN). Following a common rearing period on the control diet, all three groups were then evaluated in terms of metabolic marker gene expressions at the end of the feeding period (day 119). Whereas no gene modifications for proteins involved in energy and lipid metabolism were observed in whole alevins (short-term effect), some of these genes showed a long-term molecular adaptation in the muscle of juveniles (long-term effect). Indeed, muscle of juveniles subjected at an early feeding of the OVN diet displayed up-regulated expression of markers of lipid catabolism (3-hydroxyacyl-CoA dehydrogenase &ndash; HOAD - enzyme) and mitochondrial energy metabolism (Citrate synthase - <em>cs</em>, Ubiquitinol cytochrome <em>c</em> reductase core protein 2 - QCR2, cytochrome oxidase 4 - COX4, ATP synthase form 5 - ATP5A) compared to fish fed the NOSUP diet. Moreover, some key enzymes involved in glucose catabolism (Muscle Pyruvate kinase - PKM) and amino acid catabolism (Glutamate dehydrogenase - GDH3) were also up regulated in muscle of juvenile fish fed with the OVN diet at first-feeding compared to fish fed the NOSUP diet. We researched if these permanently modified gene expressions could be related to global modifications of epigenetic marks (global DNA methylation and global histone acetylation and methylation). There was no variation of the epigenetic marks in muscle. However, we found changes in hepatic DNA methylation, global H3 acetylation and H3K4 methylation, dependent on the vitamin intake at early life. In summary, our data show, for the first time in fish, that a short-term vitamin-stimulus during early life may durably influence muscle energy and lipid metabolism as well as some hepatic epigenetic marks in rainbow trout.</p>',
			'date' => '2017-02-01',
			'pmid' => 'http://www.sciencedirect.com/science/article/pii/S0044848616309693',
			'doi' => '',
			'modified' => '2017-01-03 15:01:50',
			'created' => '2017-01-03 15:01:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 170 => array(
			'id' => '3131',
			'name' => 'DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma',
			'authors' => 'Sheffield N.C. et al.',
			'description' => '<p>Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genetically homogeneous cancers. We performed genome-scale DNA methylation sequencing for a large cohort of Ewing sarcoma tumors and analyzed epigenetic heterogeneity on three levels: between cancers, between tumors, and within tumors. We observed consistent DNA hypomethylation at enhancers regulated by the disease-defining EWS-FLI1 fusion protein, thus establishing epigenomic enhancer reprogramming as a ubiquitous and characteristic feature of Ewing sarcoma. DNA methylation differences between tumors identified a continuous disease spectrum underlying Ewing sarcoma, which reflected the strength of an EWS-FLI1 regulatory signature and a continuum between mesenchymal and stem cell signatures. There was substantial epigenetic heterogeneity within tumors, particularly in patients with metastatic disease. In summary, our study provides a comprehensive assessment of epigenetic heterogeneity in Ewing sarcoma and thereby highlights the importance of considering nongenetic aspects of tumor heterogeneity in the context of cancer biology and personalized medicine.</p>',
			'date' => '2017-01-30',
			'pmid' => 'http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4273.html',
			'doi' => '',
			'modified' => '2017-03-07 15:33:50',
			'created' => '2017-03-07 15:33:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 171 => array(
			'id' => '3144',
			'name' => 'MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct enhancer repertoire and target the RUNX1 program in 11q23 acute myeloid leukemia.',
			'authors' => 'Prange KH et al.',
			'description' => '<p>In 11q23 leukemias, the N-terminal part of the mixed lineage leukemia (MLL) gene is fused to &gt;60 different partner genes. In order to define a core set of MLL rearranged targets, we investigated the genome-wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and associated epigenetic signatures in acute myeloid leukemia (AML) cell lines THP-1 and MV4-11. We uncovered both common as well as specific MLL-AF9 and MLL-AF4 target genes, which were all marked by H3K79me2, H3K27ac and H3K4me3. Apart from promoter binding, we also identified MLL-AF9 and MLL-AF4 binding at specific subsets of non-overlapping active distal regulatory elements. Despite this differential enhancer binding, MLL-AF9 and MLL-AF4 still direct a common gene program, which represents part of the RUNX1 gene program and constitutes of CD34<sup>+</sup> and monocyte-specific genes. Comparing these data sets identified several zinc finger transcription factors (TFs) as potential MLL-AF9 co-regulators. Together, these results suggest that MLL fusions collaborate with specific subsets of TFs to deregulate the RUNX1 gene program in 11q23 AMLs.</p>',
			'date' => '2017-01-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28114278',
			'doi' => '',
			'modified' => '2017-03-23 15:13:45',
			'created' => '2017-03-23 15:13:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 172 => array(
			'id' => '3090',
			'name' => 'Arabidopsis SWI/SNF chromatin remodeling complex binds both promoters and terminators to regulate gene expression',
			'authors' => 'Archacki R. et al.',
			'description' => '<p>ATP-dependent chromatin remodeling complexes are important regulators of gene expression in Eukaryotes. In plants, SWI/SNF-type complexes have been shown critical for transcriptional control of key developmental processes, growth and stress responses. To gain insight into mechanisms underlying these roles, we performed whole genome mapping of the SWI/SNF catalytic subunit BRM in Arabidopsis thaliana, combined with transcript profiling experiments. Our data show that BRM occupies thousands of sites in Arabidopsis genome, most of which located within or close to genes. Among identified direct BRM transcriptional targets almost equal numbers were up- and downregulated upon BRM depletion, suggesting that BRM can act as both activator and repressor of gene expression. Interestingly, in addition to genes showing canonical pattern of BRM enrichment near transcription start site, many other genes showed a transcription termination site-centred BRM occupancy profile. We found that BRM-bound 3' gene regions have promoter-like features, including presence of TATA boxes and high H3K4me3 levels, and possess high antisense transcriptional activity which is subjected to both activation and repression by SWI/SNF complex. Our data suggest that binding to gene terminators and controlling transcription of non-coding RNAs is another way through which SWI/SNF complex regulates expression of its targets.</p>',
			'date' => '2016-12-19',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27994035',
			'doi' => '',
			'modified' => '2017-01-03 10:02:56',
			'created' => '2017-01-03 10:02:56',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 173 => array(
			'id' => '3096',
			'name' => 'Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals',
			'authors' => 'Schwörer S. et al.',
			'description' => '<p>The functionality of stem cells declines during ageing, and this decline contributes to ageing-associated impairments in tissue regeneration and function. Alterations in developmental pathways have been associated with declines in stem-cell function during ageing, but the nature of this process remains poorly understood. Hox genes are key regulators of stem cells and tissue patterning during embryogenesis with an unknown role in ageing. Here we show that the epigenetic stress response in muscle stem cells (also known as satellite cells) differs between aged and young mice. The alteration includes aberrant global and site-specific induction of active chromatin marks in activated satellite cells from aged mice, resulting in the specific induction of Hoxa9 but not other Hox genes. Hoxa9 in turn activates several developmental pathways and represents a decisive factor that separates satellite cell gene expression in aged mice from that in young mice. The activated pathways include most of the currently known inhibitors of satellite cell function in ageing muscle, including Wnt, TGF&beta;, JAK/STAT and senescence signalling. Inhibition of aberrant chromatin activation or deletion of Hoxa9 improves satellite cell function and muscle regeneration in aged mice, whereas overexpression of Hoxa9 mimics ageing-associated defects in satellite cells from young mice, which can be rescued by the inhibition of Hoxa9-targeted developmental pathways. Together, these data delineate an altered epigenetic stress response in activated satellite cells from aged mice, which limits satellite cell function and muscle regeneration by Hoxa9-dependent activation of developmental pathways.</p>',
			'date' => '2016-12-15',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27919074',
			'doi' => '',
			'modified' => '2017-01-03 12:28:33',
			'created' => '2017-01-03 12:28:33',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 174 => array(
			'id' => '3111',
			'name' => 'Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity',
			'authors' => 'Arts R.J. et al.',
			'description' => '<p>Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by &beta;-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases. Furthermore, fumarate itself induced an epigenetic program similar to &beta;-glucan-induced trained immunity. In line with this, inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by &beta;-glucan. Identification of the metabolic pathways leading to induction of trained immunity contributes to our understanding of innate immune memory and opens new therapeutic avenues.</p>',
			'date' => '2016-12-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27866838',
			'doi' => '',
			'modified' => '2017-01-04 11:17:08',
			'created' => '2017-01-04 11:17:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 175 => array(
			'id' => '3110',
			'name' => 'Immunometabolic Pathways in BCG-Induced Trained Immunity',
			'authors' => 'Arts R.J. et al.',
			'description' => '<p>The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity. Here, we show that BCG induction of trained immunity in monocytes is accompanied by a strong increase in glycolysis and, to a lesser extent, glutamine metabolism, both in an in-vitro model and after vaccination of mice and humans. Pharmacological and genetic modulation of rate-limiting glycolysis enzymes inhibits trained immunity, changes that are reflected by the effects on the histone marks (H3K4me3 and H3K9me3) underlying BCG-induced trained immunity. These data demonstrate that a shift of the glucose metabolism toward glycolysis is crucial for the induction of the histone modifications and functional changes underlying BCG-induced trained immunity. The identification of these pathways may be a first step toward vaccines that combine immunological and metabolic stimulation.</p>',
			'date' => '2016-12-06',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27926861',
			'doi' => '',
			'modified' => '2017-01-04 11:15:23',
			'created' => '2017-01-04 11:15:23',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 176 => array(
			'id' => '3098',
			'name' => 'TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells',
			'authors' => 'de la Rica L. et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Ten-eleven translocation (TET) enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable elements (TEs), which make up nearly half of the mouse and human genomes. Epigenetic mechanisms controlling TEs have the potential to affect their mobility and to drive the co-adoption of TEs for the benefit of the host.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">We performed a detailed investigation of the role of TET enzymes in the regulation of TEs in mouse embryonic stem cells (ESCs). We find that TET1 and TET2 bind multiple TE classes that harbour a variety of epigenetic signatures indicative of different functional roles. TETs co-bind with pluripotency factors to enhancer-like TEs that interact with highly expressed genes in ESCs whose expression is partly maintained by TET2-mediated DNA demethylation. TETs and 5-hydroxymethylcytosine (5hmC) are also strongly enriched at the 5' UTR of full-length, evolutionarily young LINE-1 elements, a pattern that is conserved in human ESCs. TETs drive LINE-1 demethylation, but surprisingly, LINE-1s are kept repressed through additional TET-dependent activities. We find that the SIN3A co-repressive complex binds to LINE-1s, ensuring their repression in a TET1-dependent manner.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">Our data implicate TET enzymes in the evolutionary dynamics of TEs, both in the context of exaptation processes and of retrotransposition control. The dual role of TET action on LINE-1s may reflect the evolutionary battle between TEs and the host.</abstracttext></p>
</div>',
			'date' => '2016-11-18',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27863519',
			'doi' => '',
			'modified' => '2017-01-03 14:23:08',
			'created' => '2017-01-03 14:23:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 177 => array(
			'id' => '3103',
			'name' => 'β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance',
			'authors' => 'Novakovic B. et al.',
			'description' => '<p>Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as lipopolysaccharide (LPS). We apply an integrated epigenomic&nbsp;approach to characterize the molecular events involved in LPS-induced tolerance in a time-dependent manner. Mechanistically, LPS-treated monocytes fail to accumulate active histone marks at promoter and enhancers of genes in the lipid metabolism and phagocytic pathways. Transcriptional inactivity in response to a second LPS exposure in tolerized macrophages is accompanied by failure to deposit active histone marks at promoters of tolerized genes. In contrast, &beta;-glucan partially reverses the LPS-induced tolerance in&nbsp;vitro. Importantly, ex&nbsp;vivo &beta;-glucan treatment of monocytes from volunteers with experimental endotoxemia re-instates their capacity for cytokine production. Tolerance is reversed at the level of distal element histone modification and transcriptional reactivation of otherwise unresponsive genes.</p>',
			'date' => '2016-11-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27863248',
			'doi' => '',
			'modified' => '2017-01-03 15:31:46',
			'created' => '2017-01-03 15:31:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 178 => array(
			'id' => '3105',
			'name' => 'EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells',
			'authors' => 'Beringer M. et al.',
			'description' => '<p>The cellular plasticity of pluripotent stem cells is thought to be sustained by genomic regions that display both active and repressive chromatin properties. These regions exhibit low levels of gene expression, yet the mechanisms controlling these levels remain unknown. Here, we describe Elongin BC as a binding factor at the promoters of bivalent sites. Biochemical and genome-wide analyses show that Elongin BC is associated with Polycomb Repressive Complex 2 (PRC2) in pluripotent stem cells. Elongin BC is recruited to chromatin by the PRC2-associated&nbsp;factor EPOP (Elongin BC and Polycomb Repressive Complex 2 Associated Protein, also termed C17orf96, esPRC2p48, E130012A19Rik), a protein expressed in the inner cell mass of the mouse blastocyst. Both EPOP and Elongin BC are required to maintain low levels of expression at PRC2 genomic targets. Our results indicate that keeping the balance between activating and repressive cues is a more general feature of chromatin in pluripotent stem cells than previously appreciated.</p>',
			'date' => '2016-11-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27863225',
			'doi' => '',
			'modified' => '2017-01-03 16:02:21',
			'created' => '2017-01-03 16:02:21',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 179 => array(
			'id' => '3087',
			'name' => 'The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs',
			'authors' => 'Mandoli A. et al.',
			'description' => '<p>The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels of histone acetylation but also at distal elements characterized by low acetylation levels and binding of the hematopoietic transcription factors LYL1 and LMO2. In contrast, ERG, FLI1, TAL1, and RUNX1 bind at all AML1-ETO-occupied regulatory regions, including those of the AML1-ETO gene itself, suggesting their involvement in regulating AML1-ETO expression levels. While expression of AML1-ETO in myeloid differentiated induced pluripotent stem cells (iPSCs) induces leukemic characteristics, overexpression increases cell death. We find that expression of wild-type transcription factors RUNX1 and ERG in AML is required to prevent this oncogene overexpression. Together our results show that the interplay of the epigenome and transcription factors prevents apoptosis in t(8;21) AML cells.</p>',
			'date' => '2016-11-15',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27851970',
			'doi' => '',
			'modified' => '2017-01-02 11:07:24',
			'created' => '2017-01-02 11:07:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 180 => array(
			'id' => '3114',
			'name' => 'Iterative Fragmentation Improves the Detection of ChIP-seq Peaks for Inactive Histone Marks',
			'authors' => 'Laczik M. et al.',
			'description' => '<p>As chromatin immunoprecipitation (ChIP) sequencing is becoming the dominant technique for studying chromatin modifications, new protocols surface to improve the method. Bioinformatics is also essential to analyze and understand the results, and precise analysis helps us to identify the effects of protocol optimizations. We applied iterative sonication - sending the fragmented DNA after ChIP through additional round(s) of shearing - to a number of samples, testing the effects on different histone marks, aiming to uncover potential benefits of inactive histone marks specifically. We developed an analysis pipeline that utilizes our unique, enrichment-type specific approach to peak calling. With the help of this pipeline, we managed to accurately describe the advantages and disadvantages of the iterative refragmentation technique, and we successfully identified possible fields for its applications, where it enhances the results greatly. In addition to the resonication protocol description, we provide guidelines for peak calling optimization and a freely implementable pipeline for data analysis.</p>',
			'date' => '2016-10-25',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27812282',
			'doi' => '',
			'modified' => '2017-01-17 16:07:44',
			'created' => '2017-01-17 16:07:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 181 => array(
			'id' => '3033',
			'name' => 'Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition',
			'authors' => 'Sciacovelli M et al.',
			'description' => '<p>Mutations of the tricarboxylic acid cycle enzyme fumarate hydratase cause hereditary leiomyomatosis and renal cell cancer<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref1" title="Tomlinson, I. P. et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat. Genet. 30, 406&ndash;410 (2002)" id="ref-link-5">1</a></sup>. Fumarate hydratase-deficient renal cancers are highly aggressive and metastasize even when small, leading to a very poor clinical outcome<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref2" title="Schmidt, L. S. &amp; Linehan, W. M. Hereditary leiomyomatosis and renal cell carcinoma. Int. J. Nephrol. Renovasc. Dis. 7, 253&ndash;260 (2014)" id="ref-link-6">2</a></sup>. Fumarate, a small molecule metabolite that accumulates in fumarate hydratase-deficient cells, plays a key role in cell transformation, making it a <i>bona fide</i> oncometabolite<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref3" title="Yang, M., Soga, T., Pollard, P. J. &amp; Adam, J. The emerging role of fumarate as an oncometabolite. Front Oncol. 2, 85 (2012)" id="ref-link-7">3</a></sup>. Fumarate has been shown to inhibit &alpha;-ketoglutarate-dependent dioxygenases that are involved in DNA and histone demethylation<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref4" title="Laukka, T. et al. Fumarate and succinate regulate expression of hypoxia-inducible genes via TET enzymes. J. Biol. Chem. 291, 4256&ndash;4265 (2016)" id="ref-link-8">4</a>, <a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref5" title="Xiao, M. et al. Inhibition of &alpha;-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev. 26, 1326&ndash;1338 (2012)" id="ref-link-9">5</a></sup>. However, the link between fumarate accumulation, epigenetic changes, and tumorigenesis is unclear. Here we show that loss of fumarate hydratase and the subsequent accumulation of fumarate in mouse and human cells elicits an epithelial-to-mesenchymal-transition (EMT), a phenotypic switch associated with cancer initiation, invasion, and metastasis<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref6" title="De Craene, B. &amp; Berx, G. Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer 13, 97&ndash;110 (2013)" id="ref-link-10">6</a></sup>. We demonstrate that fumarate inhibits Tet-mediated demethylation of a regulatory region of the antimetastatic miRNA cluster<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref6" title="De Craene, B. &amp; Berx, G. Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer 13, 97&ndash;110 (2013)" id="ref-link-11">6</a></sup> <i>mir-200ba429</i>, leading to the expression of EMT-related transcription factors and enhanced migratory properties. These epigenetic and phenotypic changes are recapitulated by the incubation of fumarate hydratase-proficient cells with cell-permeable fumarate. Loss of fumarate hydratase is associated with suppression of miR-200 and the EMT signature in renal cancer and is associated with poor clinical outcome. These results imply that loss of fumarate hydratase and fumarate accumulation contribute to the aggressive features of fumarate hydratase-deficient tumours.</p>',
			'date' => '2016-08-31',
			'pmid' => 'http://www.nature.com/nature/journal/v537/n7621/full/nature19353.html',
			'doi' => '',
			'modified' => '2016-09-23 10:44:15',
			'created' => '2016-09-23 10:44:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 182 => array(
			'id' => '3006',
			'name' => 'reChIP-seq reveals widespread bivalency of H3K4me3 and H3K27me3 in CD4(+) memory T cells',
			'authors' => 'Kinkley S et al.',
			'description' => '<p>The combinatorial action of co-localizing chromatin modifications and regulators determines chromatin structure and function. However, identifying co-localizing chromatin features in a high-throughput manner remains a technical challenge. Here we describe a novel reChIP-seq approach and tailored bioinformatic analysis tool, normR that allows for the sequential enrichment and detection of co-localizing DNA-associated proteins in an unbiased and genome-wide manner. We illustrate the utility of the reChIP-seq method and normR by identifying H3K4me3 or H3K27me3 bivalently modified nucleosomes in primary human CD4(+) memory T cells. We unravel widespread bivalency at hypomethylated CpG-islands coinciding with inactive promoters of developmental regulators. reChIP-seq additionally uncovered heterogeneous bivalency in the population, which was undetectable by intersecting H3K4me3 and H3K27me3 ChIP-seq tracks. Finally, we provide evidence that bivalency is established and stabilized by an interplay between the genome and epigenome. Our reChIP-seq approach augments conventional ChIP-seq and is broadly applicable to unravel combinatorial modes of action.</p>',
			'date' => '2016-08-17',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27530917',
			'doi' => '',
			'modified' => '2016-08-26 11:56:46',
			'created' => '2016-08-26 11:38:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 183 => array(
			'id' => '3002',
			'name' => 'Phenotypic Plasticity through Transcriptional Regulation of the Evolutionary Hotspot Gene tan in Drosophila melanogaster',
			'authors' => 'Gibert JM et al.',
			'description' => '<p>Phenotypic plasticity is the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions. Phenotypic plasticity can be adaptive. Furthermore, it is thought to facilitate evolution. Although phenotypic plasticity is a widespread phenomenon, its molecular mechanisms are only beginning to be unravelled. Environmental conditions can affect gene expression through modification of chromatin structure, mainly via histone modifications, nucleosome remodelling or DNA methylation, suggesting that phenotypic plasticity might partly be due to chromatin plasticity. As a model of phenotypic plasticity, we study abdominal pigmentation of Drosophila melanogaster females, which is temperature sensitive. Abdominal pigmentation is indeed darker in females grown at 18&deg;C than at 29&deg;C. This phenomenon is thought to be adaptive as the dark pigmentation produced at lower temperature increases body temperature. We show here that temperature modulates the expression of tan (t), a pigmentation gene involved in melanin production. t is expressed 7 times more at 18&deg;C than at 29&deg;C in female abdominal epidermis. Genetic experiments show that modulation of t expression by temperature is essential for female abdominal pigmentation plasticity. Temperature modulates the activity of an enhancer of t without modifying compaction of its chromatin or level of the active histone mark H3K27ac. By contrast, the active mark H3K4me3 on the t promoter is strongly modulated by temperature. The H3K4 methyl-transferase involved in this process is likely Trithorax, as we show that it regulates t expression and the H3K4me3 level on the t promoter and also participates in female pigmentation and its plasticity. Interestingly, t was previously shown to be involved in inter-individual variation of female abdominal pigmentation in Drosophila melanogaster, and in abdominal pigmentation divergence between Drosophila species. Sensitivity of t expression to environmental conditions might therefore give more substrate for selection, explaining why this gene has frequently been involved in evolution of pigmentation.</p>',
			'date' => '2016-08-10',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27508387',
			'doi' => '',
			'modified' => '2016-08-25 17:23:22',
			'created' => '2016-08-25 17:23:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 184 => array(
			'id' => '3023',
			'name' => 'MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis',
			'authors' => 'Wang W et al.',
			'description' => '<p>DNA double strand break (DSB) repair is critical for generation of B-cell receptors, which are pre-requisite for B-cell progenitor survival. However, the transcription factors that promote DSB repair in B cells are not known. Here we show that MEF2C enhances the expression of DNA repair and recombination factors in B-cell progenitors, promoting DSB repair, V(D)J recombination and cell survival. Although Mef2c-deficient mice maintain relatively intact peripheral B-lymphoid cellularity during homeostasis, they exhibit poor B-lymphoid recovery after sub-lethal irradiation and 5-fluorouracil injection. MEF2C binds active regulatory regions with high-chromatin accessibility in DNA repair and V(D)J genes in both mouse B-cell progenitors and human B lymphoblasts. Loss of Mef2c in pre-B cells reduces chromatin accessibility in multiple regulatory regions of the MEF2C-activated genes. MEF2C therefore protects B lymphopoiesis during stress by ensuring proper expression of genes that encode DNA repair and B-cell factors.</p>',
			'date' => '2016-08-10',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27507714',
			'doi' => '',
			'modified' => '2016-08-31 10:42:58',
			'created' => '2016-08-31 10:42:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 185 => array(
			'id' => '3004',
			'name' => 'Toxoplasma gondii TgIST co-opts host chromatin repressors dampening STAT1-dependent gene regulation and IFN-γ-mediated host defenses',
			'authors' => 'Gay G et al.',
			'description' => '<p>An early hallmark of Toxoplasma gondii infection is the rapid control of the parasite population by a potent multifaceted innate immune response that engages resident and homing immune cells along with pro- and counter-inflammatory cytokines. In this context, IFN-&gamma; activates a variety of T. gondii-targeting activities in immune and nonimmune cells but can also contribute to host immune pathology. T. gondii has evolved mechanisms to timely counteract the host IFN-&gamma; defenses by interfering with the transcription of IFN-&gamma;-stimulated genes. We now have identified TgIST (T. gondii inhibitor of STAT1 transcriptional activity) as a critical molecular switch that is secreted by intracellular parasites and traffics to the host cell nucleus where it inhibits STAT1-dependent proinflammatory gene expression. We show that TgIST not only sequesters STAT1 on dedicated loci but also promotes shaping of a nonpermissive chromatin through its capacity to recruit the nucleosome remodeling deacetylase (NuRD) transcriptional repressor. We found that during mice acute infection, TgIST-deficient parasites are rapidly eliminated by the homing Gr1<sup>+</sup> inflammatory monocytes, thus highlighting the protective role of TgIST against IFN-&gamma;-mediated killing. By uncovering TgIST functions, this study brings novel evidence on how T. gondii has devised a molecular weapon of choice to take control over a ubiquitous immune gene expression mechanism in metazoans, as a way to promote long-term parasitism.</p>',
			'date' => '2016-08-08',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27503074',
			'doi' => '',
			'modified' => '2016-08-26 11:02:25',
			'created' => '2016-08-26 11:02:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 186 => array(
			'id' => '3003',
			'name' => 'Epigenetic dynamics of monocyte-to-macrophage differentiation',
			'authors' => 'Wallner S et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Monocyte-to-macrophage differentiation involves major biochemical and structural changes. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete transcriptome and epigenome of human monocytes that were differentiated in vitro by addition of colony-stimulating factor 1 in serum-free medium.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Numerous mRNAs and miRNAs were significantly up- or down-regulated. More than 100 discrete DNA regions, most often far away from transcription start sites, were rapidly demethylated by the ten eleven translocation enzymes, became nucleosome-free and gained histone marks indicative of active enhancers. These regions were unique for macrophages and associated with genes involved in the regulation of the actin cytoskeleton, phagocytosis and innate immune response.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">In summary, we have discovered a phagocytic gene network that is repressed by DNA methylation in monocytes and rapidly de-repressed after the onset of macrophage differentiation.</abstracttext></p>
</div>',
			'date' => '2016-07-29',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27478504',
			'doi' => '10.1186/s13072-016-0079-z',
			'modified' => '2016-08-26 11:59:54',
			'created' => '2016-08-26 10:20:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 187 => array(
			'id' => '3021',
			'name' => 'Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis',
			'authors' => 'Rinaldi L et al.',
			'description' => '<p>The genome-wide localization and function of endogenous Dnmt3a and Dnmt3b in adult stem cells are unknown. Here, we show that in human epidermal stem cells, the two proteins bind in a histone H3K36me3-dependent manner to the most active enhancers and are required to produce their associated enhancer RNAs. Both proteins prefer super-enhancers associated to genes that either define the ectodermal lineage or establish the stem cell and differentiated states. However, Dnmt3a and Dnmt3b differ in their mechanisms of enhancer regulation: Dnmt3a associates with p63 to maintain high levels of DNA hydroxymethylation at the center of enhancers in a Tet2-dependent manner, whereas Dnmt3b promotes DNA methylation along the body of the enhancer. Depletion of either protein inactivates their target enhancers and profoundly affects epidermal stem cell function. Altogether, we reveal novel functions for Dnmt3a and Dnmt3b at enhancers that could contribute to their roles in disease and tumorigenesis.</p>',
			'date' => '2016-07-26',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27476967',
			'doi' => '',
			'modified' => '2016-08-31 10:22:54',
			'created' => '2016-08-31 10:22:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 188 => array(
			'id' => '2915',
			'name' => 'PAFAH1B1 and the lncRNA NONHSAT073641 maintain an angiogenic phenotype in human endothelial cells',
			'authors' => 'Josipovic I at al.',
			'description' => '<h4>AIM:</h4>
<p><abstracttext label="AIM" nlmcategory="OBJECTIVE">Platelet-activating factor acetyl hydrolase 1B1 (PAFAH1B1, also known as Lis1) is a protein essentially involved in neurogenesis and mostly studied in the nervous system. As we observed a significant expression of PAFAH1B1 in the vascular system, we hypothesized that PAFAH1B1 is important during angiogenesis of endothelial cells as well as in human vascular diseases.</abstracttext></p>
<h4>METHOD:</h4>
<p><abstracttext label="METHOD" nlmcategory="METHODS">The functional relevance of the protein in endothelial cell angiogenic function, its downstream targets and the influence of NONHSAT073641, a long non-coding RNA (lncRNA) with 92% similarity to PAFAH1B1, were studied by knockdown and overexpression in human umbilical vein endothelial cells (HUVEC).</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Knockdown of PAFAH1B1 led to impaired tube formation of HUVEC and decreased sprouting in the spheroid assay. Accordingly, the overexpression of PAFAH1B1 increased tube number, sprout length and sprout number. LncRNA NONHSAT073641 behaved similarly. Microarray analysis after PAFAH1B1 knockdown and its overexpression indicated that the protein maintains Matrix Gla Protein (MGP) expression. Chromatin immunoprecipitation experiments revealed that PAFAH1B1 is required for active histone marks and proper binding of RNA Polymerase II to the transcriptional start site of MGP. MGP itself was required for endothelial angiogenic capacity and knockdown of both, PAFAH1B1 and MGP, reduced migration. In vascular samples of patients with chronic thromboembolic pulmonary hypertension (CTEPH), PAFAH1B1 and MGP were upregulated. The function of PAFAH1B1 required the presence of the intact protein as overexpression of NONHSAT073641, which was highly upregulated during CTEPH, did not affect PAFAH1B1 target genes.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">PAFAH1B1 and NONHSAT073641 are important for endothelial angiogenic function. This article is protected by copyright. All rights reserved.</abstracttext></p>',
			'date' => '2016-04-28',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27124368',
			'doi' => ' 10.1111/apha.12700',
			'modified' => '2016-05-12 10:42:06',
			'created' => '2016-05-12 10:42:06',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 189 => array(
			'id' => '2914',
			'name' => 'Chromatin immunoprecipitation from fixed clinical tissues reveals tumor-specific enhancer profiles.',
			'authors' => 'Cejas P et al.',
			'description' => '<p>Extensive cross-linking introduced during routine tissue fixation of clinical pathology specimens severely hampers chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) analysis from archived tissue samples. This limits the ability to study the epigenomes of valuable, clinically annotated tissue resources. Here we describe fixed-tissue chromatin immunoprecipitation sequencing (FiT-seq), a method that enables reliable extraction of soluble chromatin from formalin-fixed paraffin-embedded (FFPE) tissue samples for accurate detection of histone marks. We demonstrate that FiT-seq data from FFPE specimens are concordant with ChIP-seq data from fresh-frozen samples of the same tumors. By using multiple histone marks, we generate chromatin-state maps and identify cis-regulatory elements in clinical samples from various tumor types that can readily allow us to distinguish between cancers by the tissue of origin. Tumor-specific enhancers and superenhancers that are elucidated by FiT-seq analysis correlate with known oncogenic drivers in different tissues and can assist in the understanding of how chromatin states affect gene regulation.</p>',
			'date' => '2016-04-25',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27111282',
			'doi' => '10.1038/nm.4085',
			'modified' => '2016-05-11 17:34:25',
			'created' => '2016-05-11 17:34:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 190 => array(
			'id' => '2894',
			'name' => 'Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time',
			'authors' => 'Feichtinger J, Hernández I, Fischer C, Hanscho M, Auer N, Hackl M, Jadhav V, Baumann M, Krempl PM, Schmidl C, Farlik M, Schuster M, Merkel A, Sommer A, Heath S, Rico D, Bock C, Thallinger GG, Borth N',
			'description' => '<p>The most striking characteristic of CHO cells is their adaptability, which enables efficient production of proteins as well as growth under a variety of culture conditions, but also results in genomic and phenotypic instability. To investigate the relative contribution of genomic and epigenetic modifications towards phenotype evolution, comprehensive genome and epigenome data are presented for 6 related CHO cell lines, both in response to perturbations (different culture conditions and media as well as selection of a specific phenotype with increased transient productivity) and in steady state (prolonged time in culture under constant conditions). Clear transitions were observed in DNA-methylation patterns upon each perturbation, while few changes occurred over time under constant conditions. Only minor DNA-methylation changes were observed between exponential and stationary growth phase, however, throughout a batch culture the histone modification pattern underwent continuous adaptation. Variation in genome sequence between the 6 cell lines on the level of SNPs, InDels and structural variants is high, both upon perturbation and under constant conditions over time. The here presented comprehensive resource may open the door to improved control and manipulation of gene expression during industrial bioprocesses based on epigenetic mechanisms</p>',
			'date' => '2016-04-12',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27072894',
			'doi' => '10.1002/bit.25990',
			'modified' => '2016-04-22 12:53:44',
			'created' => '2016-04-22 12:37:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 191 => array(
			'id' => '2880',
			'name' => 'GATA-1 Inhibits PU.1 Gene via DNA and Histone H3K9 Methylation of Its Distal Enhancer in Erythroleukemia',
			'authors' => 'Burda P, Vargova J, Curik N, Salek C, Papadopoulos GL, Strouboulis J, Stopka T',
			'description' => '<p>GATA-1 and PU.1 are two important hematopoietic transcription factors that mutually inhibit each other in progenitor cells to guide entrance into the erythroid or myeloid lineage, respectively. PU.1 controls its own expression during myelopoiesis by binding to the distal URE enhancer, whose deletion leads to acute myeloid leukemia (AML). We herein present evidence that GATA-1 binds to the PU.1 gene and inhibits its expression in human AML-erythroleukemias (EL). Furthermore, GATA-1 together with DNA methyl Transferase I (DNMT1) mediate repression of the PU.1 gene through the URE. Repression of the PU.1 gene involves both DNA methylation at the URE and its histone H3 lysine-K9 methylation and deacetylation as well as the H3K27 methylation at additional DNA elements and the promoter. The GATA-1-mediated inhibition of PU.1 gene transcription in human AML-EL mediated through the URE represents important mechanism that contributes to PU.1 downregulation and leukemogenesis that is sensitive to DNA demethylation therapy.</p>',
			'date' => '2016-03-24',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27010793',
			'doi' => '10.1371/journal.pone.0152234',
			'modified' => '2016-04-06 10:26:31',
			'created' => '2016-04-06 10:26:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 192 => array(
			'id' => '2886',
			'name' => 'Role of Annexin gene and its regulation during zebrafish caudal fin regeneration',
			'authors' => 'Saxena S, Purushothaman S, Meghah V, Bhatti B, Poruri A, Meena Lakshmi MG, Sarath Babu N, Murthy CL, Mandal KK, Kumar A, Idris MM',
			'description' => '<p>The molecular mechanism of epimorphic regeneration is elusive due to its complexity and limitation in mammals. Epigenetic regulatory mechanisms play a crucial role in development and regeneration. This investigation attempted to reveal the role of epigenetic regulatory mechanisms, such as histone H3 and H4 lysine acetylation and methylation during zebrafish caudal fin regeneration. It was intriguing to observe that H3K9,14 acetylation, H4K20 trimethylation, H3K4 trimethylation and H3K9 dimethylation along with their respective regulatory genes, such as <em>GCN5, SETd8b, SETD7/9</em> and <em>SUV39h1</em>, were differentially regulated in the regenerating fin at various time points of post-amputation. Annexin genes have been associated with regeneration; this study reveals the significant upregulation of <em>ANXA2a</em> and <em>ANXA2b</em> transcripts and their protein products during the regeneration process. Chromatin Immunoprecipitation (ChIP) and PCR analysis of the regulatory regions of the <em>ANXA2a</em> and <em>ANXA2b</em> genes demonstrated the ability to repress two histone methylations, H3K27me3 and H4K20me3, in transcriptional regulation during regeneration. It is hypothesized that this novel insight into the diverse epigenetic mechanisms that play a critical role during the regeneration process may help to strategize the translational efforts, in addition to identifying the molecules involved in vertebrate regeneration.</p>',
			'date' => '2016-03-12',
			'pmid' => 'http://onlinelibrary.wiley.com/doi/10.1111/wrr.12429/abstract',
			'doi' => '10.1111/wrr.12429',
			'modified' => '2016-04-08 17:24:06',
			'created' => '2016-04-08 17:24:06',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 193 => array(
			'id' => '2856',
			'name' => 'Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis',
			'authors' => 'Weigel C. et al.',
			'description' => '<p>Radiotherapy is a fundamental part of cancer treatment but its use is limited by the onset of late adverse effects in the normal tissue, especially radiation-induced fibrosis. Since the molecular causes for fibrosis are largely unknown, we analyse if epigenetic regulation might explain inter-individual differences in fibrosis risk. DNA methylation profiling of dermal fibroblasts obtained from breast cancer patients prior to irradiation identifies differences associated with fibrosis. One region is characterized as a differentially methylated enhancer of diacylglycerol kinase alpha (<i>DGKA</i>). Decreased DNA methylation at this enhancer enables recruitment of the profibrotic transcription factor early growth response 1 (EGR1) and facilitates radiation-induced <i>DGKA</i> transcription in cells from patients later developing fibrosis. Conversely, inhibition of DGKA has pronounced effects on diacylglycerol-mediated lipid homeostasis and reduces profibrotic fibroblast activation. Collectively, DGKA is an epigenetically deregulated kinase involved in radiation response and may serve as a marker and therapeutic target for personalized radiotherapy.</p>',
			'date' => '2016-03-11',
			'pmid' => 'http://www.nature.com/ncomms/2016/160311/ncomms10893/full/ncomms10893.html',
			'doi' => '10.1038/ncomms10893',
			'modified' => '2016-03-15 11:08:21',
			'created' => '2016-03-15 11:08:21',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 194 => array(
			'id' => '2970',
			'name' => 'Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development.',
			'authors' => 'Yuan S et al.',
			'description' => '<p>Although it is believed that mammalian sperm carry small noncoding RNAs (sncRNAs) into oocytes during fertilization, it remains unknown whether these sperm-borne sncRNAs truly have any function during fertilization and preimplantation embryonic development. Germline-specific Dicer and Drosha conditional knockout (cKO) mice produce gametes (i.e. sperm and oocytes) partially deficient in miRNAs and/or endo-siRNAs, thus providing a unique opportunity for testing whether normal sperm (paternal) or oocyte (maternal) miRNA and endo-siRNA contents are required for fertilization and preimplantation development. Using the outcome of intracytoplasmic sperm injection (ICSI) as a readout, we found that sperm with altered miRNA and endo-siRNA profiles could fertilize wild-type (WT) eggs, but embryos derived from these partially sncRNA-deficient sperm displayed a significant reduction in developmental potential, which could be rescued by injecting WT sperm-derived total or small RNAs into ICSI embryos. Disrupted maternal transcript turnover and failure in early zygotic gene activation appeared to associate with the aberrant miRNA profiles in Dicer and Drosha cKO spermatozoa. Overall, our data support a crucial function of paternal miRNAs and/or endo-siRNAs in the control of the transcriptomic homeostasis in fertilized eggs, zygotes and two-cell embryos. Given that supplementation of sperm RNAs enhances both the developmental potential of preimplantation embryos and the live birth rate, it might represent a novel means to improve the success rate of assisted reproductive technologies in fertility clinics.</p>',
			'date' => '2016-02-15',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26718009',
			'doi' => '10.1242/dev.131755',
			'modified' => '2016-06-29 17:11:02',
			'created' => '2016-06-29 17:11:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 195 => array(
			'id' => '2849',
			'name' => 'MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199',
			'authors' => 'Benito JM et al.',
			'description' => '<p>Targeted therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of current research. <em>Mixed Lineage Leukemia</em> (<em>MLL</em>) mutations such as the t(4;11) translocation cause aggressive leukemias that are refractory to conventional treatment. The t(4;11) translocation produces an MLL/AF4 fusion protein that activates key target genes through both epigenetic and transcriptional elongation mechanisms. In this study, we show that t(4;11) patient cells express high levels of BCL-2 and are highly sensitive to treatment with the BCL-2-specific BH3 mimetic ABT-199. We demonstrate that MLL/AF4 specifically upregulates the <em>BCL-2</em> gene but not other BCL-2 family members via DOT1L-mediated H3K79me2/3. We use this information to show that a t(4;11) cell line is sensitive to a combination of ABT-199 and DOT1L inhibitors. In addition, ABT-199 synergizes with standard induction-type therapy in a xenotransplant model, advocating for the introduction of ABT-199 into therapeutic regimens for MLL-rearranged leukemias.</p>',
			'date' => '2015-12-29',
			'pmid' => 'http://www.cell.com/cell-reports/abstract/S2211-1247%2815%2901415-1',
			'doi' => ' http://dx.doi.org/10.1016/j.celrep.2015.12.003',
			'modified' => '2016-03-11 17:31:23',
			'created' => '2016-03-11 17:11:09',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 196 => array(
			'id' => '2810',
			'name' => 'Standardizing chromatin research: a simple and universal method for ChIP-seq',
			'authors' => 'Laura Arrigoni, Andreas S. Richter, Emily Betancourt, Kerstin Bruder, Sarah Diehl, Thomas Manke and Ulrike Bönisch',
			'description' => '<p><span>Here we&nbsp;demonstrate that harmonization of ChIP-seq workflows across cell types and conditions is possible when obtaining chromatin from properly isolated nuclei. We established an ultrasound-based nuclei extraction method (Nuclei Extraction by Sonication) that is highly effective across various organisms, cell types and cell numbers. The described method has the potential to replace complex cell-type-specific, but largely ineffective, nuclei isolation protocols. This article demonstrates protocol standardization using the Bioruptor shearing systems and the IP-Star Automation System for ChIP automation.</span></p>',
			'date' => '2015-12-23',
			'pmid' => 'http://pubmed.gov/26704968',
			'doi' => '10.1093/nar/gkv1495',
			'modified' => '2016-06-09 09:47:00',
			'created' => '2016-01-10 08:32:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 197 => array(
			'id' => '2952',
			'name' => 'Dynamic changes in histone modifications precede de novo DNA methylation in oocytes',
			'authors' => 'Stewart KR et al.',
			'description' => '<p>Erasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation establishment remain poorly understood, but a number of post-translational modifications of histones are implicated in antagonizing or recruiting the de novo DNA methylation complex. In mouse oogenesis, DNA methylation establishment occurs on a largely unmethylated genome and in nondividing cells, making it a highly informative model for examining how histone modifications can shape the DNA methylome. Using a chromatin immunoprecipitation (ChIP) and genome-wide sequencing (ChIP-seq) protocol optimized for low cell numbers and novel techniques for isolating primary and growing oocytes, profiles were generated for histone modifications implicated in promoting or inhibiting DNA methylation. CGIs destined for DNA methylation show reduced protective H3K4 dimethylation (H3K4me2) and trimethylation (H3K4me3) in both primary and growing oocytes, while permissive H3K36me3 increases specifically at these CGIs in growing oocytes. Methylome profiling of oocytes deficient in H3K4 demethylase KDM1A or KDM1B indicated that removal of H3K4 methylation is necessary for proper methylation establishment at CGIs. This work represents the first systematic study performing ChIP-seq in oocytes and shows that histone remodeling in the mammalian oocyte helps direct de novo DNA methylation events.</p>',
			'date' => '2015-12-01',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26584620',
			'doi' => '10.1101/gad.271353.115',
			'modified' => '2016-06-10 16:39:45',
			'created' => '2016-06-10 16:39:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 198 => array(
			'id' => '2963',
			'name' => 'Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma',
			'authors' => 'Aldiri I et al.',
			'description' => '<p>Retinal development requires precise temporal and spatial coordination of cell cycle exit, cell fate specification, cell migration and differentiation. When this process is disrupted, retinoblastoma, a developmental tumor of the retina, can form. Epigenetic modulators are central to precisely coordinating developmental events, and many epigenetic processes have been implicated in cancer. Studying epigenetic mechanisms in development is challenging because they often regulate multiple cellular processes; therefore, elucidating the primary molecular mechanisms involved can be difficult. Here we explore the role of Brg1 (Smarca4) in retinal development and retinoblastoma in mice using molecular and cellular approaches. Brg1 was found to regulate retinal size by controlling cell cycle length, cell cycle exit and cell survival during development. Brg1 was not required for cell fate specification but was required for photoreceptor differentiation and cell adhesion/polarity programs that contribute to proper retinal lamination during development. The combination of defective cell differentiation and lamination led to retinal degeneration in Brg1-deficient retinae. Despite the hypocellularity, premature cell cycle exit, increased cell death and extended cell cycle length, retinal progenitor cells persisted in Brg1-deficient retinae, making them more susceptible to retinoblastoma. ChIP-Seq analysis suggests that Brg1 might regulate gene expression through multiple mechanisms.</p>',
			'date' => '2015-12-01',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26628093',
			'doi' => '10.1242/dev.124800',
			'modified' => '2016-06-24 09:48:45',
			'created' => '2016-06-24 09:48:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 199 => array(
			'id' => '2964',
			'name' => 'Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization',
			'authors' => 'Kuznetsova T et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">The impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from remodeling of higher order chromatin architecture by activated transcription factors to recruitment of activated transcription factors to pre-established long-range interactions.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Using circular chromosome conformation capture coupled with next generation sequencing and high-resolution chromatin interaction analysis by paired-end tag sequencing of P300, we observed agonist-induced changes in long-range chromatin interactions, and uncovered interconnected enhancer-enhancer hubs spanning up to one megabase. The vast majority of activated glucocorticoid receptor and nuclear factor kappa-b appeared to join pre-existing P300 enhancer hubs without affecting the chromatin conformation. In contrast, binding of the activated transcription factors to loci with their consensus response elements led to the increased formation of an active epigenetic state of enhancers and a significant increase in long-range interactions within pre-existing enhancer networks. De novo enhancers or ligand-responsive enhancer hubs preferentially interacted with ligand-induced genes.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">We demonstrate that, at a subset of genomic loci, ligand-mediated induction leads to active enhancer formation and an increase in long-range interactions, facilitating efficient regulation of target genes. Therefore, our data suggest an active role of signal-dependent transcription factors in chromatin and long-range interaction remodeling.</abstracttext></p>
</div>',
			'date' => '2015-12-01',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26619937',
			'doi' => '10.1186/s13059-015-0832-9',
			'modified' => '2016-06-24 10:02:16',
			'created' => '2016-06-24 10:02:16',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 200 => array(
			'id' => '2909',
			'name' => 'Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells',
			'authors' => 'Rønningen T, Shah A, Reiner AH, Collas P, Moskaug JØ',
			'description' => '<p>Cellular metabolism confers wide-spread epigenetic modifications required for regulation of transcriptional networks that determine cellular states. Mesenchymal stromal cells are responsive to metabolic cues including circulating glucose levels and modulate inflammatory responses. We show here that long term exposure of undifferentiated human adipose tissue stromal cells (ASCs) to high glucose upregulates a subset of inflammation response (IR) genes and alters their promoter histone methylation patterns in a manner consistent with transcriptional de-repression. Modeling of chromatin states from combinations of histone modifications in nearly 500 IR genes unveil three overarching chromatin configurations reflecting repressive, active, and potentially active states in promoter and enhancer elements. Accordingly, we show that adipogenic differentiation in high glucose predominantly upregulates IR genes. Our results indicate that elevated extracellular glucose levels sensitize in ASCs an IR gene expression program which is exacerbated during adipocyte differentiation. We propose that high glucose exposure conveys an epigenetic 'priming' of IR genes, favoring a transcriptional inflammatory response upon adipogenic stimulation. Chromatin alterations at IR genes by high glucose exposure may play a role in the etiology of metabolic diseases.</p>',
			'date' => '2015-11-27',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26462465',
			'doi' => '10.1016/j.bbrc.2015.10.030',
			'modified' => '2016-05-09 22:54:48',
			'created' => '2016-05-09 22:54:48',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 201 => array(
			'id' => '2957',
			'name' => 'The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth',
			'authors' => 'Palazzo E et al.',
			'description' => '<p>Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epidermal hyperplasia and squamous tumorigenesis. By integrating genetic and transcriptomic approaches, we demonstrate that DLX3 operates through a p53-regulated network. DLX3 and p53 physically interact on the p21 promoter to enhance p21 expression. Elevating DLX3 in keratinocytes produces a G1-S blockade associated with p53 signature transcriptional profiles. In contrast, DLX3 loss promotes a mitogenic phenotype associated with constitutive activation of ERK. DLX3 expression is lost in human skin cancers and is extinguished during progression of experimentally induced mouse squamous cell carcinoma (SCC). Reinstatement of DLX3 function is sufficient to attenuate the migration of SCC cells, leading to decreased wound closure. Our data establish the DLX3-p53 interplay as a major regulatory axis in epidermal differentiation and suggest that DLX3 is a modulator of skin carcinogenesis.</p>',
			'date' => '2015-11-02',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26522723',
			'doi' => '10.1038/onc.2015.380',
			'modified' => '2016-06-15 16:18:44',
			'created' => '2016-06-15 16:18:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 202 => array(
			'id' => '2962',
			'name' => 'VEGF-mediated cell survival in non-small-cell lung cancer: implications for epigenetic targeting of VEGF receptors as a therapeutic approach',
			'authors' => 'Barr MP et al.',
			'description' => '<div class="">
<h4>AIMS:</h4>
<p><abstracttext label="AIMS" nlmcategory="OBJECTIVE">To evaluate the potential therapeutic utility of histone deacetylase inhibitors (HDACi) in targeting VEGF receptors in non-small-cell lung cancer.</abstracttext></p>
<h4>MATERIALS &amp; METHODS:</h4>
<p><abstracttext label="MATERIALS &amp; METHODS" nlmcategory="METHODS">Non-small-cell lung cancer cells were screened for the VEGF receptors at the mRNA and protein levels, while cellular responses to various HDACi were examined.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Significant effects on the regulation of the VEGF receptors were observed in response to HDACi. These were associated with decreased secretion of VEGF, decreased cellular proliferation and increased apoptosis which could not be rescued by addition of exogenous recombinant VEGF. Direct remodeling of the VEGFR1 and VEGFR2 promoters was observed. In contrast, HDACi treatments resulted in significant downregulation of the Neuropilin receptors.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">Epigenetic targeting of the Neuropilin receptors may offer an effective treatment for lung cancer patients in the clinical setting.</abstracttext></p>
</div>',
			'date' => '2015-10-07',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26479311',
			'doi' => '10.2217/epi.15.51',
			'modified' => '2016-06-23 15:24:41',
			'created' => '2016-06-23 15:24:41',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 203 => array(
			'id' => '2917',
			'name' => 'Chromatin assembly factor CAF-1 represses priming of plant defence response genes',
			'authors' => 'Mozgova I et al.',
			'description' => '<p><b>Plants have evolved efficient defence systems against pathogens that often rely on specific transcriptional responses. Priming is part of the defence syndrome, by establishing a hypersensitive state of defence genes such as after a first encounter with a pathogen. Because activation of defence responses has a fitness cost, priming must be tightly controlled to prevent spurious activation of defence. However, mechanisms that repress defence gene priming are poorly understood. Here, we show that the histone chaperone CAF-1 is required to establish a repressed chromatin state at defence genes. Absence of CAF-1 results in spurious activation of a salicylic acid-dependent pathogen defence response in plants grown under non-sterile conditions. Chromatin at defence response genes in CAF-1 mutants under non-inductive (sterile) conditions is marked by low nucleosome occupancy and high H3K4me3 at transcription start sites, resembling chromatin in primed wild-type plants. We conclude that CAF-1-mediated chromatin assembly prevents the establishment of a primed state that may under standard non-sterile growth conditions result in spurious activation of SA-dependent defence responses and consequential reduction of plant vigour.</b></p>',
			'date' => '2015-09-01',
			'pmid' => 'http://www.nature.com/articles/nplants2015127',
			'doi' => '10.1038/nplants.2015.127',
			'modified' => '2016-05-13 11:13:50',
			'created' => '2016-05-13 11:13:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 204 => array(
			'id' => '2817',
			'name' => 'Spatiotemporal control of estrogen-responsive transcription in ERα-positive breast cancer cells.',
			'authors' => 'P-Y Hsu, H-K Hsu, T-H Hsiao, Z Ye, E Wang, A L Profit, I Jatoi, Y Chen, N B Kirma, V X Jin, Z D Sharp and T H-M Huang',
			'description' => '<p><span>Recruitment of transcription machinery to target promoters for aberrant gene expression has been well studied, but underlying control directed by distant-acting enhancers remains unclear in cancer development. Our previous study demonstrated that distant estrogen response elements (DEREs) located on chromosome 20q13 are frequently amplified and translocated to other chromosomes in ER&alpha;-positive breast cancer cells. In this study, we used three-dimensional interphase fluorescence in situ hybridization to decipher spatiotemporal gathering of multiple DEREs in the nucleus. Upon estrogen stimulation, scattered 20q13 DEREs were mobilized to form regulatory depots for synchronized gene expression of target loci. A chromosome conformation capture assay coupled with chromatin immunoprecipitation further uncovered that ER&alpha;-bound regulatory depots are tethered to heterochromatin protein 1 (HP1) for coordinated chromatin movement and histone modifications of target loci, resulting in transcription repression. Neutralizing HP1 function dysregulated the formation of DERE-involved regulatory depots and transcription inactivation of candidate tumor-suppressor genes. Deletion of amplified DEREs using the CRISPR/Cas9 genomic-editing system profoundly altered transcriptional profiles of proliferation-associated signaling networks, resulting in reduction of cancer cell growth. These findings reveal a formerly uncharacterized feature wherein multiple copies of the amplicon congregate as transcriptional units in the nucleus for synchronous regulation of function-related loci in tumorigenesis. Disruption of their assembly can be a new strategy for treating breast cancers and other malignancies</span></p>',
			'date' => '2015-08-24',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26300005',
			'doi' => '10.1038/onc.2015.298',
			'modified' => '2016-02-10 16:20:01',
			'created' => '2016-02-10 16:20:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 205 => array(
			'id' => '2816',
			'name' => 'Non-coding recurrent mutations in chronic lymphocytic leukaemia.',
			'authors' => 'Xose S. Puente, Silvia Beà, Rafael Valdés-Mas, Neus Villamor, Jesús Gutiérrez-Abril et al.',
			'description' => '<p><span>Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3, ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding regions, including the 3' region of NOTCH1, which cause aberrant splicing events, increase NOTCH1 activity and result in a more aggressive disease. In addition, mutations in an enhancer located on chromosome 9p13 result in reduced expression of the B-cell-specific transcription factor PAX5. The accumulative number of driver alterations (0 to &ge;4) discriminated between patients with differences in clinical behaviour. This study provides an integrated portrait of the CLL genomic landscape, identifies new recurrent driver mutations of the disease, and suggests clinical interventions that may improve the management of this neoplasia.</span></p>',
			'date' => '2015-07-22',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26200345',
			'doi' => '10.1038/nature14666',
			'modified' => '2016-02-10 16:17:29',
			'created' => '2016-02-10 16:17:29',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 206 => array(
			'id' => '2893',
			'name' => 'Allele-specific binding of ZFP57 in the epigenetic regulation of imprinted and non-imprinted monoallelic expression',
			'authors' => 'Strogantsev R, Krueger F, Yamazawa K, Shi H, Gould P, Goldman-Roberts M, McEwen K, Sun B, Pedersen R, Ferguson-Smith AC',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Selective maintenance of genomic epigenetic imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary for maintaining the DNA methylation memory at multiple imprinting control regions in early mouse embryos and embryonic stem (ES) cells. Maternal-zygotic deletion of ZFP57 in mice presents a highly penetrant phenotype with no animals surviving to birth. Additionally, several cases of human transient neonatal diabetes are associated with somatic mutations in the ZFP57 coding sequence.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Here, we comprehensively map sequence-specific ZFP57 binding sites in an allele-specific manner using hybrid ES cell lines from reciprocal crosses between C57BL/6J and Cast/EiJ mice, assigning allele specificity to approximately two-thirds of all binding sites. While half of these are biallelic and include endogenous retrovirus (ERV) targets, the rest show monoallelic binding based either on parental origin or on genetic background of the allele. Parental-origin allele-specific binding is methylation-dependent and maps only to imprinting control differentially methylated regions (DMRs) established in the germline. We identify a novel imprinted gene, Fkbp6, which has a critical function in mouse male germ cell development. Genetic background-specific sequence differences also influence ZFP57 binding, as genetic variation that disrupts the consensus binding motif and its methylation is often associated with monoallelic expression of neighboring genes.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">The work described here uncovers further roles for ZFP57-mediated regulation of genomic imprinting and identifies a novel mechanism for genetically determined monoallelic gene expression.</abstracttext></p>
</div>',
			'date' => '2015-05-30',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26025256',
			'doi' => '10.1186/s13059-015-0672-7',
			'modified' => '2016-04-14 17:20:03',
			'created' => '2016-04-14 17:20:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 207 => array(
			'id' => '2790',
			'name' => 'Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency.',
			'authors' => 'Chen H, Aksoy I, Gonnot F, Osteil P, Aubry M, Hamela C, Rognard C, Hochard A, Voisin S, Fontaine E, Mure M, Afanassieff M, Cleroux E, Guibert S, Chen J, Vallot C, Acloque H, Genthon C, Donnadieu C, De Vos J, Sanlaville D, Guérin JF, Weber M, Stanton LW, R',
			'description' => 'Leukemia inhibitory factor (LIF)/STAT3 signalling is a hallmark of naive pluripotency in rodent pluripotent stem cells (PSCs), whereas fibroblast growth factor (FGF)-2 and activin/nodal signalling is required to sustain self-renewal of human PSCs in a condition referred to as the primed state. It is unknown why LIF/STAT3 signalling alone fails to sustain pluripotency in human PSCs. Here we show that the forced expression of the hormone-dependent STAT3-ER (ER, ligand-binding domain of the human oestrogen receptor) in combination with 2i/LIF and tamoxifen allows human PSCs to escape from the primed state and enter a state characterized by the activation of STAT3 target genes and long-term self-renewal in FGF2- and feeder-free conditions. These cells acquire growth properties, a gene expression profile and an epigenetic landscape closer to those described in mouse naive PSCs. Together, these results show that temporarily increasing STAT3 activity is sufficient to reprogramme human PSCs to naive-like pluripotent cells.',
			'date' => '2015-05-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25968054',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 208 => array(
			'id' => '2611',
			'name' => 'Opposite expression of CYP51A1 and its natural antisense transcript AluCYP51A1 in adenovirus type 37 infected retinal pigmented epithelial cells.',
			'authors' => 'Pickl JM, Kamel W, Ciftci S, Punga T, Akusjärvi G',
			'description' => 'Cytochrome P450 family member CYP51A1 is a key enzyme in cholesterol biosynthesis whose deregulation is implicated in numerous diseases, including retinal degeneration. Here we describe that HAdV-37 infection leads to downregulation of CYP51A1 expression and overexpression of its antisense non-coding Alu element (AluCYP51A1) in retinal pigment epithelium (RPE) cells. This change in gene expression is associated with a reversed accumulation of a positive histone mark at the CYP51A1 and AluCYP51A1 promoters. Further, transient AluCYP51A1 RNA overexpression correlates with reduced CYP51A1 mRNA accumulation. Collectively, our data suggest that AluCYP51A1 might control CYP51A1 gene expression in HAdV-37-infected RPE cells.',
			'date' => '2015-04-20',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25907535',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 209 => array(
			'id' => '2684',
			'name' => 'A cohesin-OCT4 complex mediates Sox enhancers to prime an early embryonic lineage.',
			'authors' => 'Abboud N, Moore-Morris T, Hiriart E, Yang H, Bezerra H, Gualazzi MG, Stefanovic S, Guénantin AC, Evans SM, Pucéat M',
			'description' => 'Short- and long-scales intra- and inter-chromosomal interactions are linked to gene transcription, but the molecular events underlying these structures and how they affect cell fate decision during embryonic development are poorly understood. One of the first embryonic cell fate decisions (that is, mesendoderm determination) is driven by the POU factor OCT4, acting in concert with the high-mobility group genes Sox-2 and Sox-17. Here we report a chromatin-remodelling mechanism and enhancer function that mediate cell fate switching. OCT4 alters the higher-order chromatin structure at both Sox-2 and Sox-17 loci. OCT4 titrates out cohesin and switches the Sox-17 enhancer from a locked (within an inter-chromosomal Sox-2 enhancer/CCCTC-binding factor CTCF/cohesin loop) to an active (within an intra-chromosomal Sox-17 promoter/enhancer/cohesin loop) state. SALL4 concomitantly mobilizes the polycomb complexes at the Soxs loci. Thus, OCT4/SALL4-driven cohesin- and polycombs-mediated changes in higher-order chromatin structure mediate instruction of early cell fate in embryonic cells.',
			'date' => '2015-04-08',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25851587',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 210 => array(
			'id' => '2625',
			'name' => 'Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1.',
			'authors' => 'Tomazou EM, Sheffield NC, Schmidl C, Schuster M, Schönegger A, Datlinger P, Kubicek S, Bock C, Kovar H',
			'description' => '<p>Transcription factor fusion proteins can transform cells by inducing global changes of the transcriptome, often creating a state of oncogene addiction. Here, we investigate the role of epigenetic mechanisms in this process, focusing on Ewing sarcoma cells that are dependent on the EWS-FLI1 fusion protein. We established reference epigenome maps comprising DNA methylation, seven histone marks, open chromatin states, and RNA levels, and we analyzed the epigenome dynamics upon downregulation of the driving oncogene. Reduced EWS-FLI1 expression led to widespread epigenetic changes in&nbsp;promoters, enhancers, and super-enhancers, and we identified histone H3K27 acetylation as the most strongly affected mark. Clustering of epigenetic promoter signatures defined classes of EWS-FLI1-regulated genes that responded differently to low-dose treatment with histone deacetylase inhibitors. Furthermore, we observed strong and opposing enrichment patterns for&nbsp;E2F and AP-1 among EWS-FLI1-correlated and anticorrelated genes. Our data describe extensive genome-wide rewiring of epigenetic cell states driven by an oncogenic fusion protein.</p>',
			'date' => '2015-02-24',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25704812',
			'doi' => '',
			'modified' => '2017-02-14 12:53:04',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 211 => array(
			'id' => '2575',
			'name' => 'Embryonic stem cell differentiation requires full length Chd1.',
			'authors' => 'Piatti P, Lim CY, Nat R, Villunger A, Geley S, Shue YT, Soratroi C, Moser M, Lusser A',
			'description' => 'The modulation of chromatin dynamics by ATP-dependent chromatin remodeling factors has been recognized as an important mechanism to regulate the balancing of self-renewal and pluripotency in embryonic stem cells (ESCs). Here we have studied the effects of a partial deletion of the gene encoding the chromatin remodeling factor Chd1 that generates an N-terminally truncated version of Chd1 in mouse ESCs in vitro as well as in vivo. We found that a previously uncharacterized serine-rich region (SRR) at the N-terminus is not required for chromatin assembly activity of Chd1 but that it is subject to phosphorylation. Expression of Chd1 lacking this region in ESCs resulted in aberrant differentiation properties of these cells. The self-renewal capacity and ESC chromatin structure, however, were not affected. Notably, we found that newly established ESCs derived from Chd1(Δ2/Δ2) mutant mice exhibited similar differentiation defects as in vitro generated mutant ESCs, even though the N-terminal truncation of Chd1 was fully compatible with embryogenesis and post-natal life in the mouse. These results underscore the importance of Chd1 for the regulation of pluripotency in ESCs and provide evidence for a hitherto unrecognized critical role of the phosphorylated N-terminal SRR for full functionality of Chd1.',
			'date' => '2015-01-26',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25620209',
			'doi' => '',
			'modified' => '2015-07-24 15:39:04',
			'created' => '2015-07-24 15:39:04',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 212 => array(
			'id' => '2552',
			'name' => 'A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus.',
			'authors' => 'Lazorthes S, Vallot C, Briois S, Aguirrebengoa M, Thuret JY, Laurent GS, Rougeulle C, Kapranov P, Mann C, Trouche D, Nicolas E',
			'description' => 'Non-coding RNAs (ncRNAs) play major roles in proper chromatin organization and function. Senescence, a strong anti-proliferative process and a major anticancer barrier, is associated with dramatic chromatin reorganization in heterochromatin foci. Here we analyze strand-specific transcriptome changes during oncogene-induced human senescence. Strikingly, while differentially expressed RNAs are mostly repressed during senescence, ncRNAs belonging to the recently described vlincRNA (very long intergenic ncRNA) class are mainly activated. We show that VAD, a novel antisense vlincRNA strongly induced during senescence, is required for the maintenance of senescence features. VAD modulates chromatin structure in cis and activates gene expression in trans at the INK4 locus, which encodes cell cycle inhibitors important for senescence-associated cell proliferation arrest. Importantly, VAD inhibits the incorporation of the repressive histone variant H2A.Z at INK4 gene promoters in senescent cells. Our data underline the importance of vlincRNAs as sensors of cellular environment changes and as mediators of the correct transcriptional response.',
			'date' => '2015-01-20',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25601475',
			'doi' => '',
			'modified' => '2015-07-24 15:39:04',
			'created' => '2015-07-24 15:39:04',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 213 => array(
			'id' => '2492',
			'name' => 'Cryosectioning the intestinal crypt-villus axis: an ex vivo method to study the dynamics of epigenetic modifications from stem cells to differentiated cells',
			'authors' => 'Vincent A, Kazmierczak C, Duchêne B, Jonckheere N, Leteurtre E, Van Seuningen I',
			'description' => 'The intestinal epithelium is a particularly attractive biological adult model to study epigenetic mechanisms driving adult stem cell renewal and cell differentiation. Since epigenetic modifications are dynamic, we have developed an original ex vivo approach to study the expression and epigenetic profiles of key genes associated with either intestinal cell pluripotency or differentiation by isolating cryosections of the intestinal crypt-villus axis. Gene expression, DNA methylation and histone modifications were studied by qRT-PCR, Methylation Specific-PCR and micro-Chromatin Immunoprecipitation, respectively. Using this approach, it was possible to identify segment-specific methylation and chromatin profiles. We show that (i) expression of intestinal stem cell markers (Lgr5, Ascl2) exclusively in the crypt is associated with active histone marks, (ii) promoters of all pluripotency genes studied and transcription factors involved in intestinal cell fate (Cdx2) harbour a bivalent chromatin pattern in the crypts, (iii) expression of differentiation markers (Muc2, Sox9) along the crypt-villus axis is associated with DNA methylation. Hence, using an original model of cryosectioning along the crypt-villus axis that allows in situ detection of dynamic epigenetic modifications, we demonstrate that regulation of pluripotency and differentiation markers in healthy intestinal mucosa involves different and specific epigenetic mechanisms.',
			'date' => '2014-12-27',
			'pmid' => 'http://www.sciencedirect.com/science/article/pii/S1873506114001585',
			'doi' => '',
			'modified' => '2015-07-24 15:39:04',
			'created' => '2015-07-24 15:39:04',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 214 => array(
			'id' => '2299',
			'name' => 'Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs.',
			'authors' => 'Adoue V, Schiavi A, Light N, Almlöf JC, Lundmark P, Ge B, Kwan T, Caron M, Rönnblom L, Wang C, Chen SH, Goodall AH, Cambien F, Deloukas P, Ouwehand WH, Syvänen AC, Pastinen T',
			'description' => 'Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40-60% of these cis-rSNPs to be shared across cell types. We uncover a new class of cis-rSNPs, which disrupt footprint-derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof-of-principle for a new approach for genome-wide functional validation of transcription factor-SNP interactions. By perturbing NFκB action in lymphoblasts, we identified 489 cis-regulated transcripts with altered AE after NFκB perturbation. Altogether, we perform a comprehensive analysis of cis-variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases. ',
			'date' => '2014-10-16',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/25326100',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 215 => array(
			'id' => '2330',
			'name' => 'Obesity increases histone H3 lysine 9 and 18 acetylation at Tnfa and Ccl2 genes in mouse liver',
			'authors' => 'Mikula M, Majewska A, Ledwon JK, Dzwonek A, Ostrowski J',
			'description' => 'Obesity contributes to the development of non‑alcoholic fatty liver disease (NAFLD), which is characterized by the upregulated expression of two key inflammatory mediators: tumor necrosis factor (Tnfa) and monocyte chemotactic protein 1 (Mcp1; also known as Ccl2). However, the chromatin make-up at these genes in the liver in obese individuals has not been explored. In this study, to identify obesity-mediated epigenetic changes at Tnfa and Ccl2, we used a murine model of obesity induced by a high-fat diet (HFD) and hyperphagic (ob/ob) mice. Chromatin immunoprecipitation (ChIP) assay was used to determine the abundance of permissive histone marks, namely histone H3 lysine 9 and 18 acetylation (H3K9/K18Ac), H3 lysine 4 trimethylation (H3K4me3) and H3 lysine 36 trimethylation (H3K36me3), in conjunction with polymerase 2 RNA (Pol2) and nuclear factor (Nf)-κB recruitment in the liver. Additionally, to correlate the liver tissue‑derived ChIP measurements with a robust in vitro transcriptional response at the Tnfa and Ccl2 genes, we used lipopolysaccharide (LPS) treatment to induce an inflammatory response in Hepa1-6 cells, a cell line derived from murine hepatocytes. ChIP revealed increased H3K9/K18Ac at Tnfa and Ccl2 in the obese mice, although the differences were only statistically significant for Tnfa (p<0.05). Unexpectedly, the levels of H3K4me3 and H3K36me3 marks, as well as Pol2 and Nf-κB recruitment, did not correspond with the increased expression of these two genes in the obese mice. By contrast, the acute treatment of Hepa1-6 cells with LPS significantly increased the H3K9/K18Ac marks, as well as Pol2 and Nf-κB recruitment at both genes, while the levels of H3K4me3 and H3K36me3 marks remained unaltered. These results demonstrate that increased Tnfa and Ccl2 expression in fatty liver at the chromatin level corresponds to changes in the level of histone H3 acetylation.',
			'date' => '2014-10-03',
			'pmid' => 'http://www.spandidos-publications.com/10.3892/ijmm.2014.1958',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 216 => array(
			'id' => '2338',
			'name' => 'The specific alteration of histone methylation profiles by DZNep during early zebrafish development.',
			'authors' => 'Ostrup O, Reiner AH, Aleström P, Collas P',
			'description' => '<p>Early embryo development constitutes a unique opportunity to study acquisition of epigenetic marks, including histone methylation. This study investigates the in vivo function and specificity of 3-deazaneplanocin A (DZNep), a promising anti-cancer drug that targets polycomb complex genes. One- to two-cell stage embryos were cultured with DZNep, and subsequently evaluated at the post-mid blastula transition stage for H3K27me3, H3K4me3 and H3K9me3 occupancy and enrichment at promoters using ChIP-chip microarrays. DZNep affected promoter enrichment of H3K27me3 and H3K9me3, whereas H3K4me3 remained stable. Interestingly, DZNep induced a loss of H3K27me3 and H3K9me3 from a substantial number of promoters but did not prevent de novo acquisition of these marks on others, indicating gene-specific targeting of its action. Loss/gain of H3K27me3 on promoters did not result in changes in gene expression levels until 24h post-fertilization. In contrast, genes gaining H3K9me3 displayed strong and constant down-regulation upon DZNep treatment. H3K9me3 enrichment on these gene promoters was observed not only in the proximal area as expected, but also over the transcription start site. Altered H3K9me3 profiles were associated with severe neuronal and cranial phenotypes at day 4-5 post-fertilization. Thus, DZNep was shown to affect enrichment patterns of H3K27me3 and H3K9me3 at promoters in a gene-specific manner.</p>',
			'date' => '2014-09-28',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25260724',
			'doi' => '',
			'modified' => '2016-04-08 09:43:32',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 217 => array(
			'id' => '2228',
			'name' => 'Interrogation of allelic chromatin states in human cells by high-density ChIP-genotyping.',
			'authors' => 'Light N, Adoue V, Ge B, Chen SH, Kwan T, Pastinen T',
			'description' => 'Allele-specific (AS) assessment of chromatin has the potential to elucidate specific cis-regulatory mechanisms, which are predicted to underlie the majority of the known genetic associations to complex disease. However, development of chromatin landscapes at allelic resolution has been challenging since sites of variable signal strength require substantial read depths not commonly applied in sequencing based approaches. In this study, we addressed this by performing parallel analyses of input DNA and chromatin immunoprecipitates (ChIP) on high-density Illumina genotyping arrays. Allele-specificity for the histone modifications H3K4me1, H3K4me3, H3K27ac, H3K27me3, and H3K36me3 was assessed using ChIP samples generated from 14 lymphoblast and 6 fibroblast cell lines. AS-ChIP SNPs were combined into domains and validated using high-confidence ChIP-seq sites. We observed characteristic patterns of allelic-imbalance for each histone-modification around allele-specifically expressed transcripts. Notably, we found H3K4me1 to be significantly anti-correlated with allelic expression (AE) at transcription start sites, indicating H3K4me1 allelic imbalance as a marker of AE. We also found that allelic chromatin domains exhibit population and cell-type specificity as well as heritability within trios. Finally, we observed that a subset of allelic chromatin domains is regulated by DNase I-sensitive quantitative trait loci and that these domains are significantly enriched for genome-wide association studies hits, with autoimmune disease associated SNPs specifically enriched in lymphoblasts. This study provides the first genome-wide maps of allelic-imbalance for five histone marks. Our results provide new insights into the role of chromatin in cis-regulation and highlight the need for high-depth sequencing in ChIP-seq studies along with the need to improve allele-specificity of ChIP-enrichment.',
			'date' => '2014-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25055051',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 218 => array(
			'id' => '2298',
			'name' => 'Differences among brain tumor stem cell types and fetal neural stem cells in focal regions of histone modifications and DNA methylation, broad regions of modifications, and bivalent promoters.',
			'authors' => 'Yoo S, Bieda MC',
			'description' => 'BACKGROUND: Aberrational epigenetic marks are believed to play a major role in establishing the abnormal features of cancer cells. Rational use and development of drugs aimed at epigenetic processes requires an understanding of the range, extent, and roles of epigenetic reprogramming in cancer cells. Using ChIP-chip and MeDIP-chip approaches, we localized well-established and prevalent epigenetic marks (H3K27me3, H3K4me3, H3K9me3, DNA methylation) on a genome scale in several lines of putative glioma stem cells (brain tumor stem cells, BTSCs) and, for comparison, normal human fetal neural stem cells (fNSCs). RESULTS: We determined a substantial "core" set of promoters possessing each mark in every surveyed BTSC cell type, which largely overlapped the corresponding fNSC sets. However, there was substantial diversity among cell types in mark localization. We observed large differences among cell types in total number of H3K9me3+ positive promoters and peaks and in broad modifications (defined as >50 kb peak length) for H3K27me3 and, to a lesser extent, H3K9me3. We verified that a change in a broad modification affected gene expression of CACNG7. We detected large numbers of bivalent promoters, but most bivalent promoters did not display direct overlap of contrasting epigenetic marks, but rather occupied nearby regions of the proximal promoter. There were significant differences in the sets of promoters bearing bivalent marks in the different cell types and few consistent differences between fNSCs and BTSCs. CONCLUSIONS: Overall, our "core set" data establishes sets of potential therapeutic targets, but the diversity in sets of sites and broad modifications among cell types underscores the need to carefully consider BTSC subtype variation in epigenetic therapy. Our results point toward substantial differences among cell types in the activity of the production/maintenance systems for H3K9me3 and for broad regions of modification (H3K27me3 or H3K9me3). Finally, the unexpected diversity in bivalent promoter sets among these multipotent cells indicates that bivalent promoters may play complex roles in the overall biology of these cells. These results provide key information for forming the basis for future rational drug therapy aimed at epigenetic processes in these cells.',
			'date' => '2014-08-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25163646',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 219 => array(
			'id' => '2201',
			'name' => 'Long Noncoding RNA TARID Directs Demethylation and Activation of the Tumor Suppressor TCF21 via GADD45A.',
			'authors' => 'Arab K, Park YJ, Lindroth AM, Schäfer A, Oakes C, Weichenhan D, Lukanova A, Lundin E, Risch A, Meister M, Dienemann H, Dyckhoff G, Herold-Mende C, Grummt I, Niehrs C, Plass C',
			'description' => 'DNA methylation is a dynamic and reversible process that governs gene expression during development and disease. Several examples of active DNA demethylation have been documented, involving genome-wide and gene-specific DNA demethylation. How demethylating enzymes are targeted to specific genomic loci remains largely unknown. We show that an antisense lncRNA, termed TARID (for TCF21 antisense RNA inducing demethylation), activates TCF21 expression by inducing promoter demethylation. TARID interacts with both the TCF21 promoter and GADD45A (growth arrest and DNA-damage-inducible, alpha), a regulator of DNA demethylation. GADD45A in turn recruits thymine-DNA glycosylase for base excision repair-mediated demethylation involving oxidation of 5-methylcytosine to 5-hydroxymethylcytosine in the TCF21 promoter by ten-eleven translocation methylcytosine dioxygenase proteins. The results reveal a function of lncRNAs, serving as a genomic address label for GADD45A-mediated demethylation of specific target genes.',
			'date' => '2014-08-21',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25087872',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 220 => array(
			'id' => '2063',
			'name' => 'Identification of a large protein network involved in epigenetic transmission in replicating DNA of embryonic stem cells.',
			'authors' => 'Aranda S, Rutishauser D, Ernfors P',
			'description' => 'Pluripotency of embryonic stem cells (ESCs) is maintained by transcriptional activities and chromatin modifying complexes highly organized within the chromatin. Although much effort has been focused on identifying genome-binding sites, little is known on their dynamic association with chromatin across cell divisions. Here, we used a modified version of the iPOND (isolation of proteins at nascent DNA) technology to identify a large protein network enriched at nascent DNA in ESCs. This comprehensive and unbiased proteomic characterization in ESCs reveals that, in addition to the core replication machinery, proteins relevant for pluripotency of ESCs are present at DNA replication sites. In particular, we show that the chromatin remodeller HDAC1-NuRD complex is enriched at nascent DNA. Interestingly, an acute block of HDAC1 in ESCs leads to increased acetylation of histone H3 lysine 9 at nascent DNA together with a concomitant loss of methylation. Consistently, in contrast to what has been described in tumour cell lines, these chromatin marks were found to be stable during cell cycle progression of ESCs. Our results are therefore compatible with a rapid deacetylation-coupled methylation mechanism during the replication of DNA in ESCs that may participate in the preservation of pluripotency of ESCs during replication.',
			'date' => '2014-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24852249',
			'doi' => '',
			'modified' => '2015-07-24 15:39:02',
			'created' => '2015-07-24 15:39:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 221 => array(
			'id' => '2107',
			'name' => 'Seminoma and embryonal carcinoma footprints identified by analysis of integrated genome-wide epigenetic and expression profiles of germ cell cancer cell lines.',
			'authors' => 'van der Zwan YG, Rijlaarsdam MA, Rossello FJ, Notini AJ, de Boer S, Watkins DN, Gillis AJ, Dorssers LC, White SJ, Looijenga LH',
			'description' => 'BACKGROUND: Originating from Primordial Germ Cells/gonocytes and developing via a precursor lesion called Carcinoma In Situ (CIS), Germ Cell Cancers (GCC) are the most common cancer in young men, subdivided in seminoma (SE) and non-seminoma (NS). During physiological germ cell formation/maturation, epigenetic processes guard homeostasis by regulating the accessibility of the DNA to facilitate transcription. Epigenetic deregulation through genetic and environmental parameters (i.e. genvironment) could disrupt embryonic germ cell development, resulting in delayed or blocked maturation. This potentially facilitates the formation of CIS and progression to invasive GCC. Therefore, determining the epigenetic and functional genomic landscape in GCC cell lines could provide insight into the pathophysiology and etiology of GCC and provide guidance for targeted functional experiments. RESULTS: This study aims at identifying epigenetic footprints in SE and EC cell lines in genome-wide profiles by studying the interaction between gene expression, DNA CpG methylation and histone modifications, and their function in the pathophysiology and etiology of GCC. Two well characterized GCC-derived cell lines were compared, one representative for SE (TCam-2) and the other for EC (NCCIT). Data were acquired using the Illumina HumanHT-12-v4 (gene expression) and HumanMethylation450 BeadChip (methylation) microarrays as well as ChIP-sequencing (activating histone modifications (H3K4me3, H3K27ac)). Results indicate known germ cell markers not only to be differentiating between SE and NS at the expression level, but also in the epigenetic landscape. CONCLUSION: The overall similarity between TCam-2/NCCIT support an erased embryonic germ cell arrested in early gonadal development as common cell of origin although the exact developmental stage from which the tumor cells are derived might differ. Indeed, subtle difference in the (integrated) epigenetic and expression profiles indicate TCam-2 to exhibit a more germ cell-like profile, whereas NCCIT shows a more pluripotent phenotype. The results provide insight into the functional genome in GCC cell lines.',
			'date' => '2014-06-02',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24887064',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 222 => array(
			'id' => '2054',
			'name' => 'Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer',
			'authors' => 'Zecchini V, Madhu B, Russell R, Pértega-Gomes N, Warren A, Gaude E, Borlido J, Stark R, Ireland-Zecchini H, Rao R, Scott H, Boren J, Massie C, Asim M, Brindle K, Griffiths J, Frezza C, Neal DE, Mills IG',
			'description' => 'Tumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. Hypoxia-inducible factor 1A (HIF1A) is a major regulator of this process, but its activation under normoxic conditions, termed pseudohypoxia, is not well documented. Here, using an integrative approach combining the first genome-wide mapping of chromatin binding for an endocytic adaptor, ARRB1, both in vitro and in vivo with gene expression profiling, we demonstrate that nuclear ARRB1 contributes to this metabolic shift in prostate cancer cells via regulation of HIF1A transcriptional activity under normoxic conditions through regulation of succinate dehydrogenase A (SDHA) and fumarate hydratase (FH) expression. ARRB1-induced pseudohypoxia may facilitate adaptation of cancer cells to growth in the harsh conditions that are frequently encountered within solid tumours. Our study is the first example of an endocytic adaptor protein regulating metabolic pathways. It implicates ARRB1 as a potential tumour promoter in prostate cancer and highlights the importance of metabolic alterations in prostate cancer.',
			'date' => '2014-05-16',
			'pmid' => 'http://onlinelibrary.wiley.com/doi/10.15252/embj.201386874/full',
			'doi' => '',
			'modified' => '2015-07-24 15:39:02',
			'created' => '2015-07-24 15:39:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 223 => array(
			'id' => '1891',
			'name' => 'Stage-specific control of early B cell development by the transcription factor Ikaros.',
			'authors' => 'Schwickert TA, Tagoh H, Gültekin S, Dakic A, Axelsson E, Minnich M, Ebert A, Werner B, Roth M, Cimmino L, Dickins RA, Zuber J, Jaritz M, Busslinger M',
			'description' => 'The transcription factor Ikaros is an essential regulator of lymphopoiesis. Here we studied its B cell-specific function by conditional inactivation of the gene encoding Ikaros (Ikzf1) in pro-B cells. B cell development was arrested at an aberrant 'pro-B cell' stage characterized by increased cell adhesion and loss of signaling via the pre-B cell signaling complex (pre-BCR). Ikaros activated genes encoding signal transducers of the pre-BCR and repressed genes involved in the downregulation of pre-BCR signaling and upregulation of the integrin signaling pathway. Unexpectedly, derepression of expression of the transcription factor Aiolos did not compensate for the loss of Ikaros in pro-B cells. Ikaros induced or suppressed active chromatin at regulatory elements of activated or repressed target genes. Notably, binding of Ikaros and expression of its target genes were dynamically regulated at distinct stages of early B lymphopoiesis.',
			'date' => '2014-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24509509',
			'doi' => '',
			'modified' => '2015-07-24 15:39:02',
			'created' => '2015-07-24 15:39:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 224 => array(
			'id' => '1793',
			'name' => 'A novel microscopy-based high-throughput screening method to identify proteins that regulate global histone modification levels.',
			'authors' => 'Baas R, Lelieveld D, van Teeffelen H, Lijnzaad P, Castelijns B, van Schaik FM, Vermeulen M, Egan DA, Timmers HT, de Graaf P',
			'description' => '<p>Posttranslational modifications of histones play an important role in the regulation of gene expression and chromatin structure in eukaryotes. The balance between chromatin factors depositing (writers) and removing (erasers) histone marks regulates the steady-state levels of chromatin modifications. Here we describe a novel microscopy-based screening method to identify proteins that regulate histone modification levels in a high-throughput fashion. We named our method CROSS, for Chromatin Regulation Ontology SiRNA Screening. CROSS is based on an siRNA library targeting the expression of 529 proteins involved in chromatin regulation. As a proof of principle, we used CROSS to identify chromatin factors involved in histone H3 methylation on either lysine-4 or lysine-27. Furthermore, we show that CROSS can be used to identify chromatin factors that affect growth in cancer cell lines. Taken together, CROSS is a powerful method to identify the writers and erasers of novel and known chromatin marks and facilitates the identification of drugs targeting epigenetic modifications.</p>',
			'date' => '2014-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24334265',
			'doi' => '',
			'modified' => '2016-04-12 09:46:40',
			'created' => '2015-07-24 15:39:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 225 => array(
			'id' => '1783',
			'name' => 'Pan-histone demethylase inhibitors simultaneously targeting Jumonji C and lysine-specific demethylases display high anticancer activities.',
			'authors' => 'Rotili D, Tomassi S, Conte M, Benedetti R, Tortorici M, Ciossani G, Valente S, Marrocco B, Labella D, Novellino E, Mattevi A, Altucci L, Tumber A, Yapp C, King ON, Hopkinson RJ, Kawamura A, Schofield CJ, Mai A',
			'description' => 'In prostate cancer, two different types of histone lysine demethylases (KDM), LSD1/KDM1 and JMJD2/KDM4, are coexpressed and colocalize with the androgen receptor. We designed and synthesized hybrid LSD1/JmjC or "pan-KDM" inhibitors 1-6 by coupling the skeleton of tranylcypromine 7, a known LSD1 inhibitor, with 4-carboxy-4'-carbomethoxy-2,2'-bipyridine 8 or 5-carboxy-8-hydroxyquinoline 9, two 2-oxoglutarate competitive templates developed for JmjC inhibition. Hybrid compounds 1-6 are able to simultaneously target both KDM families and have been validated as potential antitumor agents in cells. Among them, 2 and 3 increase H3K4 and H3K9 methylation levels in cells and cause growth arrest and substantial apoptosis in LNCaP prostate and HCT116 colon cancer cells. When tested in noncancer mesenchymal progenitor (MePR) cells, 2 and 3 induced little and no apoptosis, respectively, thus showing cancer-selective inhibiting action.',
			'date' => '2014-01-09',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24325601',
			'doi' => '',
			'modified' => '2015-07-24 15:39:01',
			'created' => '2015-07-24 15:39:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 226 => array(
			'id' => '1727',
			'name' => 'Interplay between active chromatin marks and RNA-directed DNA methylation in Arabidopsis thaliana.',
			'authors' => 'Greenberg MV, Deleris A, Hale CJ, Liu A, Feng S, Jacobsen SE',
			'description' => 'DNA methylation is an epigenetic mark that is associated with transcriptional repression of transposable elements and protein-coding genes. Conversely, transcriptionally active regulatory regions are strongly correlated with histone 3 lysine 4 di- and trimethylation (H3K4m2/m3). We previously showed that Arabidopsis thaliana plants with mutations in the H3K4m2/m3 demethylase JUMONJI 14 (JMJ14) exhibit a mild reduction in RNA-directed DNA methylation (RdDM) that is associated with an increase in H3K4m2/m3 levels. To determine whether this incomplete RdDM reduction was the result of redundancy with other demethylases, we examined the genetic interaction of JMJ14 with another class of H3K4 demethylases: lysine-specific demethylase 1-like 1 and lysine-specific demethylase 1-like 2 (LDL1 and LDL2). Genome-wide DNA methylation analyses reveal that both families cooperate to maintain RdDM patterns. ChIP-seq experiments show that regions that exhibit an observable DNA methylation decrease are co-incidental with increases in H3K4m2/m3. Interestingly, the impact on DNA methylation was stronger at DNA-methylated regions adjacent to H3K4m2/m3-marked protein-coding genes, suggesting that the activity of H3K4 demethylases may be particularly crucial to prevent spreading of active epigenetic marks. Finally, RNA sequencing analyses indicate that at RdDM targets, the increase of H3K4m2/m3 is not generally associated with transcriptional de-repression. This suggests that the histone mark itself--not transcription--impacts the extent of RdDM.',
			'date' => '2013-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24244201',
			'doi' => '',
			'modified' => '2015-07-24 15:39:01',
			'created' => '2015-07-24 15:39:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 227 => array(
			'id' => '1581',
			'name' => 'A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis.',
			'authors' => 'Kollmann K, Heller G, Schneckenleithner C, Warsch W, Scheicher R, Ott RG, Schäfer M, Fajmann S, Schlederer M, Schiefer AI, Reichart U, Mayerhofer M, Hoeller C, Zöchbauer-Müller S, Kerjaschki D, Bock C, Kenner L, Hoefler G, Freissmuth M, Green AR, Moriggl ',
			'description' => 'In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185(BCR-ABL+) B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16(INK4a) and the pro-angiogenic factor VEGF-A. This function is independent of CDK6's kinase activity. High CDK6 expression thus suppresses proliferation by upregulating p16(INK4a), providing an internal safeguard. However, in the absence of p16(INK4a), CDK6 can exert its full tumor-promoting function by enhancing proliferation and stimulating angiogenesis. The finding that CDK6 connects cell-cycle progression to angiogenesis confirms CDK6's central role in hematopoietic malignancies and could underlie the selection pressure to upregulate CDK6 and silence p16(INK4a).',
			'date' => '2013-08-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23948297',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 228 => array(
			'id' => '1512',
			'name' => 'Disease-Related Growth Factor and Embryonic Signaling Pathways Modulate an Enhancer of TCF21 Expression at the 6q23.2 Coronary Heart Disease Locus.',
			'authors' => 'Miller CL, Anderson DR, Kundu RK, Raiesdana A, Nürnberg ST, Diaz R, Cheng K, Leeper NJ, Chen CH, Chang IS, Schadt EE, Hsiung CA, Assimes TL, Quertermous T',
			'description' => 'Coronary heart disease (CHD) is the leading cause of mortality in both developed and developing countries worldwide. Genome-wide association studies (GWAS) have now identified 46 independent susceptibility loci for CHD, however, the biological and disease-relevant mechanisms for these associations remain elusive. The large-scale meta-analysis of GWAS recently identified in Caucasians a CHD-associated locus at chromosome 6q23.2, a region containing the transcription factor TCF21 gene. TCF21 (Capsulin/Pod1/Epicardin) is a member of the basic-helix-loop-helix (bHLH) transcription factor family, and regulates cell fate decisions and differentiation in the developing coronary vasculature. Herein, we characterize a cis-regulatory mechanism by which the lead polymorphism rs12190287 disrupts an atypical activator protein 1 (AP-1) element, as demonstrated by allele-specific transcriptional regulation, transcription factor binding, and chromatin organization, leading to altered TCF21 expression. Further, this element is shown to mediate signaling through platelet-derived growth factor receptor beta (PDGFR-β) and Wilms tumor 1 (WT1) pathways. A second disease allele identified in East Asians also appears to disrupt an AP-1-like element. Thus, both disease-related growth factor and embryonic signaling pathways may regulate CHD risk through two independent alleles at TCF21.',
			'date' => '2013-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23874238',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 229 => array(
			'id' => '1465',
			'name' => 'Bivalent chromatin marks developmental regulatory genes in the mouse embryonic germline in vivo.',
			'authors' => 'Sachs M, Onodera C, Blaschke K, Ebata KT, Song JS, Ramalho-Santos M',
			'description' => 'Developmental regulatory genes have both activating (H3K4me3) and repressive (H3K27me3) histone modifications in embryonic stem cells (ESCs). This bivalent configuration is thought to maintain lineage commitment programs in a poised state. However, establishing physiological relevance has been complicated by the high number of cells required for chromatin immunoprecipitation (ChIP). We developed a low-cell-number chromatin immunoprecipitation (low-cell ChIP) protocol to investigate the chromatin of mouse primordial germ cells (PGCs). Genome-wide analysis of embryonic day 11.5 (E11.5) PGCs revealed H3K4me3/H3K27me3 bivalent domains highly enriched at developmental regulatory genes in a manner remarkably similar to ESCs. Developmental regulators remain bivalent and transcriptionally silent through the initiation of sexual differentiation at E13.5. We also identified >2,500 "orphan" bivalent domains that are distal to known genes and expressed in a tissue-specific manner but silent in PGCs. Our results demonstrate the existence of bivalent domains in the germline and raise the possibility that the somatic program is continuously maintained as bivalent, potentially imparting transgenerational epigenetic inheritance.',
			'date' => '2013-06-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23727241',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 230 => array(
			'id' => '1458',
			'name' => 'Integrative analysis of deep sequencing data identifies estrogen receptor early response genes and links ATAD3B to poor survival in breast cancer.',
			'authors' => 'Ovaska K, Matarese F, Grote K, Charapitsa I, Cervera A, Liu C, Reid G, Seifert M, Stunnenberg HG, Hautaniemi S',
			'description' => 'Identification of responsive genes to an extra-cellular cue enables characterization of pathophysiologically crucial biological processes. Deep sequencing technologies provide a powerful means to identify responsive genes, which creates a need for computational methods able to analyze dynamic and multi-level deep sequencing data. To answer this need we introduce here a data-driven algorithm, SPINLONG, which is designed to search for genes that match the user-defined hypotheses or models. SPINLONG is applicable to various experimental setups measuring several molecular markers in parallel. To demonstrate the SPINLONG approach, we analyzed ChIP-seq data reporting PolII, estrogen receptor α (ERα), H3K4me3 and H2A.Z occupancy at five time points in the MCF-7 breast cancer cell line after estradiol stimulus. We obtained 777 ERa early responsive genes and compared the biological functions of the genes having ERα binding within 20 kb of the transcription start site (TSS) to genes without such binding site. Our results show that the non-genomic action of ERα via the MAPK pathway, instead of direct ERa binding, may be responsible for early cell responses to ERα activation. Our results also indicate that the ERα responsive genes triggered by the genomic pathway are transcribed faster than those without ERα binding sites. The survival analysis of the 777 ERα responsive genes with 150 primary breast cancer tumors and in two independent validation cohorts indicated the ATAD3B gene, which does not have ERα binding site within 20 kb of its TSS, to be significantly associated with poor patient survival.',
			'date' => '2013-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23818839',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 231 => array(
			'id' => '1425',
			'name' => 'Expression of a large LINE-1-driven antisense RNA is linked to epigenetic silencing of the metastasis suppressor gene TFPI-2 in cancer.',
			'authors' => 'Cruickshanks HA, Vafadar-Isfahani N, Dunican DS, Lee A, Sproul D, Lund JN, Meehan RR, Tufarelli C',
			'description' => 'LINE-1 retrotransposons are abundant repetitive elements of viral origin, which in normal cells are kept quiescent through epigenetic mechanisms. Activation of LINE-1 occurs frequently in cancer and can enable LINE-1 mobilization but also has retrotransposition-independent consequences. We previously reported that in cancer, aberrantly active LINE-1 promoters can drive transcription of flanking unique sequences giving rise to LINE-1 chimeric transcripts (LCTs). Here, we show that one such LCT, LCT13, is a large transcript (>300 kb) running antisense to the metastasis-suppressor gene TFPI-2. We have modelled antisense RNA expression at TFPI-2 in transgenic mouse embryonic stem (ES) cells and demonstrate that antisense RNA induces silencing and deposition of repressive histone modifications implying a causal link. Consistent with this, LCT13 expression in breast and colon cancer cell lines is associated with silencing and repressive chromatin at TFPI-2. Furthermore, we detected LCT13 transcripts in 56% of colorectal tumours exhibiting reduced TFPI-2 expression. Our findings implicate activation of LINE-1 elements in subsequent epigenetic remodelling of surrounding genes, thus hinting a novel retrotransposition-independent role for LINE-1 elements in malignancy.',
			'date' => '2013-05-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23703216',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 232 => array(
			'id' => '1389',
			'name' => 'The developmental epigenomics toolbox: ChIP-seq and MethylCap-seq profiling of early zebrafish embryos.',
			'authors' => 'Bogdanović O, Fernández-Miñán A, Tena JJ, de la Calle-Mustienes E, Gómez-Skarmeta JL',
			'description' => 'Genome-wide profiling of DNA methylation and histone modifications answered many questions as to how the genes are regulated on a global scale and what their epigenetic makeup is. Yet, little is known about the function of these marks during early vertebrate embryogenesis. Here we provide detailed protocols for ChIP-seq and MethylCap-seq procedures applied to zebrafish (Danio rerio) embryonic material at four developmental stages. As a proof of principle, we have profiled on a global scale a number of post-translational histone modifications including H3K4me1, H3K4me3 and H3K27ac. We demonstrate that these marks are dynamic during early development and that such developmental transitions can be detected by ChIP-seq. In addition, we applied MethylCap-seq to show that developmentally-regulated DNA methylation remodeling can be detected by such a procedure. Our MethylCap-seq data concur with previous DNA methylation studies of early zebrafish development rendering this method highly suitable for the global assessment of DNA methylation in early vertebrate embryos.',
			'date' => '2013-04-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23624103',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 233 => array(
			'id' => '1285',
			'name' => 'Genome-wide analysis of LXRα activation reveals new transcriptional networks in human atherosclerotic foam cells.',
			'authors' => 'Feldmann R, Fischer C, Kodelja V, Behrens S, Haas S, Vingron M, Timmermann B, Geikowski A, Sauer S',
			'description' => 'Increased physiological levels of oxysterols are major risk factors for developing atherosclerosis and cardiovascular disease. Lipid-loaded macrophages, termed foam cells, are important during the early development of atherosclerotic plaques. To pursue the hypothesis that ligand-based modulation of the nuclear receptor LXRα is crucial for cell homeostasis during atherosclerotic processes, we analysed genome-wide the action of LXRα in foam cells and macrophages. By integrating chromatin immunoprecipitation-sequencing (ChIP-seq) and gene expression profile analyses, we generated a highly stringent set of 186 LXRα target genes. Treatment with the nanomolar-binding ligand T0901317 and subsequent auto-regulatory LXRα activation resulted in sequence-dependent sharpening of the genome-binding patterns of LXRα. LXRα-binding loci that correlated with differential gene expression revealed 32 novel target genes with potential beneficial effects, which in part explained the implications of disease-associated genetic variation data. These observations identified highly integrated LXRα ligand-dependent transcriptional networks, including the APOE/C1/C4/C2-gene cluster, which contribute to the reversal of cholesterol efflux and the dampening of inflammation processes in foam cells to prevent atherogenesis.',
			'date' => '2013-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23393188',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 234 => array(
			'id' => '1304',
			'name' => 'Regulation of transcription through acetylation of H3K122 on the lateral surface of the histone octamer.',
			'authors' => 'Tropberger P, Pott S, Keller C, Kamieniarz-Gdula K, Caron M, Richter F, Li G, Mittler G, Liu ET, Bühler M, Margueron R, Schneider R',
			'description' => 'Histone modifications are key regulators of chromatin function. However, little is known to what extent histone modifications can directly impact on chromatin. Here, we address how a modification within the globular domain of histones regulates chromatin function. We demonstrate that H3K122ac can be sufficient to stimulate transcription and that mutation of H3K122 impairs transcriptional activation, which we attribute to a direct effect of H3K122ac on histone-DNA binding. In line with this, we find that H3K122ac defines genome-wide genetic elements and chromatin features associated with active transcription. Furthermore, H3K122ac is catalyzed by the coactivators p300/CBP and can be induced by nuclear hormone receptor signaling. Collectively, this suggests that transcriptional regulators elicit their effects not only via signaling to histone tails but also via direct structural perturbation of nucleosomes by directing acetylation to their lateral surface.',
			'date' => '2013-02-14',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23415232',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 235 => array(
			'id' => '1497',
			'name' => 'Histone lysine trimethylation or acetylation can be modulated by phytoestrogen, estrogen or anti-HDAC in breast cancer cell lines.',
			'authors' => 'Dagdemir A, Durif J, Ngollo M, Bignon YJ, Bernard-Gallon D',
			'description' => '<p>AIM: The isoflavones genistein, daidzein and equol (daidzein metabolite) have been reported to interact with epigenetic modifications, specifically hypermethylation of tumor suppressor genes. The objective of this study was to analyze and understand the mechanisms by which phytoestrogens act on chromatin in breast cancer cell lines. MATERIALS &amp; METHODS: Two breast cancer cell lines, MCF-7 and MDA-MB 231, were treated with genistein (18.5 &micro;M), daidzein (78.5 &micro;M), equol (12.8 &micro;M), 17&beta;-estradiol (10 nM) and suberoylanilide hydroxamic acid (1 &micro;M) for 48 h. A control with untreated cells was performed. 17&beta;-estradiol and an anti-HDAC were used to compare their actions with phytoestrogens. The chromatin immunoprecipitation coupled with quantitative PCR was used to follow soy phytoestrogen effects on H3 and H4 histones on H3K27me3, H3K9me3, H3K4me3, H4K8ac and H3K4ac marks, and we selected six genes (EZH2, BRCA1, ER&alpha;, ER&beta;, SRC3 and P300) for analysis. RESULTS: Soy phytoestrogens induced a decrease in trimethylated marks and an increase in acetylating marks studied at six selected genes. CONCLUSION: We demonstrated that soy phytoestrogens tend to modify transcription through the demethylation and acetylation of histones in breast cancer cell lines.</p>',
			'date' => '2013-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23414320',
			'doi' => '',
			'modified' => '2016-05-03 12:17:35',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 236 => array(
			'id' => '1267',
			'name' => 'Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA.',
			'authors' => 'Fadloun A, Le Gras S, Jost B, Ziegler-Birling C, Takahashi H, Gorab E, Carninci P, Torres-Padilla ME',
			'description' => 'How a more plastic chromatin state is maintained and reversed during development is unknown. Heterochromatin-mediated silencing of repetitive elements occurs in differentiated cells. Here, we used repetitive elements, including retrotransposons, as model loci to address how and when heterochromatin forms during development. RNA sequencing throughout early mouse embryogenesis revealed that repetitive-element expression is dynamic and stage specific, with most repetitive elements becoming repressed before implantation. We show that LINE-1 and IAP retrotransposons become reactivated from both parental genomes after fertilization. Chromatin immunoprecipitation for H3K4me3 and H3K9me3 in 2- and 8-cell embryos indicates that their developmental silencing follows loss of activating marks rather than acquisition of conventional heterochromatic marks. Furthermore, short LINE-1 RNAs regulate LINE-1 transcription in vivo. Our data indicate that reprogramming after mammalian fertilization comprises a robust transcriptional activation of retrotransposons and that repetitive elements are initially regulated through RNA.',
			'date' => '2013-01-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23353788',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 237 => array(
			'id' => '1195',
			'name' => 'Ezh2 maintains a key phase of muscle satellite cell expansion but does not regulate terminal differentiation.',
			'authors' => 'Woodhouse S, Pugazhendhi D, Brien P, Pell JM.',
			'description' => 'Tissue generation and repair requires a stepwise process of cell fate restriction to ensure adult stem cells differentiate in a timely and appropriate manner. A crucial role has been implicated for Polycomb-group (PcG) proteins and the H3K27me3 repressive histone mark, in coordinating the transcriptional programmes necessary for this process, but the targets and developmental timing for this repression remain unclear. To address these questions, we generated novel genome-wide maps of H3K27me3 and H3K4me3 in freshly isolated muscle stem cells. These data, together with the analysis of two conditional Ezh2-null mouse strains, identified a critical proliferation phase in which Ezh2 activity is essential. Mice lacking Ezh2 in satellite cells exhibited decreased muscle growth, severely impaired regeneration and reduced stem cell number, due to a profound failure of the proliferative progenitor population to expand. Surprisingly, deletion of Ezh2 after the onset of terminal differentiation did not impede muscle repair or homeostasis. Using these knockout models, RNA-Seq and the ChIP-Seq datasets we show that Ezh2 does not regulate the muscle differentiation process in vivo. These results emphasise the lineage and cell type specific functions for Ezh2 and the Polycomb repressive complex 2.',
			'date' => '2012-11-30',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/23203812',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 238 => array(
			'id' => '1162',
			'name' => 'Limitations and possibilities of low cell number ChIP-seq.',
			'authors' => 'Gilfillan GD, Hughes T, Sheng Y, Hjorthaug HS, Straub T, Gervin K, Harris JR, Undlien DE, Lyle R',
			'description' => 'ABSTRACT: BACKGROUND: Chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq) offers high resolution, genome-wide analysis of DNA-protein interactions. However, current standard methods require abundant starting material in the range of 1--20 million cells per immunoprecipitation, and remain a bottleneck to the acquisition of biologically relevant epigenetic data. Using a ChIP-seq protocol optimised for low cell numbers (down to 100,000 cells / IP), we examined the performance of the ChIP-seq technique on a series of decreasing cell numbers. RESULTS: We present an enhanced native ChIP-seq method tailored to low cell numbers that represents a 200-fold reduction in input requirements over existing protocols. The protocol was tested over a range of starting cell numbers covering three orders of magnitude, enabling determination of the lower limit of the technique. At low input cell numbers, increased levels of unmapped and duplicate reads reduce the number of unique reads generated, and can drive up sequencing costs and affect sensitivity if ChIP is attempted from too few cells. CONCLUSIONS: The optimised method presented here considerably reduces the input requirements for performing native ChIP-seq. It extends the applicability of the technique to isolated primary cells and rare cell populations (e.g. biobank samples, stem cells), and in many cases will alleviate the need for cell culture and any associated alteration of epigenetic marks. However, this study highlights a challenge inherent to ChIP-seq from low cell numbers: as cell input numbers fall, levels of unmapped sequence reads and PCR-generated duplicate reads rise. We discuss a number of solutions to overcome the effects of reducing cell number that may aid further improvements to ChIP performance.',
			'date' => '2012-11-21',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23171294',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 239 => array(
			'id' => '1143',
			'name' => 'Protein Group Modification and Synergy in the SUMO Pathway as Exemplified in DNA Repair.',
			'authors' => 'Psakhye I, Jentsch S',
			'description' => 'Protein modification by SUMO affects a wide range of protein substrates. Surprisingly, although SUMO pathway mutants display strong phenotypes, the function of individual SUMO modifications is often enigmatic, and SUMOylation-defective mutants commonly lack notable phenotypes. Here, we use DNA double-strand break repair as an example and show that DNA damage triggers a SUMOylation wave, leading to simultaneous multisite modifications of several repair proteins of the same pathway. Catalyzed by a DNA-bound SUMO ligase and triggered by single-stranded DNA, SUMOylation stabilizes physical interactions between the proteins. Notably, only wholesale elimination of SUMOylation of several repair proteins significantly affects the homologous recombination pathway by considerably slowing down DNA repair. Thus, SUMO acts synergistically on several proteins, and individual modifications only add up to efficient repair. We propose that SUMOylation may thus often target a protein group rather than individual proteins, whereas localized modification enzymes and highly specific triggers ensure specificity.',
			'date' => '2012-11-09',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23122649',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 240 => array(
			'id' => '1137',
			'name' => 'IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer.',
			'authors' => 'Baird AM, Leonard J, Naicker KM, Kilmartin L, O'Byrne KJ, Gray SG',
			'description' => 'BACKGROUND: IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC). METHODS: RT-PCR and chromatin immunopreciptiation (ChIP) were used to examine the levels, epigenetic regulation and effects of various drugs (DNA methyltransferase inhibitors, Histone Deacetylase inhibitors and Gemcitabine) on IL-23 expression in NSCLC cells and macrophages. The effects of recombinant IL-23 protein on cellular proliferation were examined by MTT assay. Statistical analysis consisted of Student's t-test or one way analysis of variance (ANOVA) where groups in the experiment were three or more. RESULTS: In a cohort of primary non-small cell lung cancer (NSCLC) tumours, IL-23A expression was significantly elevated in patient tumour samples (p<0.05). IL-23A expression is epigenetically regulated through histone post-translational modifications and DNA CpG methylation. Gemcitabine, a chemotherapy drug indicated for first-line treatment of NSCLC also induced IL-23A expression. Recombinant IL-23 significantly increased cellular proliferation in NSCLC cell lines. CONCLUSIONS: These results may therefore have important implications for treating NSCLC patients with either epigenetic targeted therapies or Gemcitabine.',
			'date' => '2012-10-29',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23116756',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 241 => array(
			'id' => '1078',
			'name' => 'New partners in regulation of gene expression: the enhancer of trithorax and polycomb corto interacts with methylated ribosomal protein l12 via its chromodomain.',
			'authors' => 'Coléno-Costes A, Jang SM, de Vanssay A, Rougeot J, Bouceba T, Randsholt NB, Gibert JM, Le Crom S, Mouchel-Vielh E, Bloyer S, Peronnet F',
			'description' => 'Chromodomains are found in many regulators of chromatin structure, and most of them recognize methylated lysines on histones. Here, we investigate the role of the Drosophila melanogaster protein Corto's chromodomain. The Enhancer of Trithorax and Polycomb Corto is involved in both silencing and activation of gene expression. Over-expression of the Corto chromodomain (CortoCD) in transgenic flies shows that it is a chromatin-targeting module, critical for Corto function. Unexpectedly, mass spectrometry analysis reveals that polypeptides pulled down by CortoCD from nuclear extracts correspond to ribosomal proteins. Furthermore, real-time interaction analyses demonstrate that CortoCD binds with high affinity RPL12 tri-methylated on lysine 3. Corto and RPL12 co-localize with active epigenetic marks on polytene chromosomes, suggesting that both are involved in fine-tuning transcription of genes in open chromatin. RNA-seq based transcriptomes of wing imaginal discs over-expressing either CortoCD or RPL12 reveal that both factors deregulate large sets of common genes, which are enriched in heat-response and ribosomal protein genes, suggesting that they could be implicated in dynamic coordination of ribosome biogenesis. Chromatin immunoprecipitation experiments show that Corto and RPL12 bind hsp70 and are similarly recruited on gene body after heat shock. Hence, Corto and RPL12 could be involved together in regulation of gene transcription. We discuss whether pseudo-ribosomal complexes composed of various ribosomal proteins might participate in regulation of gene expression in connection with chromatin regulators.',
			'date' => '2012-10-11',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23071455',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 242 => array(
			'id' => '831',
			'name' => 'Extensive promoter hypermethylation and hypomethylation is associated with aberrant microRNA expression in chronic lymphocytic leukemia.',
			'authors' => 'Baer C, Claus R, Frenzel LP, Zucknick M, Park YJ, Gu L, Weichenhan D, Fischer M, Pallasch CP, Herpel E, Rehli M, Byrd JC, Wendtner CM, Plass C',
			'description' => '<p>Dysregulated microRNA (miRNA) expression contributes to the pathogenesis of hematopoietic malignancies, including chronic lymphocytic leukemia (CLL). However, an understanding of the mechanisms that cause aberrant miRNA transcriptional control is lacking. In this study, we comprehensively investigated the role and extent of miRNA epigenetic regulation in CLL. Genome-wide profiling performed on 24 CLL and 10 healthy B cell samples revealed global DNA methylation patterns upstream of miRNA sequences that distinguished malignant from healthy cells and identified putative miRNA promoters. Integration of DNA methylation and miRNA promoter data led to the identification of 128 recurrent miRNA targets for aberrant promoter DNA methylation. DNA hypomethylation accounted for over 60% of all aberrant promoter-associated DNA methylation in CLL, and promoter DNA hypomethylation was restricted to well-defined regions. Individual hyper- and hypomethylated promoters allowed discrimination of CLL samples from healthy controls. Promoter DNA methylation patterns were confirmed in an independent patient cohort, with eleven miRNAs consistently demonstrating an inverse correlation between DNA methylation status and expression level. Together, our findings characterize the role of epigenetic changes in the regulation of miRNA transcription and create a repository of disease-specific promoter regions that may provide additional insights into the pathogenesis of CLL.</p>',
			'date' => '2012-06-18',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22710432',
			'doi' => '',
			'modified' => '2016-05-03 12:14:21',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 243 => array(
			'id' => '1204',
			'name' => 'The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells.',
			'authors' => 'Karpiuk O, Najafova Z, Kramer F, Hennion M, Galonska C, König A, Snaidero N, Vogel T, Shchebet A, Begus-Nahrmann Y, Kassem M, Simons M, Shcherbata H, Beissbarth T, Johnsen SA',
			'description' => 'Extensive changes in posttranslational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly understood. We show that histone H2B monoubiquitination (H2Bub1) significantly increases during differentiation of human mesenchymal stem cells (hMSCs) and various lineage-committed precursor cells and in diverse organisms. Furthermore, the H2B ubiquitin ligase RNF40 is required for the induction of differentiation markers and transcriptional reprogramming of hMSCs. This function is dependent upon CDK9 and the WAC adaptor protein, which are required for H2B monoubiquitination. Finally, we show that RNF40 is required for the resolution of the H3K4me3/H3K27me3 bivalent poised state on lineage-specific genes during the transition from an inactive to an active chromatin conformation. Thus, these data indicate that H2Bub1 is required for maintaining multipotency of hMSCs and plays a central role in controlling stem cell differentiation.',
			'date' => '2012-06-08',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22681891',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 244 => array(
			'id' => '792',
			'name' => 'Intronic RNAs mediate EZH2 regulation of epigenetic targets.',
			'authors' => 'Guil S, Soler M, Portela A, Carrère J, Fonalleras E, Gómez A, Villanueva A, Esteller M',
			'description' => 'Epigenetic deregulation at a number of genomic loci is one of the hallmarks of cancer. A role for some RNA molecules in guiding repressive polycomb complex PRC2 to specific chromatin regions has been proposed. Here we use an in vivo cross-linking method to detect and identify direct PRC2-RNA interactions in human cancer cells, revealing a number of intronic RNA sequences capable of binding to the core component EZH2 and regulating the transcriptional output of its genomic counterpart. Overexpression of EZH2-bound intronic RNA for the H3K4 methyltransferase gene SMYD3 is concomitant with an increase in EZH2 occupancy throughout the corresponding genomic fragment and is sufficient to reduce levels of the endogenous transcript and protein, resulting in reduced growth capability in cell culture and animal models. These findings reveal the role of intronic RNAs in fine-tuning gene expression regulation at the level of transcriptional control.',
			'date' => '2012-06-03',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22659877',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 245 => array(
			'id' => '732',
			'name' => 'The transcriptional and epigenomic foundations of ground state pluripotency.',
			'authors' => 'Marks H, Kalkan T, Menafra R, Denissov S, Jones K, Hofemeister H, Nichols J, Kranz A, Francis Stewart A, Smith A, Stunnenberg HG',
			'description' => 'Mouse embryonic stem (ES) cells grown in serum exhibit greater heterogeneity in morphology and expression of pluripotency factors than ES cells cultured in defined medium with inhibitors of two kinases (Mek and GSK3), a condition known as "2i" postulated to establish a naive ground state. We show that the transcriptome and epigenome profiles of serum- and 2i-grown ES cells are distinct. 2i-treated cells exhibit lower expression of lineage-affiliated genes, reduced prevalence at promoters of the repressive histone modification H3K27me3, and fewer bivalent domains, which are thought to mark genes poised for either up- or downregulation. Nonetheless, serum- and 2i-grown ES cells have similar differentiation potential. Precocious transcription of developmental genes in 2i is restrained by RNA polymerase II promoter-proximal pausing. These findings suggest that transcriptional potentiation and a permissive chromatin context characterize the ground state and that exit from it may not require a metastable intermediate or multilineage priming.',
			'date' => '2012-04-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22541430',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 246 => array(
			'id' => '456',
			'name' => 'Control of ground-state pluripotency by allelic regulation of Nanog.',
			'authors' => 'Miyanari Y, Torres-Padilla ME',
			'description' => 'Pluripotency is established through genome-wide reprogramming during mammalian pre-implantation development, resulting in the formation of the naive epiblast. Reprogramming involves both the resetting of epigenetic marks and the activation of pluripotent-cell-specific genes such as Nanog and Oct4 (also known as Pou5f1). The tight regulation of these genes is crucial for reprogramming, but the mechanisms that regulate their expression in vivo have not been uncovered. Here we show that Nanog-but not Oct4-is monoallelically expressed in early pre-implantation embryos. Nanog then undergoes a progressive switch to biallelic expression during the transition towards ground-state pluripotency in the naive epiblast of the late blastocyst. Embryonic stem (ES) cells grown in leukaemia inhibitory factor (LIF) and serum express Nanog mainly monoallelically and show asynchronous replication of the Nanog locus, a feature of monoallelically expressed genes, but ES cells activate both alleles when cultured under 2i conditions, which mimic the pluripotent ground state in vitro. Live-cell imaging with reporter ES cells confirmed the allelic expression of Nanog and revealed allelic switching. The allelic expression of Nanog is regulated through the fibroblast growth factor-extracellular signal-regulated kinase signalling pathway, and it is accompanied by chromatin changes at the proximal promoter but occurs independently of DNA methylation. Nanog-heterozygous blastocysts have fewer inner-cell-mass derivatives and delayed primitive endoderm formation, indicating a role for the biallelic expression of Nanog in the timely maturation of the inner cell mass into a fully reprogrammed pluripotent epiblast. We suggest that the tight regulation of Nanog dose at the chromosome level is necessary for the acquisition of ground-state pluripotency during development. Our data highlight an unexpected role for allelic expression in controlling the dose of pluripotency factors in vivo, adding an extra level to the regulation of reprogramming.',
			'date' => '2012-02-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22327294',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 247 => array(
			'id' => '919',
			'name' => 'Prepatterning of developmental gene expression by modified histones before zygotic genome activation.',
			'authors' => 'Lindeman LC, Andersen IS, Reiner AH, Li N, Aanes H, Østrup O, Winata C, Mathavan S, Müller F, Aleström P, Collas P',
			'description' => 'A hallmark of anamniote vertebrate development is a window of embryonic transcription-independent cell divisions before onset of zygotic genome activation (ZGA). Chromatin determinants of ZGA are unexplored; however, marking of developmental genes by modified histones in sperm suggests a predictive role of histone marks for ZGA. In zebrafish, pre-ZGA development for ten cell cycles provides an opportunity to examine whether genomic enrichment in modified histones is present before initiation of transcription. By profiling histone H3 trimethylation on all zebrafish promoters before and after ZGA, we demonstrate here an epigenetic prepatterning of developmental gene expression. This involves pre-ZGA marking of transcriptionally inactive genes involved in homeostatic and developmental regulation by permissive H3K4me3 with or without repressive H3K9me3 or H3K27me3. Our data suggest that histone modifications are instructive for the developmental gene expression program.',
			'date' => '2011-12-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22137762',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 248 => array(
			'id' => '913',
			'name' => 'IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF.',
			'authors' => 'Baird AM, Gray SG, O'Byrne KJ',
			'description' => 'BACKGROUND: IL-20 is a pleiotrophic member of the IL-10 family and plays a role in skin biology and the development of haematopoietic cells. Recently, IL-20 has been demonstrated to have potential anti-angiogenic effects in non-small cell lung cancer (NSCLC) by down regulating COX-2. METHODS: The expression of IL-20 and its cognate receptors (IL-20RA/B and IL-22R1) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of this family was examined in normal bronchial epithelial and NSCLC cell lines. Furthermore, the effect of IL-20 on VEGF family members was examined. RESULTS: The expression of IL-20 and its receptors are frequently dysregulated in NSCLC. IL-20RB mRNA was significantly elevated in NSCLC tumours (p<0.01). Protein levels of the receptors, IL-20RB and IL-22R1, were significantly increased (p<0.01) in the tumours of NSCLC patients. IL-20 and its receptors were found to be epigenetically regulated through histone post-translational modifications and DNA CpG residue methylation. In addition, treatment with recombinant IL-20 resulted in decreased expression of the VEGF family members at the mRNA level. CONCLUSIONS: This family of genes are dysregulated in NSCLC and are subject to epigenetic regulation. Whilst the anti-angiogenic properties of IL-20 require further clarification, targeting this family via epigenetic means may be a viable therapeutic option in lung cancer treatment.',
			'date' => '2011-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21565488',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 249 => array(
			'id' => '637',
			'name' => 'H3.5 is a novel hominid-specific histone H3 variant that is specifically expressed in the seminiferous tubules of human testes.',
			'authors' => 'Schenk R, Jenke A, Zilbauer M, Wirth S, Postberg J',
			'description' => 'The incorporation of histone variants into chromatin plays an important role for the establishment of particular chromatin states. Six human histone H3 variants are known to date, not counting CenH3 variants: H3.1, H3.2, H3.3 and the testis-specific H3.1t as well as the recently described variants H3.X and H3.Y. We report the discovery of H3.5, a novel non-CenH3 histone H3 variant. H3.5 is encoded on human chromosome 12p11.21 and probably evolved in a common ancestor of all recent great apes (Hominidae) as a consequence of H3F3B gene duplication by retrotransposition. H3.5 mRNA is specifically expressed in seminiferous tubules of human testis. Interestingly, H3.5 has two exact copies of ARKST motifs adjacent to lysine-9 or lysine-27, and lysine-79 is replaced by asparagine. In the Hek293 cell line, ectopically expressed H3.5 is assembled into chromatin and targeted by PTM. H3.5 preferentially colocalizes with euchromatin, and it is associated with actively transcribed genes and can replace an essential function of RNAi-depleted H3.3 in cell growth.',
			'date' => '2011-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21274551',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 250 => array(
			'id' => '256',
			'name' => 'Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer',
			'authors' => 'O'Byrne KJ, Baird AM, Kilmartin L, Leonard J, Sacevich C, Gray SG.',
			'description' => 'Due to their inherently hypoxic environment, cancer cells often resort to glycolysis, or the anaerobic breakdown of glucose to form ATP to provide for their energy needs, known as the Warburg effect. At the same time, overexpression of the insulin receptor in non-small cell lung cancer (NSCLC) is associated with an increased risk of metastasis and decreased survival. The uptake of glucose into cells is carried out via glucose transporters or GLUTs. Of these, GLUT-4 is essential for insulin-stimulated glucose uptake. Following treatment with the epigenetic targeting agents histone deacetylase inhibitors (HDACi), GLUT-3 and GLUT-4 expression were found to be induced in NSCLC cell lines, with minimal responses in transformed normal human bronchial epithelial cells (HBECs). Similar results for GLUT-4 were observed in cells derived from liver, muscle, kidney and pre-adipocytes. Bioinformatic analysis of the promoter for GLUT-4 indicates that it may also be regulated by several chromatin binding factors or complexes including CTCF, SP1 and SMYD3. Chromatin immunoprecipitation studies demonstrate that the promoter for GLUT-4 is dynamically remodeled in response to HDACi. Overall, these results may have value within the clinical setting as (a) it may be possible to use this to enhance fluorodeoxyglucose (18F) positron emission tomography (FDG-PET) imaging sensitivity; (b) it may be possible to target NSCLC through the use of HDACi and insulin mediated uptake of the metabolic targeting drugs such as 2-deoxyglucose (2-DG); or (c) enhance or sensitize NSCLC to chemotherapy. ',
			'date' => '2011-03-25',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/24212773',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 251 => array(
			'id' => '265',
			'name' => 'Characterisation of genome-wide PLZF/RARA target genes.',
			'authors' => 'Spicuglia S, Vincent-Fabert C, Benoukraf T, Tibéri G, Saurin AJ, Zacarias-Cabeza J, Grimwade D, Mills K, Calmels B, Bertucci F, Sieweke M, Ferrier P, Duprez E',
			'description' => 'The PLZF/RARA fusion protein generated by the t(11;17)(q23;q21) translocation in acute promyelocytic leukaemia (APL) is believed to act as an oncogenic transcriptional regulator recruiting epigenetic factors to genes important for its transforming potential. However, molecular mechanisms associated with PLZF/RARA-dependent leukaemogenesis still remain unclear.We searched for specific PLZF/RARA target genes by ChIP-on-chip in the haematopoietic cell line U937 conditionally expressing PLZF/RARA. By comparing bound regions found in U937 cells expressing endogenous PLZF with PLZF/RARA-induced U937 cells, we isolated specific PLZF/RARA target gene promoters. We next analysed gene expression profiles of our identified target genes in PLZF/RARA APL patients and analysed DNA sequences and epigenetic modification at PLZF/RARA binding sites. We identify 413 specific PLZF/RARA target genes including a number encoding transcription factors involved in the regulation of haematopoiesis. Among these genes, 22 were significantly down regulated in primary PLZF/RARA APL cells. In addition, repressed PLZF/RARA target genes were associated with increased levels of H3K27me3 and decreased levels of H3K9K14ac. Finally, sequence analysis of PLZF/RARA bound sequences reveals the presence of both consensus and degenerated RAREs as well as enrichment for tissue-specific transcription factor motifs, highlighting the complexity of targeting fusion protein to chromatin. Our study suggests that PLZF/RARA directly targets genes important for haematopoietic development and supports the notion that PLZF/RARA acts mainly as an epigenetic regulator of its direct target genes.',
			'date' => '2011-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21949697',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 252 => array(
			'id' => '585',
			'name' => 'Tiling histone H3 lysine 4 and 27 methylation in zebrafish using high-density microarrays.',
			'authors' => 'Lindeman LC, Reiner AH, Mathavan S, Aleström P, Collas P',
			'description' => 'BACKGROUND: Uncovering epigenetic states by chromatin immunoprecipitation and microarray hybridization (ChIP-chip) has significantly contributed to the understanding of gene regulation at the genome-scale level. Many studies have been carried out in mice and humans; however limited high-resolution information exists to date for non-mammalian vertebrate species. PRINCIPAL FINDINGS: We report a 2.1-million feature high-resolution Nimblegen tiling microarray for ChIP-chip interrogations of epigenetic states in zebrafish (Danio rerio). The array covers 251 megabases of the genome at 92 base-pair resolution. It includes ∼15 kb of upstream regulatory sequences encompassing all RefSeq promoters, and over 5 kb in the 5' end of coding regions. We identify with high reproducibility, in a fibroblast cell line, promoters enriched in H3K4me3, H3K27me3 or co-enriched in both modifications. ChIP-qPCR and sequential ChIP experiments validate the ChIP-chip data and support the co-enrichment of trimethylated H3K4 and H3K27 on a subset of genes. H3K4me3- and/or H3K27me3-enriched genes are associated with distinct transcriptional status and are linked to distinct functional categories. CONCLUSIONS: We have designed and validated for the scientific community a comprehensive high-resolution tiling microarray for investigations of epigenetic states in zebrafish, a widely used developmental and disease model organism.',
			'date' => '2010-12-20',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21187971',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 253 => array(
			'id' => '413',
			'name' => 'Autonomous silencing of the imprinted Cdkn1c gene in stem cells',
			'authors' => 'Wood MD, Hiura H, Tunster S, Arima T, Shin J-H, Higgins M, John1 RM',
			'description' => 'Parent-of-origin specific expression of imprinted genes relies on the differential DNA methylation of specific genomic regions. Differentially methylated regions (DMRs) acquire DNA methylation either during gametogenesis (primary DMR) or after fertilization when allele-specific expression is established (secondary DMR). Little is known about the function of these secondary DMRs. We investigated the DMR spanning Cdkn1c in mouse embryonic stem cells, androgenetic stem cells and embryonic germ stem cells. In all cases, expression of Cdkn1c was appropriately repressed in in vitro differentiated cells. However, stem cells failed to de novo methylate the silenced gene even after sustained differentiation. In the absence of maintained DNA methylation (Dnmt1-/-), Cdkn1c escapes silencing demonstrating the requirement for DNA methylation in long term silencing in vivo. We propose that post-fertilization differential methylation reflects the importance of retaining single gene dosage of a subset of imprinted loci in the adult.',
			'date' => '2010-04-01',
			'pmid' => 'http://www.pubmed/20372090',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 254 => array(
			'id' => '69',
			'name' => 'The histone variant macroH2A is an epigenetic regulator of key developmental genes.',
			'authors' => 'Buschbeck M, Uribesalgo I, Wibowo I, Rué P, Martin D, Gutierrez A, Morey L, Guigó R, López-Schier H, Di Croce L',
			'description' => 'The histone variants macroH2A1 and macroH2A2 are associated with X chromosome inactivation in female mammals. However, the physiological function of macroH2A proteins on autosomes is poorly understood. Microarray-based analysis in human male pluripotent cells uncovered occupancy of both macroH2A variants at many genes encoding key regulators of development and cell fate decisions. On these genes, the presence of macroH2A1+2 is a repressive mark that overlaps locally and functionally with Polycomb repressive complex 2. We demonstrate that macroH2A1+2 contribute to the fine-tuning of temporal activation of HOXA cluster genes during neuronal differentiation. Furthermore, elimination of macroH2A2 function in zebrafish embryos produced severe but specific phenotypes. Taken together, our data demonstrate that macroH2A variants constitute an important epigenetic mark involved in the concerted regulation of gene expression programs during cellular differentiation and vertebrate development.',
			'date' => '2009-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/19734898',
			'doi' => '',
			'modified' => '2015-07-24 15:38:56',
			'created' => '2015-07-24 15:38:56',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 255 => array(
			'id' => '117',
			'name' => 'High-resolution analysis of epigenetic changes associated with X inactivation.',
			'authors' => 'Marks H, Chow JC, Denissov S, Françoijs KJ, Brockdorff N, Heard E, Stunnenberg HG',
			'description' => 'Differentiation of female murine ES cells triggers silencing of one X chromosome through X-chromosome inactivation (XCI). Immunofluorescence studies showed that soon after Xist RNA coating the inactive X (Xi) undergoes many heterochromatic changes, including the acquisition of H3K27me3. However, the mechanisms that lead to the establishment of heterochromatin remain unclear. We first analyze chromatin changes by ChIP-chip, as well as RNA expression, around the X-inactivation center (Xic) in female and male ES cells, and their day 4 and 10 differentiated derivatives. A dynamic epigenetic landscape is observed within the Xic locus. Tsix repression is accompanied by deposition of H3K27me3 at its promoter during differentiation of both female and male cells. However, only in female cells does an active epigenetic landscape emerge at the Xist locus, concomitant with high Xist expression. Several regions within and around the Xic show unsuspected chromatin changes, and we define a series of unusual loci containing highly enriched H3K27me3. Genome-wide ChIP-seq analyses show a female-specific quantitative increase of H3K27me3 across the X chromosome as XCI proceeds in differentiating female ES cells. Using female ES cells with nonrandom XCI and polymorphic X chromosomes, we demonstrate that this increase is specific to the Xi by allele-specific SNP mapping of the ChIP-seq tags. H3K27me3 becomes evenly associated with the Xi in a chromosome-wide fashion. A selective and robust increase of H3K27me3 and concomitant decrease in H3K4me3 is observed over active genes. This indicates that deposition of H3K27me3 during XCI is tightly associated with the act of silencing of individual genes across the Xi.',
			'date' => '2009-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/19581487',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 256 => array(
			'id' => '1435',
			'name' => 'H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming.',
			'authors' => 'Daujat S, Weiss T, Mohn F, Lange UC, Ziegler-Birling C, Zeissler U, Lappe M, Schübeler D, Torres-Padilla ME, Schneider R',
			'description' => 'Histone modifications are central to the regulation of all DNA-dependent processes. Lys64 of histone H3 (H3K64) lies within the globular domain at a structurally important position. We identify trimethylation of H3K64 (H3K64me3) as a modification that is enriched at pericentric heterochromatin and associated with repeat sequences and transcriptionally inactive genomic regions. We show that this new mark is dynamic during the two main epigenetic reprogramming events in mammals. In primordial germ cells, H3K64me3 is present at the time of specification, but it disappears transiently during reprogramming. In early mouse embryos, it is inherited exclusively maternally; subsequently, the modification is rapidly removed, suggesting an important role for H3K64me3 turnover in development. Taken together, our findings establish H3K64me3 as a previously uncharacterized histone modification that is preferentially localized to repressive chromatin. We hypothesize that H3K64me3 helps to 'secure' nucleosomes, and perhaps the surrounding chromatin, in an appropriately repressed state during development.',
			'date' => '2009-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/19561610',
			'doi' => '',
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			'created' => '2015-07-24 15:39:00',
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		(int) 257 => array(
			'id' => '2600',
			'name' => 'Epigenetic-Mediated Downregulation of μ-Protocadherin in Colorectal Tumours',
			'authors' => 'Bujko M, Kober P, Statkiewicz M, Mikula M, Ligaj M, Zwierzchowski L, Ostrowski J, Siedlecki JA',
			'description' => 'Carcinogenesis involves altered cellular interaction and tissue morphology that partly arise from aberrant expression of cadherins. Mucin-like protocadherin is implicated in intercellular adhesion and its expression was found decreased in colorectal cancer (CRC). This study has compared MUPCDH (CDHR5) expression in three key types of colorectal tissue samples, for normal mucosa, adenoma, and carcinoma. A gradual decrease of mRNA levels and protein expression was observed in progressive stages of colorectal carcinogenesis which are consistent with reports of increasing MUPCDH 5′ promoter region DNA methylation. High MUPCDH methylation was also observed in HCT116 and SW480 CRC cell lines that revealed low gene expression levels compared to COLO205 and HT29 cell lines which lack DNA methylation at the MUPCDH locus. Furthermore, HCT116 and SW480 showed lower levels of RNA polymerase II and histone H3 lysine 4 trimethylation (H3K4me3) as well as higher levels of H3K27 trimethylation at the MUPCDH promoter. MUPCDH expression was however restored in HCT116 and SW480 cells in the presence of 5-Aza-2′-deoxycytidine (DNA methyltransferase inhibitor). Results indicate that μ-protocadherin downregulation occurs during early stages of tumourigenesis and progression into the adenoma-carcinoma sequence. Epigenetic mechanisms are involved in this silencing.',
			'date' => '0000-00-00',
			'pmid' => 'http://www.hindawi.com/journals/grp/2015/317093/',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
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			'name' => 'Analysis of active chromatin modifications in early mammalian embryos reveals uncoupling of H2A.Z acetylation and H3K36 trimethylation from embryonic genome activation',
			'authors' => 'Bošković A, Bender A, Gall L, Ziegler-Birling C, Beaujean N, Torres-Padilla ME',
			'description' => 'Early embryonic development is characterized by dramatic changes in cell potency and chromatin organization. The role of histone variants in the context of chromatin remodeling during embryogenesis remains under investigated. In particular, the nuclear distribution of the histone variant H2A.Z and its modifications have not been examined. Here we investigated the dynamics of acetylation of H2A.Z and two other active chromatin marks, H3K9ac and H3K36me3, throughout murine and bovine pre-implantation development. We show that H2A.Z distribution is dynamic during the earliest stages of mouse development, with protein levels significantly varying across stages and lowest at the 2-cell stage. When present, H2A.Z localizes preferentially to euchromatin at all stages analyzed. H2A.Z is acetylated in preimplantation blastomeres and is preferentially localized to euchromatin, in line with the known role of H2A.Zac in transcriptional activation. Interestingly, however, H2A.Zac is undetectable in mouse embryos at the 2-cell stage, the time of major embryonic genome activation (EGA). Similarly, H3K36me3 is present exclusively in the maternal chromatin immediately after fertilization but becomes undetectable in interphase nuclei at the 2-cell stage, suggesting uncoupling of these active marks with global embryonic transcription activation. In bovine embryos, which undergo EGA at the 8-cell stage, H2A.Zac can be detected in zygotes, 4-, 8- and 16-cell stage embryos as well as in blastocysts, indicating that the dynamics of H2A.Zac is not conserved in mammals. In contrast, H3K36me3 displays mostly undetectable and heterogeneous localization pattern throughout bovine pre-implantation development. Thus, our results suggest that ‘canonical’ active chromatin marks exhibit a dynamic behavior in embryonic nuclei, which is both stage- and speciesspecific. We hypothesize that chromatin of early embryonic nuclei is subject to fine-tuning through differential acquisition of histone marks, allowing for proper chromatin remodeling and developmental progression in a species-specific fashion.',
			'date' => '0000-00-00',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/22647320',
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			'modified' => '2015-07-24 15:38:58',
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			'description' => '<p>I have used Diagenode's antibodies for my ChIP&ndash;qPCR experiments in HK-2 cells. The antibodies performed very well in our experiments with specific signal, and good signal to noise ratio in the promoter of the gapdh gene.</p>
<center><img src="../../img/categories/antibodies/H3K4me3-hk2.png" /></center>
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong> ChIP assays were performed using human HK-2 cells, the Diagenode antibody against H3K4me3 (Cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with standard fixation and sonication protocol, using sheared chromatin from 4 million cells. A total amount of 4 ug of antibody were used per ChIP experiment, normal mouse IgG (4 &mu;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). These results are in accordance with the observation that trimethylation of K4 at histone H3 is associated with the promoters of active genes.</small></p>',
			'author' => 'Claudio Cappelli PhD. Post-Doc. Investigator, Laboratory of Molecular Pathology, Institute of Biochemestry and Microbiology, University Austral of Chile, about H3K4me3 polyclonal antibody Premium, 50 μl size.',
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			'description' => '<p>In life sciences, epigenetics is nowadays the most rapid developing field with new astonishing discoveries made every day. To keep pace with this field, we are in need of reliable tools to foster our research - tools Diagenode provides us with. From <strong>antibodies</strong> to <strong>automated solutions</strong> - all from one source and with robust support. Antibodies used in our lab: H3K27me3 polyclonal antibody &ndash; Premium, H3K4me3 polyclonal antibody &ndash; Premium, H3K9me3 polyclonal antibody &ndash; Premium, H3K4me1 polyclonal antibody &ndash; Premium, CTCF polyclonal antibody &ndash; Classic, Rabbit IgG.</p>',
			'author' => 'Dr. Florian Uhle, Dept. of Anesthesiology, Heidelberg University Hospital, Germany',
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			'description' => '<p>We use the <strong>Bioruptor</strong> sonication device and the antibody against the histone modification H3K4me3 in our lab. The Bioruptor device is used for the shearing of chromatin in ChIP-Seq experiments and for generation of protein lysates (whole cell extracts). Thanks to the Bioruptor device we achieve excellent and reproducible results in both applications. The <strong>H3K4me3 antibody</strong> is used in our ChIP-Seq experiments as well as Western Blotting. With this antibody we are able to generate highly enriched ChIP-Seq samples with extremely low background. In Western Blot we can detect one specific, strong band with the H3K4me3 antibody.</p>
<p>Diagenode provides not only very good products for research but also an excellent customer support.</p>',
			'author' => 'Dr Lora Dimitrova, Charité-Universitätsmedizin Berlin, Germany',
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			'name' => 'Thanks Diagenode for saving my PhD!',
			'description' => '<p><span>I work with Diagenode&rsquo;s <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> and shear the DNA on the <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a> for the last year and I have to say that these two products saved my PhD project! Some time ago, our well-established ChIP protocol suddenly stopped to work and after long time of figuring out the reason, we invested into <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a>. </span><span>I am very satisfied from the way it works, plus it&rsquo;s super quiet! Combining the sonicator with the <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> we finally got things working.&nbsp;</span><span>I have also decided to try the <a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns">Microplex Library Prep kit</a>, which is amazing. I have been working with other kits and I find this one efficient and very easy to use. </span><span>Recently, I have tested one of the epigenetics antibody (<a href="../products/search?keyword=H3K4me3">H3K4me3</a>) and it works very well on the plant tissue, together with the ChIP-seq kit and Bioruptor. </span></p>
<p>Thanks Diagenode for saving my PhD!</p>',
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		'id' => '2173',
		'antibody_id' => '115',
		'name' => 'H3K4me3 Antibody',
		'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
		'label1' => 'Validation data',
		'info1' => '<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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		'info2' => '<p>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called "histone code". Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Methylation of histone H3K4 is associated with activation of gene transcription.</p>
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	'id' => '2172',
	'antibody_id' => '115',
	'name' => 'H3K4me3 polyclonal antibody  (sample size)',
	'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone H3 containing the trimethylated lysine 4 (H3K4me3), using a KLH-conjugated synthetic peptide.</span></p>
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
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<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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$testimonials = '<blockquote><p>I have used Diagenode's antibodies for my ChIP&ndash;qPCR experiments in HK-2 cells. The antibodies performed very well in our experiments with specific signal, and good signal to noise ratio in the promoter of the gapdh gene.</p>
<center><img src="../../img/categories/antibodies/H3K4me3-hk2.png" /></center>
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong> ChIP assays were performed using human HK-2 cells, the Diagenode antibody against H3K4me3 (Cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with standard fixation and sonication protocol, using sheared chromatin from 4 million cells. A total amount of 4 ug of antibody were used per ChIP experiment, normal mouse IgG (4 &mu;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). These results are in accordance with the observation that trimethylation of K4 at histone H3 is associated with the promoters of active genes.</small></p><cite>Claudio Cappelli PhD. Post-Doc. Investigator, Laboratory of Molecular Pathology, Institute of Biochemestry and Microbiology, University Austral of Chile, about H3K4me3 polyclonal antibody Premium, 50 μl size.</cite></blockquote>
<blockquote><p>In life sciences, epigenetics is nowadays the most rapid developing field with new astonishing discoveries made every day. To keep pace with this field, we are in need of reliable tools to foster our research - tools Diagenode provides us with. From <strong>antibodies</strong> to <strong>automated solutions</strong> - all from one source and with robust support. Antibodies used in our lab: H3K27me3 polyclonal antibody &ndash; Premium, H3K4me3 polyclonal antibody &ndash; Premium, H3K9me3 polyclonal antibody &ndash; Premium, H3K4me1 polyclonal antibody &ndash; Premium, CTCF polyclonal antibody &ndash; Classic, Rabbit IgG.</p><cite>Dr. Florian Uhle, Dept. of Anesthesiology, Heidelberg University Hospital, Germany</cite></blockquote>
<blockquote><p>We use the <strong>Bioruptor</strong> sonication device and the antibody against the histone modification H3K4me3 in our lab. The Bioruptor device is used for the shearing of chromatin in ChIP-Seq experiments and for generation of protein lysates (whole cell extracts). Thanks to the Bioruptor device we achieve excellent and reproducible results in both applications. The <strong>H3K4me3 antibody</strong> is used in our ChIP-Seq experiments as well as Western Blotting. With this antibody we are able to generate highly enriched ChIP-Seq samples with extremely low background. In Western Blot we can detect one specific, strong band with the H3K4me3 antibody.</p>
<p>Diagenode provides not only very good products for research but also an excellent customer support.</p><cite>Dr Lora Dimitrova, Charité-Universitätsmedizin Berlin, Germany</cite></blockquote>
<blockquote><p><span>I work with Diagenode&rsquo;s <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> and shear the DNA on the <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a> for the last year and I have to say that these two products saved my PhD project! Some time ago, our well-established ChIP protocol suddenly stopped to work and after long time of figuring out the reason, we invested into <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a>. </span><span>I am very satisfied from the way it works, plus it&rsquo;s super quiet! Combining the sonicator with the <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> we finally got things working.&nbsp;</span><span>I have also decided to try the <a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns">Microplex Library Prep kit</a>, which is amazing. I have been working with other kits and I find this one efficient and very easy to use. </span><span>Recently, I have tested one of the epigenetics antibody (<a href="../products/search?keyword=H3K4me3">H3K4me3</a>) and it works very well on the plant tissue, together with the ChIP-seq kit and Bioruptor. </span></p>
<p>Thanks Diagenode for saving my PhD!</p><cite>Kamila Kwasniewska, Plant Developmental Genetics, Smurfit Institute, Trinity College, Dublin</cite></blockquote>
<blockquote><p>I am working with the <a href="../p/true-microchip-kit-x16-16-rxns">True MicroChIP</a> &amp; <a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns">Microplex Library Preparation</a> Kits and several histone modification antibodies like H3K27ac, H3K4me3, H3K36me3, and H3K27me3.&nbsp;I got always very good and reproducible results for my ChIP-seq experiments.</p><cite>Andrea Thiesen, ZMB, Developmental Biology, Prof. Dr. Andrea Vortkamp´s lab, University Duisburg-Essen, Germany</cite></blockquote>
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	'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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</div>
<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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<p><a href="https://www.diagenode.com/en/categories/cutandtag">Products for CUT&amp;Tag assay</a></p>
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	'description' => 'Early embryonic development is characterized by dramatic changes in cell potency and chromatin organization. The role of histone variants in the context of chromatin remodeling during embryogenesis remains under investigated. In particular, the nuclear distribution of the histone variant H2A.Z and its modifications have not been examined. Here we investigated the dynamics of acetylation of H2A.Z and two other active chromatin marks, H3K9ac and H3K36me3, throughout murine and bovine pre-implantation development. We show that H2A.Z distribution is dynamic during the earliest stages of mouse development, with protein levels significantly varying across stages and lowest at the 2-cell stage. When present, H2A.Z localizes preferentially to euchromatin at all stages analyzed. H2A.Z is acetylated in preimplantation blastomeres and is preferentially localized to euchromatin, in line with the known role of H2A.Zac in transcriptional activation. Interestingly, however, H2A.Zac is undetectable in mouse embryos at the 2-cell stage, the time of major embryonic genome activation (EGA). Similarly, H3K36me3 is present exclusively in the maternal chromatin immediately after fertilization but becomes undetectable in interphase nuclei at the 2-cell stage, suggesting uncoupling of these active marks with global embryonic transcription activation. In bovine embryos, which undergo EGA at the 8-cell stage, H2A.Zac can be detected in zygotes, 4-, 8- and 16-cell stage embryos as well as in blastocysts, indicating that the dynamics of H2A.Zac is not conserved in mammals. In contrast, H3K36me3 displays mostly undetectable and heterogeneous localization pattern throughout bovine pre-implantation development. Thus, our results suggest that ‘canonical’ active chromatin marks exhibit a dynamic behavior in embryonic nuclei, which is both stage- and speciesspecific. We hypothesize that chromatin of early embryonic nuclei is subject to fine-tuning through differential acquisition of histone marks, allowing for proper chromatin remodeling and developmental progression in a species-specific fashion.',
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	'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/22647320',
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<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
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<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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			'created' => '2015-06-29 14:08:20',
			'locale' => 'jpn'
		),
		'Antibody' => array(
			'host' => '*****',
			'id' => '115',
			'name' => 'H3K4me3 polyclonal antibody',
			'description' => 'Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called “histone code”. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Methylation of histone H3K4 is associated with activation of gene transcription.',
			'clonality' => '',
			'isotype' => '',
			'lot' => 'A8034D',
			'concentration' => '1.3 &micro;g/&micro;l',
			'reactivity' => 'Human, mouse, pig, zebrafish, trout, Daphnia, Arabidopsis, rice, tomato, maize, poplar, silena latifolia, wide range expected.',
			'type' => 'Polyclonal, <strong>ChIP grade, ChIP-seq grade</strong>',
			'purity' => 'Affinity purified polyclonal antibody.',
			'classification' => 'Premium',
			'application_table' => '<table>
<thead>
<tr>
<th>Applications</th>
<th>Suggested dilution</th>
<th>References</th>
</tr>
</thead>
<tbody>
<tr>
<td>ChIP/ChIP-seq<sup>*</sup></td>
<td><span style="font-family: Helvetica;">0.5 - 1&nbsp;&micro;g</span></td>
<td>Fig 1, 2</td>
</tr>
<tr>
<td>CUT&amp;Tag</td>
<td>0.5 &micro;g</td>
<td>Fig 3</td>
</tr>
<tr>
<td>ELISA</td>
<td>1:2,000</td>
<td>Fig 4</td>
</tr>
<tr>
<td>Dot Blotting</td>
<td>1:1000</td>
<td>Fig 5</td>
</tr>
<tr>
<td>Western Blotting</td>
<td>1:1,000</td>
<td>Fig 6</td>
</tr>
<tr>
<td>Immunofluorescence</td>
<td>1:200</td>
<td>Fig 7</td>
</tr>
</tbody>
</table>
<p></p>
<p><small><sup>*</sup> Please note that the optimal antibody amount per IP should be determined by the end-user. We recommend testing 0.5-5 &micro;g per IP.</small></p>',
			'storage_conditions' => 'Store at -20°C; for long storage, store at -80°C. Avoid multiple freeze-thaw cycles.',
			'storage_buffer' => 'PBS containing 0.05% azide and 0.05% ProClin 300.',
			'precautions' => 'This product is for research use only. Not for use in diagnostic or therapeutic procedures.',
			'uniprot_acc' => '',
			'slug' => '',
			'meta_keywords' => '',
			'meta_description' => '',
			'modified' => '2022-08-17 11:57:06',
			'created' => '0000-00-00 00:00:00',
			'select_label' => '115 - H3K4me3 polyclonal antibody (A8034D - 1.3 &micro;g/&micro;l - Human, mouse, pig, zebrafish, trout, Daphnia, Arabidopsis, rice, tomato, maize, poplar, silena latifolia, wide range expected. - Affinity purified polyclonal antibody. - Rabbit)'
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			(int) 232 => array(
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			(int) 233 => array(
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		'name' => 'H3K4me3 polyclonal antibody  (sample size)',
		'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone H3 containing the trimethylated lysine 4 (H3K4me3), using a KLH-conjugated synthetic peptide.</span></p>
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
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<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
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<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
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<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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		'meta_description' => 'H3K4me3 polyclonal antibody - Premium (sample size)',
		'modified' => '2022-06-29 14:43:38',
		'created' => '2015-06-29 14:08:20',
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		'id' => '115',
		'name' => 'H3K4me3 polyclonal antibody',
		'description' => 'Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called “histone code”. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Methylation of histone H3K4 is associated with activation of gene transcription.',
		'clonality' => '',
		'isotype' => '',
		'lot' => 'A8034D',
		'concentration' => '1.3 &micro;g/&micro;l',
		'reactivity' => 'Human, mouse, pig, zebrafish, trout, Daphnia, Arabidopsis, rice, tomato, maize, poplar, silena latifolia, wide range expected.',
		'type' => 'Polyclonal, <strong>ChIP grade, ChIP-seq grade</strong>',
		'purity' => 'Affinity purified polyclonal antibody.',
		'classification' => 'Premium',
		'application_table' => '<table>
<thead>
<tr>
<th>Applications</th>
<th>Suggested dilution</th>
<th>References</th>
</tr>
</thead>
<tbody>
<tr>
<td>ChIP/ChIP-seq<sup>*</sup></td>
<td><span style="font-family: Helvetica;">0.5 - 1&nbsp;&micro;g</span></td>
<td>Fig 1, 2</td>
</tr>
<tr>
<td>CUT&amp;Tag</td>
<td>0.5 &micro;g</td>
<td>Fig 3</td>
</tr>
<tr>
<td>ELISA</td>
<td>1:2,000</td>
<td>Fig 4</td>
</tr>
<tr>
<td>Dot Blotting</td>
<td>1:1000</td>
<td>Fig 5</td>
</tr>
<tr>
<td>Western Blotting</td>
<td>1:1,000</td>
<td>Fig 6</td>
</tr>
<tr>
<td>Immunofluorescence</td>
<td>1:200</td>
<td>Fig 7</td>
</tr>
</tbody>
</table>
<p></p>
<p><small><sup>*</sup> Please note that the optimal antibody amount per IP should be determined by the end-user. We recommend testing 0.5-5 &micro;g per IP.</small></p>',
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		'precautions' => 'This product is for research use only. Not for use in diagnostic or therapeutic procedures.',
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			'antibody_id' => '115',
			'name' => 'H3K4me3 Antibody',
			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
			'label1' => 'Validation data',
			'info1' => '<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
</div>
</div>
<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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			'modified' => '2024-11-19 16:51:19',
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			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/ideal-chipseq-for-histones-complete-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<p>Don&rsquo;t risk wasting your precious sequencing samples. Diagenode&rsquo;s validated <strong>iDeal ChIP-seq kit for Histones</strong> has everything you need for a successful start-to-finish <strong>ChIP of histones prior to Next-Generation Sequencing</strong>. The complete kit contains all buffers and reagents for cell lysis, chromatin shearing, immunoprecipitation and DNA purification. In addition, unlike competing solutions, the kit contains positive and negative control antibodies (H3K4me3 and IgG, respectively) as well as positive and negative control PCR primers pairs (GAPDH TSS and Myoglobin exon 2, respectively) for your convenience and a guarantee of optimal results. The kit has been validated on multiple histone marks.</p>
<p>&nbsp;The &nbsp;iDeal ChIP-seq kit for Histones<strong> </strong>is perfect for <strong>cells</strong> (<strong>100,000 cells</strong> to <strong>1,000,000 cells</strong> per IP) and has been validated for <strong>tissues</strong> (<strong>1.5 mg</strong> to <strong>5 mg</strong> of tissue per IP).</p>
<p>&nbsp;The iDeal ChIP-seq kit is the only kit on the market validated for the major sequencing systems. Our expertise in ChIP-seq tools allows reproducible and efficient results every time.</p>
<p></p>
<p>&nbsp;<strong></strong></p>
<p></p>',
			'label1' => 'Characteristics',
			'info1' => '<ul style="list-style-type: disc;">
<li>Highly <strong>optimized</strong> protocol for ChIP-seq from cells and tissues</li>
<li><strong>Validated</strong> for ChIP-seq with multiple histones marks</li>
<li>Most <strong>complete</strong> kit available (covers all steps, including the control antibodies and primers)</li>
<li>Optimized chromatin preparation in combination with the Bioruptor ensuring the best <strong>epitope integrity</strong></li>
<li>Magnetic beads make ChIP easy, fast and more <strong>reproducible</strong></li>
<li>Combination with Diagenode ChIP-seq antibodies provides high yields with excellent <strong>specificity</strong> and <strong>sensitivity</strong></li>
<li>Purified DNA suitable for any downstream application</li>
<li>Easy-to-follow protocol</li>
</ul>
<p>Note: to obtain optimal results, this kit should be used in combination with the DiaMag1.5 - magnetic rack.</p>
<h3>ChIP-seq on cells</h3>
<p><img src="https://www.diagenode.com/img/product/kits/iDeal-kit-C01010053-figure-1.jpg" alt="Figure 1A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1A. The high consistency of the iDeal ChIP-seq kit on the Ion Torrent&trade; PGM&trade; (Life Technologies) and GAIIx (Illumina<sup>&reg;</sup>)</strong><br /> ChIP was performed on sheared chromatin from 1 million HelaS3 cells using the iDeal ChIP-seq kit and 1 &micro;g of H3K4me3 positive control antibody. Two different biological samples have been analyzed using two different sequencers - GAIIx (Illumina<sup>&reg;</sup>) and PGM&trade; (Ion Torrent&trade;). The expected ChIP-seq profile for H3K4me3 on the GAPDH promoter region has been obtained.<br /> Image A shows a several hundred bp along chr12 with high similarity of read distribution despite the radically different sequencers. Image B is a close capture focusing on the GAPDH that shows that even the peak structure is similar.</p>
<p class="text-center"><strong>Perfect match between ChIP-seq data obtained with the iDeal ChIP-seq workflow and reference dataset</strong></p>
<p><img src="https://www.diagenode.com/img/product/kits/perfect-match-between-chipseq-data.png" alt="Figure 1B" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>
<p><img src="https://www.diagenode.com/img/product/kits/iDeal-kit-C01010053-figure-2.jpg" alt="Figure 2" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 2. Efficient and easy chromatin shearing using the Bioruptor<sup>&reg;</sup> and Shearing buffer iS1 from the iDeal ChIP-seq kit</strong><br /> Chromatin from 1 million of Hela cells was sheared using the Bioruptor<sup>&reg;</sup> combined with the Bioruptor<sup>&reg;</sup> Water cooler (Cat No. BioAcc-cool) during 3 rounds of 10 cycles of 30 seconds &ldquo;ON&rdquo; / 30 seconds &ldquo;OFF&rdquo; at HIGH power setting (position H). Diagenode 1.5 ml TPX tubes (Cat No. M-50001) were used for chromatin shearing. Samples were gently vortexed before and after performing each sonication round (rounds of 10 cycles), followed by a short centrifugation at 4&deg;C to recover the sample volume at the bottom of the tube. The sheared chromatin was then decross-linked as described in the kit manual and analyzed by agarose gel electrophoresis.</p>
<p><img src="https://www.diagenode.com/img/product/kits/iDeal-kit-C01010053-figure-3.jpg" alt="Figure 3" style="display: block; margin-left: auto; margin-right: auto;" width="264" height="320" /></p>
<p><strong>Figure 3. Validation of ChIP by qPCR: reliable results using Diagenode&rsquo;s ChIP-seq grade H3K4me3 antibody, isotype control and sets of validated primers</strong><br /> Specific enrichment on positive loci (GAPDH, EIF4A2, c-fos promoter regions) comparing to no enrichment on negative loci (TSH2B promoter region and Myoglobin exon 2) was detected by qPCR. Samples were prepared using the Diagenode iDeal ChIP-seq kit. Diagenode ChIP-seq grade antibody against H3K4me3 and the corresponding isotype control IgG were used for immunoprecipitation. qPCR amplification was performed with sets of validated primers.</p>
<h3>ChIP-seq on tissue</h3>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-figure-h3k4me3.jpg" alt="Figure 4A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 4A.</strong> Chromatin Immunoprecipitation has been performed using chromatin from mouse liver tissue, the iDeal ChIP-seq kit for Histones and the Diagenode ChIP-seq-grade H3K4me3 (Cat. No. C15410003) antibody. The IP'd DNA was subsequently analysed on an Illumina&reg; HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in a region surrounding the GAPDH positive control gene.</p>
<p><img src="https://www.diagenode.com/img/product/kits/match-of-the-top40-peaks-2.png" alt="Figure 4B" caption="false" style="display: block; margin-left: auto; margin-right: auto;" width="700" height="280" /></p>
<p><strong>Figure 4B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>',
			'label2' => 'Species, cell lines, tissues tested',
			'info2' => '<p>The iDeal ChIP-seq Kit for Histones is compatible with a broad variety of cell lines, tissues and species - some examples are shown below. Other species / cell lines / tissues can be used with this kit.</p>
<p><u>Cell lines:</u></p>
<p>Human: A549, A673, CD8+ T, Blood vascular endothelial cells, Lymphatic endothelial cells, fibroblasts, K562, MDA-MB231</p>
<p>Pig: Alveolar macrophages</p>
<p>Mouse: C2C12, primary HSPC, synovial fibroblasts, HeLa-S3, FACS sorted cells from embryonic kidneys, macrophages, mesodermal cells, myoblasts, NPC, salivary glands, spermatids, spermatocytes, skeletal muscle stem cells, stem cells, Th2</p>
<p>Hamster: CHO</p>
<p>Other cell lines / species: compatible, not tested</p>
<p><u>Tissues</u></p>
<p>Bee &ndash; brain</p>
<p>Daphnia &ndash; whole animal</p>
<p>Horse &ndash; brain, heart, lamina, liver, lung, skeletal muscles, ovary</p>
<p>Human &ndash; Erwing sarcoma tumor samples</p>
<p>Other tissues: compatible, not tested</p>
<p>Did you use the iDeal ChIP-seq for Histones Kit on other cell line / tissue / species? <a href="mailto:agnieszka.zelisko@diagenode.com?subject=Species, cell lines, tissues tested with the iDeal ChIP-seq Kit for TF&amp;body=Dear Customer,%0D%0A%0D%0APlease, leave below your feedback about the iDeal ChIP-seq for Transcription Factors (cell / tissue type, species, other information...).%0D%0A%0D%0AThank you for sharing with us your experience !%0D%0A%0D%0ABest regards,%0D%0A%0D%0AAgnieszka Zelisko-Schmidt, PhD">Let us know!</a></p>',
			'label3' => '  Additional solutions compatible with iDeal ChIP-seq Kit for Histones',
			'info3' => '<p><a href="../p/chromatin-shearing-optimization-kit-low-sds-100-million-cells">Chromatin EasyShear Kit - Ultra Low SDS </a>optimizes chromatin shearing, a critical step for ChIP.</p>
<p>&nbsp;The <a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq">MicroPlex Library Preparation Kit </a>provides easy and optimal &nbsp;library preparation of ChIPed samples.</p>
<p><a href="../categories/chip-seq-grade-antibodies">ChIP-seq grade anti-histone antibodies</a> provide high yields with excellent specificity and sensitivity.</p>
<p>&nbsp;Plus, for our IP-Star Automation users for automated ChIP, check out our <a href="../p/auto-ideal-chip-seq-kit-for-histones-x24-24-rxns">automated</a> version of this kit.</p>',
			'format' => '4 chrom. prep./24 IPs',
			'catalog_number' => 'C01010051',
			'old_catalog_number' => 'AB-001-0024',
			'sf_code' => 'C01010051-',
			'type' => 'RFR',
			'search_order' => '04-undefined',
			'price_EUR' => '915',
			'price_USD' => '1130',
			'price_GBP' => '840',
			'price_JPY' => '143335',
			'price_CNY' => '',
			'price_AUD' => '2825',
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			'slug' => 'ideal-chip-seq-kit-x24-24-rxns',
			'meta_title' => 'iDeal ChIP-seq kit x24',
			'meta_keywords' => '',
			'meta_description' => 'iDeal ChIP-seq kit x24',
			'modified' => '2023-04-20 16:00:20',
			'created' => '2015-06-29 14:08:20',
			'ProductsRelated' => array(
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		(int) 1 => array(
			'id' => '1839',
			'antibody_id' => null,
			'name' => 'iDeal ChIP-seq kit for Transcription Factors',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/ideal-chipseq-transcription-factors-x10-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<div class="row">
<div class="small-12 medium-8 large-8 columns"><br />
<p><span style="font-weight: 400;">Diagenode&rsquo;s <strong>iDeal ChIP-seq Kit for Transcription Factors</strong> is a highly validated solution for robust transcription factor and other non-histone proteins ChIP-seq results and contains everything you need for start-to-finish </span><b>ChIP </b><span style="font-weight: 400;">prior to </span><b>Next-Generation Sequencing</b><span style="font-weight: 400;">. This complete solution contains all buffers and reagents for cell lysis, chromatin shearing, immunoprecipitation, and DNA purification. In addition, unlike competing solutions, the kit contains positive and negative control antibodies (CTCF and IgG, respectively) as well as positive and negative control PCR primers pairs (H19 and Myoglobin exon 2, respectively) for your convenience and a guarantee of optimal results. <br /></span></p>
</div>
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<p><span style="font-weight: 400;">The </span><b>&nbsp;iDeal ChIP-seq kit for Transcription Factors </b><span style="font-weight: 400;">is compatible for cells or tissues:</span></p>
<table style="width: 419px; margin-left: auto; margin-right: auto;">
<tbody>
<tr>
<td style="width: 144px;"></td>
<td style="width: 267px; text-align: center;"><span style="font-weight: 400;">Amount per IP</span></td>
</tr>
<tr>
<td style="width: 144px;">Cells</td>
<td style="width: 267px; text-align: center;"><strong>4,000,000</strong></td>
</tr>
<tr>
<td style="width: 144px;">Tissues</td>
<td style="width: 267px; text-align: center;"><strong>30 mg</strong></td>
</tr>
</tbody>
</table>
<p><span style="font-weight: 400;">The iDeal ChIP-seq kit is the only kit on the market validated for major sequencing systems. Our expertise in ChIP-seq tools allows reproducible and efficient results every time. </span></p>
<p></p>
<p></p>',
			'label1' => 'Characteristics',
			'info1' => '<ul>
<li><span style="font-weight: 400;"><strong>Highly optimized protocol</strong> for ChIP-seq from cells and tissues</span></li>
<li><span style="font-weight: 400;"><strong>Validated</strong> for <strong>ChIP-seq</strong> with multiple transcription factors and non-histone targets<br /></span></li>
<li><span style="font-weight: 400;"><strong>Most complete kit</strong> available (covers all steps, including the control antibodies and primers)<br /></span></li>
<li><span style="font-weight: 400;"><strong>Magnetic beads</strong> make ChIP <strong>easy</strong>, <strong>fast</strong> and more <strong>reproducible</strong></span></li>
<li><span style="font-weight: 400;">Combination with Diagenode ChIP-seq antibodies provides <strong>high yields</strong> with excellent <strong>specificity</strong> and <strong>sensitivity</strong><br /></span></li>
<li><span style="font-weight: 400;">Purified DNA suitable for any downstream application</span></li>
<li><span style="font-weight: 400;">Easy-to-follow protocol</span></li>
</ul>
<p><span style="font-weight: 400;"></span></p>
<p>&nbsp;</p>
<h3>ChIP-seq on cells</h3>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-ctcf-diagenode.jpg" alt="CTCF Diagenode" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1.</strong> (A) Chromatin Immunoprecipitation has been performed using chromatin from HeLa cells, the iDeal ChIP-seq kit for Transcription Factors and the Diagenode ChIP-seq-grade CTCF antibody. The IP'd DNA was subsequently analysed on an Illumina<sup>&reg;</sup> HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in a region surrounding the GAPDH positive control gene.</p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-figure-b-total-diagendoe-peaks.png" alt="CTCF Diagenode" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>
<p>&nbsp;</p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-TF-chip-seq-A.png" alt="ChIP-seq figure A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-TF-chip-seq-B.png" alt="ChIP-seq figure B" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-TF-chip-seq-C.png" alt="ChIP-seq figure C" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 2.</strong> Chromatin Immunoprecipitation has been performed using chromatin from HeLa cells, the iDeal ChIP-seq kit for Transcription Factors and the Diagenode ChIP-seq-grade HDAC1 (A), LSD1 (B) and p53 antibody (C). The IP'd DNA was subsequently analysed on an Illumina<sup>&reg;</sup> Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in regions of chromosome 3 (A), chromosome 12 (B) and chromosome 6 (C) respectively.</p>
<p>&nbsp;</p>
<h3>ChIP-seq on tissue</h3>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-figure-3a.jpg" alt="ChIP-seq figure A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 3A.</strong> Chromatin Immunoprecipitation has been performed using chromatin from mouse liver tissue, the iDeal ChIP-seq kit for Transcription Factors and the Diagenode ChIP-seq-grade CTCF antibody. The IP'd DNA was subsequently analysed on an Illumina&reg; HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in a region surrounding the Vwf positive control gene.</p>
<p><img src="https://www.diagenode.com/img/product/kits/match-of-the-top40-peaks.png" alt="Match of the Top40 peaks" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 3B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>',
			'label2' => 'Species, cell lines, tissues tested',
			'info2' => '<p>The iDeal ChIP-seq Kit for Transcription Factors is compatible with a broad variety of cell lines, tissues and species - some examples are shown below. Other species / cell lines / tissues can be used with this kit.</p>
<p><span style="text-decoration: underline;">Cell lines:</span></p>
<p>Human: A549, A673, BT-549, CD4 T, HCC1806, HeLa, HepG2, HFF, HK-GFP-MR, ILC,&nbsp;K562, KYSE-180, LapC4, M14, MCF7, MDA-MB-231, MDA-MB-436, RDES, SKNO1, VCaP, U2-OS, ZR-75-1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;</p>
<p>Mouse: ESC, NPCs, BZ, GT1-7, acinar cells, HSPCs, Th2 cells, keratinocytes</p>
<p>Cattle: pbMEC, <span>MAC-T</span></p>
<p><span>Other cell lines / species: compatible, not tested</span></p>
<p><span style="text-decoration: underline;">Tissues:</span></p>
<p>Mouse: kidney, heart, brain, iris, liver, limbs from E10.5 embryos</p>
<p><span>Horse: l</span>iver, brain, heart, lung, skeletal muscle, lamina, ovary</p>
<p>Other tissues: compatible, not tested</p>
<p><span style="text-decoration: underline;">ChIP on yeast</span></p>
<p>The iDeal ChIP-seq kit for TF is compatible with yeast samples. Check out our <strong><a href="https://www.diagenode.com/files/products/kits/Application_Note-ChIP_on_Yeast.pdf">Application Note</a></strong>&nbsp;presenting an optimized detailed protocol for ChIP on yeast.</p>
<p></p>
<p>Did you use the iDeal ChIP-seq for Transcription Factors Kit on other cell line / tissue / species? <a href="mailto:agnieszka.zelisko@diagenode.com?subject=Species, cell lines, tissues tested with the iDeal ChIP-seq Kit for TF&amp;body=Dear Customer,%0D%0A%0D%0APlease, leave below your feedback about the iDeal ChIP-seq for Transcription Factors (cell / tissue type, species, other information...).%0D%0A%0D%0AThank you for sharing with us your experience !%0D%0A%0D%0ABest regards,%0D%0A%0D%0AAgnieszka Zelisko-Schmidt, PhD">Let us know!</a></p>',
			'label3' => 'Additional solutions compatible with iDeal ChIP-seq kit for Transcription Factors',
			'info3' => '<p><span style="font-weight: 400;">The</span> <a href="https://www.diagenode.com/en/p/chromatin-shearing-optimization-kit-low-sds-for-tfs-25-rxns"><span style="font-weight: 400;">Chromatin EasyShear Kit &ndash; Low SDS </span></a><span style="font-weight: 400;">is the kit compatible with the iDeal ChIP-seq kit for TF, recommended for the optimization of chromatin shearing, a critical step for ChIP.</span></p>
<p><a href="https://www.diagenode.com/en/p/chip-cross-link-gold-600-ul"><span style="font-weight: 400;">ChIP Cross-link Gold</span></a> <span style="font-weight: 400;">should be used in combination with formaldehyde when working with higher order and/or dynamic interactions, for efficient protein-protein fixation.</span></p>
<p><span style="font-weight: 400;">For library preparation of immunoprecipitated samples we recommend to use the </span><b>&nbsp;</b><a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq"><span style="font-weight: 400;">MicroPlex Library Preparation Kit</span></a><span style="font-weight: 400;"> - validated for library preparation from picogram inputs.</span></p>
<p><a href="https://www.diagenode.com/en/categories/chip-seq-grade-antibodies"><span style="font-weight: 400;">ChIP-seq grade antibodies</span></a><span style="font-weight: 400;"> provide high yields with excellent specificity and sensitivity.</span></p>
<p><span style="font-weight: 400;">Check the list of available </span><a href="https://www.diagenode.com/en/categories/primer-pairs"><span style="font-weight: 400;">Primer pairs</span></a><span style="font-weight: 400;"> designed for high specificity to specific genomic regions.</span></p>
<p><span style="font-weight: 400;">Plus, for our <a href="https://www.diagenode.com/en/categories/ip-star">IP-Star Automation</a> users for automated ChIP, check out our <a href="https://www.diagenode.com/en/p/auto-ideal-chip-seq-kit-for-transcription-factors-x24-24-rxns">automated version</a> of this kit.</span></p>',
			'format' => '4 chrom. prep./24 IPs',
			'catalog_number' => 'C01010055',
			'old_catalog_number' => '',
			'sf_code' => 'C01010055-',
			'type' => 'RFR',
			'search_order' => '04-undefined',
			'price_EUR' => '915',
			'price_USD' => '1130',
			'price_GBP' => '840',
			'price_JPY' => '143335',
			'price_CNY' => '',
			'price_AUD' => '2825',
			'country' => 'ALL',
			'except_countries' => 'None',
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			'in_stock' => false,
			'featured' => true,
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			'master' => true,
			'last_datasheet_update' => '0000-00-00',
			'slug' => 'ideal-chip-seq-kit-for-transcription-factors-x24-24-rxns',
			'meta_title' => 'iDeal ChIP-seq kit for Transcription Factors x24',
			'meta_keywords' => '',
			'meta_description' => 'iDeal ChIP-seq kit for Transcription Factors x24',
			'modified' => '2023-06-20 18:27:37',
			'created' => '2015-06-29 14:08:20',
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		(int) 2 => array(
			'id' => '1856',
			'antibody_id' => null,
			'name' => 'True MicroChIP-seq Kit',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/truemicrochipseq-kit-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<p>The <b>True </b><b>MicroChIP-seq</b><b> kit </b>provides a robust ChIP protocol suitable for the investigation of histone modifications within chromatin from as few as <b>10 000 cells</b>, including <b>FACS sorted cells</b>. The kit can be used for chromatin preparation for downstream ChIP-qPCR or ChIP-seq analysis. The <b>complete kit</b> contains everything you need for start-to-finish ChIP including all validated buffers and reagents for chromatin shearing, immunoprecipitation and DNA purification for exceptional <strong>ChIP-qPCR</strong> or <strong>ChIP-seq</strong> results. In addition, positive control antibodies and negative control PCR primers are included for your convenience and assurance of result sensitivity and specificity.</p>
<p>The True MicroChIP-seq kit offers unique benefits:</p>
<ul>
<li>An <b>optimized chromatin preparation </b>protocol compatible with low number of cells (<b>10.000</b>) in combination with the Bioruptor&trade; shearing device</li>
<li>Most <b>complete kit </b>available (covers all steps and includes control antibodies and primers)</li>
<li><b>Magnetic beads </b>make ChIP easy, fast, and more reproducible</li>
<li>MicroChIP DiaPure columns (included in the kit) enable the <b>maximum recovery </b>of immunoprecipitation DNA suitable for any downstream application</li>
<li><b>Excellent </b><b>ChIP</b><b>-seq </b>result when combined with <a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq">MicroPlex</a><a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq"> Library Preparation kit </a>adapted for low input</li>
</ul>
<p>For fast ChIP-seq on low input &ndash; check out Diagenode&rsquo;s <a href="https://www.diagenode.com/en/p/uchipmentation-for-histones-24-rxns">&micro;</a><a href="https://www.diagenode.com/en/p/uchipmentation-for-histones-24-rxns">ChIPmentation</a><a href="https://www.diagenode.com/en/p/uchipmentation-for-histones-24-rxns"> for histones</a>.</p>
<p><sub>The True MicroChIP-seq kit, Cat. No. C01010132 is an upgraded version of the kit True MicroChIP, Cat. No. C01010130, with the new validated protocols (e.g. FACS sorted cells) and MicroChIP DiaPure columns included in the kit.</sub></p>',
			'label1' => 'Characteristics',
			'info1' => '<ul>
<li><b>Revolutionary:</b> Only 10,000 cells needed for complete ChIP-seq procedure</li>
<li><b>Validated on</b> studies for histone marks</li>
<li><b>Automated protocol </b>for the IP-Star<sup>&reg;</sup> Compact Automated Platform available</li>
</ul>
<p></p>
<p>The True MicroChIP-seq kit protocol has been optimized for the use of 10,000 - 100,000 cells per immunoprecipitation reaction. Regarding chromatin immunoprecipitation, three protocol variants have been optimized:<br />starting with a batch, starting with an individual sample and starting with the FACS-sorted cells.</p>
<div><button id="readmorebtn" style="background-color: #b02736; color: white; border-radius: 5px; border: none; padding: 5px;">Show Workflow</button></div>
<p><br /> <img src="https://www.diagenode.com/img/product/kits/workflow-microchip.png" id="workflowchip" class="hidden" width="600px" /></p>
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<div>
<h3>High efficiency ChIP on 10,000 cells</h3>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><img src="https://www.diagenode.com/img/product/kits/true-micro-chip-histone-results.png" width="800px" /></div>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><center>
<p><small><strong>Figure 1.&nbsp;</strong>ChIP efficiency on 10,000 cells. ChIP was performed on human Hela cells using the Diagenode antibodies <a href="https://www.diagenode.com/en/p/h3k4me3-polyclonal-antibody-premium-50-ug-50-ul">H3K4me3</a> (Cat. No. C15410003), <a href="https://www.diagenode.com/en/p/h3k27ac-polyclonal-antibody-classic-50-mg-42-ml">H3K27ac</a> (C15410174), <a href="https://www.diagenode.com/en/p/h3k9me3-polyclonal-antibody-classic-50-ug">H3K9me3</a> (C15410056) and <a href="https://www.diagenode.com/en/p/h3k27me3-polyclonal-antibody-classic-50-mg-34-ml">H3K27me3</a> (C15410069). Sheared chromatin from 10,000 cells and 0.1 &micro;g (H3K27ac), 0.25 &micro;g (H3K4me3 and H3K27me3) or 0.5 &micro;g (H3K9me3) of the antibody were used per IP. Corresponding amount of IgG was used as control. Quantitative PCR was performed with primers for corresponding positive and negative loci. Figure shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
</center></div>
</div>
<div>
<h3>True MicroChIP-seq protocol in a combination with MicroPlex library preparation kit results in reliable and accurate sequencing data</h3>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><img src="https://www.diagenode.com/img/product/kits/fig2-truemicro.jpg" alt="True MicroChip results" width="800px" /></div>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><center>
<p><small><strong>Figure 2.</strong> Integrative genomics viewer (IGV) visualization of ChIP-seq experiments using 50.000 of K562 cells. ChIP has been performed accordingly to True MicroChIP protocol followed by the library preparation using MicroPlex Library Preparation Kit (C05010001). The above figure shows the peaks from ChIP-seq experiments using the following antibodies: H3K4me1 (C15410194), H3K9/14ac (C15410200), H3K27ac (C15410196) and H3K36me3 (C15410192).</small></p>
</center></div>
</div>
<div>
<h3>Successful chromatin profiling from 10.000 of FACS-sorted cells</h3>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><img src="https://www.diagenode.com/img/product/kits/fig3ab-truemicro.jpg" alt="small non coding RNA" width="800px" /></div>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><center>
<p><small><strong>Figure 3.</strong> (A) Integrative genomics viewer (IGV) visualization of ChIP-seq experiments and heatmap 3kb upstream and downstream of the TSS (B) for H3K4me3. ChIP has been performed using 10.000 of FACS-sorted cells (K562) and H3K4me3 antibody (C15410003) accordingly to True MicroChIP protocol followed by the library preparation using MicroPlex Library Preparation Kit (C05010001). Data were compared to ENCODE standards.</small></p>
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<p>
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			'label2' => 'Additional solutions compatible with the True MicroChIP-seq Kit',
			'info2' => '<p><span style="font-weight: 400;">The <a href="https://www.diagenode.com/en/p/chromatin-shearing-optimization-kit-high-sds-100-million-cells">Chromatin EasyShear Kit &ndash; High SDS</a></span><span style="font-weight: 400;">&nbsp;Recommended for the optimizing chromatin shearing.</span></p>
<p><a href="https://www.diagenode.com/en/categories/chip-seq-grade-antibodies"><span style="font-weight: 400;">ChIP-seq grade antibodies</span></a><span style="font-weight: 400;"> for high yields, specificity, and sensitivity.</span></p>
<p><span style="font-weight: 400;">Check the list of available </span><a href="https://www.diagenode.com/en/categories/primer-pairs"><span style="font-weight: 400;">primer pairs</span></a><span style="font-weight: 400;"> designed for high specificity to specific genomic regions.</span></p>
<p><span style="font-weight: 400;">For library preparation of immunoprecipitated samples we recommend to use the </span><b>&nbsp;</b><a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq"><span style="font-weight: 400;">MicroPlex Library Preparation Kit</span></a><span style="font-weight: 400;"> - validated for library preparation from picogram inputs.</span></p>
<p><span style="font-weight: 400;">For IP-Star Automation users, check out the </span><a href="https://www.diagenode.com/en/p/auto-true-microchip-kit-16-rxns"><span style="font-weight: 400;">automated version</span></a><span style="font-weight: 400;"> of this kit.</span></p>
<p><span style="font-weight: 400;">Application note: </span><a href="https://www.diagenode.com/files/application_notes/Diagenode_AATI_Joint.pdf"><span style="font-weight: 400;">Best Workflow Practices for ChIP-seq Analysis with Small Samples</span></a></p>
<p></p>',
			'label3' => 'Species, cell lines, tissues tested',
			'info3' => '<p>The True MicroChIP-seq kit is compatible with a broad variety of cell lines, tissues and species - some examples are shown below. Other species / cell lines / tissues can be used with this kit.</p>
<p><strong>Cell lines:</strong></p>
<p>Bovine: blastocysts,<br />Drosophila: embryos, salivary glands<br />Human: EndoC-ẞH1 cells, HeLa cells, PBMC, urothelial cells<br />Mouse: adipocytes, B cells, blastocysts, pre-B cells, BMDM cells, chondrocytes, embryonic stem cells, KH2 cells, LSK cells, macrophages, MEP cells, microglia, NK cells, oocytes, pancreatic cells, P19Cl6 cells, RPE cells,</p>
<p>Other cell lines / species: compatible, not tested</p>
<p><strong>Tissues:</strong></p>
<p>Horse: adipose tissue</p>
<p>Mice: intestine tissue</p>
<p>Other tissues: not tested</p>',
			'format' => '20 rxns',
			'catalog_number' => 'C01010132',
			'old_catalog_number' => 'C01010130',
			'sf_code' => 'C01010132-',
			'type' => 'RFR',
			'search_order' => '04-undefined',
			'price_EUR' => '625',
			'price_USD' => '680',
			'price_GBP' => '575',
			'price_JPY' => '97905',
			'price_CNY' => '',
			'price_AUD' => '1700',
			'country' => 'ALL',
			'except_countries' => 'None',
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			'in_stock' => false,
			'featured' => true,
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			'online' => true,
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			'last_datasheet_update' => '0000-00-00',
			'slug' => 'true-microchip-kit-x16-16-rxns',
			'meta_title' => 'True MicroChIP-seq Kit | Diagenode C01010132',
			'meta_keywords' => '',
			'meta_description' => 'True MicroChIP-seq Kit provides a robust ChIP protocol suitable for the investigation of histone modifications within chromatin from as few as 10 000 cells, including FACS sorted cells. Compatible with ChIP-qPCR as well as ChIP-seq.',
			'modified' => '2023-04-20 16:06:10',
			'created' => '2015-06-29 14:08:20',
			'ProductsRelated' => array(
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			),
			'Image' => array(
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		),
		(int) 3 => array(
			'id' => '1927',
			'antibody_id' => null,
			'name' => 'MicroPlex Library Preparation Kit v2 (12 indexes)',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/MicroPlex-Libary-Prep-Kit-v2-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<p><span><strong>Specifically optimized for ChIP-seq</strong></span><br /><br /><span>The MicroPlex Library Preparation&trade; kit is the only kit on the market which is validated for ChIP-seq and which allows the preparation of indexed libraries from just picogram inputs. In combination with the&nbsp;</span><a href="./true-microchip-kit-x16-16-rxns">True MicroChIP kit</a><span>, it allows for performing ChIP-seq on as few as 10,000 cells. Less input, fewer steps, fewer supplies, faster time to results!&nbsp;</span></p>
<p>The MicroPlex v2 kit (Cat. No. C05010012) contains all necessary reagents including single indexes for multiplexing up to 12 samples using single barcoding. For higher multiplexing (using dual indexes) check <a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns">MicroPlex Library Preparation Kits v3</a>.</p>',
			'label1' => 'Characteristics',
			'info1' => '<ul>
<li><strong>1 tube, 2 hours, 3 steps</strong> protocol</li>
<li><strong>Input: </strong>50 pg &ndash; 50 ng</li>
<li><strong>Reduce potential bias</strong> - few PCR amplification cycles needed</li>
<li><strong>High sensitivity ChIP-seq</strong> - low PCR duplication rate</li>
<li><strong>Great multiplexing flexibility</strong> with 12 barcodes (8 nt) included</li>
<li><strong>Validated with the <a href="https://www.diagenode.com/p/sx-8g-ip-star-compact-automated-system-1-unit" title="IP-Star Automated System">IP-Star<sup>&reg;</sup> Automated Platform</a></strong></li>
</ul>
<h3>How it works</h3>
<center><img src="https://www.diagenode.com/img/product/kits/microplex-method-overview-v2.png" /></center>
<p style="margin-bottom: 0;"><small><strong>Microplex workflow - protocol with single indexes</strong><br />An input of 50 pg to 50 ng of fragmented dsDNA is converted into sequencing-ready libraries for Illumina&reg; NGS platforms using a fast and simple 3-step protocol</small></p>
<ul class="accordion" data-accordion="" id="readmore" style="margin-left: 0;">
<li class="accordion-navigation"><a href="#first" style="background: #ffffff; padding: 0rem; margin: 0rem; color: #13b2a2;"><small>Read more about MicroPlex workflow</small></a>
<div id="first" class="content">
<p><small><strong>Step 1. Template Preparation</strong> provides efficient repair of the fragmented double-stranded DNA input.</small></p>
<p><small>In this step, the DNA is repaired and yields molecules with blunt ends.</small></p>
<p><small><strong>Step 2. Library Synthesis.</strong> enables ligation of MicroPlex patented stem- loop adapters.</small></p>
<p><small>In the next step, stem-loop adaptors with blocked 5&rsquo; ends are ligated with high efficiency to the 5&rsquo; end of the genomic DNA, leaving a nick at the 3&rsquo; end. The adaptors cannot ligate to each other and do not have single- strand tails, both of which contribute to non-specific background found with many other NGS preparations.</small></p>
<p><small><strong>Step 3. Library Amplification</strong> enables extension of the template, cleavage of the stem-loop adaptors, and amplification of the library. Illumina- compatible indexes are also introduced using a high-fidelity, highly- processive, low-bias DNA polymerase.</small></p>
<p><small>In the final step, the 3&rsquo; ends of the genomic DNA are extended to complete library synthesis and Illumina-compatible indexes are added through a high-fidelity amplification. Any remaining free adaptors are destroyed. Hands-on time and the risk of contamination are minimized by using a single tube and eliminating intermediate purifications.</small></p>
<p><small>Obtained libraries are purified, quantified and sized. The libraries pooling can be performed as well before sequencing.</small></p>
</div>
</li>
</ul>
<p></p>
<h3>Reliable detection of enrichments in ChIP-seq</h3>
<p><img src="https://www.diagenode.com/img/product/kits/microplex-library-prep-kit-figure-a.png" alt="Reliable detection of enrichments in ChIP-seq figure 1" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure A.</strong> ChIP has been peformed with H3K4me3 antibody, amplification of 17 pg of DNA ChIP'd from 10.000 cells and amplification of 35 pg of DNA ChIP'd from 100.000 cells (control experiment). The IP'd DNA was amplified and transformed into a sequencing-ready preparation for the Illumina plateform with the MicroPlex Library Preparation kit. The library was then analysed on an Illumina<sup>&reg;</sup> Genome Analyzer. Cluster generation and sequencing were performed according to the manufacturer's instructions.</p>
<p><img src="https://www.diagenode.com/img/product/kits/microplex-library-prep-kit-figure-b.png" alt="Reliable detection of enrichments in ChIP-seq figure 2" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure B.</strong> We observed a perfect match between the top 40% of True MicroChIP peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>',
			'label2' => '',
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			'format' => '12 rxns',
			'catalog_number' => 'C05010012',
			'old_catalog_number' => 'C05010010',
			'sf_code' => 'C05010012-',
			'type' => 'FRE',
			'search_order' => '04-undefined',
			'price_EUR' => '935',
			'price_USD' => '1215',
			'price_GBP' => '835',
			'price_JPY' => '146470',
			'price_CNY' => '',
			'price_AUD' => '3038',
			'country' => 'ALL',
			'except_countries' => 'None',
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			'last_datasheet_update' => '0000-00-00',
			'slug' => 'microplex-library-preparation-kit-v2-x12-12-indices-12-rxns',
			'meta_title' => 'MicroPlex Library Preparation Kit v2 x12 (12 indices)',
			'meta_keywords' => '',
			'meta_description' => 'MicroPlex Library Preparation Kit v2 x12 (12 indices)',
			'modified' => '2023-04-20 15:01:16',
			'created' => '2015-06-29 14:08:20',
			'ProductsRelated' => array(
				[maximum depth reached]
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			'Image' => array(
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		(int) 4 => array(
			'id' => '2264',
			'antibody_id' => '121',
			'name' => 'H3K9me3 Antibody',
			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone<strong> H3 containing the trimethylated lysine 9</strong> (<strong>H3K9me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
			'label1' => 'Validation Data',
			'info1' => '<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig1.png" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K9me3</strong><br />ChIP assays were performed using human HeLa cells, the Diagenode antibody against H3K9me3 (cat. No. C15410193) and optimized PCR primer sets for qPCR. ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using the &ldquo;iDeal ChIP-seq&rdquo; kit (cat. No. C01010051). A titration of the antibody consisting of 0.5, 1, 2, and 5 &micro;g per ChIP experiment was analysed. IgG (1 &micro;g/IP) was used as negative IP control. QPCR was performed with primers for the heterochromatin marker Sat2 and for the ZNF510 gene, used as positive controls, and for the promoters of the active EIF4A2 and GAPDH genes, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2a.png" width="700" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2b.png" width="700" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2c.png" width="700" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2d.png" width="700" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K9me3</strong><br />ChIP was performed with 0.5 &micro;g of the Diagenode antibody against H3K9me3 (cat. No. C15410193) on sheared chromatin from 1,000,000 HeLa cells using the &ldquo;iDeal ChIP-seq&rdquo; kit as described above. The IP'd DNA was subsequently analysed on an Illumina HiSeq 2000. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 50 bp tags were aligned to the human genome using the BWA algorithm. Figure 2A shows the signal distribution along the long arm of chromosome 19 and a zoomin to an enriched region containing several ZNF repeat genes. The arrows indicate two satellite repeat regions which exhibit a stronger signal. Figures 2B, 2C and 2D show the enrichment along the ZNF510 positive control target and at the H19 and KCNQ1 imprinted genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-CT-Fig3a.png" width="700" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-CT-Fig3b.png" width="700" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K9me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 1 &micro;g of the Diagenode antibody against H3K9me3 (cat. No. C15410193) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in a genomic regions on chromosome 1 containing several ZNF repeat genes and in a genomic region surrounding the KCNQ1 imprinting control gene on chromosome 11 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-Elisa-Fig4.png" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the antibody directed against human H3K9me3 (cat. No. C15410193) in antigen coated wells. The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:87,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-DB-Fig5.png" /></center></div>
<div class="small-8 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K9me3</strong><br />A Dot Blot analysis was performed to test the cross reactivity of the Diagenode antibody against H3K9me3 (cat. No. C15410193) with peptides containing other modifications and unmodified sequences of histone H3 and H4. One hundred to 0.2 pmol of the peptide containing the respective histone modification were spotted on a membrane. The antibody was used at a dilution of 1:20,000. Figure 5 shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-WB-Fig6.png" /></center></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K9me3</strong><br />Western blot was performed on whole cell (25 &micro;g, lane 1) and histone extracts (15 &micro;g, lane 2) from HeLa cells, and on 1 &micro;g of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K9me3 (cat. No. C15410193). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-IF-Fig7.png" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K9me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K9me3 (cat. No. C15410193) and with DAPI. Cells were fixed with 4% formaldehyde for 10&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labelled with the H3K9me3 antibody (middle) diluted 1:500 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The left panel shows staining of the nuclei with DAPI. A merge of both stainings is shown on the right.</small></p>
</div>
</div>',
			'label2' => 'Target Description',
			'info2' => '<p>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called &ldquo;histone code&rdquo;. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Trimethylation of histone H3K9 is associated with inactive genomic regions, satellite repeats and ZNF gene repeats.</p>',
			'label3' => '',
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			'format' => '50 μg',
			'catalog_number' => 'C15410193',
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			'sf_code' => 'C15410193-D001-000581',
			'type' => 'FRE',
			'search_order' => '03-Antibody',
			'price_EUR' => '480',
			'price_USD' => '470',
			'price_GBP' => '430',
			'price_JPY' => '75190',
			'price_CNY' => '0',
			'price_AUD' => '1175',
			'country' => 'ALL',
			'except_countries' => 'None',
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			'in_stock' => false,
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			'slug' => 'h3k9me3-polyclonal-antibody-premium-50-mg',
			'meta_title' => 'H3K9me3 Antibody - ChIP-seq Grade (C15410193) | Diagenode',
			'meta_keywords' => '',
			'meta_description' => 'H3K9me3  (Histone H3 trimethylated at lysine 9) Polyclonal Antibody validated  in ChIP-seq, ChIP-qPCR, CUT&Tag, ELISA, DB, WB and IF. Specificity confirmed by Peptide array assay. Batch-specific data available on the website. Sample size available.',
			'modified' => '2021-10-20 09:55:53',
			'created' => '2015-06-29 14:08:20',
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		(int) 5 => array(
			'id' => '2268',
			'antibody_id' => '70',
			'name' => 'H3K27me3 Antibody',
			'description' => '<p>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 27</strong> (<strong>H3K27me3</strong>), using a KLH-conjugated synthetic peptide.</p>',
			'label1' => 'Validation Data',
			'info1' => '<div class="row">
<div class="small-6 columns">
<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig1.png" alt="H3K27me3 Antibody ChIP Grade" /></p>
<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2.png" alt="H3K27me3 Antibody for ChIP" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K27me3</strong><br />ChIP assays were performed using human HeLa cells, the Diagenode antibody against H3K27me3 (Cat. No. C15410195) and optimized PCR primer pairs for qPCR. ChIP was performed with the &ldquo;iDeal ChIP-seq&rdquo; kit (Cat. No. C01010051), using sheared chromatin from 1 million cells. The chromatin was spiked with a panel of in vitro assembled nucleosomes, each containing a specific lysine methylation. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control.</small></p>
<p><small><strong>Figure 1A.</strong> Quantitative PCR was performed with primers specific for the promoter of the active GAPDH and EIF4A2 genes, used as negative controls, and for the inactive TSH2B and MYT1 genes, used as positive controls. The graph shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
<p><small><strong>Figure 1B.</strong> Recovery of the nucleosomes carrying the H3K27me1, H3K27me2, H3K27me3, H3K4me3, H3K9me3 and H3K36me3 modifications and the unmodified H3K27 as determined by qPCR. The figure clearly shows the antibody is very specific in ChIP for the H3K27me3 modification.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2a.png" alt="H3K27me3 Antibody ChIP-seq Grade" /></p>
</div>
</div>
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<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2b.png" alt="H3K27me3 Antibody for ChIP-seq" /></p>
<p>C. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2c.png" alt="H3K27me3 Antibody for ChIP-seq assay" /></p>
<p>D. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2d.png" alt="H3K27me3 Antibody validated in ChIP-seq" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K27me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLa cells using 1 &micro;g of the Diagenode antibody against H3K27me3 (Cat. No. C15410195) as described above. The IP'd DNA was subsequently analysed on an Illumina HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 50 bp tags were aligned to the human genome using the BWA algorithm. Figure 2 shows the enrichment in genomic regions of chromosome 6 and 20, surrounding the TSH2B and MYT1 positive control genes (fig 2A and 2B, respectively), and in two genomic regions of chromosome 1 and X (figure 2C and D).</small></p>
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<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-CUTTAG-Fig3A.png" /></p>
<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-CUTTAG-Fig3B.png" /></p>
</div>
</div>
<div class="row">
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<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K27me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 1 &micro;g of the Diagenode antibody against H3K27me3 (cat. No. C15410195) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions on chromosome and 13 and 20 (figure 3A and B, respectively).</small></p>
</div>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-ELISA-Fig4.png" alt="H3K27me3 Antibody ELISA Validation " /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody directed against H3K27me3 (Cat. No. C15410195). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:3,000.</small></p>
</div>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-DB-Fig5a.png" alt="H3K27me3 Antibody Dot Blot Validation " /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K27me3</strong><br />A Dot Blot analysis was performed to test the cross reactivity of the Diagenode antibody against H3K27me3 (Cat. No. C15410195) with peptides containing other modifications of histone H3 and H4 and the unmodified H3K27 sequence. One hundred to 0.2 pmol of the peptide containing the respective histone modification were spotted on a membrane. The antibody was used at a dilution of 1:5,000. Figure 5 shows a high specificity of the antibody for the modification of interest. Please note that the antibody also recognizes the modification if S28 is phosphorylated.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-WB-Fig6.png" alt="H3K27me3 Antibody validated in Western Blot" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K27me3</strong><br />Western blot was performed on whole cell (25 &micro;g, lane 1) and histone extracts (15 &micro;g, lane 2) from HeLa cells, and on 1 &micro;g of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K27me3 (cat. No. C15410195) diluted 1:500 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-IF-Fig7.png" alt="H3K27me3 Antibody validated for Immunofluorescence" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K27me3</strong><br />Human HeLa cells were stained with the Diagenode antibody against H3K27me3 (Cat. No. C15410195) and with DAPI. Cells were fixed with 4% formaldehyde for 10&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labelled with the H3K27me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The middle panel shows staining of the nuclei with DAPI. A merge of the two stainings is shown on the right.</small></p>
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			'label2' => 'Target Description',
			'info2' => '<p><small>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which alter chromatin structure to facilitate transcriptional activation, repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called &ldquo;histone code&rdquo;. Histone methylation and demethylation is regulated by histone methyl transferases and histone demethylases. Methylation of histone H3K27 is associated with inactive genomic regions.</small></p>',
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			'format' => '50 μg',
			'catalog_number' => 'C15410195',
			'old_catalog_number' => 'pAb-195-050',
			'sf_code' => 'C15410195-D001-000581',
			'type' => 'FRE',
			'search_order' => '03-Antibody',
			'price_EUR' => '480',
			'price_USD' => '470',
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			'price_JPY' => '75190',
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			'slug' => 'h3k27me3-polyclonal-antibody-premium-50-mg-27-ml',
			'meta_title' => 'H3K27me3 Antibody - ChIP-seq Grade (C15410195) | Diagenode',
			'meta_keywords' => '',
			'meta_description' => 'H3K27me3 (Histone H3 trimethylated at lysine 27) Polyclonal Antibody validated  in ChIP-seq, ChIP-qPCR, CUT&Tag, ELISA, DB, WB and IF. Specificity confirmed by Peptide array assay. Batch-specific data available on the website. Sample size available.',
			'modified' => '2024-01-17 13:55:58',
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		(int) 6 => array(
			'id' => '2262',
			'antibody_id' => '74',
			'name' => 'H3K36me3 Antibody',
			'description' => '<p>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 36</strong> (<strong>H3K36me3</strong>), using a KLH-conjugated synthetic peptide.</p>',
			'label1' => 'Validation Data',
			'info1' => '<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig1.png" alt="H3K36me3 Antibody ChIP Grade" caption="false" width="432" height="674" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K36me3</strong><br /> <strong>Figure 1A</strong> ChIP assays were performed using human HeLa cells, the Diagenode antibody against H3K36me3 (Cat. No. C15410192) and optimized PCR primer pairs for qPCR. ChIP was performed with the &ldquo;Auto Histone ChIP-seq&rdquo; kit (Cat. No. C01010022) on the IP-Star automated system, using sheared chromatin from 1,000,000 cells. A titration consisting of 1, 2, 5 and 10 &micro;g of antibody per ChIP experiment was analyzed. IgG (2 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers for the coding region of the active GAPDH and ACTB genes, used as positive controls, and for the promoter and a region located 1 kb upstream of the promoter of the GAPDH gene, used as negative controls.<br /><br /> <strong>Figure 1B</strong> ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K36me3 (Cat. No. C15410192) and optimized PCR primer pairs for qPCR. ChIP was performed with the &ldquo;iDeal ChIP-seq&rdquo; kit (Cat. No. C01010051), using sheared chromatin from 100,000 cells. A titration consisting of 0.2, 0.5, 1 and 2 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers for the coding region of the active GAPDH and ACTB genes, used as positive controls, and for the coding region of the inactive MB gene and the Sat satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig2-2.jpg" alt="H3K36me3 Antibody SNAP-ChIP validation" caption="false" width="432" height="298" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 2. ChIP results obtained with the Diagenode antibody directed against H3K36me3</strong><br /> ChIP assays were performed on sheared chromatin from 1 million human HeLa cells as described above. The chromatin was spiked with a panel of in vitro assembled nucleosomes, each containing a specific lysine methylation (SNAP-ChIP K-MetStat Panel, Epicypher). A titration consisting of 0.2, 0.5, 1 and 2 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the nucleosomes carrying the H3K36me1, H3K36me2, H3K36me3, H3K4me3, H3K9me3, H3K27me3 and H4K20me3 modifications and the unmodified H3K4. The graph shows the recovery, expressed as a % of input. These results demonstrate a high specificity of the H3K36me3 antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig2.png" alt="H3K36me3 Antibody for ChIP-seq" caption="false" width="893" height="702" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. ChIP-seq results obtained with the Diagenode antibody directed against H3K36me3</strong><br /> ChIP was performed on sheared chromatin from 100,000 K562 cells with the &ldquo;iDeal ChIP-seq&rdquo; kit (Cat. No. C01010051) using 0.5 &micro;g of the Diagenode antibody against H3K36me3 (Cat. No. C15410192) as described above. The IP&rsquo;d DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer&rsquo;s instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 3 shows the H3K36me3 signal distribution along the complete sequence and a zoomin of human chromosome 12 (figure 2A and B) and in 2 genomic regions containing the GAPDH and ACTB positive control genes (figure 3C and D).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig3.png" alt="H3K36me3 Antibody ELISA validation" caption="false" width="432" height="328" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K36me3 (Cat. No. C15410192). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:132,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns">
<p>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig4-a.png" alt="H3K36me3 Antibody Dot Blot Validation" caption="false" width="432" height="162" /></p>
<p>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig4-b.png" alt="H3K36me3 Antibody Peptide Array validation" caption="false" width="432" height="257" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K36me3</strong><br /> <strong>Figure 5A.</strong> To test the cross reactivity of the Diagenode antibody against H3K36me3 (Cat. No. C15410192), a Dot Blot analysis was performed with peptides containing other modifications or unmodified sequences of histone H3 and H4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:20,000. Figure 5A shows a high specificity of the antibody for the modification of interest. <strong>Figure 5B.</strong> The specificity of the antibody was further demonstrated by peptide array analyses on an array containing 384 peptides with different combinations of modifications from histone H3, H4, H2A and H2B. The antibody was used at a dilution of 1:10,000. Figure 5B shows the specificity factor, calculated as the ratio of the average intensity of all spots containing the mark, divided by the average intensity of all spots not containing the mark. The peptide array analysis shows a slight cross reaction with H4K20me3 that was not observed in dot blot.</small></p>
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</div>
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<div class="extra-spaced"></div>
<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig5.png" alt="H3K36me3 Antibody for Western Blot" caption="false" width="432" height="346" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K36me3</strong><br /> Western blot was performed on whole cell (25 &micro;g, lane 1) and histone extracts (15 &micro;g, lane 2) from HeLa cells, and on 1 &micro;g of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K36me3 (Cat. No. C15410192). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is shown on the right, the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig6.png" alt="H3K36me3 Antibody for Immunofluorescence " caption="false" width="893" height="232" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K36me3</strong><br /> HeLa cells were stained with the Diagenode antibody against H3K36me3 (Cat. C15410192) and with DAPI. Cells were fixed with 4% formaldehyde for 10&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labeled with the H3K36me3 antibody (left) diluted 1:500 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The middle panel shows staining of the nuclei with DAPI. A merge of the two stainings is shown on the right.</small></p>
</div>
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			'label2' => 'Target Description',
			'info2' => '<p>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called &ldquo;histone code&rdquo;. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Trimethylation of histone H3K36 is associated with active genes.</p>',
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			'format' => '50 μg',
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			'type' => 'FRE',
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			'meta_title' => 'H3K36me3 Antibody - ChIP-seq Grade (C15410192) | Diagenode',
			'meta_keywords' => '',
			'meta_description' => 'H3K36me3 (Histone H3 trimethylated at lysine 36) Polyclonal Antibody validated  in ChIP-seq, ChIP-grade, ELISA, DB, WB and IF. Specificity confirmed by Peptide array. Batch-specific data available on the website. Sample size available. ',
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			'id' => '2173',
			'antibody_id' => '115',
			'name' => 'H3K4me3 Antibody',
			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
			'label1' => 'Validation data',
			'info1' => '<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
</div>
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<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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<p>Learn more about: <a href="https://www.diagenode.com/applications/western-blot">Loading control, MW marker visualization</a><em>. <br /></em></p>
<p><em></em>Check our selection of antibodies validated in Western blot.</p>',
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<p>Diagenode offers huge selection of highly sensitive antibodies validated in IF.</p>
<p><img src="https://www.diagenode.com/img/product/antibodies/C15200229-IF.jpg" alt="" height="245" width="256" /></p>
<p><sup><strong>Immunofluorescence using the Diagenode monoclonal antibody directed against CRISPR/Cas9</strong></sup></p>
<p><sup>HeLa cells transfected with a Cas9 expression vector (left) or untransfected cells (right) were fixed in methanol at -20&deg;C, permeabilized with acetone at -20&deg;C and blocked with PBS containing 2% BSA. The cells were stained with the Cas9 C-terminal antibody (Cat. No. C15200229) diluted 1:400, followed by incubation with an anti-mouse secondary antibody coupled to AF488. The bottom images show counter-staining of the nuclei with Hoechst 33342.</sup></p>
<h5><sup>Check our selection of antibodies validated in IF.</sup></h5>',
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<p>Read more:</p>
<p><a href="https://www.diagenode.com/en/categories/cutandtag">Products for CUT&amp;Tag assay</a></p>
<p><a href="https://www.diagenode.com/en/pages/cut-and-tag">Performance of Diagenode's antibodies in CUT&amp;Tag</a></p>
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<p><span style="font-weight: 400;">Diagenode provides leading solutions for epigenetic research. Because ChIP-seq is a widely-used technique, we validate our antibodies in ChIP and ChIP-seq experiments (in addition to conventional methods like Western blot, Dot blot, ELISA, and immunofluorescence) to provide the highest quality antibody. We standardize our validation and production to guarantee high product quality without technical bias. Diagenode guarantees ChIP-seq grade antibody performance under our suggested conditions.</span></p>
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<div class="small-12 medium-9 large-9 columns">
<p><strong>ChIP-seq profile</strong> of active (H3K4me3 and H3K36me3) and inactive (H3K27me3) marks using Diagenode antibodies.</p>
<img src="https://www.diagenode.com/img/categories/antibodies/chip-seq-grade-antibodies.png" /></div>
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<p><small> ChIP was performed on sheared chromatin from 100,000 K562 cells using iDeal ChIP-seq kit for Histones (cat. No. C01010051) with 1 &micro;g of the Diagenode antibodies against H3K27me3 (cat. No. C15410195) and H3K4me3 (cat. No. C15410003), and 0.5 &micro;g of the antibody against H3K36me3 (cat. No. C15410192). The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. The figure shows the signal distribution along the complete sequence of human chromosome 3, a zoomin to a 10 Mb region and a further zoomin to a 1.5 Mb region. </small></p>
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<p>Diagenode&rsquo;s highly validated antibodies:</p>
<ul>
<li>Highly sensitive and specific</li>
<li>Cost-effective (requires less antibody per reaction)</li>
<li>Batch-specific data is available on the website</li>
<li>Expert technical support</li>
<li>Sample sizes available</li>
<li>100% satisfaction guarantee</li>
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			'name' => 'Histone antibodies',
			'description' => '<p>Histones are the main protein components of chromatin involved in the compaction of DNA into nucleosomes, the basic units of chromatin. A <strong>nucleosome</strong> consists of one pair of each of the core histones (<strong>H2A</strong>, <strong>H2B</strong>, <strong>H3</strong> and <strong>H4</strong>) forming an octameric structure wrapped by 146 base pairs of DNA. The different nucleosomes are linked by the linker histone<strong> H1, </strong>allowing for further condensation of chromatin.</p>
<p>The core histones have a globular structure with large unstructured N-terminal tails protruding from the nucleosome.&nbsp; They can undergo to multiple post-translational modifications (PTM), mainly at the N-terminal tails. These <strong>post-translational modifications </strong>include&nbsp; methylation, acetylation, phosphorylation, ubiquitinylation, citrullination, sumoylation, deamination and crotonylation.&nbsp; The most well characterized PTMs are <strong>methylation,</strong> <strong>acetylation and phosphorylation</strong>. Histone methylation occurs mainly on lysine (K) residues, which can be mono-, di- or tri-methylated, and on arginines (R), which can be mono-methylated and symmetrically or asymmetrically di-methylated. Histone acetylation occurs on lysines and histone phosphorylation mainly on serines (S), threonines (T) and tyrosines (Y).</p>
<p>The PTMs of the different residues are involved in numerous processes such as DNA repair, DNA replication and chromosome condensation. They influence the chromatin organization and can be positively or negatively associated with gene expression. Trimethylation of H3K4, H3K36 and H3K79, and lysine acetylation generally result in an open chromatin configuration (figure below) and are therefore associated with <strong>euchromatin</strong> and gene activation. Trimethylation of H3K9, K3K27 and H4K20, on the other hand, is enriched in <strong>heterochromatin </strong>and associated with gene silencing. The combination of different histone modifications is called the "<strong>histone code</strong>&rdquo;, analogous to the genetic code.</p>
<p><img src="https://www.diagenode.com/img/categories/antibodies/histone-marks-illustration.png" /></p>
<p>Diagenode is proud to offer a large range of antibodies against histones and histone modifications. Our&nbsp; antibodies are highly specific and have been validated in many applications, including <strong>ChIP</strong> and <strong>ChIP-seq</strong>.</p>
<p>Diagenode&rsquo;s collection includes antibodies recognizing:</p>
<ul>
<li><strong>Histone H1 variants</strong></li>
<li><strong>Histone H2A, H2A variants and histone H2A</strong> <strong>modifications</strong> (serine phosphorylation, lysine acetylation, lysine ubiquitinylation)</li>
<li><strong>Histone H2B and H2B</strong> <strong>modifications </strong>(serine phosphorylation, lysine acetylation)</li>
<li><strong>Histone H3 and H3 modifications </strong>(lysine methylation (mono-, di- and tri-methylated), lysine acetylation, serine phosphorylation, threonine phosphorylation, arginine methylation (mono-methylated, symmetrically and asymmetrically di-methylated))</li>
<li><strong>Histone H4 and H4 modifications (</strong>lysine methylation (mono-, di- and tri-methylated), lysine acetylation, arginine methylation (mono-methylated and symmetrically di-methylated), serine phosphorylation )</li>
</ul>
<p><span style="font-weight: 400;"><strong>HDAC's HAT's, HMT's and other</strong> <strong>enzymes</strong> which modify histones can be found in the category <a href="../categories/chromatin-modifying-proteins-histone-transferase">Histone modifying enzymes</a><br /></span></p>
<p><span style="font-weight: 400;"> Diagenode&rsquo;s highly validated antibodies:</span></p>
<ul>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Highly sensitive and specific</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Cost-effective (requires less antibody per reaction)</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Batch-specific data is available on the website</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Expert technical support</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Sample sizes available</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 100% satisfaction guarantee</span></li>
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			'description' => '<h1><strong>Validated epigenetics antibodies</strong>&nbsp;&ndash; care for a sample?<br />&nbsp;</h1>
<p>Diagenode has partnered with leading epigenetics experts and numerous epigenetics consortiums to bring to you a validated and comprehensive collection of epigenetic antibodies. As an expert in epigenetics, we are committed to offering highly-specific antibodies validated for ChIP/ChIP-seq and many other applications. All batch-specific validation data is available on our website.<br /><a href="../categories/antibodies">Read about our expertise in antibody production</a>.</p>
<ul>
<li><strong>Focused</strong> -&nbsp;Diagenode's selection of antibodies is exclusively dedicated for epigenetic research. <a title="See the full collection." href="../categories/all-antibodies">See the full collection.</a></li>
<li><strong>Strict quality standards</strong>&nbsp;with rigorous QC and validation</li>
<li><strong>Classified</strong>&nbsp;based on level of validation for flexibility of application</li>
</ul>
<p>Existing sample sizes are listed below. We will soon expand our collection. &nbsp;Are you looking for a sample size of another antibody? Just <a href="mailto:agnieszka.zelisko@diagenode.com?Subject=Sample%20Size%20Request" target="_top">Contact us</a>.</p>',
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			'meta_description' => 'Diagenode offers sample volume on selected antibodies for researchers to test, validate and provide confidence and flexibility in choosing from our wide range of antibodies ',
			'meta_title' => 'Sample-size Antibodies | Diagenode',
			'modified' => '2019-07-03 10:57:05',
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			'name' => 'All antibodies',
			'description' => '<p><span style="font-weight: 400;">All Diagenode&rsquo;s antibodies are listed below. Please, use our Quick search field to find the antibody of interest by target name, application, purity.</span></p>
<p><span style="font-weight: 400;">Diagenode&rsquo;s highly validated antibodies:</span></p>
<ul>
<li>Highly sensitive and specific</li>
<li>Cost-effective (requires less antibody per reaction)</li>
<li>Batch-specific data is available on the website</li>
<li>Expert technical support</li>
<li>Sample sizes available</li>
<li>100% satisfaction guarantee</li>
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			'meta_description' => 'Diagenode Offers Strict quality standards with Rigorous QC and validated Antibodies. Classified based on level of validation for flexibility of Application. Comprehensive selection of histone and non-histone Antibodies',
			'meta_title' => 'Diagenode's selection of Antibodies is exclusively dedicated for Epigenetic Research | Diagenode',
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			'name' => 'ChIP-grade antibodies',
			'description' => '<div class="row">
<div class="small-12 columns"><center></center>
<p><br />Chromatin immunoprecipitation (<b>ChIP</b>) is a technique to study the associations of proteins with the specific genomic regions in intact cells. One of the most important steps of this protocol is the immunoprecipitation of targeted protein using the antibody specifically recognizing it. The quality of antibodies used in ChIP is essential for the success of the experiment. Diagenode offers extensively validated ChIP-grade antibodies, confirmed for their specificity, and high level of performance in ChIP. Each batch is validated, and batch-specific data are available on the website.</p>
<p></p>
</div>
</div>
<p><strong>ChIP results</strong> obtained with the antibody directed against H3K4me3 (Cat. No. <a href="../p/h3k4me3-polyclonal-antibody-premium-50-ug-50-ul">C15410003</a>).&nbsp;</p>
<div class="row">
<div class="small-12 medium-6 large-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" alt="" width="400" height="315" />&nbsp;</div>
<div class="small-12 medium-6 large-6 columns">
<p></p>
<p></p>
<p></p>
</div>
</div>
<p></p>
<p>Our aim at Diagenode is to offer the largest collection of highly specific <strong>ChIP-grade antibodies</strong>. We add new antibodies monthly. Find your ChIP-grade antibody in the list below and check more information about tested applications, extensive validation data, and product information.</p>',
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			'meta_keywords' => 'ChIP-grade antibodies, polyclonal antibody, monoclonal antibody, Diagenode',
			'meta_description' => 'Diagenode Offers Extensively Validated ChIP-Grade Antibodies, Confirmed for their Specificity, and high level of Performance in Chromatin Immunoprecipitation ChIP',
			'meta_title' => 'Chromatin immunoprecipitation ChIP-grade antibodies | Diagenode',
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			'id' => '149',
			'position' => '42',
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			'name' => 'CUT&Tag Antibodies',
			'description' => '<p>&nbsp; &nbsp; &nbsp; &nbsp;&nbsp;</p>',
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		(int) 0 => array(
			'id' => '725',
			'name' => 'Datasheet H3K4me3 C15410003',
			'description' => '<p>Datasheet description</p>',
			'image_id' => null,
			'type' => 'Datasheet',
			'url' => 'files/products/antibodies/Datasheet_H3K4me3_C15410003.pdf',
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		(int) 1 => array(
			'id' => '11',
			'name' => 'Antibodies you can trust',
			'description' => '<p style="text-align: justify;"><span>Epigenetic research tools have evolved over time from endpoint PCR to qPCR to the analyses of large sets of genome-wide sequencing data. ChIP sequencing (ChIP-seq) has now become the gold standard method for chromatin studies, given the accuracy and coverage scale of the approach over other methods. Successful ChIP-seq, however, requires a higher level of experimental accuracy and consistency in all steps of ChIP than ever before. Particularly crucial is the quality of ChIP antibodies. </span></p>',
			'image_id' => null,
			'type' => 'Poster',
			'url' => 'files/posters/Antibodies_you_can_trust_Poster.pdf',
			'slug' => 'antibodies-you-can-trust-poster',
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			'modified' => '2015-10-01 20:18:31',
			'created' => '2015-07-03 16:05:15',
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		),
		(int) 2 => array(
			'id' => '38',
			'name' => 'Epigenetic Antibodies Brochure',
			'description' => '<p>More than in any other immuoprecipitation assays, quality antibodies are critical tools in many epigenetics experiments. Since 10 years, Diagenode has developed the most stringent quality production available on the market for antibodies exclusively focused on epigenetic uses. All our antibodies have been qualified to work in epigenetic applications.</p>',
			'image_id' => null,
			'type' => 'Brochure',
			'url' => 'files/brochures/Epigenetic_Antibodies_Brochure.pdf',
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	'Publication' => array(
		(int) 0 => array(
			'id' => '5000',
			'name' => 'Claudin-1 as a potential marker of stress-induced premature senescence in vascular smooth muscle cells',
			'authors' => 'Agnieszka Gadecka et al.',
			'description' => '<p><span>Cellular senescence, a permanent state of cell cycle arrest, can result either from external stress and is then called stress-induced premature senescence (SIPS), or from the exhaustion of cell division potential giving rise to replicative senescence (RS). Despite numerous biomarkers distinguishing SIPS from RS remains challenging. We propose claudin-1 (CLDN1) as a potential cell-specific marker of SIPS in vascular smooth muscle cells (VSMCs). In our study, VSMCs subjected to RS or SIPS exhibited significantly higher levels of CLDN1 expression exclusively in SIPS. Moreover, nuclear accumulation of this protein was also characteristic only of prematurely senescent cells. ChIP-seq results suggest that higher CLDN1 expression in SIPS might be a result of a more open chromatin state, as evidenced by a broader H3K4me3 peak in the gene promoter region. However, the broad H3K4me3 peak and relatively high&nbsp;</span><em>CLDN1</em><span><span>&nbsp;</span>expression in RS did not translate into protein level, which implies a different regulatory mechanism in this type of senescence. Elevated CLDN1 levels were also observed in VSMCs isolated from atherosclerotic plaques, although this was highly donor dependent. These findings indicate that increased CLDN1 level in prematurely senescent cells may serve as a promising cell-specific marker of SIPS in VSMCs, both in vitro and ex vivo.</span></p>',
			'date' => '2024-11-07',
			'pmid' => 'https://www.researchsquare.com/article/rs-5192437/v1',
			'doi' => 'https://doi.org/10.21203/rs.3.rs-5192437/v1',
			'modified' => '2024-11-12 09:27:24',
			'created' => '2024-11-12 09:27:24',
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			)
		),
		(int) 1 => array(
			'id' => '4965',
			'name' => 'Trained immunity is regulated by T cell-induced CD40-TRAF6 signaling',
			'authors' => 'Jacobs M.M.E. et al.',
			'description' => '<p><span>Trained immunity is characterized by histone modifications and metabolic changes in innate immune cells following exposure to inflammatory signals, leading to heightened responsiveness to secondary stimuli. Although our understanding of the molecular regulation of trained immunity has increased, the role of adaptive immune cells herein remains largely unknown. Here, we show that T&nbsp;cells modulate trained immunity via cluster of differentiation 40-tissue necrosis factor receptor-associated factor 6 (CD40-TRAF6) signaling. CD40-TRAF6 inhibition modulates functional, transcriptomic, and metabolic reprogramming and modifies histone 3 lysine 4 trimethylation associated with trained immunity. Besides&nbsp;</span><i>in&nbsp;vitro</i><span><span>&nbsp;</span>studies, we reveal that single-nucleotide polymorphisms in the proximity of<span>&nbsp;</span></span><i>CD40</i><span><span>&nbsp;</span>are linked to trained immunity responses<span>&nbsp;</span></span><i>in&nbsp;vivo</i><span><span>&nbsp;</span>and that combining CD40-TRAF6 inhibition with cytotoxic T lymphocyte antigen 4-immunoglobulin (CTLA4-Ig)-mediated co-stimulatory blockade induces long-term graft acceptance in a murine heart transplantation model. Combined, our results reveal that trained immunity is modulated by CD40-TRAF6 signaling between myeloid and adaptive immune cells and that this can be leveraged for therapeutic purposes.</span></p>',
			'date' => '2024-09-24',
			'pmid' => 'https://www.cell.com/cell-reports/fulltext/S2211-1247(24)01015-5',
			'doi' => '',
			'modified' => '2024-09-02 10:23:11',
			'created' => '2024-09-02 10:23:11',
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			)
		),
		(int) 2 => array(
			'id' => '4958',
			'name' => 'Legionella pneumophila modulates macrophage functions through epigenetic reprogramming via the C-type lectin receptor Mincle',
			'authors' => 'Stegmann F. et al.',
			'description' => '<p><em>Legionella pneumophila</em><span><span>&nbsp;</span>is a pathogen which can lead to a severe form of pneumonia in humans known as Legionnaires disease after replication in alveolar macrophages. Viable<span>&nbsp;</span></span><em>L.&nbsp;pneumophila</em><span><span>&nbsp;</span>actively secrete effector molecules to modulate the host&rsquo;s immune response. Here, we report that<span>&nbsp;</span></span><em>L.&nbsp;pneumophila</em><span>-derived factors reprogram macrophages into a tolerogenic state, a process to which the C-type lectin receptor Mincle (CLEC4E) markedly contributes. The underlying epigenetic state is characterized by increases of the closing mark H3K9me3 and decreases of the opening mark H3K4me3, subsequently leading to the reduced secretion of the cytokines TNF, IL-6, IL-12, the production of reactive oxygen species, and cell-surface expression of MHC-II and CD80 upon re-stimulation. In summary, these findings provide important implications for our understanding of Legionellosis and the contribution of Mincle to reprogramming of macrophages by<span>&nbsp;</span></span><em>L.&nbsp;pneumophila</em><span>.</span></p>',
			'date' => '2024-09-20',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S2589004224019254#:~:text=L.,crucial%20for%20mediating%20tolerance%20induction.',
			'doi' => 'https://doi.org/10.1016/j.isci.2024.110700',
			'modified' => '2024-09-02 10:06:00',
			'created' => '2024-09-02 10:06:00',
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			)
		),
		(int) 3 => array(
			'id' => '4974',
			'name' => 'Systematic prioritization of functional variants and effector genes underlying colorectal cancer risk',
			'authors' => 'Law P.J. et al.',
			'description' => '<p><span>Genome-wide association studies of colorectal cancer (CRC) have identified 170 autosomal risk loci. However, for most of these, the functional variants and their target genes are unknown. Here, we perform statistical fine-mapping incorporating tissue-specific epigenetic annotations and massively parallel reporter assays to systematically prioritize functional variants for each CRC risk locus. We identify plausible causal variants for the 170 risk loci, with a single variant for 40. We link these variants to 208 target genes by analyzing colon-specific quantitative trait loci and implementing the activity-by-contact model, which integrates epigenomic features and Micro-C data, to predict enhancer&ndash;gene connections. By deciphering CRC risk loci, we identify direct links between risk variants and target genes, providing further insight into the molecular basis of CRC susceptibility and highlighting potential pharmaceutical targets for prevention and treatment.</span></p>',
			'date' => '2024-09-16',
			'pmid' => 'https://www.nature.com/articles/s41588-024-01900-w',
			'doi' => 'https://doi.org/10.1038/s41588-024-01900-w',
			'modified' => '2024-09-23 10:14:18',
			'created' => '2024-09-23 10:14:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 4 => array(
			'id' => '4971',
			'name' => 'Bivalent chromatin accommodates survivin and BRG1/SWI complex to activate DNA damage response in CD4+ cells',
			'authors' => 'Chandrasekaran V. et al.',
			'description' => '<section aria-labelledby="Abs1" data-title="Abstract" lang="en">
<div class="c-article-section" id="Abs1-section">
<div class="c-article-section__content" id="Abs1-content">
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Background</h3>
<p>Bivalent regions of chromatin (BvCR) are characterized by trimethylated lysine 4 (H3K4me3) and lysine 27 on histone H3 (H3K27me3) deposition which aid gene expression control during cell differentiation. The role of BvCR in post-transcriptional DNA damage response remains unidentified. Oncoprotein survivin binds chromatin and mediates IFN&gamma; effects in CD4<sup>+</sup><span>&nbsp;</span>cells. In this study, we explored the role of BvCR in DNA damage response of autoimmune CD4<sup>+</sup><span>&nbsp;</span>cells in rheumatoid arthritis (RA).</p>
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Methods</h3>
<p>We performed deep sequencing of the chromatin bound to survivin, H3K4me3, H3K27me3, and H3K27ac, in human CD4<sup>+</sup><span>&nbsp;</span>cells and identified BvCR, which possessed all three histone H3 modifications. Protein partners of survivin on chromatin were predicted by integration of motif enrichment analysis, computational machine-learning, and structural modeling, and validated experimentally by mass spectrometry and peptide binding array. Survivin-dependent change in BvCR and transcription of genes controlled by the BvCR was studied in CD4<sup>+</sup><span>&nbsp;</span>cells treated with survivin inhibitor, which revealed survivin-dependent biological processes. Finally, the survivin-dependent processes were mapped to the transcriptome of CD4<sup>+</sup><span>&nbsp;</span>cells in blood and in synovial tissue of RA patients and the effect of modern immunomodulating drugs on these processes was explored.</p>
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Results</h3>
<p>We identified that BvCR dominated by H3K4me3 (H3K4me3-BvCR) accommodated survivin within<span>&nbsp;</span><i>cis</i>-regulatory elements of the genes controlling DNA damage. Inhibition of survivin or JAK-STAT signaling enhanced H3K4me3-BvCR dominance, which improved DNA damage recognition and arrested cell cycle progression in cultured CD4<sup>+</sup><span>&nbsp;</span>cells. Specifically, BvCR accommodating survivin aided sequence-specific anchoring of the BRG1/SWI chromatin-remodeling complex coordinating DNA damage response. Mapping survivin interactome to BRG1/SWI complex demonstrated interaction of survivin with the subunits anchoring the complex to chromatin. Co-expression of BRG1, survivin and IFN&gamma; in CD4<sup>+</sup><span>&nbsp;</span>cells rendered complete deregulation of DNA damage response in RA. Such cells possessed strong ability of homing to RA joints. Immunomodulating drugs inhibited the anchoring subunits of BRG1/SWI complex, which affected arthritogenic profile of CD4<sup>+</sup><span>&nbsp;</span>cells.</p>
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Conclusions</h3>
<p>BvCR execute DNA damage control to maintain genome fidelity in IFN-activated CD4<sup>+</sup><span>&nbsp;</span>cells. Survivin anchors the BRG1/SWI complex to BvCR to repress DNA damage response. These results offer a platform for therapeutic interventions targeting survivin and BRG1/SWI complex in autoimmunity.</p>
</div>
</div>
</section>
<section data-title="Background">
<div class="c-article-section" id="Sec1-section">
<h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec1"></h2>
</div>
</section>',
			'date' => '2024-09-11',
			'pmid' => 'https://biosignaling.biomedcentral.com/articles/10.1186/s12964-024-01814-4',
			'doi' => 'https://doi.org/10.1186/s12964-024-01814-4',
			'modified' => '2024-09-16 10:02:18',
			'created' => '2024-09-16 10:02:18',
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		),
		(int) 5 => array(
			'id' => '4951',
			'name' => 'LL37/self-DNA complexes mediate monocyte reprogramming',
			'authors' => 'Aman Damara et al.',
			'description' => '<p><span>LL37 alone and in complex with self-DNA triggers inflammatory responses in myeloid cells and plays a crucial role in the development of systemic autoimmune diseases, like psoriasis and systemic lupus erythematosus. We demonstrated that LL37/self-DNA complexes induce long-term metabolic and epigenetic changes in monocytes, enhancing their responsiveness to subsequent stimuli. Monocytes trained with LL37/self-DNA complexes and those derived from psoriatic patients exhibited heightened glycolytic and oxidative phosphorylation rates, elevated release of proinflammatory cytokines, and affected na&iuml;ve CD4</span><sup>+</sup><span><span>&nbsp;</span>T cells. Additionally, KDM6A/B, a demethylase of lysine 27 on histone 3, was upregulated in psoriatic monocytes and monocytes treated with LL37/self-DNA complexes. Inhibition of KDM6A/B reversed the trained immune phenotype by reducing proinflammatory cytokine production, metabolic activity, and the induction of IL-17-producing T cells by LL37/self-DNA-treated monocytes. Our findings highlight the role of LL37/self-DNA-induced innate immune memory in psoriasis pathogenesis, uncovering its impact on monocyte and T cell dynamics.</span></p>',
			'date' => '2024-08-01',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S1521661624003966',
			'doi' => 'https://doi.org/10.1016/j.clim.2024.110287',
			'modified' => '2024-07-04 15:53:17',
			'created' => '2024-07-04 15:53:17',
			'ProductsPublication' => array(
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		),
		(int) 6 => array(
			'id' => '4968',
			'name' => 'Innate immune training restores pro-reparative myeloid functions to promote remyelination in the aged central nervous system',
			'authors' => 'Tiwari V. et al.',
			'description' => '<p><span>The reduced ability of the central nervous system to regenerate with increasing age limits functional recovery following demyelinating injury. Previous work has shown that myelin debris can overwhelm the metabolic capacity of microglia, thereby impeding tissue regeneration in aging, but the underlying mechanisms are unknown. In a model of demyelination, we found that a substantial number of genes that were not effectively activated in aged myeloid cells displayed epigenetic modifications associated with restricted chromatin accessibility. Ablation of two class I histone deacetylases in microglia was sufficient to restore the capacity of aged mice to remyelinate lesioned tissue. We used Bacillus Calmette-Guerin (BCG), a live-attenuated vaccine, to train the innate immune system and detected epigenetic reprogramming of brain-resident myeloid cells and functional restoration of myelin debris clearance and lesion recovery. Our results provide insight into aging-associated decline in myeloid function and how this decay can be prevented by innate immune reprogramming.</span></p>',
			'date' => '2024-07-24',
			'pmid' => 'https://www.cell.com/immunity/fulltext/S1074-7613(24)00348-0',
			'doi' => '',
			'modified' => '2024-09-02 17:05:54',
			'created' => '2024-09-02 17:05:54',
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			)
		),
		(int) 7 => array(
			'id' => '4954',
			'name' => 'A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment',
			'authors' => 'Perez R. F. at al. ',
			'description' => '<p><span>Aging involves the deterioration of organismal function, leading to the emergence of multiple pathologies. Environmental stimuli, including lifestyle, can influence the trajectory of this process and may be used as tools in the pursuit of healthy aging. To evaluate the role of epigenetic mechanisms in this context, we have generated bulk tissue and single cell multi-omic maps of the male mouse dorsal hippocampus in young and old animals exposed to environmental stimulation in the form of enriched environments. We present a molecular atlas of the aging process, highlighting two distinct axes, related to inflammation and to the dysregulation of mRNA metabolism, at the functional RNA and protein level. Additionally, we report the alteration of heterochromatin domains, including the loss of bivalent chromatin and the uncovering of a heterochromatin-switch phenomenon whereby constitutive heterochromatin loss is partially mitigated through gains in facultative heterochromatin. Notably, we observed the multi-omic reversal of a great number of aging-associated alterations in the context of environmental enrichment, which was particularly linked to glial and oligodendrocyte pathways. In conclusion, our work describes the epigenomic landscape of environmental stimulation in the context of aging and reveals how lifestyle intervention can lead to the multi-layered reversal of aging-associated decline.</span></p>',
			'date' => '2024-07-16',
			'pmid' => 'https://www.nature.com/articles/s41467-024-49608-z',
			'doi' => 'https://doi.org/10.1038/s41467-024-49608-z',
			'modified' => '2024-07-29 11:33:49',
			'created' => '2024-07-29 11:33:49',
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			)
		),
		(int) 8 => array(
			'id' => '4946',
			'name' => 'The landscape of RNA-chromatin interaction reveals small non-coding RNAs as essential mediators of leukemia maintenance',
			'authors' => 'Haiyang Yun et al.',
			'description' => '<p><span>RNA constitutes a large fraction of chromatin. Spatial distribution and functional relevance of most of RNA-chromatin interactions remain unknown. We established a landscape analysis of RNA-chromatin interactions in human acute myeloid leukemia (AML). In total more than 50 million interactions were captured in an AML cell line. Protein-coding mRNAs and long non-coding RNAs exhibited a substantial number of interactions with chromatin in&nbsp;</span><i>cis</i><span><span>&nbsp;</span>suggesting transcriptional activity. In contrast, small nucleolar RNAs (snoRNAs) and small nuclear RNAs (snRNAs) associated with chromatin predominantly in<span>&nbsp;</span></span><i>trans</i><span><span>&nbsp;</span>suggesting chromatin specific functions. Of note, snoRNA-chromatin interaction was associated with chromatin modifications and occurred independently of the classical snoRNA-RNP complex. Two C/D box snoRNAs, namely<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span>, displayed high frequency of<span>&nbsp;</span></span><i>trans</i><span>-association with chromatin. The transcription of<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span><span>&nbsp;</span>was increased upon leukemia transformation and enriched in leukemia stem cells, but decreased during myeloid differentiation. Suppression of<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span><span>&nbsp;</span>impaired leukemia cell proliferation and colony forming capacity in AML cell lines and primary patient samples. Notably, this effect was leukemia specific with less impact on healthy CD34+ hematopoietic stem and progenitor cells. These findings highlight the functional importance of chromatin-associated RNAs overall and in particular of<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span><span>&nbsp;</span>in maintaining leukemia propagation.</span></p>',
			'date' => '2024-06-28',
			'pmid' => 'https://www.nature.com/articles/s41375-024-02322-7',
			'doi' => 'https://doi.org/10.1038/s41375-024-02322-7',
			'modified' => '2024-07-04 14:32:41',
			'created' => '2024-07-04 14:32:41',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 9 => array(
			'id' => '4948',
			'name' => 'Single-cell epigenomic reconstruction of developmental trajectories from pluripotency in human neural organoid systems',
			'authors' => 'Fides Zenk et al.',
			'description' => '<p><span>Cell fate progression of pluripotent progenitors is strictly regulated, resulting in high human cell diversity. Epigenetic modifications also orchestrate cell fate restriction. Unveiling the epigenetic mechanisms underlying human cell diversity has been difficult. In this study, we use human brain and retina organoid models and present single-cell profiling of H3K27ac, H3K27me3 and H3K4me3 histone modifications from progenitor to differentiated neural fates to reconstruct the epigenomic trajectories regulating cell identity acquisition. We capture transitions from pluripotency through neuroepithelium to retinal and brain region and cell type specification. Switching of repressive and activating epigenetic modifications can precede and predict cell fate decisions at each stage, providing a temporal census of gene regulatory elements and transcription factors. Removing H3K27me3 at the neuroectoderm stage disrupts fate restriction, resulting in aberrant cell identity acquisition. Our single-cell epigenome-wide map of human neural organoid development serves as a blueprint to explore human cell fate determination.</span></p>',
			'date' => '2024-06-24',
			'pmid' => 'https://www.nature.com/articles/s41593-024-01652-0',
			'doi' => 'https://doi.org/10.1038/s41593-024-01652-0',
			'modified' => '2024-07-04 14:54:14',
			'created' => '2024-07-04 14:54:14',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 10 => array(
			'id' => '4924',
			'name' => 'SURVIVIN IN SYNERGY WITH BAF/SWI COMPLEX BINDS BIVALENT CHROMATIN REGIONS AND ACTIVATES DNA DAMAGE RESPONSE IN CD4+ T CELLS',
			'authors' => 'Chandrasekaran V. et al.',
			'description' => '<p id="p-2">This study explores a regulatory role of oncoprotein survivin on the bivalent regions of chromatin (BvCR) characterized by concomitant deposition of trimethylated lysine of histone H3 at position 4 (H3K4me3) and 27 (H3K27me3).</p>
<p id="p-3">Intersect between BvCR and chromatin sequences bound to survivin demonstrated their co-localization on<span>&nbsp;</span><em>cis</em>-regulatory elements of genes which execute DNA damage control in primary human CD4<sup>+</sup><span>&nbsp;</span>cells. Survivin anchored BRG1-complex to BvCR to repress DNA damage repair genes in IFN&gamma;-stimulated CD4<sup>+</sup><span>&nbsp;</span>cells. In contrast, survivin inhibition shifted the functional balance of BvCR in favor of H3K4me3, which activated DNA damage recognition and repair. Co-expression of BRG1, survivin and IFN&gamma; in CD4<sup>+</sup><span>&nbsp;</span>cells of patients with rheumatoid arthritis identified arthritogenic BRG1<sup>hi</sup><span>&nbsp;</span>cells abundant in autoimmune synovia. Immunomodulating drugs inhibited the subunits anchoring BRG1-complex to BvCR, which changed the arthritogenic profile.</p>
<p id="p-4">Together, this study demonstrates the function of BvCR in DNA damage control of CD4<sup>+</sup><span>&nbsp;</span>cells offering an epigenetic platform for survivin and BRG1-complex targeting interventions to combat autoimmunity.</p>
<div id="sec-1" class="subsection">
<p id="p-5"><strong>Summary</strong><span>&nbsp;</span>This study shows that bivalent chromatin regions accommodate survivin which represses DNA repair enzymes in IFN&gamma;-stimulated CD4<sup>+</sup><span>&nbsp;</span>T cells. Survivin anchors BAF/SWI complex to these regions and supports autoimmune profile of T cells, providing novel targets for therapeutic intervention.</p>
</div>',
			'date' => '2024-03-10',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/2024.03.05.583464v1',
			'doi' => 'https://doi.org/10.1101/2024.03.05.583464',
			'modified' => '2024-03-13 17:07:31',
			'created' => '2024-03-13 17:07:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 11 => array(
			'id' => '4911',
			'name' => 'Multiomics uncovers the epigenomic and transcriptomic response to viral and bacterial stimulation in turbot',
			'authors' => 'Aramburu O. et al.',
			'description' => '<p><span>Uncovering the epigenomic regulation of immune responses is essential for a comprehensive understanding of host defence mechanisms but remains poorly described in farmed fish. Here, we report the first annotation of the innate immune regulatory response in the genome of turbot (</span><em>Scophthalmus maximus</em><span>), a farmed flatfish. We integrated RNA-Seq with ATAC-Seq and ChIP-Seq (histone marks H3K4me3, H3K27ac and H3K27me3) using samples from head kidney. Sampling was performed 24 hours post-stimulation with viral (poly I:C) and bacterial (inactivate<span>&nbsp;</span></span><em>Vibrio anguillarum</em><span>) mimics<span>&nbsp;</span></span><em>in vivo</em><span><span>&nbsp;</span>and<span>&nbsp;</span></span><em>in vitro</em><span><span>&nbsp;</span>(primary leukocyte cultures). Among the 8,797 differentially expressed genes (DEGs), we observed enrichment of transcriptional activation pathways in response to<span>&nbsp;</span></span><em>Vibrio</em><span><span>&nbsp;</span>and immune response pathways - including interferon stimulated genes - for poly I:C. Meanwhile, metabolic and cell cycle were downregulated by both mimics. We identified notable differences in chromatin accessibility (20,617<span>&nbsp;</span></span><em>in vitro</em><span>, 59,892<span>&nbsp;</span></span><em>in vivo</em><span>) and H3K4me3 bound regions (11,454<span>&nbsp;</span></span><em>in vitro</em><span>, 10,275<span>&nbsp;</span></span><em>in viv</em><span>o) - i.e. marking active promoters - between stimulations and controls. Overlaps of DEGs with promoters showing differential accessibility or histone mark binding revealed a significant coupling of the transcriptome and chromatin state. DEGs with activation marks in their promoters were enriched for similar functions to the global DEG set, but not in all cases, suggesting key regulatory genes were in poised or bivalent states. Active promoters and putative enhancers were differentially enriched in transcription factor binding motifs, many of them common to viral and bacterial responses. Finally, an in-depth analysis of immune response changes in chromatin state surrounding key DEGs encoding transcription factors was performed. This comprehensive multi-omics investigation provides an improved understanding of the epigenomic basis for the turbot immune responses and provides novel functional genomic information that can be leveraged in selective breeding towards enhanced disease resistance.</span></p>',
			'date' => '2024-02-15',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/2024.02.15.580452v1',
			'doi' => 'https://doi.org/10.1101/2024.02.15.580452',
			'modified' => '2024-02-22 11:41:27',
			'created' => '2024-02-22 11:41:27',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 12 => array(
			'id' => '4842',
			'name' => 'Alterations in the hepatocyte epigenetic landscape in steatosis.',
			'authors' => 'Maji  Ranjan K. et al.',
			'description' => '<p>Fatty liver disease or the accumulation of fat in the liver, has been reported to affect the global population. This comes with an increased risk for the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Yet, little is known about the effects of a diet containing high fat and alcohol towards epigenetic aging, with respect to changes in transcriptional and epigenomic profiles. In this study, we took up a multi-omics approach and integrated gene expression, methylation signals, and chromatin signals to study the epigenomic effects of a high-fat and alcohol-containing diet on mouse hepatocytes. We identified four relevant gene network clusters that were associated with relevant pathways that promote steatosis. Using a machine learning approach, we predict specific transcription factors that might be responsible to modulate the functionally relevant clusters. Finally, we discover four additional CpG loci and validate aging-related differential CpG methylation. Differential CpG methylation linked to aging showed minimal overlap with altered methylation in steatosis.</p>',
			'date' => '2023-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37415213',
			'doi' => '10.1186/s13072-023-00504-8',
			'modified' => '2023-08-01 14:08:16',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 13 => array(
			'id' => '4859',
			'name' => 'Sexual differentiation in human malaria parasites is regulated bycompetition between phospholipid metabolism and histone methylation.',
			'authors' => 'Harris  C. T. et al.',
			'description' => '<p>For Plasmodium falciparum, the most widespread and virulent malaria parasite that infects humans, persistence depends on continuous asexual replication in red blood cells, while transmission to their mosquito vector requires asexual blood-stage parasites to differentiate into non-replicating gametocytes. This decision is controlled by stochastic derepression of a heterochromatin-silenced locus encoding AP2-G, the master transcription factor of sexual differentiation. The frequency of ap2-g derepression was shown to be responsive to extracellular phospholipid precursors but the mechanism linking these metabolites to epigenetic regulation of ap2-g was unknown. Through a combination of molecular genetics, metabolomics and chromatin profiling, we show that this response is mediated by metabolic competition for the methyl donor S-adenosylmethionine between histone methyltransferases and phosphoethanolamine methyltransferase, a critical enzyme in the parasite's pathway for de novo phosphatidylcholine synthesis. When phosphatidylcholine precursors are scarce, increased consumption of SAM for de novo phosphatidylcholine synthesis impairs maintenance of the histone methylation responsible for silencing ap2-g, increasing the frequency of derepression and sexual differentiation. This provides a key mechanistic link that explains how LysoPC and choline availability can alter the chromatin status of the ap2-g locus controlling sexual differentiation.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37277533',
			'doi' => '10.1038/s41564-023-01396-w',
			'modified' => '2023-08-01 14:48:21',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 14 => array(
			'id' => '4862',
			'name' => 'Mutant FUS induces chromatin reorganization in the hippocampus andalters memory processes.',
			'authors' => 'Tzeplaeff  L. et al.',
			'description' => '<p>Cytoplasmic mislocalization of the nuclear Fused in Sarcoma (FUS) protein is associated to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cytoplasmic FUS accumulation is recapitulated in the frontal cortex and spinal cord of heterozygous Fus mice. Yet, the mechanisms linking FUS mislocalization to hippocampal function and memory formation are still not characterized. Herein, we show that in these mice, the hippocampus paradoxically displays nuclear FUS accumulation. Multi-omic analyses showed that FUS binds to a set of genes characterized by the presence of an ETS/ELK-binding motifs, and involved in RNA metabolism, transcription, ribosome/mitochondria and chromatin organization. Importantly, hippocampal nuclei showed a decompaction of the neuronal chromatin at highly expressed genes and an inappropriate transcriptomic response was observed after spatial training of Fus mice. Furthermore, these mice lacked precision in a hippocampal-dependent spatial memory task and displayed decreased dendritic spine density. These studies shows that mutated FUS affects epigenetic regulation of the chromatin landscape in hippocampal neurons, which could participate in FTD/ALS pathogenic events. These data call for further investigation in the neurological phenotype of FUS-related diseases and open therapeutic strategies towards epigenetic drugs.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37327984',
			'doi' => '10.1016/j.pneurobio.2023.102483',
			'modified' => '2023-08-01 14:55:49',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 15 => array(
			'id' => '4820',
			'name' => 'The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cellfate.',
			'authors' => 'Lackner  A. et al.',
			'description' => '<p><span>Placental development relies on coordinated cell fate decisions governed by signalling inputs. However, little is known about how signalling cues are transformed into repressive mechanisms triggering lineage-specific transcriptional signatures. Here, we demonstrate that upon inhibition of the Fgf/Erk pathway in mouse trophoblast stem cells (TSCs), the Ets2 repressor factor (Erf) interacts with the Nuclear Receptor Co-Repressor Complex 1 and 2 (NCoR1/2) and recruits it to key trophoblast genes. Genetic ablation of Erf or Tbl1x (a component of the NCoR1/2 complex) abrogates the Erf/NCoR1/2 interaction. This leads to mis-expression of Erf/NCoR1/2 target genes, resulting in a TSC differentiation defect. Mechanistically, Erf regulates expression of these genes by recruiting the NCoR1/2 complex and decommissioning their H3K27ac-dependent enhancers. Our findings uncover how the Fgf/Erf/NCoR1/2 repressive axis governs cell fate and placental development, providing a paradigm for Fgf-mediated transcriptional control.</span></p>',
			'date' => '2023-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37137875',
			'doi' => '10.1038/s41467-023-38101-8',
			'modified' => '2023-06-19 10:10:38',
			'created' => '2023-06-13 21:11:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 16 => array(
			'id' => '4778',
			'name' => 'Comprehensive epigenomic profiling reveals the extent of disease-specificchromatin states and informs target discovery in ankylosing spondylitis',
			'authors' => 'Brown  A.C. et al.',
			'description' => '<p>Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterized by enthesitis of the spine and sacroiliac joints. Genome-wide association studies (GWASs) have revealed more than 100 genetic associations whose functional effects remain largely unresolved. Here, we present a comprehensive transcriptomic and epigenomic map of disease-relevant blood immune cell subsets from AS patients and healthy controls.We find that, while CD14+ monocytes and CD4+ and CD8+ T cells show disease-specific differences at the RNA level, epigenomic differences are only apparent upon multi-omics integration. The latter reveals enrichment at disease-associated loci in monocytes. We link putative functional SNPs to genes using high-resolution Capture-C at 10 loci, including PTGER4 and ETS1, and show how disease-specific functional genomic data can be integrated with GWASs to enhance therapeutic target discovery. This study combines epigenetic and transcriptional analysis with GWASs to identify disease-relevant cell types and gene regulation of likely pathogenic relevance and prioritize drug targets.</p>',
			'date' => '2023-04-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.xgen.2023.100306',
			'doi' => '10.1016/j.xgen.2023.100306',
			'modified' => '2023-06-13 09:14:26',
			'created' => '2023-05-05 12:34:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 17 => array(
			'id' => '4763',
			'name' => 'Chromatin profiling identifies transcriptional readthrough as a conservedmechanism for piRNA biogenesis in mosquitoes.',
			'authors' => 'Qu  J. et al.',
			'description' => '<p>The piRNA pathway in mosquitoes differs substantially from other model organisms, with an expanded PIWI gene family and functions in antiviral defense. Here, we define core piRNA clusters as genomic loci that show ubiquitous piRNA expression in both somatic and germline tissues. These core piRNA clusters are enriched for non-retroviral endogenous viral elements (nrEVEs) in antisense orientation and depend on key biogenesis factors, Veneno, Tejas, Yb, and Shutdown. Combined transcriptome and chromatin state analyses identify transcriptional readthrough as a conserved mechanism for cluster-derived piRNA biogenesis in the vector mosquitoes Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and Anopheles gambiae. Comparative analyses between the two Aedes species suggest that piRNA clusters function as traps for nrEVEs, allowing adaptation to environmental challenges such as virus infection. Our systematic transcriptome and chromatin state analyses lay the foundation for studies of gene regulation, genome evolution, and piRNA function in these important vector species.</p>',
			'date' => '2023-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36930642',
			'doi' => '10.1016/j.celrep.2023.112257',
			'modified' => '2023-04-17 09:12:37',
			'created' => '2023-04-14 13:41:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 18 => array(
			'id' => '4765',
			'name' => 'Epigenetic dosage identifies two major and functionally distinct beta cells ubtypes.',
			'authors' => 'Dror  E.et al.',
			'description' => '<p>The mechanisms that specify and stabilize cell subtypes remain poorly understood. Here, we identify two major subtypes of pancreatic &Icirc;&sup2; cells based on histone mark heterogeneity (beta HI and beta LO). Beta HI cells exhibit 4-fold higher levels of H3K27me3, distinct chromatin organization and compaction, and a specific transcriptional pattern. B<span>eta HI and beta LO</span> cells also differ in size, morphology, cytosolic and nuclear ultrastructure, epigenomes, cell surface marker expression, and function, and can be FACS separated into CD24 and CD24 fractions. Functionally, &Icirc;&sup2; cells have increased mitochondrial mass, activity, and insulin secretion in vivo and ex vivo. Partial loss of function indicates that H3K27me3 dosage regulates <span>beta HI/beta LO&nbsp;</span>ratio in vivo, suggesting that control of <span>beta HI&nbsp;</span>cell subtype identity and ratio is at least partially uncoupled. Both subtypes are conserved in humans, with <span>beta HI</span> cells enriched in humans with type 2 diabetes. Thus, epigenetic dosage is a novel regulator of cell subtype specification and identifies two functionally distinct&nbsp;beta cell subtypes.</p>',
			'date' => '2023-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36948185',
			'doi' => '10.1016/j.cmet.2023.03.008',
			'modified' => '2023-04-17 09:26:02',
			'created' => '2023-04-14 13:41:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 19 => array(
			'id' => '4667',
			'name' => 'Detailed molecular and epigenetic characterization of the Pig IPECJ2and Chicken SL-29 cell lines',
			'authors' => 'de Vos  J. et al.',
			'description' => '<p>The pig IPECJ2 and chicken SL-29 cell lines are of interest because of their untransformed nature and wide use in functional studies. Molecular characterization of these cell lines is important to gain insight into possible molecular aberrations. The aims of this paper are providing a molecular and epigenetic characterization of the IPEC-J2 and SL-29 cell lines and providing a cell-line reference for the FAANG community, and future biomedical research. Whole genome sequencing , gene expression, DNA methylation , chromatin accessibility and ChIP-seq of four histone marks (H3K4me1, H3K4me3, H3K27ac, H3K27me3) and an insulator (CTCF) are used to achieve these aims. Heteroploidy (aneuploidy) of various chromosomes was observed from whole genome sequencing analysis in both cell lines. Furthermore, higher gene expression for genes located on chromosomes with aneuploidy in comparison to diploid chromosomes was observed. Regulatory complexity of gene expression, DNA methylation and chromatin accessibility was investigated through an integrative approach.</p>',
			'date' => '2023-02-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.isci.2023.106252',
			'doi' => '10.1016/j.isci.2023.106252',
			'modified' => '2023-04-07 16:52:26',
			'created' => '2023-02-28 12:19:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 20 => array(
			'id' => '4669',
			'name' => 'Histone remodeling reflects conserved mechanisms of bovine and humanpreimplantation development.',
			'authors' => 'Zhou  C. et al.',
			'description' => '<p>How histone modifications regulate changes in gene expression during preimplantation development in any species remains poorly understood. Using CUT\&amp;Tag to overcome limiting amounts of biological material, we profiled two activating (H3K4me3 and H3K27ac) and two repressive (H3K9me3 and H3K27me3) marks in bovine oocytes, 2-, 4-, and 8-cell embryos, morula, blastocysts, inner cell mass, and trophectoderm. In oocytes, broad bivalent domains mark developmental genes, and prior to embryonic genome activation (EGA), H3K9me3 and H3K27me3 co-occupy gene bodies, suggesting a global mechanism for transcription repression. During EGA, chromatin accessibility is established before canonical H3K4me3 and H3K27ac signatures. Embryonic transcription is required for this remodeling, indicating that maternally provided products alone are insufficient for reprogramming. Last, H3K27me3 plays a major role in restriction of cellular potency, as blastocyst lineages are defined by differential polycomb repression and transcription factor activity. Notably, inferred regulators of EGA and blastocyst formation strongly resemble those described in humans, as opposed to mice. These similarities suggest that cattle are a better model than rodents to investigate the molecular basis of human preimplantation development.</p>',
			'date' => '2023-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36779365',
			'doi' => '10.15252/embr.202255726',
			'modified' => '2023-04-14 09:34:12',
			'created' => '2023-02-28 12:19:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 21 => array(
			'id' => '4605',
			'name' => 'Gene Regulatory Interactions at Lamina-Associated Domains',
			'authors' => 'Madsen-Østerbye  J. et al.',
			'description' => '<p>The nuclear lamina provides a repressive chromatin environment at the nuclear periphery. However, whereas most genes in lamina-associated domains (LADs) are inactive, over ten percent reside in local euchromatic contexts and are expressed. How these genes are regulated and whether they are able to interact with regulatory elements remain unclear. Here, we integrate publicly available enhancer-capture Hi-C data with our own chromatin state and transcriptomic datasets to show that inferred enhancers of active genes in LADs are able to form connections with other enhancers within LADs and outside LADs. Fluorescence in situ hybridization analyses show proximity changes between differentially expressed genes in LADs and distant enhancers upon the induction of adipogenic differentiation. We also provide evidence of involvement of lamin A/C, but not lamin B1, in repressing genes at the border of an in-LAD active region within a topological domain. Our data favor a model where the spatial topology of chromatin at the nuclear lamina is compatible with gene expression in this dynamic nuclear compartment.</p>',
			'date' => '2023-01-01',
			'pmid' => 'https://doi.org/10.3390%2Fgenes14020334',
			'doi' => '10.3390/genes14020334',
			'modified' => '2023-04-04 08:57:32',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 22 => array(
			'id' => '4802',
			'name' => 'Analyzing the Genome-Wide Distribution of Histone Marks byCUT\&Tag in Drosophila Embryos.',
			'authors' => 'Zenk  F. et al.',
			'description' => '<p><span>CUT&amp;Tag is a method to map the genome-wide distribution of histone modifications and some chromatin-associated proteins. CUT&amp;Tag relies on antibody-targeted chromatin tagmentation and can easily be scaled up or automatized. This protocol provides clear experimental guidelines and helpful considerations when planning and executing CUT&amp;Tag experiments.</span></p>',
			'date' => '2023-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37212984',
			'doi' => '10.1007/978-1-0716-3143-0_1',
			'modified' => '2023-06-15 08:43:40',
			'created' => '2023-06-13 21:11:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 23 => array(
			'id' => '4545',
			'name' => 'Histone Deacetylases 1 and 2 target gene regulatory networks of nephronprogenitors to control nephrogenesis.',
			'authors' => 'Liu  Hongbing et al.',
			'description' => '<p>Our studies demonstrated the critical role of Histone deacetylases (HDACs) in the regulation of nephrogenesis. To better understand the key pathways regulated by HDAC1/2 in early nephrogenesis, we performed chromatin immunoprecipitation sequencing (ChIP-Seq) of Hdac1/2 on isolated nephron progenitor cells (NPCs) from mouse E16.5 kidneys. Our analysis revealed that 11802 (40.4\%) of Hdac1 peaks overlap with Hdac2 peaks, further demonstrates the redundant role of Hdac1 and Hdac2 during nephrogenesis. Common Hdac1/2 peaks are densely concentrated close to the transcriptional start site (TSS). GREAT Gene Ontology analysis of overlapping Hdac1/2 peaks reveals that Hdac1/2 are associated with metanephric nephron morphogenesis, chromatin assembly or disassembly, as well as other DNA checkpoints. Pathway analysis shows that negative regulation of Wnt signaling pathway is one of Hdac1/2's most significant function in NPCs. Known motif analysis indicated that Hdac1 is enriched in motifs for Six2, Hox family, and Tcf family members, which are essential for self-renewal and differentiation of nephron progenitors. Interestingly, we found the enrichment of HDAC1/2 at the enhancer and promoter regions of actively transcribed genes, especially those concerned with NPC self-renewal. HDAC1/2 simultaneously activate or repress the expression of different genes to maintain the cellular state of nephron progenitors. We used the Integrative Genomics Viewer to visualize these target genes associated with each function and found that Hdac1/2 co-bound to the enhancers or/and promoters of genes associated with nephron morphogenesis, differentiation, and cell cycle control. Taken together, our ChIP-Seq analysis demonstrates that Hdac1/2 directly regulate the molecular cascades essential for nephrogenesis.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36356658',
			'doi' => '10.1016/j.bcp.2022.115341',
			'modified' => '2022-11-24 10:24:07',
			'created' => '2022-11-24 08:49:52',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 24 => array(
			'id' => '4658',
			'name' => 'Balance between autophagy and cell death is maintained byPolycomb-mediated regulation during stem cell differentiation.',
			'authors' => 'Puri  Deepika et al.',
			'description' => '<p>Autophagy is a conserved cytoprotective process, aberrations in which lead to numerous degenerative disorders. While the cytoplasmic components of autophagy have been extensively studied, the epigenetic regulation of autophagy genes, especially in stem cells, is less understood. Deciphering the epigenetic regulation of autophagy genes becomes increasingly relevant given the therapeutic benefits of small-molecule epigenetic inhibitors in novel treatment modalities. We observe that, during retinoic acid-mediated differentiation of mouse embryonic stem cells (mESCs), autophagy is induced, and identify the Polycomb group histone methyl transferase EZH2 as a regulator of this process. In mESCs, EZH2 represses several autophagy genes, including the autophagy regulator DNA damage-regulated autophagy modulator protein 1 (Dram1). EZH2 facilitates the formation of a bivalent chromatin domain at the Dram1 promoter, allowing gene expression and autophagy induction during differentiation while retaining the repressive H3K27me3 mark. EZH2 inhibition leads to loss of the bivalent domain, with consequent "hyper-expression" of Dram1, accompanied by extensive cell death. This study shows that Polycomb group proteins help maintain a balance between autophagy and cell death during stem cell differentiation, in part by regulating the expression of the Dram1 gene.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36380631',
			'doi' => '10.1111/febs.16656',
			'modified' => '2023-03-07 08:59:36',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 25 => array(
			'id' => '4788',
			'name' => 'Dietary methionine starvation impairs acute myeloid leukemia progression.',
			'authors' => 'Cunningham  A. et al.',
			'description' => '<p>Targeting altered tumor cell metabolism might provide an attractive opportunity for patients with acute myeloid leukemia (AML). An amino acid dropout screen on primary leukemic stem cells and progenitor populations revealed a number of amino acid dependencies, of which methionine was one of the strongest. By using various metabolite rescue experiments, nuclear magnetic resonance-based metabolite quantifications and 13C-tracing, polysomal profiling, and chromatin immunoprecipitation sequencing, we identified that methionine is used predominantly for protein translation and to provide methyl groups to histones via S-adenosylmethionine for epigenetic marking. H3K36me3 was consistently the most heavily impacted mark following loss of methionine. Methionine depletion also reduced total RNA levels, enhanced apoptosis, and induced a cell cycle block. Reactive oxygen species levels were not increased following methionine depletion, and replacement of methionine with glutathione or N-acetylcysteine could not rescue phenotypes, excluding a role for methionine in controlling redox balance control in AML. Although considered to be an essential amino acid, methionine can be recycled from homocysteine. We uncovered that this is primarily performed by the enzyme methionine synthase and only when methionine availability becomes limiting. In&Acirc;&nbsp;vivo, dietary methionine starvation was not only tolerated by mice, but also significantly delayed both cell line and patient-derived AML progression. Finally, we show that inhibition of the H3K36-specific methyltransferase SETD2 phenocopies much of the cytotoxic effects of methionine depletion, providing a more targeted therapeutic approach. In conclusion, we show that methionine depletion is a vulnerability in AML that can be exploited therapeutically, and we provide mechanistic insight into how cells metabolize and recycle methionine.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://doi.org/10.33612%2Fdiss.205032978',
			'doi' => '10.1182/blood.2022017575',
			'modified' => '2023-06-12 09:01:21',
			'created' => '2023-05-05 12:34:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 26 => array(
			'id' => '4499',
			'name' => 'Trained Immunity Provides Long-Term Protection againstBacterial Infections in Channel Catfish.',
			'authors' => 'Petrie-Hanson  L. et al.',
			'description' => '<p>Beta glucan exposure induced trained immunity in channel catfish that conferred long-term protection against and infections one month post exposure. Flow cytometric analyses demonstrated that isolated macrophages and neutrophils phagocytosed higher amounts of and . Beta glucan induced changes in the distribution of histone modifications in the monomethylation and trimethylation of H3K4 and modifications in the acetylation and trimethylation of H3K27. KEGG pathway analyses revealed that these modifications affected expressions of genes controlling phagocytosis, phagosome functions and enhanced immune cell signaling. These analyses correlate the histone modifications with gene functions and to the observed enhanced phagocytosis and to the increased survival following bacterial challenge in channel catfish. These data suggest the chromatin reconfiguration that directs trained immunity as demonstrated in mammals also occurs in channel catfish. Understanding the mechanisms underlying trained immunity can help us design prophylactic and non-antibiotic based therapies and develop broad-based vaccines to limit bacterial disease outbreaks in catfish production.</p>',
			'date' => '2022-10-01',
			'pmid' => 'https://doi.org/10.3390%2Fpathogens11101140',
			'doi' => '10.3390/pathogens11101140',
			'modified' => '2022-11-21 10:31:12',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 27 => array(
			'id' => '4451',
			'name' => 'bESCs from cloned embryos do not retain transcriptomic or epigenetic memory from somatic donor cells.',
			'authors' => 'Navarro  M. et al.',
			'description' => '<p>Embryonic stem cells (ESC) indefinitely maintain the pluripotent state of the blastocyst epiblast. Stem cells are invaluable for studying development and lineage commitment, and in livestock they constitute a useful tool for genomic improvement and in vitro breeding programs. Although these cells have been recently derived from bovine blastocysts, a detailed characterization of their molecular state is still lacking. Here, we apply cutting-edge technologies to analyze the transcriptomic and epigenomic landscape of bovine ESC (bESC) obtained from in vitro fertilized (IVF) and somatic cell nuclear transfer (SCNT) embryos. Bovine ESC were efficiently derived from SCNT and IVF embryos and expressed pluripotency markers while retaining genome stability. Transcriptome analysis revealed that only 46 genes were differentially expressed between IVF- and SCNT-derived bESC, which did not reflect significant deviation in cellular function. Interrogating the histone marks H3K4me3, H3K9me3 and H3K27me3 with CUT\&amp;Tag, we found that the epigenomes of both bESC groups were virtually indistinguishable. Minor epigenetic differences were randomly distributed throughout the genome and were not associated with differentially expressed or developmentally important genes. Finally, categorization of genomic regions according to their combined histone mark signal demonstrated that all bESC shared the same epigenomic signatures, especially at promoters. Overall, we conclude that bESC derived from SCNT and IVF are transcriptomically and epigenetically analogous, allowing for the production of an unlimited source of pluripotent cells from high genetic merit organisms without resorting to genome editing techniques.</p>',
			'date' => '2022-08-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/35951478/',
			'doi' => '10.1530/REP-22-0063',
			'modified' => '2022-10-21 09:31:32',
			'created' => '2022-09-28 09:53:13',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 28 => array(
			'id' => '4416',
			'name' => 'Large-scale manipulation of promoter DNA methylation revealscontext-specific transcriptional responses and stability.',
			'authors' => 'de Mendoza  A. et al. ',
			'description' => '<p>BACKGROUND: Cytosine DNA methylation is widely described as a transcriptional repressive mark with the capacity to silence promoters. Epigenome engineering techniques enable direct testing of the effect of induced DNA methylation on endogenous promoters; however, the downstream effects have not yet been comprehensively assessed. RESULTS: Here, we simultaneously induce methylation at thousands of promoters in human cells using an engineered zinc finger-DNMT3A fusion protein, enabling us to test the effect of forced DNA methylation upon transcription, chromatin accessibility, histone modifications, and DNA methylation persistence after the removal of the fusion protein. We find that transcriptional responses to DNA methylation are highly context-specific, including lack of repression, as well as cases of increased gene expression, which appears to be driven by the eviction of methyl-sensitive transcriptional repressors. Furthermore, we find that some regulatory networks can override DNA methylation and that promoter methylation can cause alternative promoter usage. DNA methylation deposited at promoter and distal regulatory regions is rapidly erased after removal of the zinc finger-DNMT3A fusion protein, in a process combining passive and TET-mediated demethylation. Finally, we demonstrate that induced DNA methylation can exist simultaneously on promoter nucleosomes that possess the active histone modification H3K4me3, or DNA bound by the initiated form of RNA polymerase II. CONCLUSIONS: These findings have important implications for epigenome engineering and demonstrate that the response of promoters to DNA methylation is more complex than previously appreciated.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35883107',
			'doi' => '10.1186/s13059-022-02728-5',
			'modified' => '2022-09-15 09:01:24',
			'created' => '2022-09-08 16:32:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 29 => array(
			'id' => '4417',
			'name' => 'HOTAIR interacts with PRC2 complex regulating the regional preadipocytetranscriptome and human fat distribution.',
			'authors' => 'Kuo  Feng-Chih et al.',
			'description' => '<p>Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA HOTAIR (HOX transcript antisense RNA) is exclusively expressed in gluteofemoral AT, where it is essential for adipocyte development. We find that HOTAIR interacts with polycomb repressive complex 2 (PRC2) and we identify core HOTAIR-PRC2 target genes involved in adipocyte lineage determination. Repression of target genes coincides with PRC2 promoter occupancy and H3K27 trimethylation. HOTAIR is also involved in modifying the gluteal adipocyte transcriptome through alternative splicing. Gluteal-specific expression of HOTAIR is maintained by defined regions of open chromatin across the HOTAIR promoter. HOTAIR expression levels can be modified by hormonal (estrogen, glucocorticoids) and genetic variation (rs1443512 is a HOTAIR eQTL associated with reduced gynoid fat mass). These data identify HOTAIR as a dynamic regulator of the gluteal adipocyte transcriptome and epigenome with functional importance for human regional AT development.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35905723',
			'doi' => '10.1016/j.celrep.2022.111136',
			'modified' => '2022-09-27 14:41:23',
			'created' => '2022-09-08 16:32:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 30 => array(
			'id' => '4458',
			'name' => 'Epiblast inducers capture mouse trophectoderm stem cells in vitro andpattern blastoids for implantation in utero.',
			'authors' => 'Seong  Jinwoo et al.',
			'description' => '<p>The embryo instructs the allocation of cell states to spatially regulate functions. In the blastocyst, patterning of trophoblast (TR) cells ensures successful implantation and placental development. Here, we defined an optimal set of molecules secreted by the epiblast (inducers) that captures in&nbsp;vitro stable, highly self-renewing mouse trophectoderm stem cells (TESCs) resembling the blastocyst stage. When exposed to suboptimal inducers, these stem cells fluctuate to form interconvertible subpopulations with reduced self-renewal and facilitated differentiation, resembling peri-implantation cells, known as TR stem cells (TSCs). TESCs have enhanced capacity to form blastoids that implant more efficiently in utero due to inducers maintaining not only local TR proliferation and self-renewal, but also WNT6/7B secretion that stimulates uterine decidualization. Overall, the epiblast maintains sustained growth and decidualization potential of abutting TR cells, while, as known, distancing imposed by the blastocyst cavity differentiates TR cells for uterus adhesion, thus patterning the essential functions of implantation.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35803228',
			'doi' => '10.1016/j.stem.2022.06.002',
			'modified' => '2022-10-21 09:44:00',
			'created' => '2022-09-28 09:53:13',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 31 => array(
			'id' => '4386',
			'name' => 'Epigenomic analysis reveals a dynamic and context-specific macrophageenhancer landscape associated with innate immune activation and tolerance.',
			'authors' => 'Zhang  P. et al.',
			'description' => '<p>BACKGROUND: Chromatin states and enhancers associate gene expression, cell identity and disease. Here, we systematically delineate the acute innate immune response to endotoxin in terms of human macrophage enhancer activity and contrast with endotoxin tolerance, profiling the coding and non-coding transcriptome, chromatin accessibility and epigenetic modifications. RESULTS: We describe the spectrum of enhancers under acute and tolerance conditions and the regulatory networks between these enhancers and biological processes including gene expression, splicing regulation, transcription factor binding and enhancer RNA signatures. We demonstrate that the vast majority of differentially regulated enhancers on acute stimulation are subject to tolerance and that expression quantitative trait loci, disease-risk variants and eRNAs are enriched in these regulatory regions and related to context-specific gene expression. We find enrichment for context-specific eQTL involving endotoxin response and specific infections and delineate specific differential regions informative for GWAS variants in inflammatory bowel disease and multiple sclerosis, together with a context-specific enhancer involving a bacterial infection eQTL for KLF4. We show enrichment in differential enhancers for tolerance involving transcription factors NF&kappa;B-p65, STATs and IRFs and prioritize putative causal genes directly linking genetic variants and disease risk enhancers. We further delineate similarities and differences in epigenetic landscape between stem cell-derived macrophages and primary cells and characterize the context-specific enhancer activities for key innate immune response genes KLF4, SLAMF1 and IL2RA. CONCLUSIONS: Our study demonstrates the importance of context-specific macrophage enhancers in gene regulation and utility for interpreting disease associations, providing a roadmap to link genetic variants with molecular and cellular functions.</p>',
			'date' => '2022-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35751107',
			'doi' => '10.1186/s13059-022-02702-1',
			'modified' => '2022-08-11 14:07:03',
			'created' => '2022-08-11 12:14:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 32 => array(
			'id' => '4221',
			'name' => 'Epigenetic Mechanisms Mediating Cell State Transitions in Chondrocytes',
			'authors' => 'Wuelling M. et al.',
			'description' => '<p><span>Epigenetic modifications play critical roles in regulating cell lineage differentiation, but the epigenetic mechanisms guiding specific differentiation steps within a cell lineage have rarely been investigated. To decipher such mechanisms, we used the defined transition from proliferating (PC) into hypertrophic chondrocytes (HC) during endochondral ossification as a model. We established a map of activating and repressive histone modifications for each cell type. ChromHMM state transition analysis and Pareto-based integration of differential levels of mRNA and epigenetic marks revealed that differentiation-associated gene repression is initiated by the addition of H3K27me3 to promoters still carrying substantial levels of activating marks. Moreover, the integrative analysis identified genes specifically expressed in cells undergoing the transition into hypertrophy. Investigation of enhancer profiles detected surprising differences in enhancer number, location, and transcription factor binding sites between the two closely related cell types. Furthermore, cell type-specific upregulation of gene expression was associated with increased numbers of H3K27ac peaks. Pathway analysis identified PC-specific enhancers associated with chondrogenic genes, whereas HC-specific enhancers mainly control metabolic pathways linking epigenetic signature to biological functions. Since HC-specific enhancers show a higher conservation in postnatal tissues, the switch to metabolic pathways seems to be a hallmark of differentiated tissues. Surprisingly, the analysis of H3K27ac levels at super-enhancers revealed a rapid adaption of H3K27ac occupancy to changes in gene expression, supporting the importance of enhancer modulation for acute alterations in gene expression. &copy; 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).</span></p>',
			'date' => '2022-05-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/33534175/',
			'doi' => '10.1002/jbmr.4263',
			'modified' => '2022-04-25 11:46:32',
			'created' => '2022-04-21 12:00:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 33 => array(
			'id' => '4446',
			'name' => 'Variation in PU.1 binding and chromatin looping at neutrophil enhancersinfluences autoimmune disease susceptibility',
			'authors' => 'Watt  S. et al. ',
			'description' => '<p>Neutrophils play fundamental roles in innate inflammatory response, shape adaptive immunity1, and have been identified as a potentially causal cell type underpinning genetic associations with immune system traits and diseases2,3 The majority of these variants are non-coding and the underlying mechanisms are not fully understood. Here, we profiled the binding of one of the principal myeloid transcriptional regulators, PU.1, in primary neutrophils across nearly a hundred volunteers, and elucidate the coordinated genetic effects of PU.1 binding variation, local chromatin state, promoter-enhancer interactions and gene expression. We show that PU.1 binding and the associated chain of molecular changes underlie genetically-driven differences in cell count and autoimmune disease susceptibility. Our results advance interpretation for genetic loci associated with neutrophil biology and immune disease.</p>',
			'date' => '2022-05-01',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/620260v1.abstract',
			'doi' => '10.1101/620260',
			'modified' => '2022-10-14 16:39:03',
			'created' => '2022-09-28 09:53:13',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 34 => array(
			'id' => '4402',
			'name' => 'The CpG Island-Binding Protein SAMD1 Contributes to anUnfavorable Gene Signature in HepG2 Hepatocellular CarcinomaCells.',
			'authors' => 'Simon  C. et al.',
			'description' => '<p>The unmethylated CpG island-binding protein SAMD1 is upregulated in many human cancer types, but its cancer-related role has not yet been investigated. Here, we used the hepatocellular carcinoma cell line HepG2 as a cancer model and investigated the cellular and transcriptional roles of SAMD1 using ChIP-Seq and RNA-Seq. SAMD1 targets several thousand gene promoters, where it acts predominantly as a transcriptional repressor. HepG2 cells with SAMD1 deletion showed slightly reduced proliferation, but strongly impaired clonogenicity. This phenotype was accompanied by the decreased expression of pro-proliferative genes, including MYC target genes. Consistently, we observed a decrease in the active H3K4me2 histone mark at most promoters, irrespective of SAMD1 binding. Conversely, we noticed an increase in interferon response pathways and a gain of H3K4me2 at a subset of enhancers that were enriched for IFN-stimulated response elements (ISREs). We identified key transcription factor genes, such as , , and , that were directly repressed by SAMD1. Moreover, SAMD1 deletion also led to the derepression of the PI3K-inhibitor , contributing to diminished mTOR signaling and ribosome biogenesis pathways. Our work suggests that SAMD1 is involved in establishing a pro-proliferative setting in hepatocellular carcinoma cells. Inhibiting SAMD1's function in liver cancer cells may therefore lead to a more favorable gene signature.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35453756',
			'doi' => '10.3390/biology11040557',
			'modified' => '2022-08-11 14:45:43',
			'created' => '2022-08-11 12:14:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 35 => array(
			'id' => '4524',
			'name' => 'Local euchromatin enrichment in lamina-associated domains anticipatestheir repositioning in the adipogenic lineage.',
			'authors' => 'Madsen-Østerbye  J. et al.',
			'description' => '<p>BACKGROUND: Interactions of chromatin with the nuclear lamina via lamina-associated domains (LADs) confer structural stability to the genome. The dynamics of positioning of LADs during differentiation, and how LADs impinge on developmental gene expression, remains, however, elusive. RESULTS: We examined changes in the association of lamin B1 with the genome in the first 72 h of differentiation of adipose stem cells into adipocytes. We demonstrate a repositioning of entire stand-alone LADs and of LAD edges as a prominent nuclear structural feature of early adipogenesis. Whereas adipogenic genes are released from LADs, LADs sequester downregulated or repressed genes irrelevant for the adipose lineage. However, LAD repositioning only partly concurs with gene expression changes. Differentially expressed genes in LADs, including LADs conserved throughout differentiation, reside in local euchromatic and lamin-depleted sub-domains. In these sub-domains, pre-differentiation histone modification profiles correlate with the LAD versus inter-LAD outcome of these genes during adipogenic commitment. Lastly, we link differentially expressed genes in LADs to short-range enhancers which overall co-partition with these genes in LADs versus inter-LADs during differentiation. CONCLUSIONS: We conclude that LADs are predictable structural features of adipose nuclear architecture that restrain non-adipogenic genes in a repressive environment.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35410387',
			'doi' => '10.1186/s13059-022-02662-6',
			'modified' => '2022-11-24 09:08:01',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 36 => array(
			'id' => '4528',
			'name' => 'ZWC complex-mediated SPT5 phosphorylation suppresses divergentantisense RNA transcription at active gene promoters.',
			'authors' => 'Park  K. et al.',
			'description' => '<p>The human genome encodes large numbers of non-coding RNAs, including divergent antisense transcripts at transcription start sites (TSSs). However, molecular mechanisms by which divergent antisense transcription is regulated have not been detailed. Here, we report a novel ZWC complex composed of ZC3H4, WDR82&nbsp;and CK2 that suppresses divergent antisense transcription. The ZWC complex preferentially localizes at TSSs of active genes through direct interactions of ZC3H4 and WDR82 subunits with the S5p RNAPII C-terminal domain. ZC3H4 depletion leads to increased divergent antisense transcription, especially at genes that naturally produce divergent antisense transcripts. We further demonstrate that the ZWC complex phosphorylates the previously uncharacterized N-terminal acidic domain of SPT5, a subunit of the transcription-elongation factor DSIF, and that this phosphorylation is responsible for suppressing divergent antisense transcription. Our study provides evidence that the newly identified ZWC-DSIF axis regulates the direction of transcription during the transition from early to productive elongation.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35325203',
			'doi' => '10.1093/nar/gkac193',
			'modified' => '2022-11-24 09:24:05',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 37 => array(
			'id' => '4857',
			'name' => 'Broad domains of histone marks in the highly compact  macronucleargenome.',
			'authors' => 'Drews  F. et al.',
			'description' => '<p>The unicellular ciliate contains a large vegetative macronucleus with several unusual characteristics, including an extremely high coding density and high polyploidy. As macronculear chromatin is devoid of heterochromatin, our study characterizes the functional epigenomic organization necessary for gene regulation and proper Pol II activity. Histone marks (H3K4me3, H3K9ac, H3K27me3) reveal no narrow peaks but broad domains along gene bodies, whereas intergenic regions are devoid of nucleosomes. Our data implicate H3K4me3 levels inside ORFs to be the main factor associated with gene expression, and H3K27me3 appears in association with H3K4me3 in plastic genes. Silent and lowly expressed genes show low nucleosome occupancy, suggesting that gene inactivation does not involve increased nucleosome occupancy and chromatin condensation. Because of a high occupancy of Pol II along highly expressed ORFs, transcriptional elongation appears to be quite different from that of other species. This is supported by missing heptameric repeats in the C-terminal domain of Pol II and a divergent elongation system. Our data imply that unoccupied DNA is the default state, whereas gene activation requires nucleosome recruitment together with broad domains of H3K4me3. In summary, gene activation and silencing in run counter to the current understanding of chromatin biology.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35264449',
			'doi' => '10.1101/gr.276126.121',
			'modified' => '2023-08-01 14:45:37',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 38 => array(
			'id' => '4367',
			'name' => 'Cell-type specific transcriptional networks in root xylem adjacent celllayers',
			'authors' => 'Asensi Fabado  Maria Amparo et al.',
			'description' => '<p>Transport of water, ions and signals from roots to leaves via the xylem vessels is essential for plant life and needs to be tightly regulated. The final composition of the transpiration stream before passage into the shoots is controlled by the xylem-adjacent cell layers, namely xylem parenchyma and pericycle, in the upper part of the root. To unravel regulatory networks in this strategically important location, we generated Arabidopsis lines expressing a nuclear tag under the control of the HKT1 promoter. HKT1 retrieves sodium from the xylem to prevent toxic levels in the shoot, and this function depends on its specific expression in upper root xylem-adjacent tissues. Based on FACS RNA-sequencing and INTACT ChIP-sequencing, we identified the gene repertoire that is preferentially expressed in the tagged cell types and discovered transcription factors experiencing cell-type specific loss of H3K27me3 demethylation. For one of these, ZAT6, we show that H3K27me3-demethylase REF6 is required for de-repression. Analysis of zat6 mutants revealed that ZAT6 activates a suite of cell-type specific downstream genes and restricts Na+ accumulation in the shoots. The combined Files open novel opportunities for &lsquo;bottom-up&rsquo; causal dissection of cell-type specific regulatory networks that control root-to-shoot communication under environmental challenge.</p>',
			'date' => '2022-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2022.02.04.479129',
			'doi' => '10.1101/2022.02.04.479129',
			'modified' => '2022-08-04 16:17:32',
			'created' => '2022-08-04 14:55:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 39 => array(
			'id' => '4214',
			'name' => 'Comprehensive characterization of the epigenetic landscape in Multiple Myeloma',
			'authors' => 'Elina Alaterre et al.',
			'description' => '<p>Background: Human multiple myeloma (MM) cell lines (HMCLs) have been widely used to understand the<br />molecular processes that drive MM biology. Epigenetic modifications are involved in MM development,<br />progression, and drug resistance. A comprehensive characterization of the epigenetic landscape of MM would<br />advance our understanding of MM pathophysiology and may attempt to identify new therapeutic targets.<br />Methods: We performed chromatin immunoprecipitation sequencing to analyze histone mark changes<br />(H3K4me1, H3K4me3, H3K9me3, H3K27ac, H3K27me3 and H3K36me3) on 16 HMCLs.<br />Results: Differential analysis of histone modification profiles highlighted links between histone modifications<br />and cytogenetic abnormalities or recurrent mutations. Using histone modifications associated to enhancer<br />regions, we identified super-enhancers (SE) associated with genes involved in MM biology. We also identified<br />promoters of genes enriched in H3K9me3 and H3K27me3 repressive marks associated to potential tumor<br />suppressor functions. The prognostic value of genes associated with repressive domains and SE was used to<br />build two distinct scores identifying high-risk MM patients in two independent cohorts (CoMMpass cohort; n =<br />674 and Montpellier cohort; n = 69). Finally, we explored H3K4me3 marks comparing drug-resistant and<br />-sensitive HMCLs to identify regions involved in drug resistance. From these data, we developed epigenetic<br />biomarkers based on the H3K4me3 modification predicting MM cell response to lenalidomide and histone<br />deacetylase inhibitors (HDACi).<br />Conclusions: The epigenetic landscape of MM cells represents a unique resource for future biological studies.<br />Furthermore, risk-scores based on SE and repressive regions together with epigenetic biomarkers of drug<br />response could represent new tools for precision medicine in MM.</p>',
			'date' => '2022-01-16',
			'pmid' => 'https://www.thno.org/v12p1715',
			'doi' => '10.7150/thno.54453',
			'modified' => '2022-01-27 13:17:28',
			'created' => '2022-01-27 13:14:17',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 40 => array(
			'id' => '4225',
			'name' => 'Comprehensive characterization of the epigenetic landscape in Multiple
Myeloma',
			'authors' => 'Alaterre, Elina and Ovejero, Sara and Herviou, Laurie and de
Boussac, Hugues and Papadopoulos, Giorgio and Kulis, Marta and
Boireau, Stéphanie and Robert, Nicolas and Requirand, Guilhem
and Bruyer, Angélique and Cartron, Guillaume and Vincent,
Laure and M',
			'description' => 'Background: Human multiple myeloma (MM) cell lines (HMCLs) have
been widely used to understand the molecular processes that drive MM
biology. Epigenetic modifications are involved in MM development,
progression, and drug resistance. A comprehensive characterization of the
epigenetic landscape of MM would advance our understanding of MM
pathophysiology and may attempt to identify new therapeutic
targets.

Methods: We performed chromatin immunoprecipitation
sequencing to analyze histone mark changes (H3K4me1, H3K4me3,
H3K9me3, H3K27ac, H3K27me3 and H3K36me3) on 16
HMCLs.

Results: Differential analysis of histone modification
profiles highlighted links between histone modifications and cytogenetic
abnormalities or recurrent mutations. Using histone modifications
associated to enhancer regions, we identified super-enhancers (SE)
associated with genes involved in MM biology. We also identified
promoters of genes enriched in H3K9me3 and H3K27me3 repressive
marks associated to potential tumor suppressor functions. The prognostic
value of genes associated with repressive domains and SE was used to
build two distinct scores identifying high-risk MM patients in two
independent cohorts (CoMMpass cohort; n = 674 and Montpellier cohort;
n = 69). Finally, we explored H3K4me3 marks comparing drug-resistant
and -sensitive HMCLs to identify regions involved in drug resistance.
From these data, we developed epigenetic biomarkers based on the
H3K4me3 modification predicting MM cell response to lenalidomide and
histone deacetylase inhibitors (HDACi).

Conclusions: The epigenetic
landscape of MM cells represents a unique resource for future biological
studies. Furthermore, risk-scores based on SE and repressive regions
together with epigenetic biomarkers of drug response could represent new
tools for precision medicine in MM.',
			'date' => '2022-01-01',
			'pmid' => 'https://www.thno.org/v12p1715.htm',
			'doi' => '10.7150/thno.54453',
			'modified' => '2022-05-19 10:41:50',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 41 => array(
			'id' => '4326',
			'name' => 'Loss of KMT2C reprograms the epigenomic landscape in hPSCsresulting in NODAL overexpression and a failure of hemogenic endotheliumspecification.',
			'authors' => 'Maurya Shailendra et al.',
			'description' => '<p>Germline or somatic variation in the family of KMT2 lysine methyltransferases have been associated with a variety of congenital disorders and cancers. Notably, -fusions are prevalent in 70\% of infant leukaemias but fail to phenocopy short latency leukaemogenesis in mammalian models, suggesting additional factors are necessary for transformation. Given the lack of additional somatic mutation, the role of epigenetic regulation in cell specification, and our prior results of germline variation in infant leukaemia patients, we hypothesized that germline dysfunction of KMT2C altered haematopoietic specification. In isogenic KO hPSCs, we found genome-wide differences in histone modifications at active and poised enhancers, leading to gene expression profiles akin to mesendoderm rather than mesoderm highlighted by a significant increase in NODAL expression and WNT inhibition, ultimately resulting in a lack of hemogenic endothelium specification. These unbiased multi-omic results provide new evidence for germline mechanisms increasing risk of early leukaemogenesis.</p>',
			'date' => '2022-01-01',
			'pmid' => 'https://doi.org/10.1080%2F15592294.2021.1954780',
			'doi' => '10.1080/15592294.2021.1954780',
			'modified' => '2022-06-20 09:27:45',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 42 => array(
			'id' => '4238',
			'name' => 'The long noncoding RNA H19 regulates tumor plasticity inneuroendocrine prostate cancer',
			'authors' => 'Singh N. et al.',
			'description' => '<p>Neuroendocrine (NE) prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (PCa) arising either de novo or from transdifferentiated prostate adenocarcinoma following androgen deprivation therapy (ADT). Extensive computational analysis has identified a high degree of association between the long noncoding RNA (lncRNA) H19 and NEPC, with the longest isoform highly expressed in NEPC. H19 regulates PCa lineage plasticity by driving a bidirectional cell identity of NE phenotype (H19 overexpression) or luminal phenotype (H19 knockdown). It contributes to treatment resistance, with the knockdown of H19 re-sensitizing PCa to ADT. It is also essential for the proliferation and invasion of NEPC. H19 levels are negatively regulated by androgen signaling via androgen receptor (AR). When androgen is absent SOX2 levels increase, driving H19 transcription and facilitating transdifferentiation. H19 facilitates the PRC2 complex in regulating methylation changes at H3K27me3/H3K4me3 histone sites of AR-driven and NEPC-related genes. Additionally, this lncRNA induces alterations in genome-wide DNA methylation on CpG sites, further regulating genes associated with the NEPC phenotype. Our clinical data identify H19 as a candidate diagnostic marker and predictive marker of NEPC with elevated H19 levels associated with an increased probability of biochemical recurrence and metastatic disease in patients receiving ADT. Here we report H19 as an early upstream regulator of cell fate, plasticity, and treatment resistance in NEPC that can reverse/transform cells to a treatable form of PCa once therapeutically deactivated.</p>',
			'date' => '2021-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34934057',
			'doi' => '10.1038/s41467-021-26901-9',
			'modified' => '2022-05-19 17:06:50',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 43 => array(
			'id' => '4239',
			'name' => 'Epromoters function as a hub to recruit key transcription factorsrequired for the inflammatory response',
			'authors' => 'Santiago-Algarra D. et al. ',
			'description' => '<p>Gene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. Our previous results demonstrated that a subset of gene promoters, termed Epromoters, work as bona fide enhancers and regulate distal gene expression. Here, we hypothesized that Epromoters play a key role in the coordination of rapid gene induction during the inflammatory response. Using a high-throughput reporter assay we explored the function of Epromoters in response to type I interferon. We find that clusters of IFNa-induced genes are frequently associated with Epromoters and that these regulatory elements preferentially recruit the STAT1/2 and IRF transcription factors and distally regulate the activation of interferon-response genes. Consistently, we identified and validated the involvement of Epromoter-containing clusters in the regulation of LPS-stimulated macrophages. Our findings suggest that Epromoters function as a local hub recruiting the key TFs required for coordinated regulation of gene clusters during the inflammatory response.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34795220',
			'doi' => '10.1038/s41467-021-26861-0',
			'modified' => '2022-05-19 17:10:30',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 44 => array(
			'id' => '4251',
			'name' => 'Comparing the epigenetic landscape in myonuclei purified with a PCM1antibody from a fast/glycolytic and a slow/oxidative muscle.',
			'authors' => 'Bengtsen Mads et al.',
			'description' => '<p>Muscle cells have different phenotypes adapted to different usage, and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of the epigenetic landscape by ChIP-Seq in two muscle extremes, the fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where up to 60\% of the nuclei can be of a different origin. Since cellular homogeneity is critical in epigenome-wide association studies we developed a new method for purifying skeletal muscle nuclei from whole tissue, based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labelling and a magnetic-assisted sorting approach, we were able to sort out myonuclei with 95\% purity in muscles from mice, rats and humans. The sorting eliminated influence from the other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the differences in the functional properties of the two muscles, and revealed distinct regulatory programs involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles were also regulated by different sets of transcription factors; e.g. in soleus, binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SIX1 binding sites were found to be overrepresented. In addition, more novel transcription factors for muscle regulation such as members of the MAF family, ZFX and ZBTB14 were identified.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/34752468/',
			'doi' => '10.1371/journal.pgen.1009907',
			'modified' => '2022-05-20 09:39:35',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 45 => array(
			'id' => '4241',
			'name' => 'Rhesus macaques self-curing from a schistosome infection can displaycomplete immunity to challenge',
			'authors' => 'Amaral MS et al.  ',
			'description' => '<p>The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict \&gt;200 million people worldwide. By monitoring bloodstream levels of parasite-gut-derived antigen, we show that from week 10 onwards an established infection with Schistosoma mansoni is cleared in an exponential manner, eliciting resistance to reinfection. Secondary challenge at week 42 demonstrates that protection is strong in all animals and complete in some. Antibody profiles suggest that antigens mediating protection are the released products of developing schistosomula. In culture they are killed by addition of rhesus plasma, collected from week 8 post-infection onwards, and even more efficiently with post-challenge plasma. Furthermore, cultured schistosomula lose chromatin activating marks at the transcription start site of genes related to worm development and show decreased expression of genes related to lysosomes and lytic vacuoles involved with autophagy. Overall, our results indicate that enhanced antibody responses against the challenge migrating larvae mediate the naturally acquired protective immunity and will inform the route to an effective vaccine.</p>',
			'date' => '2021-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34702841',
			'doi' => '10.1038/s41467-021-26497-0',
			'modified' => '2022-05-19 17:15:53',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 46 => array(
			'id' => '4268',
			'name' => 'p300 suppresses the transition of myelodysplastic syndromes to acutemyeloid leukemia',
			'authors' => 'Man Na et al.',
			'description' => '<p>Myelodysplastic syndromes (MDS) are hematopoietic stem and progenitor cell (HSPC) malignancies characterized by ineffective hematopoiesis and an increased risk of leukemia transformation. Epigenetic regulators are recurrently mutated in MDS, directly implicating epigenetic dysregulation in MDS pathogenesis. Here, we identified a tumor suppressor role of the acetyltransferase p300 in clinically relevant MDS models driven by mutations in the epigenetic regulators TET2, ASXL1, and SRSF2. The loss of p300 enhanced the proliferation and self-renewal capacity of Tet2-deficient HSPCs, resulting in an increased HSPC pool and leukemogenicity in primary and transplantation mouse models. Mechanistically, the loss of p300 in Tet2-deficient HSPCs altered enhancer accessibility and the expression of genes associated with differentiation, proliferation, and leukemia development. Particularly, p300 loss led to an increased expression of Myb, and the depletion of Myb attenuated the proliferation of HSPCs and improved the survival of leukemia-bearing mice. Additionally, we show that chemical inhibition of p300 acetyltransferase activity phenocopied Ep300 deletion in Tet2-deficient HSPCs, whereas activation of p300 activity with a small molecule impaired the self-renewal and leukemogenicity of Tet2-deficient cells. This suggests a potential therapeutic application of p300 activators in the treatment of MDS with TET2 inactivating mutations.</p>',
			'date' => '2021-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34622806',
			'doi' => '10.1172/jci.insight.138478',
			'modified' => '2022-05-23 09:44:16',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 47 => array(
			'id' => '4231',
			'name' => 'Differential contribution to gene expression prediction of histonemodifications at enhancers or promoters.',
			'authors' => 'González-Ramírez M. et al.',
			'description' => '<p>The ChIP-seq signal of histone modifications at promoters is a good predictor of gene expression in different cellular contexts, but whether this is also true at enhancers is not clear. To address this issue, we develop quantitative models to characterize the relationship of gene expression with histone modifications at enhancers or promoters. We use embryonic stem cells (ESCs), which contain a full spectrum of active and repressed (poised) enhancers, to train predictive models. As many poised enhancers in ESCs switch towards an active state during differentiation, predictive models can also be trained on poised enhancers throughout differentiation and in development. Remarkably, we determine that histone modifications at enhancers, as well as promoters, are predictive of gene expression in ESCs and throughout differentiation and development. Importantly, we demonstrate that their contribution to the predictive models varies depending on their location in enhancers or promoters. Moreover, we use a local regression (LOESS) to normalize sequencing data from different sources, which allows us to apply predictive models trained in a specific cellular context to a different one. We conclude that the relationship between gene expression and histone modifications at enhancers is universal and different from promoters. Our study provides new insight into how histone modifications relate to gene expression based on their location in enhancers or promoters.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/34473698/',
			'doi' => '10.1371/journal.pcbi.1009368',
			'modified' => '2022-05-19 16:50:59',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 48 => array(
			'id' => '4294',
			'name' => 'DOT1L O-GlcNAcylation promotes its protein stability andMLL-fusion leukemia cell proliferation.',
			'authors' => 'Song Tanjing et al.',
			'description' => '<p>Histone lysine methylation functions at the interface of the extracellular environment and intracellular gene expression. DOT1L is a versatile histone H3K79 methyltransferase with a prominent role in MLL-fusion leukemia, yet little is known about how DOT1L responds to extracellular stimuli. Here, we report that DOT1L protein stability is regulated by the extracellular glucose level through the hexosamine biosynthetic pathway (HBP). Mechanistically, DOT1L is O-GlcNAcylated at evolutionarily conserved S1511 in its C terminus. We identify UBE3C as a DOT1L E3 ubiquitin ligase promoting DOT1L degradation whose interaction with DOT1L is susceptible to O-GlcNAcylation. Consequently, HBP enhances H3K79 methylation and expression of critical DOT1L target genes such as HOXA9/MEIS1, promoting cell proliferation in MLL-fusion leukemia. Inhibiting HBP or O-GlcNAc transferase (OGT) increases cellular sensitivity to DOT1L inhibitor. Overall, our work uncovers O-GlcNAcylation and UBE3C as critical determinants of DOT1L protein abundance, revealing a mechanism by which glucose metabolism affects malignancy progression through histone methylation.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34551297',
			'doi' => '10.1016/j.celrep.2021.109739',
			'modified' => '2022-05-24 09:20:37',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 49 => array(
			'id' => '4297',
			'name' => 'INTS11 regulates hematopoiesis by promoting PRC2 function.',
			'authors' => 'Zhang Peng et al.',
			'description' => '<p>INTS11, the catalytic subunit of the Integrator (INT) complex, is crucial for the biogenesis of small nuclear RNAs and enhancer RNAs. However, the role of INTS11 in hematopoietic stem and progenitor cell (HSPC) biology is unknown. Here, we report that INTS11 is required for normal hematopoiesis and hematopoietic-specific genetic deletion of leads to cell cycle arrest and impairment of fetal and adult HSPCs. We identified a novel INTS11-interacting protein complex, Polycomb repressive complex 2 (PRC2), that maintains HSPC functions. Loss of INTS11 destabilizes the PRC2 complex, decreases the level of histone H3 lysine 27 trimethylation (H3K27me3), and derepresses PRC2 target genes. Reexpression of INTS11 or PRC2 proteins in -deficient HSPCs restores the levels of PRC2 and H3K27me3 as well as HSPC functions. Collectively, our data demonstrate that INTS11 is an essential regulator of HSPC homeostasis through the INTS11-PRC2 axis.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34516911',
			'doi' => '10.1126/sciadv.abh1684',
			'modified' => '2022-05-30 09:31:00',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 50 => array(
			'id' => '4282',
			'name' => 'Enhanced targeted DNA methylation of the CMV and endogenous promoterswith dCas9-DNMT3A3L entails distinct subsequent histonemodification changes in CHO cells.',
			'authors' => 'Marx Nicolas et al. ',
			'description' => '<p>With the emergence of new CRISPR/dCas9 tools that enable site specific modulation of DNA methylation and histone modifications, more detailed investigations of the contribution of epigenetic regulation to the precise phenotype of cells in culture, including recombinant production subclones, is now possible. These also allow a wide range of applications in metabolic engineering once the impact of such epigenetic modifications on the chromatin state is available. In this study, enhanced DNA methylation tools were targeted to a recombinant viral promoter (CMV), an endogenous promoter that is silenced in its native state in CHO cells, but had been reactivated previously (&beta;-galactoside &alpha;-2,6-sialyltransferase 1) and an active endogenous promoter (&alpha;-1,6-fucosyltransferase), respectively. Comparative ChIP-analysis of histone modifications revealed a general loss of active promoter histone marks and the acquisition of distinct repressive heterochromatin marks after targeted methylation. On the other hand, targeted demethylation resulted in autologous acquisition of active promoter histone marks and loss of repressive heterochromatin marks. These data suggest that DNA methylation directs the removal or deposition of specific histone marks associated with either active, poised or silenced chromatin. Moreover, we show that de novo methylation of the CMV promoter results in reduced transgene expression in CHO cells. Although targeted DNA methylation is not efficient, the transgene is repressed, thus offering an explanation for seemingly conflicting reports about the source of CMV promoter instability in CHO cells. Importantly, modulation of epigenetic marks enables to nudge the cell into a specific gene expression pattern or phenotype, which is stabilized in the cell by autologous addition of further epigenetic marks. Such engineering strategies have the added advantage of being reversible and potentially tunable to not only turn on or off a targeted gene, but also to achieve the setting of a desirable expression level.</p>',
			'date' => '2021-07-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.ymben.2021.04.014',
			'doi' => '10.1016/j.ymben.2021.04.014',
			'modified' => '2022-05-23 10:09:24',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 51 => array(
			'id' => '4118',
			'name' => 'ChIP-seq protocol for sperm cells and embryos to assess environmentalimpacts and epigenetic inheritance',
			'authors' => 'Lismer, Ariane and Lambrot, Romain and Lafleur, Christine and Dumeaux,Vanessa and Kimmins, Sarah',
			'description' => '<p>In the field of epigenetic inheritance, delineating molecular mechanisms implicated in the transfer of paternal environmental conditions to descendants has been elusive. This protocol details how to track sperm chromatin intergenerationally. We describe mouse model design to probe chromatin states in single mouse sperm and techniques to assess pre-implantation embryo chromatin and gene expression. We place emphasis on how to obtain high-quality and quantifiable data sets in sperm and embryos, as well as highlight the limitations of working with low input.</p>',
			'date' => '2021-06-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.xpro.2021.100602',
			'doi' => '10.1016/j.xpro.2021.100602',
			'modified' => '2021-12-06 17:59:57',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 52 => array(
			'id' => '4318',
			'name' => 'E2F6 initiates stable epigenetic silencing of germline genes duringembryonic development',
			'authors' => 'Dahlet T. et al.',
			'description' => '<p>In mouse development, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes; however, the molecular mechanisms of this specificity remain unclear. Here, we demonstrate that the transcription factor E2F6, a member of the polycomb repressive complex 1.6 (PRC1.6), is critical to target and initiate epigenetic silencing at germline genes in early embryogenesis. Genome-wide, E2F6 binds preferentially to CpG islands in embryonic cells. E2F6 cooperates with MGA to silence a subgroup of germline genes in mouse embryonic stem cells and in embryos, a function that critically depends on the E2F6 marked box domain. Inactivation of E2f6 leads to a failure to deposit CpG island DNA methylation at these genes during implantation. Furthermore, E2F6 is required to initiate epigenetic silencing in early embryonic cells but becomes dispensable for the maintenance in differentiated cells. Our findings elucidate the mechanisms of epigenetic targeting of germline genes and provide a paradigm for how transient repression signals by DNA-binding factors in early embryonic cells are translated into long-term epigenetic silencing during mouse development.</p>',
			'date' => '2021-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34117224',
			'doi' => '10.1038/s41467-021-23596-w',
			'modified' => '2022-08-02 16:53:03',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 53 => array(
			'id' => '4349',
			'name' => 'Lasp1 regulates adherens junction dynamics and fibroblast transformationin destructive arthritis',
			'authors' => 'Beckmann D. et al.',
			'description' => '<p>The LIM and SH3 domain protein 1 (Lasp1) was originally cloned from metastatic breast cancer and characterised as an adaptor molecule associated with tumourigenesis and cancer cell invasion. However, the regulation of Lasp1 and its function in the aggressive transformation of cells is unclear. Here we use integrative epigenomic profiling of invasive fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and from mouse models of the disease, to identify Lasp1 as an epigenomically co-modified region in chronic inflammatory arthritis and a functionally important binding partner of the Cadherin-11/&beta;-Catenin complex in zipper-like cell-to-cell contacts. In vitro, loss or blocking of Lasp1 alters pathological tissue formation, migratory behaviour and platelet-derived growth factor response of arthritic FLS. In arthritic human TNF transgenic mice, deletion of Lasp1 reduces arthritic joint destruction. Therefore, we show a function of Lasp1 in cellular junction formation and inflammatory tissue remodelling and identify Lasp1 as a potential target for treating inflammatory joint disorders associated with aggressive cellular transformation.</p>',
			'date' => '2021-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34131132',
			'doi' => '10.1038/s41467-021-23706-8',
			'modified' => '2022-08-03 17:02:30',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 54 => array(
			'id' => '4143',
			'name' => 'Placental uptake and metabolism of 25(OH)Vitamin D determines itsactivity within the fetoplacental unit',
			'authors' => 'Ashley, B. et al.',
			'description' => '<p>Pregnancy 25-hydroxyvitamin D (25(OH)D) concentrations are associated with maternal and fetal health outcomes, but the underlying mechanisms have not been elucidated. Using physiological human placental perfusion approaches and intact villous explants we demonstrate a role for the placenta in regulating the relationships between maternal 25(OH)D concentrations and fetal physiology. Here, we demonstrate active placental uptake of 25(OH)D3 by endocytosis and placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the fetal and maternal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than solely the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer, including transcriptional activation and inflammatory responses. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta; with widespread effects on the placenta itself. These data show complex and synergistic interplay between vitamin D and the placenta, and inform possible interventions to optimise placental function to better support fetal growth and the maternal adaptations to pregnancy.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.03.01.431439',
			'doi' => '10.1101/2021.03.01.431439',
			'modified' => '2021-12-13 09:29:25',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 55 => array(
			'id' => '4160',
			'name' => 'Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.',
			'authors' => 'Pettinato, Anthony M. et al. ',
			'description' => '<p>Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization by unclear mechanisms. To study this process, we engineer a human cardiomyocyte model to track replication and polyploidization using fluorescently tagged cyclin B1 and cardiac troponin T. Using time-lapse imaging, in&nbsp;vitro cardiomyocyte replication patterns recapitulate the progressive mononuclear polyploidization and replicative arrest observed in&nbsp;vivo. Single-cell transcriptomics and chromatin state analyses reveal that polyploidization is preceded by sarcomere assembly, enhanced oxidative metabolism, a DNA damage response, and p53 activation. CRISPR knockout screening reveals p53 as a driver of cell-cycle arrest and polyploidization. Inhibiting sarcomere function, or scavenging ROS, inhibits cell-cycle arrest and polyploidization. Finally, we show that cardiomyocyte engraftment in infarcted rat hearts is enhanced 4-fold by the increased proliferation of troponin-knockout cardiomyocytes. Thus, the sarcomere inhibits cell division through a DNA damage response that can be targeted to improve cardiomyocyte replacement strategies.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33951429',
			'doi' => '10.1016/j.celrep.2021.109088',
			'modified' => '2021-12-16 10:58:59',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 56 => array(
			'id' => '4343',
			'name' => 'The SAM domain-containing protein 1 (SAMD1) acts as a repressivechromatin regulator at unmethylated CpG islands',
			'authors' => 'Stielow B. et al. ',
			'description' => '<p>CpG islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here, we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 has an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. The absence of SAMD1 impairs ES cell differentiation processes, leading to misregulation of key biological pathways. Together, our work establishes SAMD1 as a newly identified chromatin regulator acting at unmethylated CGIs.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33980486',
			'doi' => '10.1126/sciadv.abf2229',
			'modified' => '2022-08-03 16:34:24',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 57 => array(
			'id' => '4350',
			'name' => 'Simplification of culture conditions and feeder-free expansion of bovineembryonic stem cells',
			'authors' => 'Soto D. A. et al. ',
			'description' => '<p>Bovine embryonic stem cells (bESCs) extend the lifespan of the transient pluripotent bovine inner cell mass in vitro. After years of research, derivation of stable bESCs was only recently reported. Although successful, bESC culture relies on complex culture conditions that require a custom-made base medium and mouse embryonic fibroblasts (MEF) feeders, limiting the widespread use of bESCs. We report here simplified bESC culture conditions based on replacing custom base medium with a commercially available alternative and eliminating the need for MEF feeders by using a chemically-defined substrate. bESC lines were cultured and derived using a base medium consisting of N2B27 supplements and 1\% BSA (NBFR-bESCs). Newly derived bESC lines were easy to establish, simple to propagate and stable after long-term culture. These cells expressed pluripotency markers and actively proliferated for more than 35 passages while maintaining normal karyotype and the ability to differentiate into derivatives of all three germ lineages in embryoid bodies and teratomas. In addition, NBFR-bESCs grew for multiple passages in a feeder-free culture system based on vitronectin and Activin A medium supplementation while maintaining pluripotency. Simplified conditions will facilitate the use of bESCs for gene editing applications and pluripotency and lineage commitment studies.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34040070',
			'doi' => '10.1038/s41598-021-90422-0',
			'modified' => '2022-08-03 16:38:27',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 58 => array(
			'id' => '4161',
			'name' => 'The anti-inflammatory cytokine interleukin-37 is an inhibitor of trainedimmunity.',
			'authors' => 'Cavalli, Giulio and Tengesdal, Isak W and Gresnigt, Mark and Nemkov, Travisand Arts, Rob J W and Domínguez-Andrés, Jorge and Molteni, Raffaella andStefanoni, Davide and Cantoni, Eleonora and Cassina, Laura and Giugliano,Silvia and Schraa, Kiki and Mill',
			'description' => '<p>Trained immunity (TI) is a de facto innate immune memory program induced in monocytes/macrophages by exposure to pathogens or vaccines, which evolved as protection against infections. TI is characterized by immunometabolic changes and histone post-translational modifications, which enhance production of pro-inflammatory cytokines. As aberrant activation of TI is implicated in inflammatory diseases, tight regulation is critical; however, the mechanisms responsible for this modulation remain elusive. Interleukin-37 (IL-37) is an anti-inflammatory cytokine that curbs inflammation and modulates metabolic pathways. In this study, we show that administration of recombinant IL-37 abrogates the protective effects of TI in&nbsp;vivo, as revealed by reduced host pro-inflammatory responses and survival to disseminated candidiasis. Mechanistically, IL-37 reverses the immunometabolic changes and histone post-translational modifications characteristic of TI in monocytes, thus suppressing cytokine production in response to infection. IL-37 thereby emerges as an inhibitor of TI and as a potential therapeutic target in immune-mediated pathologies.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33826894',
			'doi' => '10.1016/j.celrep.2021.108955',
			'modified' => '2021-12-21 15:16:27',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 59 => array(
			'id' => '4178',
			'name' => 'Comparative analysis of histone H3K4me3 modifications between blastocystsand somatic tissues in cattle.',
			'authors' => 'Ishibashi, Mao et al.',
			'description' => '<p>Epigenetic changes induced in the early developmental stages by the surrounding environment can have not only short-term but also long-term consequences throughout life. This concept constitutes the "Developmental Origins of Health and Disease" (DOHaD) hypothesis and encompasses the possibility of controlling livestock health and diseases by epigenetic regulation during early development. As a preliminary step for examining changes of epigenetic modifications in early embryos and their long-lasting effects in fully differentiated somatic tissues, we aimed to obtain high-throughput genome-wide histone H3 lysine 4 trimethylation (H3K4me3) profiles of bovine blastocysts and to compare these data with those from adult somatic tissues in order to extract common and typical features between these tissues in terms of H3K4me3 modifications. Bovine blastocysts were produced in vitro and subjected to chromatin immunoprecipitation-sequencing analysis of H3K4me3. Comparative analysis of the blastocyst-derived H3K4me3 profile with publicly available data from adult liver and muscle tissues revealed that the blastocyst profile could be used as a "sieve" to extract somatic tissue-specific modifications in genes closely related to tissue-specific functions. Furthermore, principal component analysis of the level of common modifications between blastocysts and somatic tissues in meat production-related and imprinted genes well characterized inter- and intra-tissue differences. The results of this study produced a referential genome-wide H3K4me3 profile of bovine blastocysts within the limits of their in vitro source and revealed its common and typical features in relation to the profiles of adult tissues.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33859293',
			'doi' => '10.1038/s41598-021-87683-0',
			'modified' => '2021-12-21 16:40:41',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 60 => array(
			'id' => '4181',
			'name' => 'Genetic perturbation of PU.1 binding and chromatin looping at neutrophilenhancers associates with autoimmune disease.',
			'authors' => 'Watt, Stephen et al.',
			'description' => '<p>Neutrophils play fundamental roles in innate immune response, shape adaptive immunity, and are a potentially causal cell type underpinning genetic associations with immune system traits and diseases. Here, we profile the binding of myeloid master regulator PU.1 in primary neutrophils across nearly a hundred volunteers. We show that variants associated with differential PU.1 binding underlie genetically-driven differences in cell count and susceptibility to autoimmune and inflammatory diseases. We integrate these results with other multi-individual genomic readouts, revealing coordinated effects of PU.1 binding variants on the local chromatin state, enhancer-promoter contacts and downstream gene expression, and providing a functional interpretation for 27 genes underlying immune traits. Collectively, these results demonstrate the functional role of PU.1 and its target enhancers in neutrophil transcriptional control and immune disease susceptibility.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33863903',
			'doi' => '10.1038/s41467-021-22548-8',
			'modified' => '2021-12-21 16:50:30',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 61 => array(
			'id' => '4138',
			'name' => 'Loss of SETD1B results in the redistribution of genomic H3K4me3 in theoocyte',
			'authors' => 'Hanna, C. W. et al. ',
			'description' => '<p>Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransferases SETD1B and MLL2 are essential for oogenesis. We investigated changes in H3K4me3 in Setd1b conditional knockout (cKO) GV oocytes using ultra-low input ChIP-seq, in conjunction with DNA methylation and gene expression analysis. Setd1b cKO oocytes showed a redistribution of H3K4me3, with a marked loss at active gene promoters associated with downregulated gene expression. Remarkably, many regions gained H3K4me3 in Setd1b cKOs, in particular those that were DNA hypomethylated, transcriptionally inactive and CpGrich - hallmarks of MLL2 targets. Thus, loss of SETD1B appears to enable enhanced MLL2 activity. Our work reveals two distinct, complementary mechanisms of genomic targeting of H3K4me3 in oogenesis, with SETD1B linked to gene expression in the oogenic program and MLL2 to CpG content.</p>',
			'date' => '2021-03-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.03.11.434836',
			'doi' => '10.1101/2021.03.11.434836',
			'modified' => '2021-12-13 09:15:06',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 62 => array(
			'id' => '4162',
			'name' => 'Epigenomic tensor predicts disease subtypes and reveals constrained tumorevolution.',
			'authors' => 'Leistico, Jacob R et al.',
			'description' => '<p>Understanding the epigenomic evolution and specificity of disease subtypes from complex patient data remains a major biomedical problem. We here present DeCET (decomposition and classification of epigenomic tensors), an integrative computational approach for simultaneously analyzing hierarchical heterogeneous data, to identify robust epigenomic differences among tissue types, differentiation states, and disease subtypes. Applying DeCET to our own data from 21 uterine benign tumor (leiomyoma) patients identifies distinct epigenomic features discriminating normal myometrium and leiomyoma subtypes. Leiomyomas possess preponderant alterations in distal enhancers and long-range histone modifications confined to chromatin contact domains that constrain the evolution of pathological epigenomes. Moreover, we demonstrate the power and advantage of DeCET on multiple publicly available epigenomic datasets representing different cancers and cellular states. Epigenomic features extracted by DeCET can thus help improve our understanding of disease states, cellular development, and differentiation, thereby facilitating future therapeutic, diagnostic, and prognostic strategies.</p>',
			'date' => '2021-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33789109',
			'doi' => '10.1016/j.celrep.2021.108927',
			'modified' => '2021-12-21 15:19:13',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 63 => array(
			'id' => '4196',
			'name' => 'Functional annotations of three domestic animal genomes provide vitalresources for comparative and agricultural research.',
			'authors' => 'Kern C. et al.',
			'description' => '<p>Gene regulatory elements are central drivers of phenotypic variation and thus of critical importance towards understanding the genetics of complex traits. The Functional Annotation of Animal Genomes consortium was formed to collaboratively annotate the functional elements in animal genomes, starting with domesticated animals. Here we present an expansive collection of datasets from eight diverse tissues in three important agricultural species: chicken (Gallus gallus), pig (Sus scrofa), and cattle (Bos taurus). Comparative analysis of these datasets and those from the human and mouse Encyclopedia of DNA Elements projects reveal that a core set of regulatory elements are functionally conserved independent of divergence between species, and that tissue-specific transcription factor occupancy at regulatory elements and their predicted target genes are also conserved. These datasets represent a unique opportunity for the emerging field of comparative epigenomics, as well as the agricultural research community, including species that are globally important food resources.</p>',
			'date' => '2021-03-01',
			'pmid' => 'https://doi.org/10.1038%2Fs41467-021-22100-8',
			'doi' => '10.1038/s41467-021-22100-8',
			'modified' => '2022-01-06 14:30:41',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 64 => array(
			'id' => '4127',
			'name' => 'The histone modification H3K4me3 is altered at the  locus in Alzheimer'sdisease brain.',
			'authors' => 'Smith, Adam et al.',
			'description' => '<p>Several epigenome-wide association studies of DNA methylation have highlighted altered DNA methylation in the gene in Alzheimer's disease (AD) brain samples. However, no study has specifically examined histone modifications in the disease. We use chromatin immunoprecipitation-qPCR to quantify tri-methylation at histone 3 lysine 4 (H3K4me3) and 27 (H3K27me3) in the gene in entorhinal cortex from donors with high (n&nbsp;=&nbsp;59) or low (n&nbsp;=&nbsp;29) Alzheimer's disease&nbsp;pathology. We demonstrate decreased levels of H3K4me3, a marker of active gene transcription, with no change in H3K27me3, a marker of inactive genes. H3K4me3 is negatively correlated with DNA methylation in specific regions of the gene. Our study suggests that the gene shows altered epigenetic marks indicative of reduced gene activation in Alzheimer's disease.</p>',
			'date' => '2021-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33815817',
			'doi' => '10.2144/fsoa-2020-0161',
			'modified' => '2021-12-07 10:16:08',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 65 => array(
			'id' => '4146',
			'name' => 'The G2-phase enriched lncRNA SNHG26 is necessary for proper cell cycleprogression and proliferation',
			'authors' => 'Samdal, H. et al.',
			'description' => '<p>Long noncoding RNAs (lncRNAs) are involved in the regulation of cell cycle, although only a few have been functionally characterized. By combining RNA sequencing and ChIP sequencing of cell cycle synchronized HaCaT cells we have previously identified lncRNAs highly enriched for cell cycle functions. Based on a cyclic expression profile and an overall high correlation to histone 3 lysine 4 trimethylation (H3K4me3) and RNA polymerase II (Pol II) signals, the lncRNA SNHG26 was identified as a top candidate. In the present study we report that downregulation of SNHG26 affects mitochondrial stress, proliferation, cell cycle phase distribution, and gene expression in cis- and in trans, and that this effect is reversed by upregulation of SNHG26. We also find that the effect on cell cycle phase distribution is cell type specific and stable over time. Results indicate an oncogenic role of SNHG26, possibly by affecting cell cycle progression through the regulation of downstream MYC-responsive genes.</p>',
			'date' => '2021-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.02.22.432245',
			'doi' => '10.1101/2021.02.22.432245',
			'modified' => '2021-12-14 09:21:27',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 66 => array(
			'id' => '4151',
			'name' => 'The epigenetic landscape in purified myonuclei from fast and slow muscles',
			'authors' => 'Bengtsen, M. et al.',
			'description' => '<p>Muscle cells have different phenotypes adapted to different usage and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of chromatin environment by ChIP-Seq in two muscle extremes, the almost completely fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where less than 60\% of the nuclei are inside muscle fibers. Since cellular homogeneity is critical in epigenome-wide association studies we devised a new method for purifying skeletal muscle nuclei from whole tissue based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labeling and a magnetic-assisted sorting approach we were able to sort out myonuclei with 95\% purity. The sorting eliminated influence from other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the functional properties of the two muscles each with a distinct regulatory program involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles are also regulated by different sets of transcription factors; e.g. in soleus binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SOX1 binding sites were found to be overrepresented. In addition, novel factors for muscle regulation such as MAF, ZFX and ZBTB14 were identified.</p>',
			'date' => '2021-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.02.04.429545',
			'doi' => '10.1101/2021.02.04.429545',
			'modified' => '2021-12-14 09:40:02',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 67 => array(
			'id' => '4198',
			'name' => 'WAPL maintains a cohesin loading cycle to preserve cell-type-specificdistal gene regulation.',
			'authors' => 'Liu N. Q.et al.',
			'description' => '<p>The cohesin complex has an essential role in maintaining genome organization. However, its role in gene regulation remains largely unresolved. Here we report that the cohesin release factor WAPL creates a pool of free cohesin, in a process known as cohesin turnover, which reloads it to cell-type-specific binding sites. Paradoxically, stabilization of cohesin binding, following WAPL ablation, results in depletion of cohesin from these cell-type-specific regions, loss of gene expression and differentiation. Chromosome conformation capture experiments show that cohesin turnover is important for maintaining promoter-enhancer loops. Binding of cohesin to cell-type-specific sites is dependent on the pioneer transcription factors OCT4 (POU5F1) and SOX2, but not NANOG. We show the importance of cohesin turnover in controlling transcription and propose that a cycle of cohesin loading and off-loading, instead of static cohesin binding, mediates promoter and enhancer interactions critical for gene regulation.</p>',
			'date' => '2020-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33318687',
			'doi' => '10.1038/s41588-020-00744-4',
			'modified' => '2022-01-06 14:38:26',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 68 => array(
			'id' => '4061',
			'name' => 'Dissecting Herpes Simplex Virus 1-Induced Host Shutoff at the RNA Level.',
			'authors' => 'Friedel, Caroline C and Whisnant, Adam W and Djakovic, Lara and Rutkowski,Andrzej J and Friedl, Marie-Sophie and Kluge, Michael and Williamson, JamesC and Sai, Somesh and Vidal, Ramon Oliveira and Sauer, Sascha and Hennig,Thomas and Grothey, Arnhild an',
			'description' => '<p>Herpes simplex virus 1 (HSV-1) induces a profound host shut-off during lytic infection. The virion host shut-off () protein plays a key role in this process by efficiently cleaving host and viral mRNAs. Furthermore, the onset of viral DNA replication is accompanied by a rapid decline in host transcriptional activity. To dissect relative contributions of both mechanisms and elucidate gene-specific host transcriptional responses throughout the first 8h of lytic HSV-1 infection, we employed RNA-seq of total, newly transcribed (4sU-labelled) and chromatin-associated RNA in wild-type (WT) and &Delta; infection of primary human fibroblasts. Following virus entry, v activity rapidly plateaued at an elimination rate of around 30\% of cellular mRNAs per hour until 8h p.i. In parallel, host transcriptional activity dropped to 10-20\%. While the combined effects of both phenomena dominated infection-induced changes in total RNA, extensive gene-specific transcriptional regulation was observable in chromatin-associated RNA and was surprisingly concordant between WT and &Delta; infection. Both induced strong transcriptional up-regulation of a small subset of genes that were poorly expressed prior to infection but already primed by H3K4me3 histone marks at their promoters. Most interestingly, analysis of chromatin-associated RNA revealed -nuclease-activity-dependent transcriptional down-regulation of at least 150 cellular genes, in particular of many integrin adhesome and extracellular matrix components. This was accompanied by a -dependent reduction in protein levels by 8h p.i. for many of these genes. In summary, our study provides a comprehensive picture of the molecular mechanisms that govern cellular RNA metabolism during the first 8h of lytic HSV-1 infection. The HSV-1 virion host shut-off () protein efficiently cleaves both host and viral mRNAs in a translation-dependent manner. In this study, we model and quantify changes in activity as well as virus-induced global loss of host transcriptional activity during productive HSV-1 infection. In general, HSV-1-induced alterations in total RNA levels were dominated by these two global effects. In contrast, chromatin-associated RNA depicted gene-specific transcriptional changes. This revealed highly concordant transcriptional changes in WT and infection, confirmed DUX4 as a key transcriptional regulator in HSV-1 infection and depicted -dependent, transcriptional down-regulation of the integrin adhesome and extracellular matrix components. The latter explained seemingly gene-specific effects previously attributed to -mediated mRNA degradation and resulted in a concordant loss in protein levels by 8h p.i. for many of the respective genes.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33148793',
			'doi' => '10.1128/JVI.01399-20',
			'modified' => '2021-02-19 17:31:53',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 69 => array(
			'id' => '4069',
			'name' => 'Increased H3K4me3 methylation and decreased miR-7113-5p expression lead toenhanced Wnt/β-catenin signaling in immune cells from PTSD patientsleading to inflammatory phenotype.',
			'authors' => 'Bam, Marpe and Yang, Xiaoming and Busbee, Brandon P and Aiello, Allison Eand Uddin, Monica and Ginsberg, Jay P and Galea, Sandro and Nagarkatti,Prakash S and Nagarkatti, Mitzi',
			'description' => '<p>BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric disorder accompanied by chronic peripheral inflammation. What triggers inflammation in PTSD is currently unclear. In the present study, we identified potential defects in signaling pathways in peripheral blood mononuclear cells (PBMCs) from individuals with PTSD. METHODS: RNAseq (5 samples each for controls and PTSD), ChIPseq (5 samples each) and miRNA array (6 samples each) were used in combination with bioinformatics tools to identify dysregulated genes in PBMCs. Real time qRT-PCR (24 samples each) and in vitro assays were employed to validate our primary findings and hypothesis. RESULTS: By RNA-seq analysis of PBMCs, we found that Wnt signaling pathway was upregulated in PTSD when compared to normal controls. Specifically, we found increased expression of WNT10B in the PTSD group when compared to controls. Our findings were confirmed using NCBI's GEO database involving a larger sample size. Additionally, in vitro activation studies revealed that activated but not na&iuml;ve PBMCs from control individuals expressed more IFN&gamma; in the presence of recombinant WNT10B suggesting that Wnt signaling played a crucial role in exacerbating inflammation. Next, we investigated the mechanism of induction of WNT10B and found that increased expression of WNT10B may result from epigenetic modulation involving downregulation of hsa-miR-7113-5p which targeted WNT10B. Furthermore, we also observed that WNT10B overexpression was linked to higher expression of H3K4me3 histone modification around the promotor of WNT10B. Additionally, knockdown of histone demethylase specific to H3K4me3, using siRNA, led to increased expression of WNT10B providing conclusive evidence that H3K4me3 indeed controlled WNT10B expression. CONCLUSIONS: In summary, our data demonstrate for the first time that Wnt signaling pathway is upregulated in PBMCs of PTSD patients resulting from epigenetic changes involving microRNA dysregulation and histone modifications, which in turn may promote the inflammatory phenotype in such cells.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33189141',
			'doi' => '10.1186/s10020-020-00238-3',
			'modified' => '2021-02-19 17:54:52',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 70 => array(
			'id' => '4084',
			'name' => 'BCG Vaccination Induces Long-Term Functional Reprogramming of HumanNeutrophils.',
			'authors' => 'Moorlag, Simone J C F M and Rodriguez-Rosales, Yessica Alina and Gillard,Joshua and Fanucchi, Stephanie and Theunissen, Kate and Novakovic, Borisand de Bont, Cynthia M and Negishi, Yutaka and Fok, Ezio T and Kalafati,Lydia and Verginis, Panayotis and M',
			'description' => '<p>The tuberculosis vaccine bacillus Calmette-Gu&eacute;rin (BCG) protects against some heterologous infections, probably via induction of non-specific innate immune memory in monocytes and natural killer (NK) cells, a process known as trained immunity. Recent studies have revealed that the induction of trained immunity is associated with a bias toward granulopoiesis in bone marrow hematopoietic progenitor cells, but it is unknown whether BCG vaccination also leads to functional reprogramming of mature neutrophils. Here, we show that BCG vaccination of healthy humans induces long-lasting changes in neutrophil phenotype, characterized by increased expression of activation markers and antimicrobial function. The enhanced function of human neutrophils persists for at least 3&nbsp;months after vaccination and is associated with genome-wide epigenetic modifications in trimethylation at histone 3 lysine 4. Functional reprogramming of neutrophils by the induction of trained immunity might offer novel therapeutic strategies in clinical conditions that could benefit from modulation of neutrophil effector function.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33207187',
			'doi' => '10.1016/j.celrep.2020.108387',
			'modified' => '2021-03-15 17:07:29',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 71 => array(
			'id' => '4095',
			'name' => 'ZNF354C is a transcriptional repressor that inhibits endothelialangiogenic sprouting.',
			'authors' => 'Oo, James A and Irmer, Barnabas and Günther, Stefan and Warwick, Timothyand Pálfi, Katalin and Izquierdo Ponce, Judit and Teichmann, Tom andPflüger-Müller, Beatrice and Gilsbach, Ralf and Brandes, Ralf P andLeisegang, Matthias S',
			'description' => '<p>Zinc finger proteins (ZNF) are a large group of transcription factors with diverse functions. We recently discovered that endothelial cells harbour a specific mechanism to limit the action of ZNF354C, whose function in endothelial cells is unknown. Given that ZNF354C&nbsp;has so far only been studied in bone and tumour, its function was determined in endothelial cells. ZNF354C is expressed in vascular cells and localises to the nucleus and cytoplasm. Overexpression of ZNF354C in human endothelial cells results in a marked inhibition of endothelial sprouting. RNA-sequencing of human microvascular endothelial cells with and without overexpression of ZNF354C revealed that the protein is a potent transcriptional repressor. ZNF354C contains an active KRAB domain which mediates this suppression as shown by mutagenesis analysis. ZNF354C interacts with dsDNA, TRIM28 and histones, as observed by proximity ligation and immunoprecipitation. Moreover, chromatin immunoprecipitation revealed that the ZNF binds to specific endothelial-relevant target-gene promoters. ZNF354C suppresses these genes as shown by CRISPR/Cas knockout and RNAi. Inhibition of endothelial sprouting by ZNF354C is dependent on the amino acids DV and MLE of the KRAB domain. These results demonstrate that ZNF354C is a repressive transcription factor which acts through a KRAB domain to inhibit endothelial angiogenic sprouting.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33154469',
			'doi' => '10.1038/s41598-020-76193-0',
			'modified' => '2021-03-17 17:19:53',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 72 => array(
			'id' => '4197',
			'name' => 'Derivation of Intermediate Pluripotent Stem Cells Amenable to PrimordialGerm Cell Specification.',
			'authors' => 'Yu L. et al.',
			'description' => '<p>Dynamic pluripotent stem cell (PSC) states are in&nbsp;vitro adaptations of pluripotency continuum in&nbsp;vivo. Previous studies have generated a number of PSCs with distinct properties. To date, however, no known PSCs have demonstrated dual competency for chimera formation and direct responsiveness to primordial germ cell (PGC) specification, a unique functional feature of formative pluripotency. Here, by modulating fibroblast growth factor (FGF), transforming growth factor &beta; (TGF-&beta;), and WNT pathways, we derived PSCs from mice, horses, and humans (designated as XPSCs) that are permissive for direct PGC-like cell induction in&nbsp;vitro and are capable of contributing to intra- or inter-species chimeras in&nbsp;vivo. XPSCs represent a pluripotency state between naive and primed pluripotency and harbor molecular, cellular, and phenotypic features characteristic of formative pluripotency. XPSCs open new avenues for studying mammalian pluripotency and dissecting the molecular mechanisms governing PGC specification. Our method may be broadly applicable for the derivation of analogous stem cells from other mammalian species.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33271070',
			'doi' => '10.1016/j.stem.2020.11.003',
			'modified' => '2022-01-06 14:35:44',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 73 => array(
			'id' => '4201',
			'name' => 'The epigenetic regulator RINF (CXXC5) maintains SMAD7 expression in human immature erythroid cells and sustains red blood cellsexpansion.',
			'authors' => 'Astori A. et al.',
			'description' => '<p>The gene CXXC5, encoding a Retinoid-Inducible Nuclear Factor (RINF), is located within a region at 5q31.2 commonly deleted in myelodysplastic syndrome (MDS) and adult acute myeloid leukemia (AML). RINF may act as an epigenetic regulator and has been proposed as a tumor suppressor in hematopoietic malignancies. However, functional studies in normal hematopoiesis are lacking, and its mechanism of action is unknow. Here, we evaluated the consequences of RINF silencing on cytokineinduced erythroid differentiation of human primary CD34+ progenitors. We found that RINF is expressed in immature erythroid cells and that RINF-knockdown accelerated erythropoietin-driven maturation, leading to a significant reduction (~45\%) in the number of red blood cells (RBCs), without affecting cell viability. The phenotype induced by RINF-silencing was TGF&beta;-dependent and mediated by SMAD7, a TGF&beta;- signaling inhibitor. RINF upregulates SMAD7 expression by direct binding to its promoter and we found a close correlation between RINF and SMAD7 mRNA levels both in CD34+ cells isolated from bone marrow of healthy donors and MDS patients with del(5q). Importantly, RINF knockdown attenuated SMAD7 expression in primary cells and ectopic SMAD7 expression was sufficient to prevent the RINF knockdowndependent erythroid phenotype. Finally, RINF silencing affects 5&rsquo;-hydroxymethylation of human erythroblasts, in agreement with its recently described role as a Tet2- anchoring platform in mouse. Altogether, our data bring insight into how the epigenetic factor RINF, as a transcriptional regulator of SMAD7, may fine-tune cell sensitivity to TGF&beta; superfamily cytokines and thus play an important role in both normal and pathological erythropoiesis.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33241676',
			'doi' => '10.3324/haematol.2020.263558',
			'modified' => '2022-01-06 14:46:32',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 74 => array(
			'id' => '4052',
			'name' => 'StE(z)2, a Polycomb group methyltransferase and deposition of H3K27me3 andH3K4me3 regulate the expression of tuberization genes in potato.',
			'authors' => 'Kumar, Amit and Kondhare, Kirtikumar R and Malankar, Nilam N and Banerjee,Anjan K',
			'description' => '<p>Polycomb Repressive Complex (PRC) group proteins regulate various developmental processes in plants by repressing the target genes via H3K27 trimethylation, whereas their function is antagonized by Trithorax group proteins-mediated H3K4 trimethylation. Tuberization in potato is widely studied, but the role of histone modifications in this process is unknown. Recently, we showed that overexpression of StMSI1 (a PRC2 member) alters the expression of tuberization genes in potato. As MSI1 lacks histone-modification activity, we hypothesized that this altered expression could be caused by another PRC2 member, StE(z)2 (a potential H3K27 methyltransferase in potato). Here, we demonstrate that short-day photoperiod influences StE(z)2 expression in leaf and stolon. Moreover, StE(z)2 overexpression alters plant architecture and reduces tuber yield, whereas its knockdown enhanced the yield. ChIP-sequencing using short-day induced stolons revealed that several tuberization and phytohormone-related genes, such as StBEL5/11/29, StSWEET11B, StGA2OX1 and StPIN1 carry H3K4me3 or H3K27me3 marks and/or are StE(z)2 targets. Interestingly, we noticed that another important tuberization gene, StSP6A is targeted by StE(z)2 in leaves and had increased deposition of H3K27me3 under non-induced (long-day) conditions compared to SD. Overall, we show that StE(z)2 and deposition of H3K27me3 and/or H3K4me3 marks could regulate the expression of key tuberization genes in potato.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33048134',
			'doi' => '10.1093/jxb/eraa468',
			'modified' => '2021-02-19 14:55:34',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 75 => array(
			'id' => '4053',
			'name' => 'Priming for enhanced ARGONAUTE2 activation accompanies induced resistanceto cucumber mosaic virus in Arabidopsis thaliana.',
			'authors' => 'Ando, Sugihiro and Jaskiewicz, Michal and Mochizuki, Sei and Koseki, Saekoand Miyashita, Shuhei and Takahashi, Hideki and Conrath, Uwe',
			'description' => '<p>Systemic acquired resistance (SAR) is a broad-spectrum disease resistance response that can be induced upon infection from pathogens or by chemical treatment, such as with benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH). SAR involves priming for more robust activation of defence genes upon pathogen attack. Whether priming for SAR would involve components of RNA silencing remained unknown. Here, we show that upon leaf infiltration of water, BTH-primed Arabidopsis thaliana plants accumulate higher amounts of mRNA of ARGONAUTE (AGO)2 and AGO3, key components of RNA silencing. The enhanced AGO2 expression is associated with prior-to-activation trimethylation of lysine 4 in histone H3 and acetylation of histone H3 in the AGO2 promoter and with induced resistance to the yellow strain of cucumber mosaic virus (CMV[Y]). The results suggest that priming A.&nbsp;thaliana for enhanced defence involves modification of histones in the AGO2 promoter that condition AGO2 for enhanced activation, associated with resistance to CMV(Y). Consistently, the fold-reduction in CMV(Y) coat protein accumulation by BTH pretreatment was lower in ago2 than in wild type, pointing to reduced capacity of ago2 to activate BTH-induced CMV(Y) resistance. A role of AGO2 in pathogen-induced SAR is suggested by the enhanced activation of AGO2 after infiltrating systemic leaves of plants expressing a localized hypersensitive response upon CMV(Y) infection. In addition, local inoculation of SAR-inducing Pseudomonas syringae pv. maculicola causes systemic priming for enhanced AGO2 expression. Together our results indicate that defence priming targets the AGO2 component of RNA silencing whose enhanced expression is likely to contribute to SAR.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33073913',
			'doi' => '10.1111/mpp.13005',
			'modified' => '2021-02-19 14:57:21',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 76 => array(
			'id' => '4062',
			'name' => 'Digging Deeper into Breast Cancer Epigenetics: Insights from ChemicalInhibition of Histone Acetyltransferase TIP60 .',
			'authors' => 'Idrissou, Mouhamed and Lebert, Andre and Boisnier, Tiphanie and Sanchez,Anna and Houfaf Khoufaf, Fatma Zohra and Penault-Llorca, Frédérique andBignon, Yves-Jean and Bernard-Gallon, Dominique',
			'description' => '<p>Breast cancer is often sporadic due to several factors. Among them, the deregulation of epigenetic proteins may be involved. TIP60 or KAT5 is an acetyltransferase that regulates gene transcription through the chromatin structure. This pleiotropic protein acts in several cellular pathways by acetylating proteins. RNA and protein expressions of TIP60 were shown to decrease in some breast cancer subtypes, particularly in triple-negative breast cancer (TNBC), where a low expression of TIP60 was exhibited compared with luminal subtypes. In this study, the inhibition of the residual activity of TIP60 in breast cancer cell lines was investigated by using two chemical inhibitors, TH1834 and NU9056, first on the acetylation of the specific target, lysine 4 of histone 3 (H3K4) by immunoblotting, and second, by chromatin immunoprecipitation (ChIP)-qPCR (-quantitative Polymerase Chain Reaction). Subsequently, significant decreases or a trend toward decrease of H3K4ac in the different chromatin compartments were observed. In addition, the expression of 48 human nuclear receptors was studied with TaqMan Low-Density Array in these breast cancer cell lines treated with TIP60 inhibitors. The statistical analysis allowed us to comprehensively characterize the androgen receptor and receptors in TNBC cell lines after TH1834 or NU9056 treatment. The understanding of the residual activity of TIP60 in the evolution of breast cancer might be a major asset in the fight against this disease, and could allow TIP60 to be used as a biomarker or therapeutic target for breast cancer progression in the future.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32960142',
			'doi' => '10.1089/omi.2020.0104',
			'modified' => '2021-02-19 17:39:52',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 77 => array(
			'id' => '4073',
			'name' => 'NSD1-deposited H3K36me2 directs de novo methylation in the mouse malegermline and counteracts Polycomb-associated silencing.',
			'authors' => 'Shirane, Kenjiro and Miura, Fumihito and Ito, Takashi and Lorincz, MatthewC',
			'description' => '<p>De novo DNA methylation (DNAme) in mammalian germ cells is dependent on DNMT3A and DNMT3L. However, oocytes and spermatozoa show distinct patterns of DNAme. In mouse oocytes, de novo DNAme requires the lysine methyltransferase (KMTase) SETD2, which deposits H3K36me3. We show here that SETD2 is dispensable for de novo DNAme in the male germline. Instead, the lysine methyltransferase NSD1, which broadly deposits H3K36me2 in euchromatic regions, plays a critical role in de novo DNAme in prospermatogonia, including at imprinted genes. However, males deficient in germline NSD1 show a more severe defect in spermatogenesis than Dnmt3l males. Notably, unlike DNMT3L, NSD1 safeguards a subset of genes against H3K27me3-associated transcriptional silencing. In contrast, H3K36me2 in oocytes is predominantly dependent on SETD2 and coincides with H3K36me3. Furthermore, females with NSD1-deficient oocytes are fertile. Thus, the sexually dimorphic pattern of DNAme in mature mouse gametes is orchestrated by distinct profiles of H3K36 methylation.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32929285',
			'doi' => '10.1038/s41588-020-0689-z',
			'modified' => '2021-02-19 18:02:40',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 78 => array(
			'id' => '4078',
			'name' => 'Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth andPotentiates Checkpoint Inhibition.',
			'authors' => 'Priem, Bram and van Leent, Mandy M T and Teunissen, Abraham J P and Sofias,Alexandros Marios and Mourits, Vera P and Willemsen, Lisa and Klein, Emma Dand Oosterwijk, Roderick S and Meerwaldt, Anu E and Munitz, Jazz andPrévot, Geoffrey and Vera Verschuu',
			'description' => '<p>Trained immunity, a functional state of myeloid cells, has been proposed as a compelling immune-oncological target. Its efficient induction requires direct engagement of myeloid progenitors in the bone marrow. For this purpose, we developed a bone marrow-avid nanobiologic platform designed specifically to induce trained immunity. We established the potent anti-tumor capabilities of our lead candidate MTP-HDL in a B16F10 mouse melanoma model. These anti-tumor effects result from trained immunity-induced myelopoiesis caused by epigenetic rewiring of multipotent progenitors in the bone marrow, which overcomes the immunosuppressive tumor microenvironment. Furthermore, MTP-HDL nanotherapy potentiates checkpoint inhibition in this melanoma model refractory to anti-PD-1 and anti-CTLA-4 therapy. Finally, we determined MTP-HDL's favorable biodistribution and safety profile in non-human primates. In conclusion, we show that rationally designed nanobiologics can promote trained immunity and elicit a durable anti-tumor response either as a monotherapy or in combination with checkpoint inhibitor drugs.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33125893',
			'doi' => '10.1016/j.cell.2020.09.059',
			'modified' => '2021-03-15 16:51:03',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 79 => array(
			'id' => '4092',
			'name' => 'Formation of the CenH3-Deficient Holocentromere in Lepidoptera AvoidsActive Chromatin.',
			'authors' => 'Senaratne, Aruni P and Muller, Héloïse and Fryer, Kelsey A and Kawamoto,Munetaka and Katsuma, Susumu and Drinnenberg, Ines A',
			'description' => '<p>Despite the essentiality for faithful chromosome segregation, centromere architectures are diverse among eukaryotes and embody two main configurations: mono- and holocentromeres, referring, respectively, to localized or unrestricted distribution of centromeric activity. Of the two, some holocentromeres offer the curious condition of having arisen independently in multiple insects, most of which have lost the otherwise essential centromere-specifying factor CenH3 (first described as CENP-A in humans). The loss of CenH3 raises intuitive questions about how holocentromeres are organized and regulated in CenH3-lacking insects. Here, we report the first chromatin-level description of CenH3-deficient holocentromeres by leveraging recently identified centromere components and genomics approaches to map and characterize the holocentromeres of the silk moth Bombyx mori, a representative lepidopteran insect lacking CenH3. This uncovered a robust correlation between the distribution of centromere sites and regions of low chromatin activity along B.&nbsp;mori chromosomes. Transcriptional perturbation experiments recapitulated the exclusion of B.&nbsp;mori centromeres from active chromatin. Based on reciprocal centromere occupancy patterns observed along differentially expressed orthologous genes of Lepidoptera, we further found that holocentromere formation in a manner that is recessive to chromatin dynamics is evolutionarily conserved. Our results help us discuss the plasticity of centromeres in the context of a role for the chromosome-wide chromatin landscape in conferring centromere identity rather than the presence of CenH3. Given the co-occurrence of CenH3 loss and holocentricity in insects, we further propose that the evolutionary establishment of holocentromeres in insects was facilitated through the loss of a CenH3-specified centromere.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33125865',
			'doi' => '10.1016/j.cub.2020.09.078',
			'modified' => '2021-03-17 17:13:50',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 80 => array(
			'id' => '4091',
			'name' => 'Epigenetic regulation of the lineage specificity of primary human dermallymphatic and blood vascular endothelial cells.',
			'authors' => 'Tacconi, Carlotta and He, Yuliang and Ducoli, Luca and Detmar, Michael',
			'description' => '<p>Lymphatic and blood vascular endothelial cells (ECs) share several molecular and developmental features. However, these two cell types possess distinct phenotypic signatures, reflecting their different biological functions. Despite significant advances in elucidating how the specification of lymphatic and blood vascular ECs is regulated at the transcriptional level during development, the key molecular mechanisms governing their lineage identity under physiological or pathological conditions remain poorly understood. To explore the epigenomic signatures in the maintenance of EC lineage specificity, we compared the transcriptomic landscapes, histone composition (H3K4me3 and H3K27me3) and DNA methylomes of cultured matched human primary dermal lymphatic and blood vascular ECs. Our findings reveal that blood vascular lineage genes manifest a more 'repressed' histone composition in lymphatic ECs, whereas DNA methylation at promoters is less linked to the differential transcriptomes of lymphatic versus blood vascular ECs. Meta-analyses identified two transcriptional regulators, BCL6 and MEF2C, which potentially govern endothelial lineage specificity. Notably, the blood vascular endothelial lineage markers CD34, ESAM and FLT1 and the lymphatic endothelial lineage markers PROX1, PDPN and FLT4 exhibited highly differential epigenetic profiles and responded in distinct manners to epigenetic drug treatments. The perturbation of histone and DNA methylation selectively promoted the expression of blood vascular endothelial markers in lymphatic endothelial cells, but not vice versa. Overall, our study reveals that the fine regulation of lymphatic and blood vascular endothelial transcriptomes is maintained via several epigenetic mechanisms, which are crucial to the maintenance of endothelial cell identity.</p>',
			'date' => '2020-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32918672',
			'doi' => '10.1007/s10456-020-09743-9',
			'modified' => '2021-03-17 17:09:36',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 81 => array(
			'id' => '3978',
			'name' => 'OxLDL-mediated immunologic memory in endothelial cells.',
			'authors' => 'Sohrabi Y, Lagache SMM, Voges VC, Semo D, Sonntag G, Hanemann I, Kahles F, Waltenberger J, Findeisen HM',
			'description' => '<p>Trained innate immunity describes the metabolic reprogramming and long-term proinflammatory activation of innate immune cells in response to different pathogen or damage associated molecular patterns, such as oxidized low-density lipoprotein (oxLDL). Here, we have investigated whether the regulatory networks of trained innate immunity also control endothelial cell activation following oxLDL treatment. Human aortic endothelial cells (HAECs) were primed with oxLDL for 24 h. After a resting time of 4 days, cells were restimulated with the TLR2-agonist PAM3cys4. OxLDL priming induced a proinflammatory memory with increased production of inflammatory cytokines such as IL-6, IL-8 and MCP-1 in response to PAM3cys4 restimulation. This memory formation was dependent on TLR2 activation. Furthermore, oxLDL priming of HAECs caused characteristic metabolic and epigenetic reprogramming, including activated mTOR-HIF1&alpha;-signaling with increases in glucose consumption and lactate production, as well as epigenetic modifications in inflammatory gene promoters. Inhibition of mTOR-HIF1&alpha;-signaling or histone methyltransferases blocked the observed phenotype. Furthermore, primed HAECs showed epigenetic activation of ICAM-1 and increased ICAM-1 expression in a HIF1&alpha;-dependent manner. Accordingly, live cell imaging revealed increased monocyte adhesion and transmigration following oxLDL priming. In summary, we demonstrate that oxLDL-mediated endothelial cell activation represents an immunologic event, which triggers metabolic and epigenetic reprogramming. Molecular mechanisms regulating trained innate immunity in innate immune cells also regulate this sustained proinflammatory phenotype in HAECs with enhanced atheroprone cell functions. Further research is necessary to elucidate the detailed metabolic regulation and the functional relevance for atherosclerosis formation in vivo.</p>',
			'date' => '2020-07-26',
			'pmid' => 'http://www.pubmed.gov/32726647',
			'doi' => '10.1016/j.yjmcc.2020.07.006',
			'modified' => '2020-08-10 13:08:21',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 82 => array(
			'id' => '3997',
			'name' => 'The Human Integrator Complex Facilitates Transcriptional Elongation by Endonucleolytic Cleavage of Nascent Transcripts.',
			'authors' => 'Beckedorff F, Blumenthal E, daSilva LF, Aoi Y, Cingaram PR, Yue J, Zhang A, Dokaneheifard S, Valencia MG, Gaidosh G, Shilatifard A, Shiekhattar R',
			'description' => '<p>Transcription by RNA polymerase II (RNAPII) is pervasive in the human genome. However, the mechanisms controlling transcription at promoters and enhancers remain enigmatic. Here, we demonstrate that Integrator subunit 11 (INTS11), the catalytic subunit of the Integrator complex, regulates transcription at these loci through its endonuclease activity. Promoters of genes require INTS11 to cleave nascent transcripts associated with paused RNAPII and induce their premature termination in the proximity of the&nbsp;+1 nucleosome. The turnover of RNAPII permits the subsequent recruitment of an elongation-competent RNAPII complex, leading to productive elongation. In contrast, enhancers require INTS11 catalysis not to evict paused RNAPII but rather to terminate enhancer RNA transcription beyond the&nbsp;+1 nucleosome. These findings are supported by the differential occupancy of negative elongation factor (NELF), SPT5, and tyrosine-1-phosphorylated RNAPII. This study elucidates the role of Integrator in mediating transcriptional elongation at human promoters through the endonucleolytic cleavage of nascent transcripts and the dynamic turnover of RNAPII.</p>',
			'date' => '2020-07-21',
			'pmid' => 'http://www.pubmed.gov/32697989',
			'doi' => '10.1016/j.celrep.2020.107917',
			'modified' => '2020-09-01 14:44:33',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 83 => array(
			'id' => '3996',
			'name' => 'Prostate cancer reactivates developmental epigenomic programs during metastatic progression.',
			'authors' => 'Pomerantz MM, Qiu X, Zhu Y, Takeda DY, Pan W, Baca SC, Gusev A, Korthauer KD, Severson TM, Ha G, Viswanathan SR, Seo JH, Nguyen HM, Zhang B, Pasaniuc B, Giambartolomei C, Alaiwi SA, Bell CA, O'Connor EP, Chabot MS, Stillman DR, Lis R, Font-Tello A, Li L, ',
			'description' => '<p>Epigenetic processes govern prostate cancer (PCa) biology, as evidenced by the dependency of PCa cells on the androgen receptor (AR), a prostate master transcription factor. We generated 268 epigenomic datasets spanning two state transitions-from normal prostate epithelium to localized PCa to metastases-in specimens derived from human tissue. We discovered that reprogrammed AR sites in metastatic PCa are not created de novo; rather, they are prepopulated by the transcription factors FOXA1 and HOXB13 in normal prostate epithelium. Reprogrammed regulatory elements commissioned in metastatic disease hijack latent developmental programs, accessing sites that are implicated in prostate organogenesis. Analysis of reactivated regulatory elements enabled the identification and functional validation of previously unknown metastasis-specific enhancers at HOXB13, FOXA1 and NKX3-1. Finally, we observed that prostate lineage-specific regulatory elements were strongly associated with PCa risk heritability and somatic mutation density. Examining prostate biology through an epigenomic lens is fundamental for understanding the mechanisms underlying tumor progression.</p>',
			'date' => '2020-07-20',
			'pmid' => 'http://www.pubmed.gov/32690948',
			'doi' => '10.1038/s41588-020-0664-8',
			'modified' => '2020-09-01 14:45:54',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 84 => array(
			'id' => '3987',
			'name' => 'The hypomethylation of imprinted genes in IVF/ICSI placenta samples is associated with concomitant changes in histone modifications.',
			'authors' => 'Choux C, Petazzi P, Sanchez-Delgado M, Hernandez Mora JR, Monteagudo A, Sagot P, Monk D, Fauque P',
			'description' => '<p>Although more and more children are born by Assisted Reproductive Technologies (ART), ART safety has not fully been demonstrated. Notably, ART could disturb the delicate step of implantation, and trigger placenta-related adverse outcomes with potential long-term effects, through disrupted epigenetic regulation. We have previously demonstrated that placental DNA methylation was significantly lower after IVF/ICSI than following natural conception at two differentially methylated regions (DMRs) associated with imprinted genes (IGs): and . As histone modifications are critical for placental physiology, the aim of this study was to profile permissive and repressive histone marks in placenta biopsies to reveal a better understanding of the epigenetic changes in the context of ART. Utilizing chromatin immunoprecipitation (ChIP) coupled with quantitative PCR, permissive (H3K4me3, H3K4me2, and H3K9ac) and repressive (H3K9me3 and H3K9me2) post-translational histone modifications were quantified. The analyses revealed a significantly higher quantity of H3K4me2 precipitation in the IVF/ICSI group than in the natural conception group for and DMRs (P&nbsp;=&nbsp;0.016 and 0.003, respectively). Conversely, the quantity of both repressive marks at and DMRs was significantly lower in the IVF/ICSI group than in the natural conception group (P&nbsp;=&nbsp;0.011 and 0.027 for ; and P&nbsp;=&nbsp;0.010 and 0.035 for ). These novel findings highlight that DNA hypomethylation at imprinted DMRs following ART is linked with increased permissive/decreased repressive histone marks, altogether promoting a more permissive chromatin conformation. This concomitant change in epigenetic state at IGs at birth might be an important developmental event because of ART manipulations.</p>',
			'date' => '2020-06-23',
			'pmid' => 'http://www.pubmed.gov/32573317',
			'doi' => '10.1080/15592294.2020.1783168',
			'modified' => '2020-09-01 15:10:37',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 85 => array(
			'id' => '3986',
			'name' => 'Epigenetic priming by Dppa2 and 4 in pluripotency facilitates multi-lineage commitment.',
			'authors' => 'Eckersley-Maslin MA, Parry A, Blotenburg M, Krueger C, Ito Y, Franklin VNR, Narita M, D'Santos CS, Reik W',
			'description' => '<p>How the epigenetic landscape is established in development is still being elucidated. Here, we uncover developmental pluripotency associated 2 and 4 (DPPA2/4) as epigenetic priming factors that establish a permissive epigenetic landscape at a subset of developmentally important bivalent promoters characterized by low expression and poised RNA-polymerase. Differentiation assays reveal that Dppa2/4 double knockout mouse embryonic stem cells fail to exit pluripotency and differentiate efficiently. DPPA2/4 bind both H3K4me3-marked and bivalent gene promoters and associate with COMPASS- and Polycomb-bound chromatin. Comparing knockout and inducible knockdown systems, we find that acute depletion of DPPA2/4 results in rapid loss of H3K4me3 from key bivalent genes, while H3K27me3 is initially more stable but lost following extended culture. Consequently, upon DPPA2/4 depletion, these promoters gain DNA methylation and are unable to be activated upon differentiation. Our findings uncover a novel epigenetic priming mechanism at developmental promoters, poising them for future lineage-specific activation.</p>',
			'date' => '2020-06-22',
			'pmid' => 'http://www.pubmed.gov/32572255',
			'doi' => '10.1038/s41594-020-0443-3',
			'modified' => '2020-09-01 15:12:03',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 86 => array(
			'id' => '3982',
			'name' => 'Genomic deregulation of PRMT5 supports growth and stress tolerance in chronic lymphocytic leukemia.',
			'authors' => 'Schnormeier AK, Pommerenke C, Kaufmann M, Drexler HG, Koeppel M',
			'description' => '<p>Patients suffering from chronic lymphocytic leukemia (CLL) display highly diverse clinical courses ranging from indolent cases to aggressive disease, with genetic and epigenetic features resembling this diversity. Here, we developed a comprehensive approach combining a variety of molecular and clinical data to pinpoint translocation events disrupting long-range chromatin interactions and causing cancer-relevant transcriptional deregulation. Thereby, we discovered a B cell specific cis-regulatory element restricting the expression of genes in the associated locus, including PRMT5 and DAD1, two factors with oncogenic potential. Experimental PRMT5 inhibition identified transcriptional programs similar to those in patients with differences in PRMT5 abundance, especially MYC-driven and stress response pathways. In turn, such inhibition impairs factors involved in DNA repair, sensitizing cells for apoptosis. Moreover, we show that artificial deletion of the regulatory element from its endogenous context resulted in upregulation of corresponding genes, including PRMT5. Furthermore, such disruption renders PRMT5 transcription vulnerable to additional stimuli and subsequently alters the expression of downstream PRMT5 targets. These studies provide a mechanism of PRMT5 deregulation in CLL and the molecular dependencies identified might have therapeutic implementations.</p>',
			'date' => '2020-06-17',
			'pmid' => 'http://www.pubmed.gov/32555249',
			'doi' => '10.1038/s41598-020-66224-1',
			'modified' => '2020-09-01 15:17:40',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 87 => array(
			'id' => '4360',
			'name' => 'The hypomethylation of imprinted genes in IVF/ICSI placenta samplesis associated with concomitant changes in histone modifications.',
			'authors' => 'Choux C. et al. ',
			'description' => '<p>Although more and more children are born by Assisted Reproductive Technologies (ART), ART safety has not fully been demonstrated. Notably, ART could disturb the delicate step of implantation, and trigger placenta-related adverse outcomes with potential long-term effects, through disrupted epigenetic regulation. We have previously demonstrated that placental DNA methylation was significantly lower after IVF/ICSI than following natural conception at two differentially methylated regions (DMRs) associated with imprinted genes (IGs): and . As histone modifications are critical for placental physiology, the aim of this study was to profile permissive and repressive histone marks in placenta biopsies to reveal a better understanding of the epigenetic changes in the context of ART. Utilizing chromatin immunoprecipitation (ChIP) coupled with quantitative PCR, permissive (H3K4me3, H3K4me2, and H3K9ac) and repressive (H3K9me3 and H3K9me2) post-translational histone modifications were quantified. The analyses revealed a significantly higher quantity of H3K4me2 precipitation in the IVF/ICSI group than in the natural conception group for and DMRs (P = 0.016 and 0.003, respectively). Conversely, the quantity of both repressive marks at and DMRs was significantly lower in the IVF/ICSI group than in the natural conception group (P = 0.011 and 0.027 for ; and P = 0.010 and 0.035 for ). These novel findings highlight that DNA hypomethylation at imprinted DMRs following ART is linked with increased permissive/decreased repressive histone marks, altogether promoting a more permissive chromatin conformation. This concomitant change in epigenetic state at IGs at birth might be an important developmental event because of ART manipulations.</p>',
			'date' => '2020-06-01',
			'pmid' => 'http://www.pubmed.gov/32573317',
			'doi' => '10.1080/15592294.2020.1783168',
			'modified' => '2022-08-03 17:14:32',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 88 => array(
			'id' => '4005',
			'name' => 'Measuring Histone Modifications in the Human Parasite Schistosoma mansoni ',
			'authors' => 'de Carvalho Augusto R, Roquis D, Al Picard M, Chaparro C, Cosseau C, Grunau C.',
			'description' => '<p>DNA-binding proteins play critical roles in many major processes such as development and sexual biology of Schistosoma mansoni and are important for the pathogenesis of schistosomiasis. Chromatin immunoprecipitation (ChIP) experiments followed by sequencing (ChIP-seq) are useful to characterize the association of genomic regions with posttranslational chemical modifications of histone proteins. Challenges in the standard ChIP protocol have motivated recent enhancements in this approach, such as reducing the number of cells required and increasing the resolution. In this chapter, we describe the latest advances made by our group in the ChIP methods to improve the standard ChIP protocol to reduce the number of input cells required and to increase the resolution and robustness of ChIP in S. mansoni.</p>',
			'date' => '2020-05-26',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/32451999/',
			'doi' => '10.1007/978-1-0716-0635-3_9 ',
			'modified' => '2020-09-11 15:31:21',
			'created' => '2020-09-11 15:25:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 89 => array(
			'id' => '3965',
			'name' => 'Histone post-translational modifications in Silene latifolia X and Y chromosomes suggest a mammal-like dosage compensation system',
			'authors' => 'Luis Rodríguez Lorenzo José, Hubinský Marcel, Vyskot Boris, Hobza Roman',
			'description' => '<p>Silene latifolia is a model organism to study evolutionary young heteromorphic sex chromosome evolution in plants. Previous research indicates a Y-allele gene degeneration and a dosage compensation system already operating. Here, we propose an epigenetic approach based on analysis of several histone post-translational modifications (PTMs) to find the first epigenetic hints of the X:Y sex chromosome system regulation in S. latifolia. Through chromatin immunoprecipitation we interrogated six genes from X and Y alleles. Several histone PTMS linked to DNA methylation and transcriptional repression (H3K27me3, H3K23me, H3K9me2 and H3K9me3) and to transcriptional activation (H3K4me3 and H4K5, 8, 12, 16ac) were used. DNA enrichment (Immunoprecipitated DNA/input DNA) was analyzed and showed three main results: i) promoters of the Y allele are associated with heterochromatin marks, ii) promoters of the X allele in males are associated with activation of transcription marks and finally, iii) promoters of X alleles in females are associated with active and repressive marks. Our finding indicates a transcription activation of X allele and transcription repression of Y allele in males. In females we found a possible differential regulation (up X1, down X2) of each female X allele. These results agree with the mammal-like epigenetic dosage compensation regulation.</p>',
			'date' => '2020-05-24',
			'pmid' => 'https://www.sciencedirect.com/science/article/abs/pii/S0168945220301333',
			'doi' => '10.1016/j.plantsci.2020.110528',
			'modified' => '2020-08-12 09:42:21',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 90 => array(
			'id' => '3952',
			'name' => 'TET3 controls the expression of the H3K27me3 demethylase Kdm6b during neural commitment.',
			'authors' => 'Montibus B, Cercy J, Bouschet T, Charras A, Maupetit-Méhouas S, Nury D, Gonthier-Guéret C, Chauveau S, Allegre N, Chariau C, Hong CC, Vaillant I, Marques CJ, Court F, Arnaud P',
			'description' => '<p>The acquisition of cell identity is associated with developmentally regulated changes in the cellular histone methylation signatures. For instance, commitment to neural differentiation relies on the tightly controlled gain or loss of H3K27me3, a hallmark of polycomb-mediated transcriptional gene silencing, at specific gene sets. The KDM6B demethylase, which removes H3K27me3 marks at defined promoters and enhancers, is a key factor in neurogenesis. Therefore, to better understand the epigenetic regulation of neural fate acquisition, it is important to determine how Kdm6b expression is regulated. Here, we investigated the molecular mechanisms involved in the induction of Kdm6b expression upon neural commitment of mouse embryonic stem cells. We found that the increase in Kdm6b expression is linked to a rearrangement between two 3D configurations defined by the promoter contact with two different regions in the Kdm6b locus. This is associated with changes in 5-hydroxymethylcytosine (5hmC) levels at these two regions, and requires a functional ten-eleven-translocation (TET) 3 protein. Altogether, our data support a model whereby Kdm6b induction upon neural commitment relies on an intronic enhancer the activity of which is defined by its TET3-mediated 5-hmC level. This original observation reveals an unexpected interplay between the 5-hmC and H3K27me3 pathways during neural lineage commitment in mammals. It also questions to which extent KDM6B-mediated changes in H3K27me3 level account for the TET-mediated effects on gene expression.</p>',
			'date' => '2020-05-14',
			'pmid' => 'http://www.pubmed.gov/32405722',
			'doi' => '10.1007/s00018-020-03541-8',
			'modified' => '2020-08-17 09:53:08',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 91 => array(
			'id' => '3951',
			'name' => 'In vitro capture and characterization of embryonic rosette-stage pluripotency between naive and primed states.',
			'authors' => 'Neagu A, van Genderen E, Escudero I, Verwegen L, Kurek D, Lehmann J, Stel J, Dirks RAM, van Mierlo G, Maas A, Eleveld C, Ge Y, den Dekker AT, Brouwer RWW, van IJcken WFJ, Modic M, Drukker M, Jansen JH, Rivron NC, Baart EB, Marks H, Ten Berge D',
			'description' => '<p>Following implantation, the naive pluripotent epiblast of the mouse blastocyst generates a rosette, undergoes lumenogenesis and forms the primed pluripotent egg cylinder, which is able to generate the embryonic tissues. How pluripotency progression and morphogenesis are linked and whether intermediate pluripotent states exist remain controversial. We identify here a rosette pluripotent state defined by the co-expression of naive factors with the transcription factor OTX2. Downregulation of blastocyst WNT signals drives the transition into rosette pluripotency by inducing OTX2. The rosette then activates MEK signals that induce lumenogenesis and drive progression to primed pluripotency. Consequently, combined WNT and MEK inhibition supports rosette-like stem cells, a self-renewing naive-primed intermediate. Rosette-like stem cells erase constitutive heterochromatin marks and display a primed chromatin landscape, with bivalently marked primed pluripotency genes. Nonetheless, WNT induces reversion to naive pluripotency. The rosette is therefore a reversible pluripotent intermediate whereby control over both pluripotency progression and morphogenesis pivots from WNT to MEK signals.</p>',
			'date' => '2020-05-01',
			'pmid' => 'http://www.pubmed.gov/32367046',
			'doi' => '10.1038/s41556-020-0508-x',
			'modified' => '2020-08-17 09:55:37',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 92 => array(
			'id' => '3929',
			'name' => 'The TGF-β profibrotic cascade targets ecto-5'-nucleotidase gene in proximal tubule epithelial cells and is a traceable marker of progressive diabetic kidney disease.',
			'authors' => 'Cappelli C, Tellez A, Jara C, Alarcón S, Torres A, Mendoza P, Podestá L, Flores C, Quezada C, Oyarzún C, Martín RS',
			'description' => '<p>Progressive diabetic nephropathy (DN) and loss of renal function correlate with kidney fibrosis. Crosstalk between TGF-&beta; and adenosinergic signaling contributes to the phenotypic transition of cells and to renal fibrosis in DN models. We evaluated the role of TGF-&beta; on NT5E gene expression coding for the ecto-5`-nucleotidase CD73, the limiting enzyme in extracellular adenosine production. We showed that high d-glucose may predispose HK-2 cells towards active transcription of the proximal promoter region of the NT5E gene while additional TGF-&beta; results in full activation. The epigenetic landscape of the NT5E gene promoter was modified by concurrent TGF-&beta; with occupancy by the p300 co-activator and the phosphorylated forms of the Smad2/3 complex and RNA Pol II. Transcriptional induction at NT5E in response to TGF-&beta; was earlier compared to the classic responsiveness genes PAI-1 and Fn1. CD73 levels and AMPase activity were concomitantly increased by TGF-&beta; in HK-2 cells. Interestingly, we found increased CD73 content in urinary extracellular vesicles only in diabetic patients with renal repercussions. Further, CD73-mediated AMPase activity was increased in the urinary sediment of DN patients. We conclude that the NT5E gene is a target of the profibrotic TGF-&beta; cascade and is a traceable marker of progressive DN.</p>',
			'date' => '2020-04-11',
			'pmid' => 'http://www.pubmed.gov/32289379',
			'doi' => '10.1016/j.bbadis.2020.165796',
			'modified' => '2020-08-17 10:46:30',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 93 => array(
			'id' => '3889',
			'name' => 'LXR Activation Induces a Proinflammatory Trained Innate Immunity-Phenotype in Human Monocytes',
			'authors' => 'Sohrabi Yahya, Sonntag Glenn V. H., Braun Laura C., Lagache Sina M. M., Liebmann Marie, Klotz Luisa, Godfrey Rinesh, Kahles Florian, Waltenberger Johannes, Findeisen Hannes M.',
			'description' => '<p>The concept of trained innate immunity describes a long-term proinflammatory memory in innate immune cells. Trained innate immunity is regulated through reprogramming of cellular metabolic pathways including cholesterol and fatty acid synthesis. Here, we have analyzed the role of Liver X Receptor (LXR), a key regulator of cholesterol and fatty acid homeostasis, in trained innate immunity.</p>',
			'date' => '2020-03-10',
			'pmid' => 'https://www.frontiersin.org/articles/10.3389/fimmu.2020.00353/full',
			'doi' => '10.3389/ﬁmmu.2020.00353',
			'modified' => '2020-03-20 17:19:37',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 94 => array(
			'id' => '3884',
			'name' => 'A MORC-driven transcriptional switch controls Toxoplasma developmental trajectories and sexual commitment.',
			'authors' => 'Farhat DC, Swale C, Dard C, Cannella D, Ortet P, Barakat M, Sindikubwabo F, Belmudes L, De Bock PJ, Couté Y, Bougdour A, Hakimi MA',
			'description' => '<p>Toxoplasma gondii has a complex life cycle that is typified by asexual development that takes place in vertebrates, and sexual reproduction, which occurs exclusively in felids and is therefore less studied. The developmental transitions rely on changes in the patterns of gene expression, and recent studies have assigned roles for chromatin shapers, including histone modifications, in establishing specific epigenetic programs for each given stage. Here, we identified the T. gondii microrchidia (MORC) protein as an upstream transcriptional repressor of sexual commitment. MORC, in a complex with Apetala 2 (AP2) transcription factors, was shown to recruit the histone deacetylase HDAC3, thereby impeding the accessibility of chromatin at the genes that are exclusively expressed during sexual stages. We found that MORC-depleted cells underwent marked transcriptional changes, resulting in the expression of a specific repertoire of genes, and revealing a shift from asexual proliferation to sexual differentiation. MORC acts as a master regulator that directs the hierarchical expression of secondary AP2 transcription factors, and these transcription factors potentially contribute to the unidirectionality of the life cycle. Thus, MORC plays a cardinal role in the T. gondii life cycle, and its conditional depletion offers a method to study the sexual development of the parasite in vitro, and is proposed as an alternative to the requirement of T. gondii infections in cats.</p>',
			'date' => '2020-02-24',
			'pmid' => 'http://www.pubmed.gov/32094587',
			'doi' => '10.1038/s41564-020-0674-4',
			'modified' => '2020-03-20 17:27:25',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 95 => array(
			'id' => '3874',
			'name' => 'Recombination may occur in the absence of transcription in the immunoglobulin heavy chain recombination centre.',
			'authors' => 'Oudinet C, Braikia FZ, Dauba A, Khamlichi AA',
			'description' => '<p>Developing B cells undergo V(D)J recombination to generate a vast repertoire of Ig molecules. V(D)J recombination is initiated by the RAG1/RAG2 complex in recombination centres (RCs), where gene segments become accessible to the complex. Whether transcription is the causal factor of accessibility or whether it is a side product of other processes that generate accessibility remains a controversial issue. At the IgH locus, V(D)J recombination is controlled by E&mu; enhancer, which directs the transcriptional, epigenetic and recombinational events in the IgH RC. Deletion of E&mu; enhancer affects both transcription and recombination, making it difficult to conclude if E&mu; controls the two processes through the same or different mechanisms. By using a mouse line carrying a CpG-rich sequence upstream of E&mu; enhancer and analyzing transcription and recombination at the single-cell level, we found that recombination could occur in the RC in the absence of detectable transcription, suggesting that E&mu; controls transcription and recombination through distinct mechanisms. Moreover, while the normally E&mu;-dependent transcription and demethylating activities were impaired, recruitment of chromatin remodeling complexes was unaffected. RAG1 was efficiently recruited, thus compensating for the defective transcription-associated recruitment of RAG2, and providing a mechanistic basis for RAG1/RAG2 assembly to initiate V(D)J recombination.</p>',
			'date' => '2020-02-22',
			'pmid' => 'http://www.pubmed.gov/32086526',
			'doi' => '10.1093/nar/gkaa108',
			'modified' => '2020-03-20 17:40:41',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 96 => array(
			'id' => '3873',
			'name' => 'Inhibition of methyltransferase activity of enhancer of zeste 2 leads to enhanced lipid accumulation and altered chromatin status in zebrafish.',
			'authors' => 'den Broeder MJ, Ballangby J, Kamminga LM, Aleström P, Legler J, Lindeman LC, Kamstra JH',
			'description' => '<p>BACKGROUND: Recent studies indicate that exposure to environmental chemicals may increase susceptibility to developing metabolic diseases. This susceptibility may in part be caused by changes to the epigenetic landscape which consequently affect gene expression and lead to changes in lipid metabolism. The epigenetic modifier enhancer of zeste 2 (Ezh2) is a histone H3K27 methyltransferase implicated to play a role in lipid metabolism and adipogenesis. In this study, we used the zebrafish (Danio rerio) to investigate the role of Ezh2 on lipid metabolism and chromatin status following developmental exposure to the Ezh1/2 inhibitor PF-06726304 acetate. We used the environmental chemical tributyltin (TBT) as a positive control, as this chemical is known to act on lipid metabolism via EZH-mediated pathways in mammals. RESULTS: Zebrafish embryos (0-5&nbsp;days post-fertilization, dpf) exposed to non-toxic concentrations of PF-06726304 acetate (5&nbsp;&mu;M) and TBT (1&nbsp;nM) exhibited increased lipid accumulation. Changes in chromatin were analyzed by the assay for transposase-accessible chromatin sequencing (ATAC-seq) at 50% epiboly (5.5 hpf). We observed 349 altered chromatin regions, predominantly located at H3K27me3 loci and mostly more open chromatin in the exposed samples. Genes associated to these loci were linked to metabolic pathways. In addition, a selection of genes involved in lipid homeostasis, adipogenesis and genes specifically targeted by PF-06726304 acetate via altered chromatin accessibility were differentially expressed after TBT and PF-06726304 acetate exposure at 5 dpf, but not at 50% epiboly stage. One gene, cebpa, did not show a change in chromatin, but did show a change in gene expression at 5 dpf. Interestingly, underlying H3K27me3 marks were significantly decreased at this locus at 50% epiboly. CONCLUSIONS: Here, we show for the first time the applicability of ATAC-seq as a tool to investigate toxicological responses in zebrafish. Our analysis indicates that Ezh2 inhibition leads to a partial primed state of chromatin linked to metabolic pathways which results in gene expression changes later in development, leading to enhanced lipid accumulation. Although ATAC-seq seems promising, our in-depth assessment of the cebpa locus indicates that we need to consider underlying epigenetic marks as well.</p>',
			'date' => '2020-02-12',
			'pmid' => 'http://www.pubmed.gov/32051014',
			'doi' => '10.1186/s13072-020-0329-y',
			'modified' => '2020-03-20 17:42:02',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 97 => array(
			'id' => '3883',
			'name' => 'Targeting Macrophage Histone H3 Modification as a Leishmania Strategy to Dampen the NF-κB/NLRP3-Mediated Inflammatory Response.',
			'authors' => 'Lecoeur H, Prina E, Rosazza T, Kokou K, N'Diaye P, Aulner N, Varet H, Bussotti G, Xing Y, Milon G, Weil R, Meng G, Späth GF',
			'description' => '<p>Aberrant macrophage activation during intracellular infection generates immunopathologies that can cause severe human morbidity. A better understanding of immune subversion strategies and macrophage phenotypic and functional responses is necessary to design host-directed intervention strategies. Here, we uncover a fine-tuned transcriptional response that is induced in primary and lesional macrophages infected by the parasite Leishmania amazonensis and dampens NF-&kappa;B and NLRP3 inflammasome activation. Subversion is amastigote-specific and characterized by a decreased expression of activating and increased expression of de-activating components of these pro-inflammatory pathways, thus revealing a regulatory dichotomy that abrogates the anti-microbial response. Changes in transcript abundance correlate with histone H3K9/14 hypoacetylation and H3K4 hypo-trimethylation in infected primary and lesional macrophages at promoters of NF-&kappa;B-related, pro-inflammatory genes. Our results reveal a Leishmania immune subversion strategy targeting host cell epigenetic regulation to establish conditions beneficial for parasite survival and open avenues for host-directed, anti-microbial drug discovery.</p>',
			'date' => '2020-02-11',
			'pmid' => 'http://www.pubmed.gov/32049017',
			'doi' => '10.1016/j.celrep.2020.01.030',
			'modified' => '2020-03-20 17:29:47',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 98 => array(
			'id' => '3868',
			'name' => 'Replicational Dilution of H3K27me3 in Mammalian Cells and the Role of Poised Promoters.',
			'authors' => 'Jadhav U, Manieri E, Nalapareddy K, Madha S, Chakrabarti S, Wucherpfennig K, Barefoot M, Shivdasani RA',
			'description' => '<p>Polycomb repressive complex 2 (PRC2) places H3K27me3 at developmental genes and is causally implicated in keeping bivalent genes silent. It is unclear if that silence requires minimum H3K27me3 levels and how the mark transmits faithfully across mammalian somatic cell generations. Mouse intestinal cells lacking EZH2 methyltransferase reduce H3K27me3 proportionately at all PRC2 target sites, but &sim;40% uniform residual levels keep target genes inactive. These genes, derepressed in PRC2-null villus cells, remain silent in intestinal stem cells (ISCs). Quantitative chromatin immunoprecipitation and computational modeling indicate that because unmodified histones dilute H3K27me3 by 50% each time DNA replicates, PRC2-deficient ISCs initially retain sufficient H3K27me3 to avoid gene derepression. EZH2 mutant human lymphoma cells also require multiple divisions before H3K27me3 dilution relieves gene silencing. In both cell types, promoters with high basal H3K4me2/3 activate in spite of some residual H3K27me3, compared to less-poised promoters. These findings have implications for PRC2 inhibition in cancer therapy.</p>',
			'date' => '2020-01-29',
			'pmid' => 'http://www.pubmed.gov/32027840',
			'doi' => '10.1016/j.molcel.2020.01.017',
			'modified' => '2020-03-20 17:46:30',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 99 => array(
			'id' => '3848',
			'name' => 'A comprehensive epigenomic analysis of phenotypically distinguishable, genetically identical female and male Daphnia pulex.',
			'authors' => 'Kvist J, Athanàsio CG, Pfrender ME, Brown JB, Colbourne JK, Mirbahai L',
			'description' => '<p>BACKGROUND: Daphnia species reproduce by cyclic parthenogenesis involving both sexual and asexual reproduction. The sex of the offspring is environmentally determined and mediated via endocrine signalling by the mother. Interestingly, male and female Daphnia can be genetically identical, yet display large differences in behaviour, morphology, lifespan and metabolic activity. Our goal was to integrate multiple omics datasets, including gene expression, splicing, histone modification and DNA methylation data generated from genetically identical female and male Daphnia pulex under controlled laboratory settings with the aim of achieving a better understanding of the underlying epigenetic factors that may contribute to the phenotypic differences observed between the two genders. RESULTS: In this study we demonstrate that gene expression level is positively correlated with increased DNA methylation, and histone H3 trimethylation at lysine&thinsp;4 (H3K4me3) at predicted promoter regions. Conversely, elevated histone H3 trimethylation at lysine&thinsp;27 (H3K27me3), distributed across the entire transcript length, is negatively correlated with gene expression level. Interestingly, male Daphnia are dominated with epigenetic modifications that globally promote elevated gene expression, while female Daphnia are dominated with epigenetic modifications that reduce gene expression globally. For examples, CpG methylation (positively correlated with gene expression level) is significantly higher in almost all differentially methylated sites in male compared to female Daphnia. Furthermore, H3K4me3 modifications are higher in male compared to female Daphnia in more than 3/4 of the differentially regulated promoters. On the other hand, H3K27me3 is higher in female compared to male Daphnia in more than 5/6 of differentially modified sites. However, both sexes demonstrate roughly equal number of genes that are up-regulated in one gender compared to the other sex. Since, gene expression analyses typically assume that most genes are expressed at equal level among samples and different conditions, and thus cannot detect global changes affecting most genes. CONCLUSIONS: The epigenetic differences between male and female in Daphnia pulex are vast and dominated by changes that promote elevated gene expression in male Daphnia. Furthermore, the differences observed in both gene expression changes and epigenetic modifications between the genders relate to pathways that are physiologically relevant to the observed phenotypic differences.</p>',
			'date' => '2020-01-06',
			'pmid' => 'http://www.pubmed.gov/31906859',
			'doi' => '10.1186/s12864-019-6415-5',
			'modified' => '2020-02-20 11:34:47',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 100 => array(
			'id' => '3802',
			'name' => 'Analysis of Histone Modifications in Rodent Pancreatic Islets by Native Chromatin Immunoprecipitation.',
			'authors' => 'Sandovici I, Nicholas LM, O'Neill LP',
			'description' => '<p>The islets of Langerhans are clusters of cells dispersed throughout the pancreas that produce several hormones essential for controlling a variety of metabolic processes, including glucose homeostasis and lipid metabolism. Studying the transcriptional control of pancreatic islet cells has important implications for understanding the mechanisms that control their normal development, as well as the pathogenesis of metabolic diseases such as diabetes. Histones represent the main protein components of the chromatin and undergo diverse covalent modifications that are very important for gene regulation. Here we describe the isolation of pancreatic islets from rodents and subsequently outline the methods used to immunoprecipitate and analyze the native chromatin obtained from these cells.</p>',
			'date' => '2020-01-01',
			'pmid' => 'http://www.pubmed.gov/31586329',
			'doi' => '10.1007/978-1-4939-9882-1',
			'modified' => '2019-12-05 11:28:01',
			'created' => '2019-12-02 15:25:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 101 => array(
			'id' => '4096',
			'name' => 'Changes in H3K27ac at Gene Regulatory Regions in Porcine AlveolarMacrophages Following LPS or PolyIC Exposure.',
			'authors' => 'Herrera-Uribe, Juber and Liu, Haibo and Byrne, Kristen A and Bond, Zahra Fand Loving, Crystal L and Tuggle, Christopher K',
			'description' => '<p>Changes in chromatin structure, especially in histone modifications (HMs), linked with chromatin accessibility for transcription machinery, are considered to play significant roles in transcriptional regulation. Alveolar macrophages (AM) are important immune cells for protection against pulmonary pathogens, and must readily respond to bacteria and viruses that enter the airways. Mechanism(s) controlling AM innate response to different pathogen-associated molecular patterns (PAMPs) are not well defined in pigs. By combining RNA sequencing (RNA-seq) with chromatin immunoprecipitation and sequencing (ChIP-seq) for four histone marks (H3K4me3, H3K4me1, H3K27ac and H3K27me3), we established a chromatin state map for AM stimulated with two different PAMPs, lipopolysaccharide (LPS) and Poly(I:C), and investigated the potential effect of identified histone modifications on transcription factor binding motif (TFBM) prediction and RNA abundance changes in these AM. The integrative analysis suggests that the differential gene expression between non-stimulated and stimulated AM is significantly associated with changes in the H3K27ac level at active regulatory regions. Although global changes in chromatin states were minor after stimulation, we detected chromatin state changes for differentially expressed genes involved in the TLR4, TLR3 and RIG-I signaling pathways. We found that regions marked by H3K27ac genome-wide were enriched for TFBMs of TF that are involved in the inflammatory response. We further documented that TF whose expression was induced by these stimuli had TFBMs enriched within H3K27ac-marked regions whose chromatin state changed by these same stimuli. Given that the dramatic transcriptomic changes and minor chromatin state changes occurred in response to both stimuli, we conclude that regulatory elements (i.e. active promoters) that contain transcription factor binding motifs were already active/poised in AM for immediate inflammatory response to PAMPs. In summary, our data provides the first chromatin state map of porcine AM in response to bacterial and viral PAMPs, contributing to the Functional Annotation of Animal Genomes (FAANG) project, and demonstrates the role of HMs, especially H3K27ac, in regulating transcription in AM in response to LPS and Poly(I:C).</p>',
			'date' => '2020-01-01',
			'pmid' => 'https://www.frontiersin.org/articles/10.3389/fgene.2020.00817/full',
			'doi' => '10.3389/fgene.2020.00817',
			'modified' => '2021-03-17 17:22:56',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 102 => array(
			'id' => '3839',
			'name' => 'Functionally Annotating Regulatory Elements in the Equine Genome Using Histone Mark ChIP-Seq.',
			'authors' => 'Kingsley NB, Kern C, Creppe C, Hales EN, Zhou H, Kalbfleisch TS, MacLeod JN, Petersen JL, Finno CJ, Bellone RR',
			'description' => '<p>One of the primary aims of the Functional Annotation of ANimal Genomes (FAANG) initiative is to characterize tissue-specific regulation within animal genomes. To this end, we used chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to map four histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me3) in eight prioritized tissues collected as part of the FAANG equine biobank from two thoroughbred mares. Data were generated according to optimized experimental parameters developed during quality control testing. To ensure that we obtained sufficient ChIP and successful peak-calling, data and peak-calls were assessed using six quality metrics, replicate comparisons, and site-specific evaluations. Tissue specificity was explored by identifying binding motifs within unique active regions, and motifs were further characterized by gene ontology (GO) and protein-protein interaction analyses. The histone marks identified in this study represent some of the first resources for tissue-specific regulation within the equine genome. As such, these publicly available annotation data can be used to advance equine studies investigating health, performance, reproduction, and other traits of economic interest in the horse.</p>',
			'date' => '2019-12-18',
			'pmid' => 'http://www.pubmed.gov/31861495',
			'doi' => '10.3390/genes11010003',
			'modified' => '2020-02-20 11:20:25',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 103 => array(
			'id' => '3837',
			'name' => 'H3K4me1 Supports Memory-like NK Cells Induced by Systemic Inflammation.',
			'authors' => 'Rasid O, Chevalier C, Camarasa TM, Fitting C, Cavaillon JM, Hamon MA',
			'description' => '<p>Natural killer (NK) cells are unique players in innate immunity and, as such, an attractive target for immunotherapy. NK cells display immune memory properties in certain models, but the long-term status of NK cells following systemic inflammation is unknown. Here we show that following LPS-induced endotoxemia in mice, NK cells acquire cell-intrinsic memory-like properties, showing increased production of IFN&gamma; upon specific secondary stimulation. The NK cell memory response is detectable for at least 9&nbsp;weeks and contributes to protection from E.&nbsp;coli infection upon adoptive transfer. Importantly, we reveal a mechanism essential for NK cell memory, whereby an H3K4me1-marked latent enhancer is uncovered at the ifng locus. Chemical inhibition of histone methyltransferase activity erases the enhancer and abolishes NK cell memory. Thus, NK cell memory develops after endotoxemia in a histone methylation-dependent manner, ensuring a heightened response to secondary stimulation.</p>',
			'date' => '2019-12-17',
			'pmid' => 'http://www.pubmed.gov/31851924',
			'doi' => '10.1016/j.celrep.2019.11.043',
			'modified' => '2020-02-20 11:24:10',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 104 => array(
			'id' => '3830',
			'name' => 'Trained immunity modulates inflammation-induced fibrosis.',
			'authors' => 'Jeljeli M, Riccio LGC, Doridot L, Chêne C, Nicco C, Chouzenoux S, Deletang Q, Allanore Y, Kavian N, Batteux F',
			'description' => '<p>Chronic inflammation and fibrosis can result from inappropriately activated immune responses that are mediated by macrophages. Macrophages can acquire memory-like characteristics in response to antigen exposure. Here, we show the effect of BCG or low-dose LPS stimulation on macrophage phenotype, cytokine production, chromatin and metabolic modifications. Low-dose LPS training alleviates fibrosis and inflammation in a mouse model of systemic sclerosis (SSc), whereas BCG-training exacerbates disease in this model. Adoptive transfer of low-dose LPS-trained or BCG-trained macrophages also has beneficial or harmful effects, respectively. Furthermore, coculture with low-dose LPS trained macrophages reduces the fibro-inflammatory profile of fibroblasts from mice and patients with SSc, indicating that trained immunity might be a phenomenon that can be targeted to treat SSc and other autoimmune and inflammatory fibrotic disorders.</p>',
			'date' => '2019-12-11',
			'pmid' => 'http://www.pubmed.gov/31827093',
			'doi' => '10.1038/s41467-019-13636-x',
			'modified' => '2020-02-25 13:32:01',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 105 => array(
			'id' => '3826',
			'name' => 'MicroRNA-708 is a novel regulator of the Hoxa9 program in myeloid cells.',
			'authors' => 'Schneider E, Pochert N, Ruess C, MacPhee L, Escano L, Miller C, Krowiorz K, Delsing Malmberg E, Heravi-Moussavi A, Lorzadeh A, Ashouri A, Grasedieck S, Sperb N, Kumar Kopparapu P, Iben S, Staffas A, Xiang P, Rösler R, Kanduri M, Larsson E, Fogelstrand L, ',
			'description' => '<p>MicroRNAs (miRNAs) are commonly deregulated in acute myeloid leukemia (AML), affecting critical genes not only through direct targeting, but also through modulation of downstream effectors. Homeobox (Hox) genes balance self-renewal, proliferation, cell death, and differentiation in many tissues and aberrant Hox gene expression can create a predisposition to leukemogenesis in hematopoietic cells. However, possible linkages between the regulatory pathways of Hox genes and miRNAs are not yet fully resolved. We identified miR-708 to be upregulated in Hoxa9/Meis1 AML inducing cell lines as well as in AML patients. We further showed Meis1 directly targeting miR-708 and modulating its expression through epigenetic transcriptional regulation. CRISPR/Cas9 mediated knockout of miR-708 in Hoxa9/Meis1 cells delayed disease onset in vivo, demonstrating for the first time a pro-leukemic contribution of miR-708 in this context. Overexpression of miR-708 however strongly impeded Hoxa9 mediated transformation and homing capacity in vivo through modulation of adhesion factors and induction of myeloid differentiation. Taken together, we reveal miR-708, a putative tumor suppressor miRNA and direct target of Meis1, as a potent antagonist of the Hoxa9 phenotype but an effector of transformation in Hoxa9/Meis1. This unexpected finding highlights the yet unexplored role of miRNAs as indirect regulators of the Hox program during normal and aberrant hematopoiesis.</p>',
			'date' => '2019-11-25',
			'pmid' => 'http://www.pubmed.gov/31768018',
			'doi' => '10.1038/s41375-019-0651-1',
			'modified' => '2020-02-25 13:36:10',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 106 => array(
			'id' => '3807',
			'name' => 'Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.',
			'authors' => 'Aloia L, McKie MA, Vernaz G, Cordero-Espinoza L, Aleksieva N, van den Ameele J, Antonica F, Font-Cunill B, Raven A, Aiese Cigliano R, Belenguer G, Mort RL, Brand AH, Zernicka-Goetz M, Forbes SJ, Miska EA, Huch M',
			'description' => '<p>Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal cells. However, the molecular mechanisms by which adult ductal-committed cells acquire cellular plasticity, initiate organoids and regenerate the damaged tissue remain largely unknown. Here, we describe that ductal cells undergo a transient, genome-wide, remodelling of their transcriptome and epigenome during organoid initiation and in vivo following tissue damage. TET1-mediated hydroxymethylation licences differentiated ductal cells to initiate organoids and activate the regenerative programme through the transcriptional regulation of stem-cell genes and regenerative pathways including the YAP-Hippo signalling. Our results argue in favour of the remodelling of genomic methylome/hydroxymethylome landscapes as a general mechanism by which differentiated cells exit a committed state in response to tissue damage.</p>',
			'date' => '2019-11-04',
			'pmid' => 'http://www.pubmed.gov/31685987',
			'doi' => '10.1038/s41556-019-0402-6',
			'modified' => '2019-12-05 11:19:34',
			'created' => '2019-12-02 15:25:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 107 => array(
			'id' => '3824',
			'name' => 'Transcriptional alterations in glioma result primarily from DNA methylation-independent mechanisms.',
			'authors' => 'Court F, Le Boiteux E, Fogli A, Müller-Barthélémy M, Vaurs-Barrière C, Chautard E, Pereira B, Biau J, Kemeny JL, Khalil T, Karayan-Tapon L, Verrelle P, Arnaud P',
			'description' => '<p>In cancer cells, aberrant DNA methylation is commonly associated with transcriptional alterations, including silencing of tumor suppressor genes. However, multiple epigenetic mechanisms, including polycomb repressive marks, contribute to gene deregulation in cancer. To dissect the relative contribution of DNA methylation-dependent and -independent mechanisms to transcriptional alterations at CpG island/promoter-associated genes in cancer, we studied 70 samples of adult glioma, a widespread type of brain tumor, classified according to their isocitrate dehydrogenase () mutation status. We found that most transcriptional alterations in tumor samples were DNA methylation-independent. Instead, altered histone H3 trimethylation at lysine 27 (H3K27me3) was the predominant molecular defect at deregulated genes. Our results also suggest that the presence of a bivalent chromatin signature at CpG island promoters in stem cells predisposes not only to hypermethylation, as widely documented, but more generally to all types of transcriptional alterations in transformed cells. In addition, the gene expression strength in healthy brain cells influences the choice between DNA methylation- and H3K27me3-associated silencing in glioma. Highly expressed genes were more likely to be repressed by H3K27me3 than by DNA methylation. Our findings support a model in which altered H3K27me3 dynamics, more specifically defects in the interplay between polycomb protein complexes and the brain-specific transcriptional machinery, is the main cause of transcriptional alteration in glioma cells. Our study provides the first comprehensive description of epigenetic changes in glioma and their relative contribution to transcriptional changes. It may be useful for the design of drugs targeting cancer-related epigenetic defects.</p>',
			'date' => '2019-10-01',
			'pmid' => 'http://www.pubmed.gov/31533980',
			'doi' => '10.1101/gr.249219.119.',
			'modified' => '2020-02-25 13:41:40',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 108 => array(
			'id' => '3781',
			'name' => 'Functional analyses of a low-penetrance risk variant rs6702619/1p21.2 associating with colorectal cancer in Polish population.',
			'authors' => 'Statkiewicz M, Maryan N, Kulecka M, Kuklinska U, Ostrowski J, Mikula M',
			'description' => '<p>Several studies employed the genome-wide association (GWA) analysis of single-nucleotide polymorphisms (SNPs) to identify susceptibility regions in colorectal cancer (CRC). However, the functional studies exploring the role of associating SNPs with cancer biology are limited. Herein, using chromatin immunoprecipitation assay (ChIP), reporter assay and chromosome conformation capture sequencing (3C-Seq) augmented with publically available genomic and epigenomic databases we aimed to define the function of rs6702619/1p21.2 region associated with CRC in the Polish population. Using ChIP we confirmed that rs6702619 region is occupied by a CTCF, a master regulator of long-range genomic interactions, and is decorated with enhancer-like histone modifications. The enhancer blocking assay revealed that rs6702619 region acts as an insulator with activity dependent on the SNP genotype. Finally, a 3C-Seq survey indicated more than a hundred loci in the rs6702619 locus interactome, including GNAS gene that is frequently amplified in CRC. Taken together, we showed that the CRC-associated rs6702619 region has in vitro and in vivo properties of an insulator that demonstrates long-range physical interactions with CRC-relevant loci.</p>',
			'date' => '2019-09-17',
			'pmid' => 'http://www.pubmed.gov/31531420',
			'doi' => '10.1093/nar/gkm875.',
			'modified' => '2019-10-02 16:51:42',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 109 => array(
			'id' => '3776',
			'name' => 'β-Glucan-Induced Trained Immunity Protects against Leishmania braziliensis Infection: a Crucial Role for IL-32.',
			'authors' => 'Dos Santos JC, Barroso de Figueiredo AM, Teodoro Silva MV, Cirovic B, de Bree LCJ, Damen MSMA, Moorlag SJCFM, Gomes RS, Helsen MM, Oosting M, Keating ST, Schlitzer A, Netea MG, Ribeiro-Dias F, Joosten LAB',
			'description' => '<p>American tegumentary leishmaniasis is a vector-borne parasitic disease caused by Leishmania protozoans. Innate immune cells undergo long-term functional reprogramming in response to infection or Bacillus Calmette-Gu&eacute;rin (BCG) vaccination via a process called trained immunity, conferring non-specific protection from secondary infections. Here, we demonstrate that monocytes trained with the fungal cell wall component &beta;-glucan confer enhanced protection against infections caused by Leishmania braziliensis through the enhanced production of proinflammatory cytokines. Mechanistically, this augmented immunological response is dependent on increased expression of interleukin 32 (IL-32). Studies performed using a humanized IL-32 transgenic mouse highlight the clinical implications of these findings in&nbsp;vivo. This study represents a definitive characterization of the role of IL-32&gamma; in the trained phenotype induced by &beta;-glucan or BCG, the results of which improve our understanding of the molecular mechanisms governing trained immunity and Leishmania infection control.</p>',
			'date' => '2019-09-03',
			'pmid' => 'http://www.pubmed.gov/31484076',
			'doi' => '10.1016/j.celrep.2019.08.004',
			'modified' => '2019-10-02 17:00:49',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 110 => array(
			'id' => '3774',
			'name' => 'Reactivation of super-enhancers by KLF4 in human Head and Neck Squamous Cell Carcinoma.',
			'authors' => 'Tsompana M, Gluck C, Sethi I, Joshi I, Bard J, Nowak NJ, Sinha S, Buck MJ',
			'description' => '<p>Head and neck squamous cell carcinoma (HNSCC) is a disease of significant morbidity and mortality and rarely diagnosed in early stages. Despite extensive genetic and genomic characterization, targeted therapeutics and diagnostic markers of HNSCC are lacking due to the inherent heterogeneity and complexity of the disease. Herein, we have generated the global histone mark based epigenomic and transcriptomic cartogram of SCC25, a representative cell type of mesenchymal HNSCC and its normal oral keratinocyte counterpart. Examination of genomic regions marked by differential chromatin states and associated with misregulated gene expression led us to identify SCC25 enriched regulatory sequences and transcription factors (TF) motifs. These findings were further strengthened by ATAC-seq based open chromatin and TF footprint analysis which unearthed Kr&uuml;ppel-like Factor 4 (KLF4) as a potential key regulator of the SCC25 cistrome. We reaffirm the results obtained from in silico and chromatin studies in SCC25 by ChIP-seq of KLF4 and identify &Delta;Np63 as a co-oncogenic driver of the cancer-specific gene expression milieu. Taken together, our results lead us to propose a model where elevated KLF4 levels sustains the oncogenic state of HNSCC by reactivating repressed chromatin domains at key downstream genes, often by targeting super-enhancers.</p>',
			'date' => '2019-09-02',
			'pmid' => 'http://www.pubmed.gov/31477832',
			'doi' => '10.1038/s41388-019-0990-4',
			'modified' => '2019-10-02 17:05:36',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 111 => array(
			'id' => '3777',
			'name' => 'Nucleome Dynamics during Retinal Development.',
			'authors' => 'Norrie JL, Lupo MS, Xu B, Al Diri I, Valentine M, Putnam D, Griffiths L, Zhang J, Johnson D, Easton J, Shao Y, Honnell V, Frase S, Miller S, Stewart V, Zhou X, Chen X, Dyer MA',
			'description' => '<p>More than 8,000 genes are turned on or off as progenitor cells produce the 7 classes of retinal cell types during development. Thousands of enhancers are also active in the developing retinae, many having features of cell- and developmental stage-specific activity. We studied dynamic changes in the 3D chromatin landscape important for precisely orchestrated changes in gene expression during retinal development by ultra-deep in situ Hi-C analysis on murine retinae. We identified developmental-stage-specific changes in chromatin compartments and enhancer-promoter interactions. We developed a machine learning-based algorithm to map euchromatin and heterochromatin domains genome-wide and overlaid it with chromatin compartments identified by Hi-C. Single-cell ATAC-seq and RNA-seq were integrated with our Hi-C and previous ChIP-seq data to identify cell- and developmental-stage-specific super-enhancers (SEs). We identified a bipolar neuron-specific core regulatory circuit SE upstream of Vsx2, whose deletion in mice led to the loss of bipolar neurons.</p>',
			'date' => '2019-08-21',
			'pmid' => 'http://www.pubmed.gov/31493975',
			'doi' => '10.1016/j.neuron.2019.08.002',
			'modified' => '2019-10-02 16:58:50',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 112 => array(
			'id' => '3742',
			'name' => 'Development and epigenetic plasticity of murine Müller glia.',
			'authors' => 'Dvoriantchikova G, Seemungal RJ, Ivanov D',
			'description' => '<p>The ability to regenerate the entire retina and restore lost sight after injury is found in some species and relies mostly on the epigenetic plasticity of M&uuml;ller glia. To understand the role of mammalian M&uuml;ller glia as a source of progenitors for retinal regeneration, we investigated changes in gene expression during differentiation of retinal progenitor cells (RPCs) into M&uuml;ller glia. We also analyzed the global epigenetic profile of adult M&uuml;ller glia. We observed significant changes in gene expression during differentiation of RPCs into M&uuml;ller glia in only a small group of genes. We found a high similarity between RPCs and M&uuml;ller glia on the transcriptomic and epigenomic levels. Our findings also indicate that M&uuml;ller glia are epigenetically very close to late-born retinal neurons, but not early-born retinal neurons. Importantly, we found that key genes required for phototransduction were highly methylated. Thus, our data suggest that M&uuml;ller glia are epigenetically very similar to late RPCs. Meanwhile, obstacles for regeneration of the entire mammalian retina from M&uuml;ller glia may consist of repressive chromatin and highly methylated DNA in the promoter regions of many genes required for the development of early-born retinal neurons. In addition, DNA demethylation may be required for proper reprogramming and differentiation of M&uuml;ller glia into rod photoreceptors.</p>
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			'date' => '2019-07-02',
			'pmid' => 'http://www.pubmed.gov/31276697',
			'doi' => '10.1016/j.bbamcr.2019.06.019',
			'modified' => '2019-08-13 10:50:24',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 113 => array(
			'id' => '3754',
			'name' => 'The alarmin S100A9 hampers osteoclast differentiation from human circulating precursors by reducing the expression of RANK.',
			'authors' => 'Di Ceglie I, Blom AB, Davar R, Logie C, Martens JHA, Habibi E, Böttcher LM, Roth J, Vogl T, Goodyear CS, van der Kraan PM, van Lent PL, van den Bosch MH',
			'description' => '<p>The alarmin S100A8/A9 is implicated in sterile inflammation-induced bone resorption and has been shown to increase the bone-resorptive capacity of mature osteoclasts. Here, we investigated the effects of S100A9 on osteoclast differentiation from human CD14 circulating precursors. Hereto, human CD14 monocytes were isolated and differentiated toward osteoclasts with M-CSF and receptor activator of NF-&kappa;B (RANK) ligand (RANKL) in the presence or absence of S100A9. Tartrate-resistant acid phosphatase staining showed that exposure to S100A9 during monocyte-to-osteoclast differentiation strongly decreased the numbers of multinucleated osteoclasts. This was underlined by a decreased resorption of a hydroxyapatite-like coating. The thus differentiated cells showed a high mRNA and protein production of proinflammatory factors after 16 h of exposure. In contrast, at d 4, the cells showed a decreased production of the osteoclast-promoting protein TNF-&alpha;. Interestingly, S100A9 exposure during the first 16 h of culture only was sufficient to reduce osteoclastogenesis. Using fluorescently labeled RANKL, we showed that, within this time frame, S100A9 inhibited the M-CSF-mediated induction of RANK. Chromatin immunoprecipitation showed that this was associated with changes in various histone marks at the epigenetic level. This S100A9-induced reduction in RANK was in part recovered by blocking TNF-&alpha; but not IL-1. Together, our data show that S100A9 impedes monocyte-to-osteoclast differentiation, probably a reduction in RANK expression.-Di Ceglie, I., Blom, A. B., Davar, R., Logie, C., Martens, J. H. A., Habibi, E., B&ouml;ttcher, L.-M., Roth, J., Vogl, T., Goodyear, C. S., van der Kraan, P. M., van Lent, P. L., van den Bosch, M. H. The alarmin S100A9 hampers osteoclast differentiation from human circulating precursors by reducing the expression of RANK.</p>',
			'date' => '2019-06-14',
			'pmid' => 'http://www.pubmed.gov/31199668',
			'doi' => '10.1096/fj.201802691RR',
			'modified' => '2019-10-03 12:20:02',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 114 => array(
			'id' => '3737',
			'name' => 'Probing the Tumor Suppressor Function of BAP1 in CRISPR-Engineered Human Liver Organoids.',
			'authors' => 'Artegiani B, van Voorthuijsen L, Lindeboom RGH, Seinstra D, Heo I, Tapia P, López-Iglesias C, Postrach D, Dayton T, Oka R, Hu H, van Boxtel R, van Es JH, Offerhaus J, Peters PJ, van Rheenen J, Vermeulen M, Clevers H',
			'description' => '<p>The deubiquitinating enzyme BAP1 is a tumor suppressor, among others involved in cholangiocarcinoma. BAP1 has many proposed molecular targets, while its Drosophila homolog is known to deubiquitinate histone H2AK119. We introduce BAP1 loss-of-function by CRISPR/Cas9 in normal human cholangiocyte organoids. We find that BAP1 controls&nbsp;the expression of junctional and cytoskeleton components by regulating chromatin accessibility. Consequently, we observe loss of multiple epithelial characteristics while motility increases. Importantly, restoring the catalytic activity of BAP1 in the nucleus rescues these cellular and molecular changes. We engineer human liver organoids to combine four common cholangiocarcinoma mutations (TP53, PTEN, SMAD4, and NF1). In this genetic background, BAP1 loss results in acquisition of malignant features upon xenotransplantation. Thus, control of epithelial identity through the regulation of chromatin accessibility appears to be a key aspect of BAP1's tumor suppressor function. Organoid technology combined with CRISPR/Cas9 provides an experimental platform for mechanistic studies of cancer gene function in a human context.</p>',
			'date' => '2019-06-06',
			'pmid' => 'http://www.pubmed.gov/31130514',
			'doi' => '10.1016/j.stem.2019.04.017',
			'modified' => '2019-08-06 16:58:50',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 115 => array(
			'id' => '3713',
			'name' => 'Complementary Activity of ETV5, RBPJ, and TCF3 Drives Formative Transition from Naive Pluripotency.',
			'authors' => 'Kalkan T, Bornelöv S, Mulas C, Diamanti E, Lohoff T, Ralser M, Middelkamp S, Lombard P, Nichols J, Smith A',
			'description' => '<p>The gene regulatory network (GRN) of naive mouse embryonic stem cells (ESCs) must be reconfigured to enable lineage commitment. TCF3 sanctions rewiring by suppressing components of the ESC transcription factor circuitry. However, TCF3 depletion only delays and does not prevent transition to formative pluripotency. Here, we delineate additional contributions of the ETS-family transcription factor ETV5 and the repressor RBPJ. In response to ERK signaling, ETV5 switches activity from supporting self-renewal and undergoes genome relocation linked to commissioning of enhancers activated in formative epiblast. Independent upregulation of RBPJ prevents re-expression of potent naive factors, TBX3 and NANOG, to secure exit from the naive state. Triple deletion of Etv5, Rbpj, and Tcf3 disables ESCs, such that they remain largely undifferentiated and locked in self-renewal, even in the presence of differentiation stimuli. Thus, genetic elimination of three complementary drivers of network transition stalls developmental progression, emulating environmental insulation by small-molecule inhibitors.</p>',
			'date' => '2019-05-02',
			'pmid' => 'http://www.pubmed.gov/31031137',
			'doi' => '10.1016/j.stem.2019.03.017',
			'modified' => '2019-07-05 14:28:38',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 116 => array(
			'id' => '3692',
			'name' => 'PML modulates H3.3 targeting to telomeric and centromeric repeats in mouse fibroblasts.',
			'authors' => 'Spirkoski J, Shah A, Reiner AH, Collas P, Delbarre E',
			'description' => '<p>Targeted deposition of histone variant H3.3 into chromatin is paramount for proper regulation of chromatin integrity, particularly in heterochromatic regions including repeats. We have recently shown that the promyelocytic leukemia (PML) protein prevents H3.3 from being deposited in large heterochromatic PML-associated domains (PADs). However, to what extent PML modulates H3.3 loading on chromatin in other areas of the genome remains unexplored. Here, we examined the impact of PML on targeting of H3.3 to genes and repeat regions that reside outside PADs. We show that loss of PML increases H3.3 deposition in subtelomeric, telomeric, pericentric and centromeric repeats in mouse embryonic fibroblasts, while other repeat classes are not affected. Expression of major satellite, minor satellite and telomeric non-coding transcripts is altered in Pml-null cells. In particular, telomeric Terra transcripts are strongly upregulated, in concordance with a marked reduction in H4K20me3 at these sites. Lastly, for most genes H3.3 enrichment or gene expression outcomes are independent of PML. Our data argue towards the importance of a PML-H3.3 axis in preserving a heterochromatin state at centromeres and telomeres.</p>',
			'date' => '2019-04-16',
			'pmid' => 'http://www.pubmed.gov/30850162',
			'doi' => '10.1016/j.bbrc.2019.02.087',
			'modified' => '2019-06-28 13:50:40',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 117 => array(
			'id' => '3711',
			'name' => 'Long intergenic non-coding RNAs regulate human lung fibroblast function: Implications for idiopathic pulmonary fibrosis.',
			'authors' => 'Hadjicharalambous MR, Roux BT, Csomor E, Feghali-Bostwick CA, Murray LA, Clarke DL, Lindsay MA',
			'description' => '<p>Phenotypic changes in lung fibroblasts are believed to contribute to the development of Idiopathic Pulmonary Fibrosis (IPF), a progressive and fatal lung disease. Long intergenic non-coding RNAs (lincRNAs) have been identified as novel regulators of gene expression and protein activity. In non-stimulated cells, we observed reduced proliferation and inflammation but no difference in the fibrotic response of IPF fibroblasts. These functional changes in non-stimulated cells were associated with changes in the expression of the histone marks, H3K4me1, H3K4me3 and H3K27ac indicating a possible involvement of epigenetics. Following activation with TGF-&beta;1 and IL-1&beta;, we demonstrated an increased fibrotic but reduced inflammatory response in IPF fibroblasts. There was no significant difference in proliferation following PDGF exposure. The lincRNAs, LINC00960 and LINC01140 were upregulated in IPF fibroblasts. Knockdown studies showed that LINC00960 and LINC01140 were positive regulators of proliferation in both control and IPF fibroblasts but had no effect upon the fibrotic response. Knockdown of LINC01140 but not LINC00960 increased the inflammatory response, which was greater in IPF compared to control fibroblasts. Overall, these studies demonstrate for the first time that lincRNAs are important regulators of proliferation and inflammation in human lung fibroblasts and that these might mediate the reduced inflammatory response observed in IPF-derived fibroblasts.</p>',
			'date' => '2019-04-15',
			'pmid' => 'http://www.pubmed.gov/30988425',
			'doi' => '10.1038/s41598-019-42292-w',
			'modified' => '2019-07-05 14:31:28',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 118 => array(
			'id' => '3702',
			'name' => 'Identification of ADGRE5 as discriminating MYC target between Burkitt lymphoma and diffuse large B-cell lymphoma.',
			'authors' => 'Kleo K, Dimitrova L, Oker E, Tomaszewski N, Berg E, Taruttis F, Engelmann JC, Schwarzfischer P, Reinders J, Spang R, Gronwald W, Oefner PJ, Hummel M',
			'description' => '<p>BACKGROUND: MYC is a heterogeneously expressed transcription factor that plays a multifunctional role in many biological processes such as cell proliferation and differentiation. It is also associated with many types of cancer including the malignant lymphomas. There are two types of aggressive B-cell lymphoma, namely Burkitt lymphoma (BL) and a subgroup of diffuse large cell lymphoma (DLBCL), which both carry MYC translocations and overexpress MYC but both differ significantly in their clinical outcome. In DLBCL, MYC translocations are associated with an aggressive behavior and poor outcome, whereas MYC-positive BL show a superior outcome. METHODS: To shed light on this phenomenon, we investigated the different modes of actions of MYC in aggressive B-cell lymphoma cell lines subdivided into three groups: (i) MYC-positive BL, (ii) DLBCL with MYC translocation (DLBCLpos) and (iii) DLBCL without MYC translocation (DLBCLneg) for control. In order to identify genome-wide MYC-DNA binding sites a chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) was performed. In addition, ChIP-Seq for H3K4me3 was used for determination of genomic regions accessible for transcriptional activity. These data were supplemented with gene expression data derived from RNA-Seq. RESULTS: Bioinformatics integration of all data sets revealed different MYC-binding patterns and transcriptional profiles in MYC-positive BL and DLBCL cell lines indicating different functional roles of MYC for gene regulation in aggressive B-cell lymphomas. Based on this multi-omics analysis we identified ADGRE5 (alias CD97) - a member of the EGF-TM7 subfamily of adhesion G protein-coupled receptors - as a MYC target gene, which is specifically expressed in BL but not in DLBCL regardless of MYC translocation. CONCLUSION: Our study describes a diverse genome-wide MYC-DNA binding pattern in BL and DLBCL cell lines with and without MYC translocations. Furthermore, we identified ADREG5 as a MYC target gene able to discriminate between BL and DLBCL irrespectively of the presence of MYC breaks in DLBCL. Since ADGRE5 plays an important role in tumor cell formation, metastasis and invasion, it might also be instrumental to better understand the different pathobiology of BL and DLBCL and help to explain discrepant clinical characteristics of BL and DLBCL.</p>',
			'date' => '2019-04-05',
			'pmid' => 'http://www.pubmed.gov/30953469',
			'doi' => '10.1186/s12885-019-5537-0',
			'modified' => '2019-07-05 14:41:38',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 119 => array(
			'id' => '3732',
			'name' => 'Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis.',
			'authors' => 'Mallaney C, Ostrander EL, Celik H, Kramer AC, Martens A, Kothari A, Koh WK, Haussler E, Iwamori N, Gontarz P, Zhang B, Challen GA',
			'description' => '<p>The histone demethylase KDM6B (JMJD3) is upregulated in blood disorders, suggesting that it may have important pathogenic functions. Here we examined the function of Kdm6b in hematopoietic stem cells (HSC) to evaluate its potential as a therapeutic target. Loss of Kdm6b lead to depletion of phenotypic and functional HSCs in adult mice, and Kdm6b is necessary for HSC self-renewal in response to inflammatory and proliferative stress. Loss of Kdm6b leads to a pro-differentiation poised state in HSCs due to the increased expression of the AP-1 transcription factor complex (Fos and Jun) and immediate early response (IER) genes. These gene expression changes occurred independently of chromatin modifications. Targeting AP-1 restored function of Kdm6b-deficient HSCs, suggesting that Kdm6b regulates this complex during HSC stress response. We also show Kdm6b supports developmental context-dependent leukemogenesis for T-cell acute lymphoblastic leukemia (T-ALL) and M5 acute myeloid leukemia (AML). Kdm6b is required for effective fetal-derived T-ALL and adult-derived AML, but not vice versa. These studies identify a crucial role for Kdm6b in regulating HSC self-renewal in different contexts, and highlight the potential of KDM6B as a therapeutic target in different hematopoietic malignancies.</p>',
			'date' => '2019-04-01',
			'pmid' => 'http://www.pubmed.gov/30936419',
			'doi' => '10.1038/s41375-019-0462-4',
			'modified' => '2019-08-07 09:14:05',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 120 => array(
			'id' => '3700',
			'name' => 'A critical regulator of Bcl2 revealed by systematic transcript discovery of lncRNAs associated with T-cell differentiation.',
			'authors' => 'Saadi W, Kermezli Y, Dao LTM, Mathieu E, Santiago-Algarra D, Manosalva I, Torres M, Belhocine M, Pradel L, Loriod B, Aribi M, Puthier D, Spicuglia S',
			'description' => '<p>Normal T-cell differentiation requires a complex regulatory network which supports a series of maturation steps, including lineage commitment, T-cell receptor (TCR) gene rearrangement, and thymic positive and negative selection. However, the underlying molecular mechanisms are difficult to assess due to limited T-cell models. Here we explore the use of the pro-T-cell line P5424 to study early T-cell differentiation. Stimulation of P5424 cells by the calcium ionophore ionomycin together with PMA resulted in gene regulation of T-cell differentiation and activation markers, partially mimicking the CD4CD8 double negative (DN) to double positive (DP) transition and some aspects of subsequent T-cell maturation and activation. Global analysis of gene expression, along with kinetic experiments, revealed a significant association between the dynamic expression of coding genes and neighbor lncRNAs including many newly-discovered transcripts, thus suggesting potential co-regulation. CRISPR/Cas9-mediated genetic deletion of Robnr, an inducible lncRNA located downstream of the anti-apoptotic gene Bcl2, demonstrated a critical role of the Robnr locus in the induction of Bcl2. Thus, the pro-T-cell line P5424 is a powerful model system to characterize regulatory networks involved in early T-cell differentiation and maturation.</p>',
			'date' => '2019-03-18',
			'pmid' => 'http://www.pubmed.gov/30886319',
			'doi' => '10.1038/s41598-019-41247-5',
			'modified' => '2019-07-05 14:43:51',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 121 => array(
			'id' => '3571',
			'name' => 'The role of TCF3 as potential master regulator in blastemal Wilms tumors.',
			'authors' => 'Kehl T, Schneider L, Kattler K, Stöckel D, Wegert J, Gerstner N, Ludwig N, Distler U, Tenzer S, Gessler M, Walter J, Keller A, Graf N, Meese E, Lenhof HP',
			'description' => '<p>Wilms tumors are the most common type of pediatric kidney tumors. While the overall prognosis for patients is favorable, especially tumors that exhibit a blastemal subtype after preoperative chemotherapy have a poor prognosis. For an improved risk assessment and therapy stratification, it is essential to identify the driving factors that are distinctive for this aggressive subtype. In our study, we compared gene expression profiles of 33 tumor biopsies (17 blastemal and 16 other tumors) after neoadjuvant chemotherapy. The analysis of this dataset using the Regulator Gene Association Enrichment algorithm successfully identified several biomarkers and associated molecular mechanisms that distinguish between blastemal and nonblastemal Wilms tumors. Specifically, regulators involved in embryonic development and epigenetic processes like chromatin remodeling and histone modification play an essential role in blastemal tumors. In this context, we especially identified TCF3 as the central regulatory element. Furthermore, the comparison of ChIP-Seq data of Wilms tumor cell cultures from a blastemal mouse xenograft and a stromal tumor provided further evidence that the chromatin states of blastemal cells share characteristics with embryonic stem cells that are not present in the stromal tumor cell line. These stem-cell like characteristics could potentially add to the increased malignancy and chemoresistance of the blastemal subtype. Along with TCF3, we detected several additional biomarkers that are distinctive for blastemal Wilms tumors after neoadjuvant chemotherapy and that may provide leads for new therapeutic regimens.</p>',
			'date' => '2019-03-15',
			'pmid' => 'http://www.pubmed.gov/30155889',
			'doi' => '10.1002/ijc.31834',
			'modified' => '2019-03-21 17:10:17',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 122 => array(
			'id' => '3611',
			'name' => 'Extensive Recovery of Embryonic Enhancer and Gene Memory Stored in Hypomethylated Enhancer DNA.',
			'authors' => 'Jadhav U, Cavazza A, Banerjee KK, Xie H, O'Neill NK, Saenz-Vash V, Herbert Z, Madha S, Orkin SH, Zhai H, Shivdasani RA',
			'description' => '<p>Developing and adult tissues use different cis-regulatory elements. Although DNA at some decommissioned embryonic enhancers is hypomethylated in adult cells, it is unknown whether this putative epigenetic memory is complete and recoverable. We find that, in adult mouse cells, hypomethylated CpG dinucleotides preserve a nearly complete archive of tissue-specific developmental enhancers. Sites that carry the active histone mark H3K4me1, and are therefore considered "primed," are mainly cis elements that act late in organogenesis. In contrast, sites decommissioned early in development retain hypomethylated DNA as a singular property. In adult intestinal and blood cells, sustained absence of polycomb repressive complex 2 indirectly reactivates most-and only-hypomethylated developmental enhancers. Embryonic and fetal transcriptional programs re-emerge as a result, in reverse chronology to cis element inactivation during development. Thus, hypomethylated DNA in adult cells preserves a "fossil record" of tissue-specific developmental enhancers, stably marking decommissioned sites and enabling recovery of this epigenetic memory.</p>',
			'date' => '2019-03-15',
			'pmid' => 'http://www.pubmed.gov/30905509',
			'doi' => '10.1016/j.molcel.2019.02.024',
			'modified' => '2019-04-17 14:46:15',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 123 => array(
			'id' => '3569',
			'name' => 'The epigenetic basis for the impaired ability of adult murine retinal pigment epithelium cells to regenerate retinal tissue.',
			'authors' => 'Dvoriantchikova G, Seemungal RJ, Ivanov D',
			'description' => '<p>The epigenetic plasticity of amphibian retinal pigment epithelium (RPE) allows them to regenerate the entire retina, a trait known to be absent in mammals. In this study, we investigated the epigenetic plasticity of adult murine RPE to identify possible mechanisms that prevent mammalian RPE from regenerating retinal tissue. RPE were analyzed using microarray, ChIP-seq, and whole-genome bisulfite sequencing approaches. We found that the majority of key genes required for progenitor phenotypes were in a permissive chromatin state and unmethylated in RPE. We observed that the majority of non-photoreceptor genes had promoters in a repressive chromatin state, but these promoters were in unmethylated or low-methylated regions. Meanwhile, the majority of promoters for photoreceptor genes were found in a permissive chromatin state, but were highly-methylated. Methylome states of photoreceptor-related genes in adult RPE and embryonic retina (which mostly contain progenitors) were very similar. However, promoters of these genes were demethylated and activated during retinal development. Our data suggest that, epigenetically, adult murine RPE cells are a progenitor-like cell type. Most likely two mechanisms prevent adult RPE from reprogramming and differentiating into retinal neurons: 1) repressive chromatin in the promoter regions of non-photoreceptor retinal neuron genes; 2) highly-methylated promoters of photoreceptor-related genes.</p>',
			'date' => '2019-03-07',
			'pmid' => 'http://www.pubmed.gov/30846751',
			'doi' => '10.1038/s41598-019-40262-w',
			'modified' => '2019-05-09 17:33:09',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 124 => array(
			'id' => '3671',
			'name' => 'Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes.',
			'authors' => 'Yi G, Wierenga ATJ, Petraglia F, Narang P, Janssen-Megens EM, Mandoli A, Merkel A, Berentsen K, Kim B, Matarese F, Singh AA, Habibi E, Prange KHM, Mulder AB, Jansen JH, Clarke L, Heath S, van der Reijden BA, Flicek P, Yaspo ML, Gut I, Bock C, Schuringa JJ',
			'description' => '<p>Global investigation of histone marks in acute myeloid leukemia (AML) remains limited. Analyses of 38 AML samples through integrated transcriptional and chromatin mark analysis exposes 2 major subtypes. One subtype is dominated by patients with&nbsp;NPM1 mutations or MLL-fusion genes, shows activation of the regulatory pathways involving HOX-family genes as targets, and displays high self-renewal capacity and stemness. The second subtype is enriched for RUNX1 or spliceosome mutations, suggesting potential interplay between the 2 aberrations, and mainly depends on IRF family regulators. Cellular consequences in prognosis predict a relatively worse outcome for the first subtype. Our integrated profiling establishes a rich resource to probe AML subtypes on the basis of expression and chromatin data.</p>',
			'date' => '2019-01-22',
			'pmid' => 'http://www.pubmed.gov/30673601',
			'doi' => '10.1016/j.celrep.2018.12.098',
			'modified' => '2019-07-01 11:30:31',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 125 => array(
			'id' => '3629',
			'name' => 'Comprehensive Analysis of Chromatin States in Atypical Teratoid/Rhabdoid Tumor Identifies Diverging Roles for SWI/SNF and Polycomb in Gene Regulation.',
			'authors' => 'Erkek S, Johann PD, Finetti MA, Drosos Y, Chou HC, Zapatka M, Sturm D, Jones DTW, Korshunov A, Rhyzova M, Wolf S, Mallm JP, Beck K, Witt O, Kulozik AE, Frühwald MC, Northcott PA, Korbel JO, Lichter P, Eils R, Gajjar A, Roberts CWM, Williamson D, Hasselbla',
			'description' => '<p>Biallelic inactivation of SMARCB1, encoding a member of the SWI/SNF chromatin remodeling complex, is the hallmark genetic aberration of atypical teratoid rhabdoid tumors (ATRT). Here, we report how loss of SMARCB1 affects the epigenome in these tumors. Using chromatin immunoprecipitation sequencing (ChIP-seq) on primary tumors for a series of active and repressive histone marks, we identified the chromatin states differentially represented in ATRTs compared with other brain tumors and non-neoplastic brain. Re-expression of SMARCB1 in ATRT cell lines enabled confirmation of our genome-wide findings for the chromatin states. Additional generation of ChIP-seq data for SWI/SNF and Polycomb group proteins and the transcriptional repressor protein REST determined differential dependencies of SWI/SNF and Polycomb complexes in regulation of diverse gene sets in ATRTs.</p>',
			'date' => '2019-01-14',
			'pmid' => 'http://www.pubmed.gov/30595504',
			'doi' => '10.1016/j.ccell.2018.11.014',
			'modified' => '2019-05-08 12:27:57',
			'created' => '2019-04-25 11:11:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 126 => array(
			'id' => '3658',
			'name' => 'The Wnt-Driven Mll1 Epigenome Regulates Salivary Gland and Head and Neck Cancer.',
			'authors' => 'Zhu Q, Fang L, Heuberger J, Kranz A, Schipper J, Scheckenbach K, Vidal RO, Sunaga-Franze DY, Müller M, Wulf-Goldenberg A, Sauer S, Birchmeier W',
			'description' => '<p>We identified a regulatory system that acts downstream of Wnt/&beta;-catenin signaling in salivary gland and head and neck carcinomas. We show in a mouse tumor model of K14-Cre-induced Wnt/&beta;-catenin gain-of-function and Bmpr1a loss-of-function mutations that tumor-propagating cells exhibit increased Mll1 activity and genome-wide increased H3K4 tri-methylation at promoters. Null mutations of Mll1 in tumor mice and in xenotransplanted human head and neck tumors resulted in loss of self-renewal of tumor-propagating cells and in block of tumor formation but did not alter normal tissue homeostasis. CRISPR/Cas9 mutagenesis and pharmacological interference of Mll1 at sequences that inhibit essential protein-protein interactions or the SET enzyme active site also blocked the self-renewal of mouse and human tumor-propagating cells. Our work provides strong genetic evidence for a crucial role of Mll1 in solid tumors. Moreover, inhibitors targeting specific Mll1 interactions might offer additional directions for therapies to treat these aggressive tumors.</p>',
			'date' => '2019-01-08',
			'pmid' => 'http://www.pubmed.gov/30625324',
			'doi' => '10.1016/j.celrep.2018.12.059',
			'modified' => '2019-06-07 09:00:14',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 127 => array(
			'id' => '3686',
			'name' => 'Gamma radiation induces locus specific changes to histone modification enrichment in zebrafish and Atlantic salmon.',
			'authors' => 'Lindeman LC, Kamstra JH, Ballangby J, Hurem S, Martín LM, Brede DA, Teien HC, Oughton DH, Salbu B, Lyche JL, Aleström P',
			'description' => '<p>Ionizing radiation is a recognized genotoxic agent, however, little is known about the role of the functional form of DNA in these processes. Post translational modifications on histone proteins control the organization of chromatin and hence control transcriptional responses that ultimately affect the phenotype. The purpose of this study was to investigate effects on chromatin caused by ionizing radiation in fish. Direct exposure of zebrafish (Danio rerio) embryos to gamma radiation (10.9 mGy/h for 3h) induced hyper-enrichment of H3K4me3 at the genes hnf4a, gmnn and vegfab. A similar relative hyper-enrichment was seen at the hnf4a loci of irradiated Atlantic salmon (Salmo salar) embryos (30 mGy/h for 10 days). At the selected genes in ovaries of adult zebrafish irradiated during gametogenesis (8.7 and 53 mGy/h for 27 days), a reduced enrichment of H3K4me3 was observed, which was correlated with reduced levels of histone H3 was observed. F1 embryos of the exposed parents showed hyper-methylation of H3K4me3, H3K9me3 and H3K27me3 on the same three loci, while these differences were almost negligible in F2 embryos. Our results from three selected loci suggest that ionizing radiation can affect chromatin structure and organization, and that these changes can be detected in F1 offspring, but not in subsequent generations.</p>',
			'date' => '2019-01-01',
			'pmid' => 'http://www.pubmed.gov/30759148',
			'doi' => '10.1371/journal.pone.0212123',
			'modified' => '2019-06-28 13:57:39',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 128 => array(
			'id' => '3607',
			'name' => 'Mutant p63 Affects Epidermal Cell Identity through Rewiring the Enhancer Landscape.',
			'authors' => 'Qu J, Tanis SEJ, Smits JPH, Kouwenhoven EN, Oti M, van den Bogaard EH, Logie C, Stunnenberg HG, van Bokhoven H, Mulder KW, Zhou H',
			'description' => '<p>Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Mutations in the p63 DNA-binding domain are associated with ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome. However, the underlying molecular mechanism of these mutations remains unclear. Here, we characterized the transcriptome and epigenome of p63 mutant keratinocytes derived from EEC patients. The transcriptome of p63 mutant keratinocytes deviated from the normal epidermal cell identity. Epigenomic analyses showed an altered enhancer landscape in p63 mutant keratinocytes contributed by loss of p63-bound active enhancers and unexpected gain of enhancers. The gained enhancers were frequently bound by deregulated transcription factors such as RUNX1. Reversing RUNX1 overexpression partially rescued deregulated gene expression and the altered enhancer landscape. Our findings identify a disease mechanism whereby mutant p63 rewires the enhancer landscape and affects epidermal cell identity, consolidating the pivotal role of p63 in controlling the enhancer landscape of epidermal keratinocytes.</p>',
			'date' => '2018-12-18',
			'pmid' => 'http://www.pubmed.gov/30566872',
			'doi' => '10.1016/j.celrep.2018.11.039',
			'modified' => '2019-04-17 14:51:18',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 129 => array(
			'id' => '3509',
			'name' => 'Promoter bivalency favors an open chromatin architecture in embryonic stem cells.',
			'authors' => 'Mas G, Blanco E, Ballaré C, Sansó M, Spill YG, Hu D, Aoi Y, Le Dily F, Shilatifard A, Marti-Renom MA, Di Croce L',
			'description' => '<p>In embryonic stem cells (ESCs), developmental gene promoters are characterized by their bivalent chromatin state, with simultaneous modification by MLL2 and Polycomb complexes. Although essential for embryogenesis, bivalency is functionally not well understood. Here, we show that MLL2 plays a central role in ESC genome organization. We generate a catalog of bona fide bivalent genes in ESCs and demonstrate that loss of MLL2 leads to increased Polycomb occupancy. Consequently, promoters lose accessibility, long-range interactions are redistributed, and ESCs fail to differentiate. We pose that bivalency balances accessibility and long-range connectivity of promoters, allowing developmental gene expression to be properly modulated.</p>',
			'date' => '2018-10-17',
			'pmid' => 'http://www.pubmed.gov/30224650',
			'doi' => '10.1038/s41588-018-0218-5',
			'modified' => '2019-02-27 15:45:37',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 130 => array(
			'id' => '3552',
			'name' => 'PRC2 targeting is a therapeutic strategy for EZ score defined high-risk multiple myeloma patients and overcome resistance to IMiDs.',
			'authors' => 'Herviou L, Kassambara A, Boireau S, Robert N, Requirand G, Müller-Tidow C, Vincent L, Seckinger A, Goldschmidt H, Cartron G, Hose D, Cavalli G, Moreaux J',
			'description' => '<p>BACKGROUND: Multiple myeloma (MM) is a malignant plasma cell disease with a poor survival, characterized by the accumulation of myeloma cells (MMCs) within the bone marrow. Epigenetic modifications in MM are associated not only with cancer development and progression, but also with drug resistance. METHODS: We identified a significant upregulation of the polycomb repressive complex 2 (PRC2) core genes in MM cells in association with proliferation. We used EPZ-6438, a specific small molecule inhibitor of EZH2 methyltransferase activity, to evaluate its effects on MM cells phenotype and gene expression prolile. RESULTS: PRC2 targeting results in growth inhibition due to cell cycle arrest and apoptosis together with polycomb, DNA methylation, TP53, and RB1 target genes induction. Resistance to EZH2 inhibitor is mediated by DNA methylation of PRC2 target genes. We also demonstrate a synergistic effect of EPZ-6438 and lenalidomide, a conventional drug used for MM treatment, activating B cell transcription factors and tumor suppressor gene expression in concert with MYC repression. We establish a gene expression-based EZ score allowing to identify poor prognosis patients that could benefit from EZH2 inhibitor treatment. CONCLUSIONS: These data suggest that PRC2 targeting in association with IMiDs could have a therapeutic interest in MM patients characterized by high EZ score values, reactivating B cell transcription factors, and tumor suppressor genes.</p>',
			'date' => '2018-10-03',
			'pmid' => 'http://www.pubmed.org/30285865',
			'doi' => '10.1186/s13148-018-0554-4',
			'modified' => '2019-03-21 16:45:55',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 131 => array(
			'id' => '3396',
			'name' => 'The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity',
			'authors' => 'Domínguez-Andrés Jorge, Novakovic Boris, Li Yang, Scicluna Brendon P., Gresnigt Mark S., Arts Rob J.W., Oosting Marije, Moorlag Simone J.C.F.M., Groh Laszlo A., Zwaag Jelle, Koch Rebecca M., ter Horst Rob, Joosten Leo A.B., Wijmenga Cisca, Michelucci Ales',
			'description' => '<p>Sepsis involves simultaneous hyperactivation of the immune system and immune paralysis, leading to both organ dysfunction and increased susceptibility to secondary infections. Acute activation of myeloid cells induced itaconate synthesis, which subsequently mediated innate immune tolerance in human monocytes. In contrast, induction of trained immunity by b-glucan counteracted tolerance induced in a model of human endotoxemia by inhibiting the expression of immune-responsive gene 1 (IRG1), the enzyme that controls itaconate synthesis. b-Glucan also increased the expression of succinate dehydrogenase (SDH), contributing to the integrity of the TCA cycle and leading to an enhanced innate immune response after secondary stimulation. The role of itaconate was further validated by IRG1 and SDH polymorphisms that modulate induction of tolerance and trained immunity in human monocytes. These data demonstrate the importance of the IRG1-itaconateSDH axis in the development of immune tolerance and training and highlight the potential of b-glucaninduced trained immunity to revert immunoparalysis.</p>',
			'date' => '2018-10-01',
			'pmid' => 'http://www.pubmed.gov/30293776',
			'doi' => '10.1016/j.cmet.2018.09.003',
			'modified' => '2018-11-22 15:18:30',
			'created' => '2018-11-08 12:59:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 132 => array(
			'id' => '3566',
			'name' => 'Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes.',
			'authors' => 'Ferguson GB, Van Handel B, Bay M, Fiziev P, Org T, Lee S, Shkhyan R, Banks NW, Scheinberg M, Wu L, Saitta B, Elphingstone J, Larson AN, Riester SM, Pyle AD, Bernthal NM, Mikkola HK, Ernst J, van Wijnen AJ, Bonaguidi M, Evseenko D',
			'description' => '<p>Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application of cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differentiation. Network analysis delineated five tissue-specific gene modules; these modules and chromatin state analysis defined broad similarities in gene expression during cartilage specification and maturation in vitro and in vivo, including early expression and progressive silencing of muscle- and bone-specific genes. Finally, ontogenetic analysis of freshly isolated and pluripotent stem cell-derived articular chondrocytes identified that integrin alpha 4 defines 2 subsets of functionally and molecularly distinct chondrocytes characterized by their gene expression, osteochondral potential in vitro and proliferative signature in vivo. These analyses provide new insight into human musculoskeletal development and provide an essential comparative resource for disease modeling and regenerative medicine.</p>',
			'date' => '2018-09-07',
			'pmid' => 'http://www.pubmed.gov/30194383',
			'doi' => '10.1038/s41467-018-05573-y',
			'modified' => '2019-03-25 11:14:45',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 133 => array(
			'id' => '3596',
			'name' => 'RNA Sequencing and Pathway Analysis Identify Important Pathways Involved in Hypertrichosis and Intellectual Disability in Patients with Wiedemann-Steiner Syndrome.',
			'authors' => 'Mietton L, Lebrun N, Giurgea I, Goldenberg A, Saintpierre B, Hamroune J, Afenjar A, Billuart P, Bienvenu T',
			'description' => '<p>A growing number of histone modifiers are involved in human neurodevelopmental disorders, suggesting that proper regulation of chromatin state is essential for the development of the central nervous system. Among them, heterozygous de novo variants in KMT2A, a gene coding for histone methyltransferase, have been associated with Wiedemann-Steiner syndrome (WSS), a rare developmental disorder mainly characterized by intellectual disability (ID) and hypertrichosis. As KMT2A is known to regulate the expression of multiple target genes through methylation of lysine 4 of histone 3 (H3K4me), we sought to investigate the transcriptomic consequences of KMT2A variants involved in WSS. Using fibroblasts from four WSS patients harboring loss-of-function KMT2A variants, we performed RNA sequencing and identified a number of genes for which transcription was altered in KMT2A-mutated cells compared to the control ones. Strikingly, analysis of the pathways and biological functions significantly deregulated between patients with WSS and healthy individuals revealed a number of processes predicted to be altered that are relevant for hypertrichosis and intellectual disability, the cardinal signs of this disease.</p>',
			'date' => '2018-09-01',
			'pmid' => 'http://www.pubmed.gov/30014449',
			'doi' => '10.1007/s12017-018-8502-1',
			'modified' => '2019-04-17 15:10:22',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 134 => array(
			'id' => '3564',
			'name' => 'Atopic asthma after rhinovirus-induced wheezing is associated with DNA methylation change in the SMAD3 gene promoter.',
			'authors' => 'Lund RJ, Osmala M, Malonzo M, Lukkarinen M, Leino A, Salmi J, Vuorikoski S, Turunen R, Vuorinen T, Akdis C, Lähdesmäki H, Lahesmaa R, Jartti T',
			'description' => '<p>Children with rhinovirus-induced severe early wheezing have an increased risk of developing asthma later in life. The exact molecular mechanisms for this association are still mostly unknown. To identify potential changes in the transcriptional and epigenetic regulation in rhinovirus-associated atopic or nonatopic asthma, we analyzed a cohort of 5-year-old children (n&nbsp;=&nbsp;45) according to the virus etiology of the first severe wheezing episode at the mean age of 13&nbsp;months and to 5-year asthma outcome. The development of atopic asthma in children with early rhinovirus-induced wheezing was associated with DNA methylation changes at several genomic sites in chromosomal regions previously linked to asthma. The strongest changes in atopic asthma were detected in the promoter region of SMAD3 gene at chr 15q22.33 and introns of DDO/METTL24 genes at 6q21. These changes were validated to be present also at the average age of 8&nbsp;years.</p>',
			'date' => '2018-08-01',
			'pmid' => 'http://www.pubmed.gov/29729188',
			'doi' => '10.1111/all.13473',
			'modified' => '2019-03-25 11:19:56',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 135 => array(
			'id' => '3515',
			'name' => 'Integrative multi-omics analysis of intestinal organoid differentiation',
			'authors' => 'Rik GH Lindeboom, Lisa van Voorthuijsen1, Koen C Oost, Maria J Rodríguez-Colman, Maria V Luna-Velez, Cristina Furlan, Floriane Baraille, Pascal WTC Jansen, Agnès Ribeiro, Boudewijn MT Burgering, Hugo J Snippert, & Michiel Vermeulen',
			'description' => '<p>Intestinal organoids accurately recapitulate epithelial homeostasis in vivo, thereby representing a powerful in vitro system to investigate lineage specification and cellular differentiation. Here, we applied a multi-omics framework on stem cell-enriched and stem cell-depleted mouse intestinal organoids to obtain a holistic view of the molecular mechanisms that drive differential gene expression during adult intestinal stem cell differentiation. Our data revealed a global rewiring of the transcriptome and proteome between intestinal stem cells and enterocytes, with the majority of dynamic protein expression being transcription-driven. Integrating absolute mRNA and protein copy numbers revealed post-transcriptional regulation of gene expression. Probing the epigenetic landscape identified a large number of cell-type-specific regulatory elements, which revealed Hnf4g as a major driver of enterocyte differentiation. In summary, by applying an integrative systems biology approach, we uncovered multiple layers of gene expression regulation, which contribute to lineage specification and plasticity of the mouse small intestinal epithelium.</p>',
			'date' => '2018-06-26',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/29945941/',
			'doi' => '10.15252/msb.20188227',
			'modified' => '2022-05-18 18:45:53',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 136 => array(
			'id' => '3423',
			'name' => 'The Polycomb-Dependent Epigenome Controls β Cell Dysfunction, Dedifferentiation, and Diabetes.',
			'authors' => 'Lu TT, Heyne S, Dror E, Casas E, Leonhardt L, Boenke T, Yang CH, Sagar , Arrigoni L, Dalgaard K, Teperino R, Enders L, Selvaraj M, Ruf M, Raja SJ, Xie H, Boenisch U, Orkin SH, Lynn FC, Hoffman BG, Grün D, Vavouri T, Lempradl AM, Pospisilik JA',
			'description' => '<p>To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single-cell transcriptomics to mine for evidence of chromatin dysregulation in type 2 diabetes. We find two chromatin-state signatures that track &beta; cell dysfunction in mice and humans: ectopic activation of bivalent Polycomb-silenced domains and loss of expression at an epigenomically unique class of lineage-defining genes. &beta; cell-specific Polycomb (Eed/PRC2) loss of function in mice triggers diabetes-mimicking transcriptional signatures and highly penetrant, hyperglycemia-independent dedifferentiation, indicating that PRC2 dysregulation contributes to disease. The work provides novel resources for exploring &beta;&nbsp;cell transcriptional regulation and identifies PRC2 as necessary for long-term maintenance of &beta; cell identity. Importantly, the data suggest a two-hit (chromatin and hyperglycemia) model for loss of &beta;&nbsp;cell identity in diabetes.</p>',
			'date' => '2018-06-05',
			'pmid' => 'http://www.pubmed.gov/29754954',
			'doi' => '10.1016/j.cmet.2018.04.013',
			'modified' => '2018-12-31 11:43:24',
			'created' => '2018-12-04 09:51:07',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 137 => array(
			'id' => '3380',
			'name' => 'The reference epigenome and regulatory chromatin landscape of chronic lymphocytic leukemia',
			'authors' => 'Beekman R. et al.',
			'description' => '<p>Chronic lymphocytic leukemia (CLL) is a frequent hematological neoplasm in which underlying epigenetic alterations are only partially understood. Here, we analyze the reference epigenome of seven primary CLLs and the regulatory chromatin landscape of 107 primary cases in the context of normal B cell differentiation. We identify that the CLL chromatin landscape is largely influenced by distinct dynamics during normal B cell maturation. Beyond this, we define extensive catalogues of regulatory elements de novo reprogrammed in CLL as a whole and in its major clinico-biological subtypes classified by IGHV somatic hypermutation levels. We uncover that IGHV-unmutated CLLs harbor more active and open chromatin than IGHV-mutated cases. Furthermore, we show that de novo active regions in CLL are enriched for NFAT, FOX and TCF/LEF transcription factor family binding sites. Although most genetic alterations are not associated with consistent epigenetic profiles, CLLs with MYD88 mutations and trisomy 12 show distinct chromatin configurations. Furthermore, we observe that non-coding mutations in IGHV-mutated CLLs are enriched in H3K27ac-associated regulatory elements outside accessible chromatin. Overall, this study provides an integrative portrait of the CLL epigenome, identifies extensive networks of altered regulatory elements and sheds light on the relationship between the genetic and epigenetic architecture of the disease.</p>',
			'date' => '2018-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29785028',
			'doi' => '',
			'modified' => '2018-07-27 17:10:43',
			'created' => '2018-07-27 17:10:43',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 138 => array(
			'id' => '3469',
			'name' => 'Increased H3K9 methylation and impaired expression of Protocadherins are associated with the cognitive dysfunctions of the Kleefstra syndrome.',
			'authors' => 'Iacono G, Dubos A, Méziane H, Benevento M, Habibi E, Mandoli A, Riet F, Selloum M, Feil R, Zhou H, Kleefstra T, Kasri NN, van Bokhoven H, Herault Y, Stunnenberg HG',
			'description' => '<p>Kleefstra syndrome, a disease with intellectual disability, autism spectrum disorders and other developmental defects is caused in humans by haploinsufficiency of EHMT1. Although EHMT1 and its paralog EHMT2 were shown to be histone methyltransferases responsible for deposition of the di-methylated H3K9 (H3K9me2), the exact nature of epigenetic dysfunctions in Kleefstra syndrome remains unknown. Here, we found that the epigenome of Ehmt1+/- adult mouse brain displays a marked increase of H3K9me2/3 which correlates with impaired expression of protocadherins, master regulators of neuronal diversity. Increased H3K9me3 was present already at birth, indicating that aberrant methylation patterns are established during embryogenesis. Interestingly, we found that Ehmt2+/- mice do not present neither the marked increase of H3K9me2/3 nor the cognitive deficits found in Ehmt1+/- mice, indicating an evolutionary diversification of functions. Our finding of increased H3K9me3 in Ehmt1+/- mice is the first one supporting the notion that EHMT1 can quench the deposition of tri-methylation by other Histone methyltransferases, ultimately leading to impaired neurocognitive functioning. Our insights into the epigenetic pathophysiology of Kleefstra syndrome may offer guidance for future developments of therapeutic strategies for this disease.</p>',
			'date' => '2018-06-01',
			'pmid' => 'http://www.pubmed.gov/29554304',
			'doi' => '10.1093/nar/gky196',
			'modified' => '2019-02-15 21:04:02',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 139 => array(
			'id' => '3478',
			'name' => 'Pro-inflammatory cytokines activate hypoxia-inducible factor 3α via epigenetic changes in mesenchymal stromal/stem cells.',
			'authors' => 'Cuomo F, Coppola A, Botti C, Maione C, Forte A, Scisciola L, Liguori G, Caiafa I, Ursini MV, Galderisi U, Cipollaro M, Altucci L, Cobellis G',
			'description' => '<p>Human mesenchymal stromal/stem cells (hMSCs) emerged as a promising therapeutic tool for ischemic disorders, due to their ability to regenerate damaged tissues, promote angiogenesis and reduce inflammation, leading to encouraging, but still limited results. The outcomes in clinical trials exploring hMSC therapy are influenced by low cell retention and survival in affected tissues, partially influenced by lesion's microenvironment, where low oxygen conditions (i.e. hypoxia) and inflammation coexist. Hypoxia and inflammation are pathophysiological stresses, sharing common activators, such as hypoxia-inducible factors (HIFs) and NF-&kappa;B. HIF1&alpha; and HIF2&alpha; respond essentially to hypoxia, activating pathways involved in tissue repair. Little is known about the regulation of HIF3&alpha;. Here we investigated the role of HIF3&alpha; in vitro and in vivo. Human MSCs expressed HIF3&alpha;, differentially regulated by pro-inflammatory cytokines in an oxygen-independent manner, a novel and still uncharacterized mechanism, where NF-&kappa;B is critical for its expression. We investigated if epigenetic modifications are involved in HIF3&alpha; expression by methylation-specific PCR and histone modifications. Robust hypermethylation of histone H3 was observed across HIF3A locus driven by pro-inflammatory cytokines. Experiments in a murine model of arteriotomy highlighted the activation of Hif3&alpha; expression in infiltrated inflammatory cells, suggesting a new role for Hif3&alpha; in inflammation in vivo.</p>',
			'date' => '2018-04-11',
			'pmid' => 'http://www.pubmed.gov/29643458',
			'doi' => '10.1038/s41598-018-24221-5',
			'modified' => '2019-02-15 20:21:28',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 140 => array(
			'id' => '3463',
			'name' => 'Epigenetic modifiers promote mitochondrial biogenesis and oxidative metabolism leading to enhanced differentiation of neuroprogenitor cells.',
			'authors' => 'Martine Uittenbogaard, Christine A. Brantner, Anne Chiaramello1',
			'description' => '<p>During neural development, epigenetic modulation of chromatin acetylation is part of a dynamic, sequential and critical process to steer the fate of multipotent neural progenitors toward a specific lineage. Pan-HDAC inhibitors (HDCis) trigger neuronal differentiation by generating an "acetylation" signature and promoting the expression of neurogenic bHLH transcription factors. Our studies and others have revealed a link between neuronal differentiation and increase of mitochondrial mass. However, the neuronal regulation of mitochondrial biogenesis has remained largely unexplored. Here, we show that the HDACi, sodium butyrate (NaBt), promotes mitochondrial biogenesis via the NRF-1/Tfam axis in embryonic hippocampal progenitor cells and neuroprogenitor-like PC12-NeuroD6 cells, thereby enhancing their neuronal differentiation competency. Increased mitochondrial DNA replication by several pan-HDACis indicates a common mechanism by which they regulate mitochondrial biogenesis. NaBt also induces coordinates mitochondrial ultrastructural changes and enhanced OXPHOS metabolism, thereby increasing key mitochondrial bioenergetics parameters in neural progenitor cells. NaBt also endows the neuronal cells with increased mitochondrial spare capacity to confer resistance to oxidative stress associated with neuronal differentiation. We demonstrate that mitochondrial biogenesis is under HDAC-mediated epigenetic regulation, the timing of which is consistent with its integrative role during neuronal differentiation. Thus, our findings add a new facet to our mechanistic understanding of how pan-HDACis induce differentiation of neuronal progenitor cells. Our results reveal the concept that epigenetic modulation of the mitochondrial pool prior to neurotrophic signaling dictates the efficiency of initiation of neuronal differentiation during the transition from progenitor to differentiating neuronal cells. The histone acetyltransferase CREB-binding protein plays a key role in regulating the mitochondrial biomass. By ChIP-seq analysis, we show that NaBt confers an H3K27ac epigenetic signature in several interconnected nodes of nuclear genes vital for neuronal differentiation and mitochondrial reprogramming. Collectively, our study reports a novel developmental epigenetic layer that couples mitochondrial biogenesis to neuronal differentiation.</p>',
			'date' => '2018-03-02',
			'pmid' => 'http://www.pubmed.gov/29500414',
			'doi' => '10.1038/s41419-018-0396-1',
			'modified' => '2019-02-15 21:21:45',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 141 => array(
			'id' => '3361',
			'name' => 'Micro-ribonucleic acid-155 is a direct target of Meis1, but not a driver in acute myeloid leukemia',
			'authors' => 'Schneider E. et al.',
			'description' => '<p>Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute myeloid leukemia. The additional overexpression of miR-155 accelerated the formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells <i>in vivo</i> However, in the absence or following the removal of miR-155, leukemia onset and progression were unaffected. Although miR-155 accelerated growth and homing in addition to impairing differentiation, our data underscore the pathophysiological relevance of miR-155 as an accelerator rather than a driver of leukemogenesis. This further highlights the complexity of the oncogenic program of Meis1 to compensate for the loss of a potent oncogene such as miR-155. These findings are highly relevant to current and developing approaches for targeting miR-155 in acute myeloid leukemia.</p>',
			'date' => '2018-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29217774',
			'doi' => '',
			'modified' => '2018-04-06 15:39:36',
			'created' => '2018-04-06 15:39:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 142 => array(
			'id' => '3446',
			'name' => 'Metabolic Induction of Trained Immunity through the Mevalonate Pathway.',
			'authors' => 'Bekkering S, Arts RJW, Novakovic B, Kourtzelis I, van der Heijden CDCC, Li Y, Popa CD, Ter Horst R, van Tuijl J, Netea-Maier RT, van de Veerdonk FL, Chavakis T, Joosten LAB, van der Meer JWM, Stunnenberg H, Riksen NP, Netea MG',
			'description' => '<p>Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that activation of the cholesterol synthesis pathway, but not the synthesis of cholesterol itself, is essential for training of myeloid cells. Rather, the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways. Statins, which block mevalonate generation, prevent trained immunity induction. Furthermore, monocytes of patients with hyper immunoglobulin D syndrome (HIDS), who are mevalonate kinase deficient and accumulate mevalonate, have a constitutive trained immunity phenotype at both immunological and epigenetic levels, which could explain the attacks of sterile inflammation that these patients experience. Unraveling the role of mevalonate in trained immunity contributes to our understanding of the pathophysiology of HIDS and identifies novel therapeutic targets for clinical conditions with excessive activation of trained immunity.</p>',
			'date' => '2018-01-11',
			'pmid' => 'http://www.pubmed.gov/29328908',
			'doi' => '10.1016/j.cell.2017.11.025',
			'modified' => '2019-02-15 21:37:39',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 143 => array(
			'id' => '3408',
			'name' => 'BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity.',
			'authors' => 'Arts RJW, Moorlag SJCFM, Novakovic B, Li Y, Wang SY, Oosting M, Kumar V, Xavier RJ, Wijmenga C, Joosten LAB, Reusken CBEM, Benn CS, Aaby P, Koopmans MP, Stunnenberg HG, van Crevel R, Netea MG',
			'description' => '<p>The tuberculosis vaccine bacillus Calmette-Gu&eacute;rin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was accompanied by functional changes indicative of trained immunity. Reduction of viremia was highly correlated with the upregulation of IL-1&beta;, a heterologous cytokine associated with the induction of trained immunity, but not with&nbsp;the specific IFN&gamma; response. The importance of IL-1&beta; for the induction of trained immunity was validated through genetic, epigenetic, and immunological studies. In conclusion, BCG induces epigenetic reprogramming in human monocytes in&nbsp;vivo, followed by functional reprogramming and protection against non-related viral infections, with a key role for IL-1&beta; as a mediator of trained immunity responses.</p>',
			'date' => '2018-01-10',
			'pmid' => 'http://www.pubmed.gov/29324233',
			'doi' => '10.1016/j.chom.2017.12.010',
			'modified' => '2018-11-22 15:15:09',
			'created' => '2018-11-08 12:59:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 144 => array(
			'id' => '3440',
			'name' => 'Senescence-associated reprogramming promotes cancer stemness.',
			'authors' => 'Milanovic M, Fan DNY, Belenki D, Däbritz JHM, Zhao Z, Yu Y, Dörr JR, Dimitrova L, Lenze D, Monteiro Barbosa IA, Mendoza-Parra MA, Kanashova T, Metzner M, Pardon K, Reimann M, Trumpp A, Dörken B, Zuber J, Gronemeyer H, Hummel M, Dittmar G, Lee S, Schmitt C',
			'description' => '<p>Cellular senescence is a stress-responsive cell-cycle arrest program that terminates the further expansion of (pre-)malignant cells. Key signalling components of the senescence machinery, such as p16, p21 and p53, as well as trimethylation of lysine 9 at histone H3 (H3K9me3), also operate as critical regulators of stem-cell functions (which are collectively termed 'stemness'). In cancer cells, a gain of stemness may have profound implications for tumour aggressiveness and clinical outcome. Here we investigated whether chemotherapy-induced senescence could change stem-cell-related properties of malignant cells. Gene expression and functional analyses comparing senescent and non-senescent B-cell lymphomas from E&mu;-Myc transgenic mice revealed substantial upregulation of an adult tissue stem-cell signature, activated Wnt signalling, and distinct stem-cell markers in senescence. Using genetically switchable models of senescence targeting H3K9me3 or p53 to mimic spontaneous escape from the arrested condition, we found that cells released from senescence re-entered the cell cycle with strongly enhanced and Wnt-dependent clonogenic growth potential compared to virtually identical populations that had been equally exposed to chemotherapy but had never been senescent. In vivo, these previously senescent cells presented with a much higher tumour initiation potential. Notably, the temporary enforcement of senescence in p53-regulatable models of acute lymphoblastic leukaemia and acute myeloid leukaemia was found to reprogram non-stem bulk leukaemia cells into self-renewing, leukaemia-initiating stem cells. Our data, which are further supported by consistent results in human cancer cell lines and primary samples of human haematological malignancies, reveal that senescence-associated stemness is an unexpected, cell-autonomous feature that exerts its detrimental, highly aggressive growth potential upon escape from cell-cycle blockade, and is enriched in relapse tumours. These findings have profound implications for cancer therapy, and provide new mechanistic insights into the plasticity of cancer cells.</p>',
			'date' => '2018-01-04',
			'pmid' => 'http://www.pubmed.org/29258294',
			'doi' => '10.1038/nature25167',
			'modified' => '2019-02-15 21:39:11',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 145 => array(
			'id' => '3385',
			'name' => 'MLL2 conveys transcription-independent H3K4 trimethylation in oocytes',
			'authors' => 'Hanna C.W. et al.',
			'description' => '<p>Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyte provides an attractive system to investigate these mechanisms, because extensive H3K4me3 acquisition occurs in nondividing cells. We developed low-input chromatin immunoprecipitation to interrogate H3K4me3, H3K27ac and H3K27me3 marks throughout oogenesis. In nongrowing oocytes, H3K4me3 was restricted to active promoters, but as oogenesis progressed, H3K4me3 accumulated in a transcription-independent manner and was targeted to intergenic regions, putative enhancers and silent H3K27me3-marked promoters. Ablation of the H3K4 methyltransferase&nbsp;gene Mll2 resulted in loss of transcription-independent H3K4 trimethylation but had limited effects on transcription-coupled H3K4 trimethylation or gene expression. Deletion of Dnmt3a and Dnmt3b showed that DNA methylation protects regions from acquiring H3K4me3. Our findings reveal two independent mechanisms of targeting H3K4me3 to genomic elements, with MLL2 recruited to unmethylated CpG-rich regions independently of transcription.</p>',
			'date' => '2018-01-02',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29323282',
			'doi' => '',
			'modified' => '2018-08-07 10:26:20',
			'created' => '2018-08-07 10:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 146 => array(
			'id' => '3330',
			'name' => 'The histone code reader Spin1 controls skeletal muscle development',
			'authors' => 'Greschik H. et al.',
			'description' => '<p>While several studies correlated increased expression of the histone code reader Spin1 with tumor formation or growth, little is known about physiological functions of the protein. We generated Spin1<sup>M5</sup> mice with ablation of Spin1 in myoblast precursors using the Myf5-Cre deleter strain. Most Spin1<sup>M5</sup> mice die shortly after birth displaying severe sarcomere disorganization and necrosis. Surviving Spin1<sup>M5</sup> mice are growth-retarded and exhibit the most prominent defects in soleus, tibialis anterior, and diaphragm muscle. Transcriptome analyses of limb muscle at embryonic day (E) 15.5, E16.5, and at three weeks of age provided evidence for aberrant fetal myogenesis and identified deregulated skeletal muscle (SkM) functional networks. Determination of genome-wide chromatin occupancy in primary myoblast revealed direct Spin1 target genes and suggested that deregulated basic helix-loop-helix transcription factor networks account for developmental defects in Spin1<sup>M5</sup> fetuses. Furthermore, correlating histological and transcriptome analyses, we show that aberrant expression of titin-associated proteins, abnormal glycogen metabolism, and neuromuscular junction defects contribute to SkM pathology in Spin1<sup>M5</sup> mice. Together, we describe the first example of a histone code reader controlling SkM development in mice, which hints at Spin1 as a potential player in human SkM disease.</p>',
			'date' => '2017-11-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29168801',
			'doi' => '',
			'modified' => '2018-02-07 10:20:01',
			'created' => '2018-02-07 10:20:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 147 => array(
			'id' => '3322',
			'name' => 'In Situ Fixation Redefines Quiescence and Early Activation of Skeletal Muscle Stem Cells',
			'authors' => 'Machado L. et al.',
			'description' => '<div class="abstract">
<h2 class="sectionTitle" tabindex="0">Summary</h2>
<div class="content">
<p>State of the art techniques have been developed to isolate and analyze cells from various tissues, aiming to capture their <em>in&nbsp;vivo</em> state. However, the majority of cell isolation protocols involve lengthy mechanical and enzymatic dissociation steps followed by flow cytometry, exposing cells to stress and disrupting their physiological niche. Focusing on adult skeletal muscle stem cells, we have developed a protocol that circumvents the impact of isolation procedures and captures cells in their native quiescent state. We show that current isolation protocols induce major transcriptional changes accompanied by specific histone modifications while having negligible effects on DNA methylation. In addition to proposing a protocol to avoid isolation-induced artifacts, our study reveals previously undetected quiescence and early activation genes of potential biological interest.</p>
</div>
</div>',
			'date' => '2017-11-14',
			'pmid' => 'http://www.cell.com/cell-reports/abstract/S2211-1247(17)31543-7',
			'doi' => '',
			'modified' => '2022-05-19 16:11:43',
			'created' => '2018-02-02 16:36:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 148 => array(
			'id' => '3309',
			'name' => 'GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency',
			'authors' => 'Krendl C. et al.',
			'description' => '<p>To elucidate the molecular basis of BMP4-induced differentiation of human pluripotent stem cells (PSCs) toward progeny with trophectoderm characteristics, we produced transcriptome, epigenome H3K4me3, H3K27me3, and CpG methylation maps of trophoblast progenitors, purified using the surface marker APA. We combined them with the temporally resolved transcriptome of the preprogenitor phase and of single APA+ cells. This revealed a circuit of bivalent TFAP2A, TFAP2C, GATA2, and GATA3 transcription factors, coined collectively the "trophectoderm four" (TEtra), which are also present in human trophectoderm in vivo. At the onset of differentiation, the TEtra factors occupy multiple sites in epigenetically inactive placental genes and in <i>OCT4</i> Functional manipulation of <i>GATA3</i> and <i>TFAP2A</i> indicated that they directly couple trophoblast-specific gene induction with suppression of pluripotency. In accordance, knocking down <i>GATA3</i> in primate embryos resulted in a failure to form trophectoderm. The discovery of the TEtra circuit indicates how trophectoderm commitment is regulated in human embryogenesis.</p>',
			'date' => '2017-11-07',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29078328',
			'doi' => '',
			'modified' => '2018-01-04 10:23:33',
			'created' => '2018-01-04 10:23:33',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 149 => array(
			'id' => '3302',
			'name' => 'The mixed lineage leukemia 4 (MLL4) methyltransferase complex is involved in transforming growth factor beta (TGF-β)-activated gene transcription.',
			'authors' => 'Baas R. et al.',
			'description' => '<p>Sma and Mad related (SMAD)-mediated Transforming Growth Factor &beta; (TGF-&beta;) and Bone Morphogenetic Protein (BMP) signaling is required for various cellular processes. The activated heterotrimeric SMAD protein complexes associate with nuclear proteins such as the histone acetyltransferases p300, PCAF and the Mixed Lineage Leukemia 4 (MLL4) subunit Pax Transactivation domain-Interacting Protein (PTIP) to regulate gene transcription. We investigated the functional role of PTIP and PTIP Interacting protein 1 (PA1) in relation to TGF-&beta;-activated SMAD signaling. We immunoprecipitated PTIP and PA1 with all SMAD family members to identify the TGF-&beta; and not BMP-specific SMADs as interacting proteins. Gene silencing experiments of MLL4 and the subunits PA1 and PTIP confirm TGF-&beta;-specific genes to be regulated by the MLL4 complex, which links TGF-&beta; signaling to transcription regulation by the MLL4 methyltransferase complex.</p>',
			'date' => '2017-10-04',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28976802',
			'doi' => '',
			'modified' => '2017-12-05 10:50:08',
			'created' => '2017-12-05 10:50:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 150 => array(
			'id' => '3296',
			'name' => 'Predicting stimulation-dependent enhancer-promoter interactions from ChIP-Seq time course data',
			'authors' => 'Dzida T. et al.',
			'description' => '<p>We have developed a machine learning approach to predict stimulation-dependent enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ER&alpha;), RNA polymerase (Pol II) and histone marks H2AZ and H3K4me3 were measured over time using ChIP-Seq experiments in MCF7 cells stimulated with estrogen. A Bayesian classifier was developed which uses the correlation of temporal binding patterns at enhancers and promoters and genomic proximity as features to predict interactions. This method was trained using experimentally determined interactions from the same system and was shown to achieve much higher precision than predictions based on the genomic proximity of nearest ER&alpha;&nbsp;binding. We use the method to identify a genome-wide confident set of ER&alpha;&nbsp;target genes and their regulatory enhancers genome-wide. Validation with publicly available GRO-Seq data demonstrates that our predicted targets are much more likely to show early nascent transcription than predictions based on genomic ER&alpha;&nbsp;binding proximity alone.</p>',
			'date' => '2017-09-28',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28970965',
			'doi' => '',
			'modified' => '2017-12-04 11:06:11',
			'created' => '2017-12-04 11:06:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 151 => array(
			'id' => '3303',
			'name' => 'Genetic Predisposition to Multiple Myeloma at 5q15 Is Mediated by an ELL2 Enhancer Polymorphism',
			'authors' => 'Li N. et al.',
			'description' => '<p>Multiple myeloma (MM) is a malignancy of plasma cells. Genome-wide association studies have shown that variation at 5q15 influences MM risk. Here, we have sought to decipher the causal variant at 5q15 and the mechanism by which it influences tumorigenesis. We show that rs6877329&nbsp;G &gt; C resides in a predicted enhancer element that physically interacts with the transcription start site of ELL2. The rs6877329-C risk allele is associated with reduced enhancer activity and lowered ELL2 expression. Since ELL2 is critical to the B cell differentiation process, reduced ELL2 expression is consistent with inherited genetic variation contributing to arrest of plasma cell development, facilitating MM clonal expansion. These data provide evidence for a biological mechanism underlying a hereditary risk of MM at 5q15.</p>',
			'date' => '2017-09-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28903037',
			'doi' => '',
			'modified' => '2018-01-02 17:58:38',
			'created' => '2018-01-02 17:58:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 152 => array(
			'id' => '3298',
			'name' => 'Chromosome contacts in activated T cells identify autoimmune disease candidate genes',
			'authors' => 'Burren OS et al.',
			'description' => '<div class="abstr">
<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Autoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4<sup>+</sup> T cells. Linking such regulatory regions to gene promoters in disease-relevant cell contexts facilitates identification of candidate disease genes.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Within 4&nbsp;h, activation of CD4<sup>+</sup> T cells invokes changes in histone modifications and enhancer RNA transcription that correspond to altered expression of the interacting genes identified by promoter capture Hi-C. By integrating promoter capture Hi-C data with genetic associations for five autoimmune diseases, we prioritised 245 candidate genes with a median distance from peak signal to prioritised gene of 153&nbsp;kb. Just under half (108/245) prioritised genes related to activation-sensitive interactions. This included IL2RA, where allele-specific expression analyses were consistent with its interaction-mediated regulation, illustrating the utility of the approach.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">Our systematic experimental framework offers an alternative approach to candidate causal gene identification for variants with cell state-specific functional effects, with achievable sample sizes.</abstracttext></p>
</div>
</div>',
			'date' => '2017-09-04',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28870212',
			'doi' => '',
			'modified' => '2017-12-04 11:25:15',
			'created' => '2017-12-04 11:25:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 153 => array(
			'id' => '3262',
			'name' => 'A lncRNA fine tunes the dynamics of a cell state transition involving Lin28, let-7 and de novo DNA methylation',
			'authors' => 'Li M.A. et al.',
			'description' => '<p>Execution of pluripotency requires progression from the na&iuml;ve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) <em>linc1281,</em> hereafter <em>Ephemeron</em> (<em>Eprn</em>), that modulates the dynamics of exit from na&iuml;ve pluripotency. <em>Eprn</em> deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression. In the absence of <em>Eprn</em>, <em>Lin28a</em> expression is reduced which results in persistence of <em>let-7 microRNAs, and</em> the up-regulation of de novo methyltransferases Dnmt3a/b is delayed. <em>Dnmt3a/b</em> deletion retards ES cell transition, correlating with delayed <em>Nanog</em> promoter methylation and phenocopying loss of <em>Eprn</em> or <em>Lin28a</em>. The connection from lncRNA to miRNA and DNA methylation facilitates the acute extinction of na&iuml;ve pluripotency, a pre-requisite for rapid progression from preimplantation epiblast to gastrulation in rodents. <em>Eprn</em> illustrates how lncRNAs may introduce species-specific network modulations.</p>',
			'date' => '2017-08-18',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562443/',
			'doi' => '',
			'modified' => '2017-10-09 15:55:39',
			'created' => '2017-10-09 15:55:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 154 => array(
			'id' => '3240',
			'name' => 'Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation',
			'authors' => 'Pünzeler S. et al.',
			'description' => '<p>Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine the comprehensive interactome of H2A.Z and identify PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A is a functionally uncharacterized, vertebrate-specific protein that binds very tightly to chromatin through a concerted multivalent binding mode. Two internal protein regions mediate H2A.Z-specificity and nucleosome interaction, whereas the PWWP domain exhibits direct DNA binding. Genome-wide mapping reveals that PWWP2A binds selectively to H2A.Z-containing nucleosomes with strong preference for promoters of highly transcribed genes. In human cells, its depletion affects gene expression and impairs proliferation via a mitotic delay. While PWWP2A does not influence H2A.Z occupancy, the C-terminal tail of H2A.Z is one important mediator to recruit PWWP2A to chromatin. Knockdown of PWWP2A in <i>Xenopus</i> results in severe cranial facial defects, arising from neural crest cell differentiation and migration problems. Thus, PWWP2A is a novel H2A.Z-specific multivalent chromatin binder providing a surprising link between H2A.Z, chromosome segregation, and organ development.</p>',
			'date' => '2017-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28645917',
			'doi' => '',
			'modified' => '2017-08-29 09:45:44',
			'created' => '2017-08-29 09:45:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 155 => array(
			'id' => '3270',
			'name' => 'Mouse models of 17q21.31 microdeletion and microduplication syndromes highlight the importance of Kansl1 for cognition',
			'authors' => 'Arbogast T. et al.',
			'description' => '<p>Koolen-de Vries syndrome (KdVS) is a multi-system disorder characterized by intellectual disability, friendly behavior, and congenital malformations. The syndrome is caused either by microdeletions in the 17q21.31 chromosomal region or by variants in the KANSL1 gene. The reciprocal 17q21.31 microduplication syndrome is associated with psychomotor delay, and reduced social interaction. To investigate the pathophysiology of 17q21.31 microdeletion and microduplication syndromes, we generated three mouse models: 1) the deletion (Del/+); or 2) the reciprocal duplication (Dup/+) of the 17q21.31 syntenic region; and 3) a heterozygous Kansl1 (Kans1+/-) model. We found altered weight, general activity, social behaviors, object recognition, and fear conditioning memory associated with craniofacial and brain structural changes observed in both Del/+ and Dup/+ animals. By investigating hippocampus function, we showed synaptic transmission defects in Del/+ and Dup/+ mice. Mutant mice with a heterozygous loss-of-function mutation in Kansl1 displayed similar behavioral and anatomical phenotypes compared to Del/+ mice with the exception of sociability phenotypes. Genes controlling chromatin organization, synaptic transmission and neurogenesis were upregulated in the hippocampus of Del/+ and Kansl1+/- animals. Our results demonstrate the implication of KANSL1 in the manifestation of KdVS phenotypes and extend substantially our knowledge about biological processes affected by these mutations. Clear differences in social behavior and gene expression profiles between Del/+ and Kansl1+/- mice suggested potential roles of other genes affected by the 17q21.31 deletion. Together, these novel mouse models provide new genetic tools valuable for the development of therapeutic approaches.</p>',
			'date' => '2017-07-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28704368',
			'doi' => '',
			'modified' => '2017-10-10 17:25:37',
			'created' => '2017-10-10 17:25:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 156 => array(
			'id' => '3339',
			'name' => 'Platelet function is modified by common sequence variation in megakaryocyte super enhancers',
			'authors' => 'Petersen R. et al.',
			'description' => '<p>Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quantitative traits using cell type-matched epigenomic data and promoter long-range interactions. We identify potential regulatory functions for 423 of 565 (75%) non-coding variants associated with platelet traits and we demonstrate, through <em>ex vivo</em> and proof of principle genome editing validation, that variants in super enhancers play an important role in controlling archetypical platelet functions.</p>',
			'date' => '2017-07-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511350/#S1',
			'doi' => '',
			'modified' => '2018-02-15 10:25:39',
			'created' => '2018-02-15 10:25:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 157 => array(
			'id' => '3234',
			'name' => 'Chromatin Immunoprecipitation (ChIP) in Mouse T-cell Lines',
			'authors' => 'Giaimo B.D. et al.',
			'description' => '<p>Signaling pathways regulate gene expression programs via the modulation of the chromatin structure at different levels, such as by post-translational modifications (PTMs) of histone tails, the exchange of canonical histones with histone variants, and nucleosome eviction. Such regulation requires the binding of signal-sensitive transcription factors (TFs) that recruit chromatin-modifying enzymes at regulatory elements defined as enhancers. Understanding how signaling cascades regulate enhancer activity requires a comprehensive analysis of the binding of TFs, chromatin modifying enzymes, and the occupancy of specific histone marks and histone variants. Chromatin immunoprecipitation (ChIP) assays utilize highly specific antibodies to immunoprecipitate specific protein/DNA complexes. The subsequent analysis of the purified DNA allows for the identification the region occupied by the protein recognized by the antibody. This work describes a protocol to efficiently perform ChIP of histone proteins in a mature mouse T-cell line. The presented protocol allows for the performance of ChIP assays in a reasonable timeframe and with high reproducibility.</p>',
			'date' => '2017-06-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28654055',
			'doi' => '',
			'modified' => '2017-08-24 10:13:18',
			'created' => '2017-08-24 10:13:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 158 => array(
			'id' => '3222',
			'name' => 'DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats',
			'authors' => 'Brocks D. et al.',
			'description' => '<p>Several mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known about their genome-wide transcriptional and epigenomic consequences. By mapping global transcription start site (TSS) and chromatin dynamics, we observed the cryptic transcription of thousands of treatment-induced non-annotated TSSs (TINATs) following DNMTi and HDACi treatment. The resulting transcripts frequently splice into protein-coding exons and encode truncated or chimeric ORFs translated into products with predicted abnormal or immunogenic functions. TINAT transcription after DNMTi treatment coincided with DNA hypomethylation and gain of classical promoter histone marks, while HDACi specifically induced a subset of TINATs in association with H2AK9ac, H3K14ac, and H3K23ac. Despite this mechanistic difference, both inhibitors convergently induced transcription from identical sites, as we found TINATs to be encoded in solitary long terminal repeats of the ERV9/LTR12 family, which are epigenetically repressed in virtually all normal cells.</p>',
			'date' => '2017-06-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28604729',
			'doi' => '',
			'modified' => '2017-08-18 14:14:48',
			'created' => '2017-08-18 14:14:48',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 159 => array(
			'id' => '3241',
			'name' => 'Evolutionary re-wiring of p63 and the epigenomic regulatory landscape in keratinocytes and its potential implications on species-specific gene expression and phenotypes',
			'authors' => 'Sethi I. et al.',
			'description' => '<p>Although epidermal keratinocyte development and differentiation proceeds in similar fashion between humans and mice, evolutionary pressures have also wrought significant species-specific physiological differences. These differences between species could arise in part, by the rewiring of regulatory network due to changes in the global targets of lineage-specific transcriptional master regulators such as p63. Here we have performed a systematic and comparative analysis of the p63 target gene network within the integrated framework of the transcriptomic and epigenomic landscape of mouse and human keratinocytes. We determined that there exists a core set of &sim;1600 genomic regions distributed among enhancers and super-enhancers, which are conserved and occupied by p63 in keratinocytes from both species. Notably, these DNA segments are typified by consensus p63 binding motifs under purifying selection and are associated with genes involved in key keratinocyte and skin-centric biological processes. However, the majority of the p63-bound mouse target regions consist of either murine-specific DNA elements that are not alignable to the human genome or exhibit no p63 binding in the orthologous syntenic regions, typifying an occupancy lost subset. Our results suggest that these evolutionarily divergent regions have undergone significant turnover of p63 binding sites and are associated with an underlying inactive and inaccessible chromatin state, indicative of their selective functional activity in the transcriptional regulatory network in mouse but not human. Furthermore, we demonstrate that this selective targeting of genes by p63 correlates with subtle, but measurable transcriptional differences in mouse and human keratinocytes that converges on major metabolic processes, which often exhibit species-specific trends. Collectively our study offers possible molecular explanation for the observable phenotypic differences between the mouse and human skin and broadly informs on the prevailing principles that govern the tug-of-war between evolutionary forces of rigidity and plasticity over transcriptional regulatory programs.</p>',
			'date' => '2017-05-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28505376',
			'doi' => '',
			'modified' => '2017-08-29 12:01:20',
			'created' => '2017-08-29 12:01:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 160 => array(
			'id' => '3201',
			'name' => 'RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA(+) and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells.',
			'authors' => 'Lund R.J. et al.',
			'description' => '<p>POLR3G is expressed at high levels in human pluripotent stem cells (hPSCs) and is required for maintenance of stem cell state through mechanisms not known in detail. To explore how POLR3G regulates stem cell state, we carried out deep-sequencing analysis&nbsp;of polyA<sup>+</sup> and smallRNA transcriptomes present in hPSCs and regulated in POLR3G-dependent manner. Our data reveal that&nbsp;POLR3G regulates a specific subset of the hPSC transcriptome, including multiple transcript types, such as protein-coding genes,&nbsp;long intervening non-coding RNAs, microRNAs and small nucleolar RNAs, and affects RNA splicing. The primary function of POLR3G is in the maintenance rather than repression of transcription. The majority of POLR3G polyA<sup>+</sup> transcriptome is regulated&nbsp;during differentiation, and the key pluripotency factors bind to the promoters of at least 30% of the POLR3G-regulated transcripts. Among the direct targets of POLR3G, POLG is potentially important in sustaining stem cell status in a POLR3G-dependent manner.</p>',
			'date' => '2017-05-09',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28494942',
			'doi' => '',
			'modified' => '2017-07-03 10:04:16',
			'created' => '2017-07-03 10:04:16',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 161 => array(
			'id' => '3211',
			'name' => 'The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis.',
			'authors' => 'Aldiri I. et al.',
			'description' => '<p>In the developing retina, multipotent neural progenitors undergo unidirectional differentiation in a precise spatiotemporal order. Here we profile the epigenetic and transcriptional changes that occur during retinogenesis in mice and humans. Although some progenitor genes and cell cycle genes were epigenetically silenced during retinogenesis, the most dramatic change was derepression of cell-type-specific differentiation programs. We identified developmental-stage-specific super-enhancers and showed that most epigenetic changes are conserved in humans and mice. To determine how the epigenome changes during tumorigenesis and reprogramming, we performed integrated epigenetic analysis of murine and human retinoblastomas and induced pluripotent stem cells (iPSCs) derived from murine rod photoreceptors. The retinoblastoma epigenome mapped to the developmental stage when retinal progenitors switch from neurogenic to terminal patterns of cell division. The epigenome of retinoblastomas was more similar to that of the normal retina than that of retina-derived iPSCs, and we identified retina-specific epigenetic memory.</p>',
			'date' => '2017-05-03',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28472656',
			'doi' => '',
			'modified' => '2017-07-07 17:04:39',
			'created' => '2017-07-07 17:04:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 162 => array(
			'id' => '3187',
			'name' => 'Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions',
			'authors' => 'Frank-Bertoncelj M, Trenkmann M, Klein K, Karouzakis E, Rehrauer H, Bratus A, Kolling C, Armaka M, Filer A, Michel BA, Gay RE, Buckley CD, Kollias G, Gay S, Ospelt C',
			'description' => '<p>A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNF, creating a unique microenvironment in each joint. These findings indicate that local stroma might control positional disease patterns not only in arthritis but in any disease with a prominent stromal component.</p>',
			'date' => '2017-03-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28332497',
			'doi' => '',
			'modified' => '2017-05-24 17:07:07',
			'created' => '2017-05-24 17:07:07',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 163 => array(
			'id' => '3159',
			'name' => 'Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells',
			'authors' => 'Tumber A. et al.',
			'description' => '<p>Methylation of lysine residues on histone tail is a dynamic epigenetic modification that plays a key role in chromatin structure and gene regulation. Members of the KDM5 (also known as JARID1) sub-family are 2-oxoglutarate (2-OG) and Fe<sup>2+</sup>-dependent oxygenases acting as histone 3 lysine 4 trimethyl (H3K4me3) demethylases, regulating proliferation, stem cell self-renewal, and differentiation. Here we present the characterization of KDOAM-25, an inhibitor of KDM5 enzymes. KDOAM-25 shows biochemical half maximal inhibitory concentration values of&nbsp;&lt;100&nbsp;nM for KDM5A-D in&nbsp;vitro, high selectivity toward other 2-OG oxygenases sub-families, and no off-target activity on a panel of 55 receptors and enzymes. In human cell assay systems, KDOAM-25 has a half maximal effective concentration of &sim;50&nbsp;&mu;M and good selectivity toward other demethylases. KDM5B is overexpressed in multiple myeloma and negatively correlated with the overall survival. Multiple myeloma MM1S cells treated with KDOAM-25 show increased global H3K4 methylation at transcriptional start sites and impaired proliferation.</p>',
			'date' => '2017-03-16',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28262558',
			'doi' => '',
			'modified' => '2017-04-12 14:51:37',
			'created' => '2017-04-12 14:51:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 164 => array(
			'id' => '3172',
			'name' => 'Decoupling of DNA methylation and activity of intergenic LINE-1 promoters in colorectal cancer',
			'authors' => 'Vafadar-Isfahani N. et al.',
			'description' => '<p>Hypomethylation of LINE-1 repeats in cancer has been proposed as the main mechanism behind their activation; this assumption, however, was based on findings from early studies that were biased toward young and transpositionally active elements. Here, we investigate the relationship between methylation of 2 intergenic, transpositionally inactive LINE-1 elements and expression of the LINE-1 chimeric transcript (LCT) 13 and LCT14 driven by their antisense promoters (L1-ASP). Our data from DNA modification, expression, and 5'RACE analyses suggest that colorectal cancer methylation in the regions analyzed is not always associated with LCT repression. Consistent with this, in HCT116 colorectal cancer cells lacking DNA methyltransferases DNMT1 or DNMT3B, LCT13 expression decreases, while cells lacking both DNMTs or treated with the DNMT inhibitor 5-azacytidine (5-aza) show no change in LCT13 expression. Interestingly, levels of the H4K20me3 histone modification are inversely associated with LCT13 and LCT14 expression. Moreover, at these LINE-1s, H4K20me3 levels rather than DNA methylation seem to be good predictor of their sensitivity to 5-aza treatment. Therefore, by studying individual LINE-1 promoters we have shown that in some cases these promoters can be active without losing methylation; in addition, we provide evidence that other factors (e.g., H4K20me3 levels) play prominent roles in their regulation.</p>',
			'date' => '2017-03-16',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28300471',
			'doi' => '',
			'modified' => '2017-05-10 16:26:24',
			'created' => '2017-05-10 16:26:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 165 => array(
			'id' => '3165',
			'name' => 'Assessing histone demethylase inhibitors in cells: lessons learned',
			'authors' => 'Hatch S.B. et al.',
			'description' => '<div xmlns="http://www.w3.org/1999/xhtml" class="AbstractSection" id="ASec1">
<h3 xmlns="" class="Heading">Background</h3>
<p id="Par1" class="Para">Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The first KDM inhibitors for KDM1 have entered clinical trials, and efforts are ongoing to develop potent, selective and cell-active &lsquo;probe&rsquo; molecules for this target class. Robust cellular assays to assess the specific engagement of KDM inhibitors in cells as well as their cellular selectivity are a prerequisite for the development of high-quality inhibitors. Here we describe the use of a high-content cellular immunofluorescence assay as a method for demonstrating target engagement in cells.</p>
</div>
<div xmlns="http://www.w3.org/1999/xhtml" class="AbstractSection" id="ASec2">
<h3 xmlns="" class="Heading">Results</h3>
<p id="Par2" class="Para">A panel of assays for the Jumonji C subfamily of KDMs was developed to encompass all major branches of the JmjC phylogenetic tree. These assays compare compound activity against wild-type KDM proteins to a catalytically inactive version of the KDM, in which residues involved in the active-site iron coordination are mutated to inactivate the enzyme activity. These mutants are critical for assessing the specific effect of KDM inhibitors and for revealing indirect effects on histone methylation status. The reported assays make use of ectopically expressed demethylases, and we demonstrate their use to profile several recently identified classes of KDM inhibitors and their structurally matched inactive controls. The generated data correlate well with assay results assessing endogenous KDM inhibition and confirm the selectivity observed in biochemical assays with isolated enzymes. We find that both cellular permeability and competition with 2-oxoglutarate affect the translation of biochemical activity to cellular inhibition.</p>
</div>
<div xmlns="http://www.w3.org/1999/xhtml" class="AbstractSection" id="ASec3">
<h3 xmlns="" class="Heading">Conclusions</h3>
<p id="Par3" class="Para">High-content-based immunofluorescence assays have been established for eight KDM members of the 2-oxoglutarate-dependent oxygenases covering all major branches of the JmjC-KDM phylogenetic tree. The usage of both full-length, wild-type and catalytically inactive mutant ectopically expressed protein, as well as structure-matched inactive control compounds, allowed for detection of nonspecific effects causing changes in histone methylation as a result of compound toxicity. The developed assays offer a histone lysine demethylase family-wide tool for assessing KDM inhibitors for cell activity and on-target efficacy. In addition, the presented data may inform further studies to assess the cell-based activity of histone lysine methylation inhibitors.</p>
</div>',
			'date' => '2017-03-01',
			'pmid' => 'https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-017-0116-6',
			'doi' => '',
			'modified' => '2017-05-09 10:02:47',
			'created' => '2017-05-09 10:02:47',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 166 => array(
			'id' => '3149',
			'name' => 'RNF40 regulates gene expression in an epigenetic context-dependent manner',
			'authors' => 'Xie W. et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlates with increased gene expression. In contrast, depletion of the H2B ubiquitin ligases RNF20 or RNF40 alters the expression of only a subset of genes.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Using conditional Rnf40 knockout mouse embryo fibroblasts, we show that genes occupied by low to moderate amounts of H2Bub1 are selectively regulated in response to Rnf40 deletion, whereas genes marked by high levels of H2Bub1 are mostly unaffected by Rnf40 loss. Furthermore, we find that decreased expression of RNF40-dependent genes is highly associated with widespread narrowing of H3K4me3 peaks. H2Bub1 promotes the broadening of H3K4me3 to increase transcriptional elongation, which together lead to increased tissue-specific gene transcription. Notably, genes upregulated following Rnf40 deletion, including Foxl2, are enriched for H3K27me3, which is decreased following Rnf40 deletion due to decreased expression of the Ezh2 gene. As a consequence, increased expression of some RNF40-"suppressed" genes is associated with enhancer activation via FOXL2.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">Together these findings reveal the complexity and context-dependency whereby one histone modification can have divergent effects on gene transcription. Furthermore, we show that these effects are dependent upon the activity of other epigenetic regulatory proteins and histone modifications.</abstracttext></p>
</div>',
			'date' => '2017-02-16',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28209164',
			'doi' => '',
			'modified' => '2017-03-24 17:22:20',
			'created' => '2017-03-24 17:22:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 167 => array(
			'id' => '3140',
			'name' => 'Menin regulates Inhbb expression through an Akt/Ezh2-mediated H3K27 histone modification',
			'authors' => 'Gherardi S. et al.',
			'description' => '<p>Although Men1 is a well-known tumour suppressor gene, little is known about the functions of Menin, the protein it encodes for. Since few years, numerous publications support a major role of Menin in the control of epigenetics gene regulation. While Menin interaction with MLL complex favours transcriptional activation of target genes through H3K4me3 marks, Menin also represses gene expression via mechanisms involving the Polycomb repressing complex (PRC). Interestingly, Ezh2, the PRC-methyltransferase that catalyses H3K27me3 repressive marks and Menin have been shown to co-occupy a large number of promoters. However, lack of binding between Menin and Ezh2 suggests that another member of the PRC complex is mediating this indirect interaction. Having found that ActivinB - a TGF&beta; superfamily member encoded by the Inhbb gene - is upregulated in insulinoma tumours caused by Men1 invalidation, we hypothesize that Menin could directly participate in the epigenetic-repression of Inhbb gene expression. Using Animal model and cell lines, we report that loss of Menin is directly associated with ActivinB-induced expression both in vivo and in vitro. Our work further reveals that ActivinB expression is mediated through a direct modulation of H3K27me3 marks on the Inhbb locus in Menin-KO cell lines. More importantly, we show that Menin binds on the promoter of Inhbb gene where it favours the recruitment of Ezh2 via an indirect mechanism involving Akt-phosphorylation. Our data suggests therefore that Menin could take an important part to the Ezh2-epigenetic repressive landscape in many cells and tissues through its capacity to modulate Akt phosphorylation.</p>',
			'date' => '2017-02-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28215965',
			'doi' => '',
			'modified' => '2017-03-22 12:07:48',
			'created' => '2017-03-22 12:07:48',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 168 => array(
			'id' => '3139',
			'name' => 'A novel DLX3-PKC integrated signaling network drives keratinocyte differentiation',
			'authors' => 'Palazzo E. et al.',
			'description' => '<p>Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regulate cell cycle-related signaling and that this mechanism is functionally involved in cutaneous squamous cell carcinoma development. Here we show that DLX3 expression and its downstream signaling depend on protein kinase C &alpha; (PKC&alpha;) activity in skin. We found that following 12-O-tetradecanoyl-phorbol-13-acetate (TPA) topical treatment, DLX3 expression is significantly upregulated in the epidermis and keratinocytes from mice overexpressing PKC&alpha; by transgenic targeting (K5-PKC&alpha;), resulting in cell cycle block and terminal differentiation. Epidermis lacking DLX3 (DLX3cKO), which is linked to the development of a DLX3-dependent epidermal hyperplasia with hyperkeratosis and dermal leukocyte recruitment, displays enhanced PKC&alpha; activation, suggesting a feedback regulation of DLX3 and PKC&alpha;. Of particular significance, transcriptional activation of epidermal barrier, antimicrobial peptide and cytokine genes is significantly increased in DLX3cKO skin and further increased by TPA-dependent PKC activation. Furthermore, when inhibiting PKC activity, we show that epidermal thickness, keratinocyte proliferation and inflammatory cell infiltration are reduced and the PKC-DLX3-dependent gene expression signature is normalized. Independently of PKC, DLX3 expression specifically modulates regulatory networks such as Wnt signaling, phosphatase activity and cell adhesion. Chromatin immunoprecipitation sequencing analysis of primary suprabasal keratinocytes showed binding of DLX3 to the proximal promoter regions of genes associated with cell cycle regulation, and of structural proteins and transcription factors involved in epidermal differentiation. These results indicate that Dlx3 potentially regulates a set of crucial genes necessary during the epidermal differentiation process. Altogether, we demonstrate the existence of a robust DLX3-PKC&alpha; signaling pathway in keratinocytes that is crucial to epidermal differentiation control and cutaneous homeostasis.</p>',
			'date' => '2017-02-10',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28186503',
			'doi' => '',
			'modified' => '2017-03-22 12:00:37',
			'created' => '2017-03-22 12:00:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 169 => array(
			'id' => '3100',
			'name' => 'Muscle catabolic capacities and global hepatic epigenome are modified in juvenile rainbow trout fed different vitamin levels at first feeding',
			'authors' => 'Panserat S. et al.',
			'description' => '<p>Based on the concept of nutritional programming in mammals, we tested whether a short term hyper or hypo vitamin stimulus during first-feeding could induce long-lasting changes in nutrient metabolism in rainbow trout. Trout alevins received during the 4 first weeks of exogenous feeding a diet either without supplemental vitamins (NOSUP), a diet supplemented with a vitamin premix to satisfy the minimal requirement in all the vitamins (NRC) or a diet with a vitamin premix corresponding to an optimal vitamin nutrition (OVN). Following a common rearing period on the control diet, all three groups were then evaluated in terms of metabolic marker gene expressions at the end of the feeding period (day 119). Whereas no gene modifications for proteins involved in energy and lipid metabolism were observed in whole alevins (short-term effect), some of these genes showed a long-term molecular adaptation in the muscle of juveniles (long-term effect). Indeed, muscle of juveniles subjected at an early feeding of the OVN diet displayed up-regulated expression of markers of lipid catabolism (3-hydroxyacyl-CoA dehydrogenase &ndash; HOAD - enzyme) and mitochondrial energy metabolism (Citrate synthase - <em>cs</em>, Ubiquitinol cytochrome <em>c</em> reductase core protein 2 - QCR2, cytochrome oxidase 4 - COX4, ATP synthase form 5 - ATP5A) compared to fish fed the NOSUP diet. Moreover, some key enzymes involved in glucose catabolism (Muscle Pyruvate kinase - PKM) and amino acid catabolism (Glutamate dehydrogenase - GDH3) were also up regulated in muscle of juvenile fish fed with the OVN diet at first-feeding compared to fish fed the NOSUP diet. We researched if these permanently modified gene expressions could be related to global modifications of epigenetic marks (global DNA methylation and global histone acetylation and methylation). There was no variation of the epigenetic marks in muscle. However, we found changes in hepatic DNA methylation, global H3 acetylation and H3K4 methylation, dependent on the vitamin intake at early life. In summary, our data show, for the first time in fish, that a short-term vitamin-stimulus during early life may durably influence muscle energy and lipid metabolism as well as some hepatic epigenetic marks in rainbow trout.</p>',
			'date' => '2017-02-01',
			'pmid' => 'http://www.sciencedirect.com/science/article/pii/S0044848616309693',
			'doi' => '',
			'modified' => '2017-01-03 15:01:50',
			'created' => '2017-01-03 15:01:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 170 => array(
			'id' => '3131',
			'name' => 'DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma',
			'authors' => 'Sheffield N.C. et al.',
			'description' => '<p>Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genetically homogeneous cancers. We performed genome-scale DNA methylation sequencing for a large cohort of Ewing sarcoma tumors and analyzed epigenetic heterogeneity on three levels: between cancers, between tumors, and within tumors. We observed consistent DNA hypomethylation at enhancers regulated by the disease-defining EWS-FLI1 fusion protein, thus establishing epigenomic enhancer reprogramming as a ubiquitous and characteristic feature of Ewing sarcoma. DNA methylation differences between tumors identified a continuous disease spectrum underlying Ewing sarcoma, which reflected the strength of an EWS-FLI1 regulatory signature and a continuum between mesenchymal and stem cell signatures. There was substantial epigenetic heterogeneity within tumors, particularly in patients with metastatic disease. In summary, our study provides a comprehensive assessment of epigenetic heterogeneity in Ewing sarcoma and thereby highlights the importance of considering nongenetic aspects of tumor heterogeneity in the context of cancer biology and personalized medicine.</p>',
			'date' => '2017-01-30',
			'pmid' => 'http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4273.html',
			'doi' => '',
			'modified' => '2017-03-07 15:33:50',
			'created' => '2017-03-07 15:33:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 171 => array(
			'id' => '3144',
			'name' => 'MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct enhancer repertoire and target the RUNX1 program in 11q23 acute myeloid leukemia.',
			'authors' => 'Prange KH et al.',
			'description' => '<p>In 11q23 leukemias, the N-terminal part of the mixed lineage leukemia (MLL) gene is fused to &gt;60 different partner genes. In order to define a core set of MLL rearranged targets, we investigated the genome-wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and associated epigenetic signatures in acute myeloid leukemia (AML) cell lines THP-1 and MV4-11. We uncovered both common as well as specific MLL-AF9 and MLL-AF4 target genes, which were all marked by H3K79me2, H3K27ac and H3K4me3. Apart from promoter binding, we also identified MLL-AF9 and MLL-AF4 binding at specific subsets of non-overlapping active distal regulatory elements. Despite this differential enhancer binding, MLL-AF9 and MLL-AF4 still direct a common gene program, which represents part of the RUNX1 gene program and constitutes of CD34<sup>+</sup> and monocyte-specific genes. Comparing these data sets identified several zinc finger transcription factors (TFs) as potential MLL-AF9 co-regulators. Together, these results suggest that MLL fusions collaborate with specific subsets of TFs to deregulate the RUNX1 gene program in 11q23 AMLs.</p>',
			'date' => '2017-01-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28114278',
			'doi' => '',
			'modified' => '2017-03-23 15:13:45',
			'created' => '2017-03-23 15:13:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 172 => array(
			'id' => '3090',
			'name' => 'Arabidopsis SWI/SNF chromatin remodeling complex binds both promoters and terminators to regulate gene expression',
			'authors' => 'Archacki R. et al.',
			'description' => '<p>ATP-dependent chromatin remodeling complexes are important regulators of gene expression in Eukaryotes. In plants, SWI/SNF-type complexes have been shown critical for transcriptional control of key developmental processes, growth and stress responses. To gain insight into mechanisms underlying these roles, we performed whole genome mapping of the SWI/SNF catalytic subunit BRM in Arabidopsis thaliana, combined with transcript profiling experiments. Our data show that BRM occupies thousands of sites in Arabidopsis genome, most of which located within or close to genes. Among identified direct BRM transcriptional targets almost equal numbers were up- and downregulated upon BRM depletion, suggesting that BRM can act as both activator and repressor of gene expression. Interestingly, in addition to genes showing canonical pattern of BRM enrichment near transcription start site, many other genes showed a transcription termination site-centred BRM occupancy profile. We found that BRM-bound 3' gene regions have promoter-like features, including presence of TATA boxes and high H3K4me3 levels, and possess high antisense transcriptional activity which is subjected to both activation and repression by SWI/SNF complex. Our data suggest that binding to gene terminators and controlling transcription of non-coding RNAs is another way through which SWI/SNF complex regulates expression of its targets.</p>',
			'date' => '2016-12-19',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27994035',
			'doi' => '',
			'modified' => '2017-01-03 10:02:56',
			'created' => '2017-01-03 10:02:56',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 173 => array(
			'id' => '3096',
			'name' => 'Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals',
			'authors' => 'Schwörer S. et al.',
			'description' => '<p>The functionality of stem cells declines during ageing, and this decline contributes to ageing-associated impairments in tissue regeneration and function. Alterations in developmental pathways have been associated with declines in stem-cell function during ageing, but the nature of this process remains poorly understood. Hox genes are key regulators of stem cells and tissue patterning during embryogenesis with an unknown role in ageing. Here we show that the epigenetic stress response in muscle stem cells (also known as satellite cells) differs between aged and young mice. The alteration includes aberrant global and site-specific induction of active chromatin marks in activated satellite cells from aged mice, resulting in the specific induction of Hoxa9 but not other Hox genes. Hoxa9 in turn activates several developmental pathways and represents a decisive factor that separates satellite cell gene expression in aged mice from that in young mice. The activated pathways include most of the currently known inhibitors of satellite cell function in ageing muscle, including Wnt, TGF&beta;, JAK/STAT and senescence signalling. Inhibition of aberrant chromatin activation or deletion of Hoxa9 improves satellite cell function and muscle regeneration in aged mice, whereas overexpression of Hoxa9 mimics ageing-associated defects in satellite cells from young mice, which can be rescued by the inhibition of Hoxa9-targeted developmental pathways. Together, these data delineate an altered epigenetic stress response in activated satellite cells from aged mice, which limits satellite cell function and muscle regeneration by Hoxa9-dependent activation of developmental pathways.</p>',
			'date' => '2016-12-15',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27919074',
			'doi' => '',
			'modified' => '2017-01-03 12:28:33',
			'created' => '2017-01-03 12:28:33',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 174 => array(
			'id' => '3111',
			'name' => 'Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity',
			'authors' => 'Arts R.J. et al.',
			'description' => '<p>Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by &beta;-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases. Furthermore, fumarate itself induced an epigenetic program similar to &beta;-glucan-induced trained immunity. In line with this, inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by &beta;-glucan. Identification of the metabolic pathways leading to induction of trained immunity contributes to our understanding of innate immune memory and opens new therapeutic avenues.</p>',
			'date' => '2016-12-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27866838',
			'doi' => '',
			'modified' => '2017-01-04 11:17:08',
			'created' => '2017-01-04 11:17:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 175 => array(
			'id' => '3110',
			'name' => 'Immunometabolic Pathways in BCG-Induced Trained Immunity',
			'authors' => 'Arts R.J. et al.',
			'description' => '<p>The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity. Here, we show that BCG induction of trained immunity in monocytes is accompanied by a strong increase in glycolysis and, to a lesser extent, glutamine metabolism, both in an in-vitro model and after vaccination of mice and humans. Pharmacological and genetic modulation of rate-limiting glycolysis enzymes inhibits trained immunity, changes that are reflected by the effects on the histone marks (H3K4me3 and H3K9me3) underlying BCG-induced trained immunity. These data demonstrate that a shift of the glucose metabolism toward glycolysis is crucial for the induction of the histone modifications and functional changes underlying BCG-induced trained immunity. The identification of these pathways may be a first step toward vaccines that combine immunological and metabolic stimulation.</p>',
			'date' => '2016-12-06',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27926861',
			'doi' => '',
			'modified' => '2017-01-04 11:15:23',
			'created' => '2017-01-04 11:15:23',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 176 => array(
			'id' => '3098',
			'name' => 'TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells',
			'authors' => 'de la Rica L. et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Ten-eleven translocation (TET) enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable elements (TEs), which make up nearly half of the mouse and human genomes. Epigenetic mechanisms controlling TEs have the potential to affect their mobility and to drive the co-adoption of TEs for the benefit of the host.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">We performed a detailed investigation of the role of TET enzymes in the regulation of TEs in mouse embryonic stem cells (ESCs). We find that TET1 and TET2 bind multiple TE classes that harbour a variety of epigenetic signatures indicative of different functional roles. TETs co-bind with pluripotency factors to enhancer-like TEs that interact with highly expressed genes in ESCs whose expression is partly maintained by TET2-mediated DNA demethylation. TETs and 5-hydroxymethylcytosine (5hmC) are also strongly enriched at the 5' UTR of full-length, evolutionarily young LINE-1 elements, a pattern that is conserved in human ESCs. TETs drive LINE-1 demethylation, but surprisingly, LINE-1s are kept repressed through additional TET-dependent activities. We find that the SIN3A co-repressive complex binds to LINE-1s, ensuring their repression in a TET1-dependent manner.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">Our data implicate TET enzymes in the evolutionary dynamics of TEs, both in the context of exaptation processes and of retrotransposition control. The dual role of TET action on LINE-1s may reflect the evolutionary battle between TEs and the host.</abstracttext></p>
</div>',
			'date' => '2016-11-18',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27863519',
			'doi' => '',
			'modified' => '2017-01-03 14:23:08',
			'created' => '2017-01-03 14:23:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 177 => array(
			'id' => '3103',
			'name' => 'β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance',
			'authors' => 'Novakovic B. et al.',
			'description' => '<p>Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as lipopolysaccharide (LPS). We apply an integrated epigenomic&nbsp;approach to characterize the molecular events involved in LPS-induced tolerance in a time-dependent manner. Mechanistically, LPS-treated monocytes fail to accumulate active histone marks at promoter and enhancers of genes in the lipid metabolism and phagocytic pathways. Transcriptional inactivity in response to a second LPS exposure in tolerized macrophages is accompanied by failure to deposit active histone marks at promoters of tolerized genes. In contrast, &beta;-glucan partially reverses the LPS-induced tolerance in&nbsp;vitro. Importantly, ex&nbsp;vivo &beta;-glucan treatment of monocytes from volunteers with experimental endotoxemia re-instates their capacity for cytokine production. Tolerance is reversed at the level of distal element histone modification and transcriptional reactivation of otherwise unresponsive genes.</p>',
			'date' => '2016-11-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27863248',
			'doi' => '',
			'modified' => '2017-01-03 15:31:46',
			'created' => '2017-01-03 15:31:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 178 => array(
			'id' => '3105',
			'name' => 'EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells',
			'authors' => 'Beringer M. et al.',
			'description' => '<p>The cellular plasticity of pluripotent stem cells is thought to be sustained by genomic regions that display both active and repressive chromatin properties. These regions exhibit low levels of gene expression, yet the mechanisms controlling these levels remain unknown. Here, we describe Elongin BC as a binding factor at the promoters of bivalent sites. Biochemical and genome-wide analyses show that Elongin BC is associated with Polycomb Repressive Complex 2 (PRC2) in pluripotent stem cells. Elongin BC is recruited to chromatin by the PRC2-associated&nbsp;factor EPOP (Elongin BC and Polycomb Repressive Complex 2 Associated Protein, also termed C17orf96, esPRC2p48, E130012A19Rik), a protein expressed in the inner cell mass of the mouse blastocyst. Both EPOP and Elongin BC are required to maintain low levels of expression at PRC2 genomic targets. Our results indicate that keeping the balance between activating and repressive cues is a more general feature of chromatin in pluripotent stem cells than previously appreciated.</p>',
			'date' => '2016-11-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27863225',
			'doi' => '',
			'modified' => '2017-01-03 16:02:21',
			'created' => '2017-01-03 16:02:21',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 179 => array(
			'id' => '3087',
			'name' => 'The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs',
			'authors' => 'Mandoli A. et al.',
			'description' => '<p>The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels of histone acetylation but also at distal elements characterized by low acetylation levels and binding of the hematopoietic transcription factors LYL1 and LMO2. In contrast, ERG, FLI1, TAL1, and RUNX1 bind at all AML1-ETO-occupied regulatory regions, including those of the AML1-ETO gene itself, suggesting their involvement in regulating AML1-ETO expression levels. While expression of AML1-ETO in myeloid differentiated induced pluripotent stem cells (iPSCs) induces leukemic characteristics, overexpression increases cell death. We find that expression of wild-type transcription factors RUNX1 and ERG in AML is required to prevent this oncogene overexpression. Together our results show that the interplay of the epigenome and transcription factors prevents apoptosis in t(8;21) AML cells.</p>',
			'date' => '2016-11-15',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27851970',
			'doi' => '',
			'modified' => '2017-01-02 11:07:24',
			'created' => '2017-01-02 11:07:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 180 => array(
			'id' => '3114',
			'name' => 'Iterative Fragmentation Improves the Detection of ChIP-seq Peaks for Inactive Histone Marks',
			'authors' => 'Laczik M. et al.',
			'description' => '<p>As chromatin immunoprecipitation (ChIP) sequencing is becoming the dominant technique for studying chromatin modifications, new protocols surface to improve the method. Bioinformatics is also essential to analyze and understand the results, and precise analysis helps us to identify the effects of protocol optimizations. We applied iterative sonication - sending the fragmented DNA after ChIP through additional round(s) of shearing - to a number of samples, testing the effects on different histone marks, aiming to uncover potential benefits of inactive histone marks specifically. We developed an analysis pipeline that utilizes our unique, enrichment-type specific approach to peak calling. With the help of this pipeline, we managed to accurately describe the advantages and disadvantages of the iterative refragmentation technique, and we successfully identified possible fields for its applications, where it enhances the results greatly. In addition to the resonication protocol description, we provide guidelines for peak calling optimization and a freely implementable pipeline for data analysis.</p>',
			'date' => '2016-10-25',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27812282',
			'doi' => '',
			'modified' => '2017-01-17 16:07:44',
			'created' => '2017-01-17 16:07:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 181 => array(
			'id' => '3033',
			'name' => 'Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition',
			'authors' => 'Sciacovelli M et al.',
			'description' => '<p>Mutations of the tricarboxylic acid cycle enzyme fumarate hydratase cause hereditary leiomyomatosis and renal cell cancer<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref1" title="Tomlinson, I. P. et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat. Genet. 30, 406&ndash;410 (2002)" id="ref-link-5">1</a></sup>. Fumarate hydratase-deficient renal cancers are highly aggressive and metastasize even when small, leading to a very poor clinical outcome<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref2" title="Schmidt, L. S. &amp; Linehan, W. M. Hereditary leiomyomatosis and renal cell carcinoma. Int. J. Nephrol. Renovasc. Dis. 7, 253&ndash;260 (2014)" id="ref-link-6">2</a></sup>. Fumarate, a small molecule metabolite that accumulates in fumarate hydratase-deficient cells, plays a key role in cell transformation, making it a <i>bona fide</i> oncometabolite<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref3" title="Yang, M., Soga, T., Pollard, P. J. &amp; Adam, J. The emerging role of fumarate as an oncometabolite. Front Oncol. 2, 85 (2012)" id="ref-link-7">3</a></sup>. Fumarate has been shown to inhibit &alpha;-ketoglutarate-dependent dioxygenases that are involved in DNA and histone demethylation<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref4" title="Laukka, T. et al. Fumarate and succinate regulate expression of hypoxia-inducible genes via TET enzymes. J. Biol. Chem. 291, 4256&ndash;4265 (2016)" id="ref-link-8">4</a>, <a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref5" title="Xiao, M. et al. Inhibition of &alpha;-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev. 26, 1326&ndash;1338 (2012)" id="ref-link-9">5</a></sup>. However, the link between fumarate accumulation, epigenetic changes, and tumorigenesis is unclear. Here we show that loss of fumarate hydratase and the subsequent accumulation of fumarate in mouse and human cells elicits an epithelial-to-mesenchymal-transition (EMT), a phenotypic switch associated with cancer initiation, invasion, and metastasis<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref6" title="De Craene, B. &amp; Berx, G. Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer 13, 97&ndash;110 (2013)" id="ref-link-10">6</a></sup>. We demonstrate that fumarate inhibits Tet-mediated demethylation of a regulatory region of the antimetastatic miRNA cluster<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref6" title="De Craene, B. &amp; Berx, G. Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer 13, 97&ndash;110 (2013)" id="ref-link-11">6</a></sup> <i>mir-200ba429</i>, leading to the expression of EMT-related transcription factors and enhanced migratory properties. These epigenetic and phenotypic changes are recapitulated by the incubation of fumarate hydratase-proficient cells with cell-permeable fumarate. Loss of fumarate hydratase is associated with suppression of miR-200 and the EMT signature in renal cancer and is associated with poor clinical outcome. These results imply that loss of fumarate hydratase and fumarate accumulation contribute to the aggressive features of fumarate hydratase-deficient tumours.</p>',
			'date' => '2016-08-31',
			'pmid' => 'http://www.nature.com/nature/journal/v537/n7621/full/nature19353.html',
			'doi' => '',
			'modified' => '2016-09-23 10:44:15',
			'created' => '2016-09-23 10:44:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 182 => array(
			'id' => '3006',
			'name' => 'reChIP-seq reveals widespread bivalency of H3K4me3 and H3K27me3 in CD4(+) memory T cells',
			'authors' => 'Kinkley S et al.',
			'description' => '<p>The combinatorial action of co-localizing chromatin modifications and regulators determines chromatin structure and function. However, identifying co-localizing chromatin features in a high-throughput manner remains a technical challenge. Here we describe a novel reChIP-seq approach and tailored bioinformatic analysis tool, normR that allows for the sequential enrichment and detection of co-localizing DNA-associated proteins in an unbiased and genome-wide manner. We illustrate the utility of the reChIP-seq method and normR by identifying H3K4me3 or H3K27me3 bivalently modified nucleosomes in primary human CD4(+) memory T cells. We unravel widespread bivalency at hypomethylated CpG-islands coinciding with inactive promoters of developmental regulators. reChIP-seq additionally uncovered heterogeneous bivalency in the population, which was undetectable by intersecting H3K4me3 and H3K27me3 ChIP-seq tracks. Finally, we provide evidence that bivalency is established and stabilized by an interplay between the genome and epigenome. Our reChIP-seq approach augments conventional ChIP-seq and is broadly applicable to unravel combinatorial modes of action.</p>',
			'date' => '2016-08-17',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27530917',
			'doi' => '',
			'modified' => '2016-08-26 11:56:46',
			'created' => '2016-08-26 11:38:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 183 => array(
			'id' => '3002',
			'name' => 'Phenotypic Plasticity through Transcriptional Regulation of the Evolutionary Hotspot Gene tan in Drosophila melanogaster',
			'authors' => 'Gibert JM et al.',
			'description' => '<p>Phenotypic plasticity is the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions. Phenotypic plasticity can be adaptive. Furthermore, it is thought to facilitate evolution. Although phenotypic plasticity is a widespread phenomenon, its molecular mechanisms are only beginning to be unravelled. Environmental conditions can affect gene expression through modification of chromatin structure, mainly via histone modifications, nucleosome remodelling or DNA methylation, suggesting that phenotypic plasticity might partly be due to chromatin plasticity. As a model of phenotypic plasticity, we study abdominal pigmentation of Drosophila melanogaster females, which is temperature sensitive. Abdominal pigmentation is indeed darker in females grown at 18&deg;C than at 29&deg;C. This phenomenon is thought to be adaptive as the dark pigmentation produced at lower temperature increases body temperature. We show here that temperature modulates the expression of tan (t), a pigmentation gene involved in melanin production. t is expressed 7 times more at 18&deg;C than at 29&deg;C in female abdominal epidermis. Genetic experiments show that modulation of t expression by temperature is essential for female abdominal pigmentation plasticity. Temperature modulates the activity of an enhancer of t without modifying compaction of its chromatin or level of the active histone mark H3K27ac. By contrast, the active mark H3K4me3 on the t promoter is strongly modulated by temperature. The H3K4 methyl-transferase involved in this process is likely Trithorax, as we show that it regulates t expression and the H3K4me3 level on the t promoter and also participates in female pigmentation and its plasticity. Interestingly, t was previously shown to be involved in inter-individual variation of female abdominal pigmentation in Drosophila melanogaster, and in abdominal pigmentation divergence between Drosophila species. Sensitivity of t expression to environmental conditions might therefore give more substrate for selection, explaining why this gene has frequently been involved in evolution of pigmentation.</p>',
			'date' => '2016-08-10',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27508387',
			'doi' => '',
			'modified' => '2016-08-25 17:23:22',
			'created' => '2016-08-25 17:23:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 184 => array(
			'id' => '3023',
			'name' => 'MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis',
			'authors' => 'Wang W et al.',
			'description' => '<p>DNA double strand break (DSB) repair is critical for generation of B-cell receptors, which are pre-requisite for B-cell progenitor survival. However, the transcription factors that promote DSB repair in B cells are not known. Here we show that MEF2C enhances the expression of DNA repair and recombination factors in B-cell progenitors, promoting DSB repair, V(D)J recombination and cell survival. Although Mef2c-deficient mice maintain relatively intact peripheral B-lymphoid cellularity during homeostasis, they exhibit poor B-lymphoid recovery after sub-lethal irradiation and 5-fluorouracil injection. MEF2C binds active regulatory regions with high-chromatin accessibility in DNA repair and V(D)J genes in both mouse B-cell progenitors and human B lymphoblasts. Loss of Mef2c in pre-B cells reduces chromatin accessibility in multiple regulatory regions of the MEF2C-activated genes. MEF2C therefore protects B lymphopoiesis during stress by ensuring proper expression of genes that encode DNA repair and B-cell factors.</p>',
			'date' => '2016-08-10',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27507714',
			'doi' => '',
			'modified' => '2016-08-31 10:42:58',
			'created' => '2016-08-31 10:42:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 185 => array(
			'id' => '3004',
			'name' => 'Toxoplasma gondii TgIST co-opts host chromatin repressors dampening STAT1-dependent gene regulation and IFN-γ-mediated host defenses',
			'authors' => 'Gay G et al.',
			'description' => '<p>An early hallmark of Toxoplasma gondii infection is the rapid control of the parasite population by a potent multifaceted innate immune response that engages resident and homing immune cells along with pro- and counter-inflammatory cytokines. In this context, IFN-&gamma; activates a variety of T. gondii-targeting activities in immune and nonimmune cells but can also contribute to host immune pathology. T. gondii has evolved mechanisms to timely counteract the host IFN-&gamma; defenses by interfering with the transcription of IFN-&gamma;-stimulated genes. We now have identified TgIST (T. gondii inhibitor of STAT1 transcriptional activity) as a critical molecular switch that is secreted by intracellular parasites and traffics to the host cell nucleus where it inhibits STAT1-dependent proinflammatory gene expression. We show that TgIST not only sequesters STAT1 on dedicated loci but also promotes shaping of a nonpermissive chromatin through its capacity to recruit the nucleosome remodeling deacetylase (NuRD) transcriptional repressor. We found that during mice acute infection, TgIST-deficient parasites are rapidly eliminated by the homing Gr1<sup>+</sup> inflammatory monocytes, thus highlighting the protective role of TgIST against IFN-&gamma;-mediated killing. By uncovering TgIST functions, this study brings novel evidence on how T. gondii has devised a molecular weapon of choice to take control over a ubiquitous immune gene expression mechanism in metazoans, as a way to promote long-term parasitism.</p>',
			'date' => '2016-08-08',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27503074',
			'doi' => '',
			'modified' => '2016-08-26 11:02:25',
			'created' => '2016-08-26 11:02:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 186 => array(
			'id' => '3003',
			'name' => 'Epigenetic dynamics of monocyte-to-macrophage differentiation',
			'authors' => 'Wallner S et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Monocyte-to-macrophage differentiation involves major biochemical and structural changes. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete transcriptome and epigenome of human monocytes that were differentiated in vitro by addition of colony-stimulating factor 1 in serum-free medium.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Numerous mRNAs and miRNAs were significantly up- or down-regulated. More than 100 discrete DNA regions, most often far away from transcription start sites, were rapidly demethylated by the ten eleven translocation enzymes, became nucleosome-free and gained histone marks indicative of active enhancers. These regions were unique for macrophages and associated with genes involved in the regulation of the actin cytoskeleton, phagocytosis and innate immune response.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">In summary, we have discovered a phagocytic gene network that is repressed by DNA methylation in monocytes and rapidly de-repressed after the onset of macrophage differentiation.</abstracttext></p>
</div>',
			'date' => '2016-07-29',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27478504',
			'doi' => '10.1186/s13072-016-0079-z',
			'modified' => '2016-08-26 11:59:54',
			'created' => '2016-08-26 10:20:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 187 => array(
			'id' => '3021',
			'name' => 'Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis',
			'authors' => 'Rinaldi L et al.',
			'description' => '<p>The genome-wide localization and function of endogenous Dnmt3a and Dnmt3b in adult stem cells are unknown. Here, we show that in human epidermal stem cells, the two proteins bind in a histone H3K36me3-dependent manner to the most active enhancers and are required to produce their associated enhancer RNAs. Both proteins prefer super-enhancers associated to genes that either define the ectodermal lineage or establish the stem cell and differentiated states. However, Dnmt3a and Dnmt3b differ in their mechanisms of enhancer regulation: Dnmt3a associates with p63 to maintain high levels of DNA hydroxymethylation at the center of enhancers in a Tet2-dependent manner, whereas Dnmt3b promotes DNA methylation along the body of the enhancer. Depletion of either protein inactivates their target enhancers and profoundly affects epidermal stem cell function. Altogether, we reveal novel functions for Dnmt3a and Dnmt3b at enhancers that could contribute to their roles in disease and tumorigenesis.</p>',
			'date' => '2016-07-26',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27476967',
			'doi' => '',
			'modified' => '2016-08-31 10:22:54',
			'created' => '2016-08-31 10:22:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 188 => array(
			'id' => '2915',
			'name' => 'PAFAH1B1 and the lncRNA NONHSAT073641 maintain an angiogenic phenotype in human endothelial cells',
			'authors' => 'Josipovic I at al.',
			'description' => '<h4>AIM:</h4>
<p><abstracttext label="AIM" nlmcategory="OBJECTIVE">Platelet-activating factor acetyl hydrolase 1B1 (PAFAH1B1, also known as Lis1) is a protein essentially involved in neurogenesis and mostly studied in the nervous system. As we observed a significant expression of PAFAH1B1 in the vascular system, we hypothesized that PAFAH1B1 is important during angiogenesis of endothelial cells as well as in human vascular diseases.</abstracttext></p>
<h4>METHOD:</h4>
<p><abstracttext label="METHOD" nlmcategory="METHODS">The functional relevance of the protein in endothelial cell angiogenic function, its downstream targets and the influence of NONHSAT073641, a long non-coding RNA (lncRNA) with 92% similarity to PAFAH1B1, were studied by knockdown and overexpression in human umbilical vein endothelial cells (HUVEC).</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Knockdown of PAFAH1B1 led to impaired tube formation of HUVEC and decreased sprouting in the spheroid assay. Accordingly, the overexpression of PAFAH1B1 increased tube number, sprout length and sprout number. LncRNA NONHSAT073641 behaved similarly. Microarray analysis after PAFAH1B1 knockdown and its overexpression indicated that the protein maintains Matrix Gla Protein (MGP) expression. Chromatin immunoprecipitation experiments revealed that PAFAH1B1 is required for active histone marks and proper binding of RNA Polymerase II to the transcriptional start site of MGP. MGP itself was required for endothelial angiogenic capacity and knockdown of both, PAFAH1B1 and MGP, reduced migration. In vascular samples of patients with chronic thromboembolic pulmonary hypertension (CTEPH), PAFAH1B1 and MGP were upregulated. The function of PAFAH1B1 required the presence of the intact protein as overexpression of NONHSAT073641, which was highly upregulated during CTEPH, did not affect PAFAH1B1 target genes.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">PAFAH1B1 and NONHSAT073641 are important for endothelial angiogenic function. This article is protected by copyright. All rights reserved.</abstracttext></p>',
			'date' => '2016-04-28',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27124368',
			'doi' => ' 10.1111/apha.12700',
			'modified' => '2016-05-12 10:42:06',
			'created' => '2016-05-12 10:42:06',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 189 => array(
			'id' => '2914',
			'name' => 'Chromatin immunoprecipitation from fixed clinical tissues reveals tumor-specific enhancer profiles.',
			'authors' => 'Cejas P et al.',
			'description' => '<p>Extensive cross-linking introduced during routine tissue fixation of clinical pathology specimens severely hampers chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) analysis from archived tissue samples. This limits the ability to study the epigenomes of valuable, clinically annotated tissue resources. Here we describe fixed-tissue chromatin immunoprecipitation sequencing (FiT-seq), a method that enables reliable extraction of soluble chromatin from formalin-fixed paraffin-embedded (FFPE) tissue samples for accurate detection of histone marks. We demonstrate that FiT-seq data from FFPE specimens are concordant with ChIP-seq data from fresh-frozen samples of the same tumors. By using multiple histone marks, we generate chromatin-state maps and identify cis-regulatory elements in clinical samples from various tumor types that can readily allow us to distinguish between cancers by the tissue of origin. Tumor-specific enhancers and superenhancers that are elucidated by FiT-seq analysis correlate with known oncogenic drivers in different tissues and can assist in the understanding of how chromatin states affect gene regulation.</p>',
			'date' => '2016-04-25',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27111282',
			'doi' => '10.1038/nm.4085',
			'modified' => '2016-05-11 17:34:25',
			'created' => '2016-05-11 17:34:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 190 => array(
			'id' => '2894',
			'name' => 'Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time',
			'authors' => 'Feichtinger J, Hernández I, Fischer C, Hanscho M, Auer N, Hackl M, Jadhav V, Baumann M, Krempl PM, Schmidl C, Farlik M, Schuster M, Merkel A, Sommer A, Heath S, Rico D, Bock C, Thallinger GG, Borth N',
			'description' => '<p>The most striking characteristic of CHO cells is their adaptability, which enables efficient production of proteins as well as growth under a variety of culture conditions, but also results in genomic and phenotypic instability. To investigate the relative contribution of genomic and epigenetic modifications towards phenotype evolution, comprehensive genome and epigenome data are presented for 6 related CHO cell lines, both in response to perturbations (different culture conditions and media as well as selection of a specific phenotype with increased transient productivity) and in steady state (prolonged time in culture under constant conditions). Clear transitions were observed in DNA-methylation patterns upon each perturbation, while few changes occurred over time under constant conditions. Only minor DNA-methylation changes were observed between exponential and stationary growth phase, however, throughout a batch culture the histone modification pattern underwent continuous adaptation. Variation in genome sequence between the 6 cell lines on the level of SNPs, InDels and structural variants is high, both upon perturbation and under constant conditions over time. The here presented comprehensive resource may open the door to improved control and manipulation of gene expression during industrial bioprocesses based on epigenetic mechanisms</p>',
			'date' => '2016-04-12',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27072894',
			'doi' => '10.1002/bit.25990',
			'modified' => '2016-04-22 12:53:44',
			'created' => '2016-04-22 12:37:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 191 => array(
			'id' => '2880',
			'name' => 'GATA-1 Inhibits PU.1 Gene via DNA and Histone H3K9 Methylation of Its Distal Enhancer in Erythroleukemia',
			'authors' => 'Burda P, Vargova J, Curik N, Salek C, Papadopoulos GL, Strouboulis J, Stopka T',
			'description' => '<p>GATA-1 and PU.1 are two important hematopoietic transcription factors that mutually inhibit each other in progenitor cells to guide entrance into the erythroid or myeloid lineage, respectively. PU.1 controls its own expression during myelopoiesis by binding to the distal URE enhancer, whose deletion leads to acute myeloid leukemia (AML). We herein present evidence that GATA-1 binds to the PU.1 gene and inhibits its expression in human AML-erythroleukemias (EL). Furthermore, GATA-1 together with DNA methyl Transferase I (DNMT1) mediate repression of the PU.1 gene through the URE. Repression of the PU.1 gene involves both DNA methylation at the URE and its histone H3 lysine-K9 methylation and deacetylation as well as the H3K27 methylation at additional DNA elements and the promoter. The GATA-1-mediated inhibition of PU.1 gene transcription in human AML-EL mediated through the URE represents important mechanism that contributes to PU.1 downregulation and leukemogenesis that is sensitive to DNA demethylation therapy.</p>',
			'date' => '2016-03-24',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27010793',
			'doi' => '10.1371/journal.pone.0152234',
			'modified' => '2016-04-06 10:26:31',
			'created' => '2016-04-06 10:26:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 192 => array(
			'id' => '2886',
			'name' => 'Role of Annexin gene and its regulation during zebrafish caudal fin regeneration',
			'authors' => 'Saxena S, Purushothaman S, Meghah V, Bhatti B, Poruri A, Meena Lakshmi MG, Sarath Babu N, Murthy CL, Mandal KK, Kumar A, Idris MM',
			'description' => '<p>The molecular mechanism of epimorphic regeneration is elusive due to its complexity and limitation in mammals. Epigenetic regulatory mechanisms play a crucial role in development and regeneration. This investigation attempted to reveal the role of epigenetic regulatory mechanisms, such as histone H3 and H4 lysine acetylation and methylation during zebrafish caudal fin regeneration. It was intriguing to observe that H3K9,14 acetylation, H4K20 trimethylation, H3K4 trimethylation and H3K9 dimethylation along with their respective regulatory genes, such as <em>GCN5, SETd8b, SETD7/9</em> and <em>SUV39h1</em>, were differentially regulated in the regenerating fin at various time points of post-amputation. Annexin genes have been associated with regeneration; this study reveals the significant upregulation of <em>ANXA2a</em> and <em>ANXA2b</em> transcripts and their protein products during the regeneration process. Chromatin Immunoprecipitation (ChIP) and PCR analysis of the regulatory regions of the <em>ANXA2a</em> and <em>ANXA2b</em> genes demonstrated the ability to repress two histone methylations, H3K27me3 and H4K20me3, in transcriptional regulation during regeneration. It is hypothesized that this novel insight into the diverse epigenetic mechanisms that play a critical role during the regeneration process may help to strategize the translational efforts, in addition to identifying the molecules involved in vertebrate regeneration.</p>',
			'date' => '2016-03-12',
			'pmid' => 'http://onlinelibrary.wiley.com/doi/10.1111/wrr.12429/abstract',
			'doi' => '10.1111/wrr.12429',
			'modified' => '2016-04-08 17:24:06',
			'created' => '2016-04-08 17:24:06',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 193 => array(
			'id' => '2856',
			'name' => 'Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis',
			'authors' => 'Weigel C. et al.',
			'description' => '<p>Radiotherapy is a fundamental part of cancer treatment but its use is limited by the onset of late adverse effects in the normal tissue, especially radiation-induced fibrosis. Since the molecular causes for fibrosis are largely unknown, we analyse if epigenetic regulation might explain inter-individual differences in fibrosis risk. DNA methylation profiling of dermal fibroblasts obtained from breast cancer patients prior to irradiation identifies differences associated with fibrosis. One region is characterized as a differentially methylated enhancer of diacylglycerol kinase alpha (<i>DGKA</i>). Decreased DNA methylation at this enhancer enables recruitment of the profibrotic transcription factor early growth response 1 (EGR1) and facilitates radiation-induced <i>DGKA</i> transcription in cells from patients later developing fibrosis. Conversely, inhibition of DGKA has pronounced effects on diacylglycerol-mediated lipid homeostasis and reduces profibrotic fibroblast activation. Collectively, DGKA is an epigenetically deregulated kinase involved in radiation response and may serve as a marker and therapeutic target for personalized radiotherapy.</p>',
			'date' => '2016-03-11',
			'pmid' => 'http://www.nature.com/ncomms/2016/160311/ncomms10893/full/ncomms10893.html',
			'doi' => '10.1038/ncomms10893',
			'modified' => '2016-03-15 11:08:21',
			'created' => '2016-03-15 11:08:21',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 194 => array(
			'id' => '2970',
			'name' => 'Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development.',
			'authors' => 'Yuan S et al.',
			'description' => '<p>Although it is believed that mammalian sperm carry small noncoding RNAs (sncRNAs) into oocytes during fertilization, it remains unknown whether these sperm-borne sncRNAs truly have any function during fertilization and preimplantation embryonic development. Germline-specific Dicer and Drosha conditional knockout (cKO) mice produce gametes (i.e. sperm and oocytes) partially deficient in miRNAs and/or endo-siRNAs, thus providing a unique opportunity for testing whether normal sperm (paternal) or oocyte (maternal) miRNA and endo-siRNA contents are required for fertilization and preimplantation development. Using the outcome of intracytoplasmic sperm injection (ICSI) as a readout, we found that sperm with altered miRNA and endo-siRNA profiles could fertilize wild-type (WT) eggs, but embryos derived from these partially sncRNA-deficient sperm displayed a significant reduction in developmental potential, which could be rescued by injecting WT sperm-derived total or small RNAs into ICSI embryos. Disrupted maternal transcript turnover and failure in early zygotic gene activation appeared to associate with the aberrant miRNA profiles in Dicer and Drosha cKO spermatozoa. Overall, our data support a crucial function of paternal miRNAs and/or endo-siRNAs in the control of the transcriptomic homeostasis in fertilized eggs, zygotes and two-cell embryos. Given that supplementation of sperm RNAs enhances both the developmental potential of preimplantation embryos and the live birth rate, it might represent a novel means to improve the success rate of assisted reproductive technologies in fertility clinics.</p>',
			'date' => '2016-02-15',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26718009',
			'doi' => '10.1242/dev.131755',
			'modified' => '2016-06-29 17:11:02',
			'created' => '2016-06-29 17:11:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 195 => array(
			'id' => '2849',
			'name' => 'MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199',
			'authors' => 'Benito JM et al.',
			'description' => '<p>Targeted therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of current research. <em>Mixed Lineage Leukemia</em> (<em>MLL</em>) mutations such as the t(4;11) translocation cause aggressive leukemias that are refractory to conventional treatment. The t(4;11) translocation produces an MLL/AF4 fusion protein that activates key target genes through both epigenetic and transcriptional elongation mechanisms. In this study, we show that t(4;11) patient cells express high levels of BCL-2 and are highly sensitive to treatment with the BCL-2-specific BH3 mimetic ABT-199. We demonstrate that MLL/AF4 specifically upregulates the <em>BCL-2</em> gene but not other BCL-2 family members via DOT1L-mediated H3K79me2/3. We use this information to show that a t(4;11) cell line is sensitive to a combination of ABT-199 and DOT1L inhibitors. In addition, ABT-199 synergizes with standard induction-type therapy in a xenotransplant model, advocating for the introduction of ABT-199 into therapeutic regimens for MLL-rearranged leukemias.</p>',
			'date' => '2015-12-29',
			'pmid' => 'http://www.cell.com/cell-reports/abstract/S2211-1247%2815%2901415-1',
			'doi' => ' http://dx.doi.org/10.1016/j.celrep.2015.12.003',
			'modified' => '2016-03-11 17:31:23',
			'created' => '2016-03-11 17:11:09',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 196 => array(
			'id' => '2810',
			'name' => 'Standardizing chromatin research: a simple and universal method for ChIP-seq',
			'authors' => 'Laura Arrigoni, Andreas S. Richter, Emily Betancourt, Kerstin Bruder, Sarah Diehl, Thomas Manke and Ulrike Bönisch',
			'description' => '<p><span>Here we&nbsp;demonstrate that harmonization of ChIP-seq workflows across cell types and conditions is possible when obtaining chromatin from properly isolated nuclei. We established an ultrasound-based nuclei extraction method (Nuclei Extraction by Sonication) that is highly effective across various organisms, cell types and cell numbers. The described method has the potential to replace complex cell-type-specific, but largely ineffective, nuclei isolation protocols. This article demonstrates protocol standardization using the Bioruptor shearing systems and the IP-Star Automation System for ChIP automation.</span></p>',
			'date' => '2015-12-23',
			'pmid' => 'http://pubmed.gov/26704968',
			'doi' => '10.1093/nar/gkv1495',
			'modified' => '2016-06-09 09:47:00',
			'created' => '2016-01-10 08:32:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 197 => array(
			'id' => '2952',
			'name' => 'Dynamic changes in histone modifications precede de novo DNA methylation in oocytes',
			'authors' => 'Stewart KR et al.',
			'description' => '<p>Erasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation establishment remain poorly understood, but a number of post-translational modifications of histones are implicated in antagonizing or recruiting the de novo DNA methylation complex. In mouse oogenesis, DNA methylation establishment occurs on a largely unmethylated genome and in nondividing cells, making it a highly informative model for examining how histone modifications can shape the DNA methylome. Using a chromatin immunoprecipitation (ChIP) and genome-wide sequencing (ChIP-seq) protocol optimized for low cell numbers and novel techniques for isolating primary and growing oocytes, profiles were generated for histone modifications implicated in promoting or inhibiting DNA methylation. CGIs destined for DNA methylation show reduced protective H3K4 dimethylation (H3K4me2) and trimethylation (H3K4me3) in both primary and growing oocytes, while permissive H3K36me3 increases specifically at these CGIs in growing oocytes. Methylome profiling of oocytes deficient in H3K4 demethylase KDM1A or KDM1B indicated that removal of H3K4 methylation is necessary for proper methylation establishment at CGIs. This work represents the first systematic study performing ChIP-seq in oocytes and shows that histone remodeling in the mammalian oocyte helps direct de novo DNA methylation events.</p>',
			'date' => '2015-12-01',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26584620',
			'doi' => '10.1101/gad.271353.115',
			'modified' => '2016-06-10 16:39:45',
			'created' => '2016-06-10 16:39:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 198 => array(
			'id' => '2963',
			'name' => 'Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma',
			'authors' => 'Aldiri I et al.',
			'description' => '<p>Retinal development requires precise temporal and spatial coordination of cell cycle exit, cell fate specification, cell migration and differentiation. When this process is disrupted, retinoblastoma, a developmental tumor of the retina, can form. Epigenetic modulators are central to precisely coordinating developmental events, and many epigenetic processes have been implicated in cancer. Studying epigenetic mechanisms in development is challenging because they often regulate multiple cellular processes; therefore, elucidating the primary molecular mechanisms involved can be difficult. Here we explore the role of Brg1 (Smarca4) in retinal development and retinoblastoma in mice using molecular and cellular approaches. Brg1 was found to regulate retinal size by controlling cell cycle length, cell cycle exit and cell survival during development. Brg1 was not required for cell fate specification but was required for photoreceptor differentiation and cell adhesion/polarity programs that contribute to proper retinal lamination during development. The combination of defective cell differentiation and lamination led to retinal degeneration in Brg1-deficient retinae. Despite the hypocellularity, premature cell cycle exit, increased cell death and extended cell cycle length, retinal progenitor cells persisted in Brg1-deficient retinae, making them more susceptible to retinoblastoma. ChIP-Seq analysis suggests that Brg1 might regulate gene expression through multiple mechanisms.</p>',
			'date' => '2015-12-01',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26628093',
			'doi' => '10.1242/dev.124800',
			'modified' => '2016-06-24 09:48:45',
			'created' => '2016-06-24 09:48:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 199 => array(
			'id' => '2964',
			'name' => 'Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization',
			'authors' => 'Kuznetsova T et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">The impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from remodeling of higher order chromatin architecture by activated transcription factors to recruitment of activated transcription factors to pre-established long-range interactions.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Using circular chromosome conformation capture coupled with next generation sequencing and high-resolution chromatin interaction analysis by paired-end tag sequencing of P300, we observed agonist-induced changes in long-range chromatin interactions, and uncovered interconnected enhancer-enhancer hubs spanning up to one megabase. The vast majority of activated glucocorticoid receptor and nuclear factor kappa-b appeared to join pre-existing P300 enhancer hubs without affecting the chromatin conformation. In contrast, binding of the activated transcription factors to loci with their consensus response elements led to the increased formation of an active epigenetic state of enhancers and a significant increase in long-range interactions within pre-existing enhancer networks. De novo enhancers or ligand-responsive enhancer hubs preferentially interacted with ligand-induced genes.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">We demonstrate that, at a subset of genomic loci, ligand-mediated induction leads to active enhancer formation and an increase in long-range interactions, facilitating efficient regulation of target genes. Therefore, our data suggest an active role of signal-dependent transcription factors in chromatin and long-range interaction remodeling.</abstracttext></p>
</div>',
			'date' => '2015-12-01',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26619937',
			'doi' => '10.1186/s13059-015-0832-9',
			'modified' => '2016-06-24 10:02:16',
			'created' => '2016-06-24 10:02:16',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 200 => array(
			'id' => '2909',
			'name' => 'Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells',
			'authors' => 'Rønningen T, Shah A, Reiner AH, Collas P, Moskaug JØ',
			'description' => '<p>Cellular metabolism confers wide-spread epigenetic modifications required for regulation of transcriptional networks that determine cellular states. Mesenchymal stromal cells are responsive to metabolic cues including circulating glucose levels and modulate inflammatory responses. We show here that long term exposure of undifferentiated human adipose tissue stromal cells (ASCs) to high glucose upregulates a subset of inflammation response (IR) genes and alters their promoter histone methylation patterns in a manner consistent with transcriptional de-repression. Modeling of chromatin states from combinations of histone modifications in nearly 500 IR genes unveil three overarching chromatin configurations reflecting repressive, active, and potentially active states in promoter and enhancer elements. Accordingly, we show that adipogenic differentiation in high glucose predominantly upregulates IR genes. Our results indicate that elevated extracellular glucose levels sensitize in ASCs an IR gene expression program which is exacerbated during adipocyte differentiation. We propose that high glucose exposure conveys an epigenetic 'priming' of IR genes, favoring a transcriptional inflammatory response upon adipogenic stimulation. Chromatin alterations at IR genes by high glucose exposure may play a role in the etiology of metabolic diseases.</p>',
			'date' => '2015-11-27',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26462465',
			'doi' => '10.1016/j.bbrc.2015.10.030',
			'modified' => '2016-05-09 22:54:48',
			'created' => '2016-05-09 22:54:48',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 201 => array(
			'id' => '2957',
			'name' => 'The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth',
			'authors' => 'Palazzo E et al.',
			'description' => '<p>Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epidermal hyperplasia and squamous tumorigenesis. By integrating genetic and transcriptomic approaches, we demonstrate that DLX3 operates through a p53-regulated network. DLX3 and p53 physically interact on the p21 promoter to enhance p21 expression. Elevating DLX3 in keratinocytes produces a G1-S blockade associated with p53 signature transcriptional profiles. In contrast, DLX3 loss promotes a mitogenic phenotype associated with constitutive activation of ERK. DLX3 expression is lost in human skin cancers and is extinguished during progression of experimentally induced mouse squamous cell carcinoma (SCC). Reinstatement of DLX3 function is sufficient to attenuate the migration of SCC cells, leading to decreased wound closure. Our data establish the DLX3-p53 interplay as a major regulatory axis in epidermal differentiation and suggest that DLX3 is a modulator of skin carcinogenesis.</p>',
			'date' => '2015-11-02',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26522723',
			'doi' => '10.1038/onc.2015.380',
			'modified' => '2016-06-15 16:18:44',
			'created' => '2016-06-15 16:18:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 202 => array(
			'id' => '2962',
			'name' => 'VEGF-mediated cell survival in non-small-cell lung cancer: implications for epigenetic targeting of VEGF receptors as a therapeutic approach',
			'authors' => 'Barr MP et al.',
			'description' => '<div class="">
<h4>AIMS:</h4>
<p><abstracttext label="AIMS" nlmcategory="OBJECTIVE">To evaluate the potential therapeutic utility of histone deacetylase inhibitors (HDACi) in targeting VEGF receptors in non-small-cell lung cancer.</abstracttext></p>
<h4>MATERIALS &amp; METHODS:</h4>
<p><abstracttext label="MATERIALS &amp; METHODS" nlmcategory="METHODS">Non-small-cell lung cancer cells were screened for the VEGF receptors at the mRNA and protein levels, while cellular responses to various HDACi were examined.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Significant effects on the regulation of the VEGF receptors were observed in response to HDACi. These were associated with decreased secretion of VEGF, decreased cellular proliferation and increased apoptosis which could not be rescued by addition of exogenous recombinant VEGF. Direct remodeling of the VEGFR1 and VEGFR2 promoters was observed. In contrast, HDACi treatments resulted in significant downregulation of the Neuropilin receptors.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">Epigenetic targeting of the Neuropilin receptors may offer an effective treatment for lung cancer patients in the clinical setting.</abstracttext></p>
</div>',
			'date' => '2015-10-07',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26479311',
			'doi' => '10.2217/epi.15.51',
			'modified' => '2016-06-23 15:24:41',
			'created' => '2016-06-23 15:24:41',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 203 => array(
			'id' => '2917',
			'name' => 'Chromatin assembly factor CAF-1 represses priming of plant defence response genes',
			'authors' => 'Mozgova I et al.',
			'description' => '<p><b>Plants have evolved efficient defence systems against pathogens that often rely on specific transcriptional responses. Priming is part of the defence syndrome, by establishing a hypersensitive state of defence genes such as after a first encounter with a pathogen. Because activation of defence responses has a fitness cost, priming must be tightly controlled to prevent spurious activation of defence. However, mechanisms that repress defence gene priming are poorly understood. Here, we show that the histone chaperone CAF-1 is required to establish a repressed chromatin state at defence genes. Absence of CAF-1 results in spurious activation of a salicylic acid-dependent pathogen defence response in plants grown under non-sterile conditions. Chromatin at defence response genes in CAF-1 mutants under non-inductive (sterile) conditions is marked by low nucleosome occupancy and high H3K4me3 at transcription start sites, resembling chromatin in primed wild-type plants. We conclude that CAF-1-mediated chromatin assembly prevents the establishment of a primed state that may under standard non-sterile growth conditions result in spurious activation of SA-dependent defence responses and consequential reduction of plant vigour.</b></p>',
			'date' => '2015-09-01',
			'pmid' => 'http://www.nature.com/articles/nplants2015127',
			'doi' => '10.1038/nplants.2015.127',
			'modified' => '2016-05-13 11:13:50',
			'created' => '2016-05-13 11:13:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 204 => array(
			'id' => '2817',
			'name' => 'Spatiotemporal control of estrogen-responsive transcription in ERα-positive breast cancer cells.',
			'authors' => 'P-Y Hsu, H-K Hsu, T-H Hsiao, Z Ye, E Wang, A L Profit, I Jatoi, Y Chen, N B Kirma, V X Jin, Z D Sharp and T H-M Huang',
			'description' => '<p><span>Recruitment of transcription machinery to target promoters for aberrant gene expression has been well studied, but underlying control directed by distant-acting enhancers remains unclear in cancer development. Our previous study demonstrated that distant estrogen response elements (DEREs) located on chromosome 20q13 are frequently amplified and translocated to other chromosomes in ER&alpha;-positive breast cancer cells. In this study, we used three-dimensional interphase fluorescence in situ hybridization to decipher spatiotemporal gathering of multiple DEREs in the nucleus. Upon estrogen stimulation, scattered 20q13 DEREs were mobilized to form regulatory depots for synchronized gene expression of target loci. A chromosome conformation capture assay coupled with chromatin immunoprecipitation further uncovered that ER&alpha;-bound regulatory depots are tethered to heterochromatin protein 1 (HP1) for coordinated chromatin movement and histone modifications of target loci, resulting in transcription repression. Neutralizing HP1 function dysregulated the formation of DERE-involved regulatory depots and transcription inactivation of candidate tumor-suppressor genes. Deletion of amplified DEREs using the CRISPR/Cas9 genomic-editing system profoundly altered transcriptional profiles of proliferation-associated signaling networks, resulting in reduction of cancer cell growth. These findings reveal a formerly uncharacterized feature wherein multiple copies of the amplicon congregate as transcriptional units in the nucleus for synchronous regulation of function-related loci in tumorigenesis. Disruption of their assembly can be a new strategy for treating breast cancers and other malignancies</span></p>',
			'date' => '2015-08-24',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26300005',
			'doi' => '10.1038/onc.2015.298',
			'modified' => '2016-02-10 16:20:01',
			'created' => '2016-02-10 16:20:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 205 => array(
			'id' => '2816',
			'name' => 'Non-coding recurrent mutations in chronic lymphocytic leukaemia.',
			'authors' => 'Xose S. Puente, Silvia Beà, Rafael Valdés-Mas, Neus Villamor, Jesús Gutiérrez-Abril et al.',
			'description' => '<p><span>Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3, ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding regions, including the 3' region of NOTCH1, which cause aberrant splicing events, increase NOTCH1 activity and result in a more aggressive disease. In addition, mutations in an enhancer located on chromosome 9p13 result in reduced expression of the B-cell-specific transcription factor PAX5. The accumulative number of driver alterations (0 to &ge;4) discriminated between patients with differences in clinical behaviour. This study provides an integrated portrait of the CLL genomic landscape, identifies new recurrent driver mutations of the disease, and suggests clinical interventions that may improve the management of this neoplasia.</span></p>',
			'date' => '2015-07-22',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26200345',
			'doi' => '10.1038/nature14666',
			'modified' => '2016-02-10 16:17:29',
			'created' => '2016-02-10 16:17:29',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 206 => array(
			'id' => '2893',
			'name' => 'Allele-specific binding of ZFP57 in the epigenetic regulation of imprinted and non-imprinted monoallelic expression',
			'authors' => 'Strogantsev R, Krueger F, Yamazawa K, Shi H, Gould P, Goldman-Roberts M, McEwen K, Sun B, Pedersen R, Ferguson-Smith AC',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Selective maintenance of genomic epigenetic imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary for maintaining the DNA methylation memory at multiple imprinting control regions in early mouse embryos and embryonic stem (ES) cells. Maternal-zygotic deletion of ZFP57 in mice presents a highly penetrant phenotype with no animals surviving to birth. Additionally, several cases of human transient neonatal diabetes are associated with somatic mutations in the ZFP57 coding sequence.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Here, we comprehensively map sequence-specific ZFP57 binding sites in an allele-specific manner using hybrid ES cell lines from reciprocal crosses between C57BL/6J and Cast/EiJ mice, assigning allele specificity to approximately two-thirds of all binding sites. While half of these are biallelic and include endogenous retrovirus (ERV) targets, the rest show monoallelic binding based either on parental origin or on genetic background of the allele. Parental-origin allele-specific binding is methylation-dependent and maps only to imprinting control differentially methylated regions (DMRs) established in the germline. We identify a novel imprinted gene, Fkbp6, which has a critical function in mouse male germ cell development. Genetic background-specific sequence differences also influence ZFP57 binding, as genetic variation that disrupts the consensus binding motif and its methylation is often associated with monoallelic expression of neighboring genes.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">The work described here uncovers further roles for ZFP57-mediated regulation of genomic imprinting and identifies a novel mechanism for genetically determined monoallelic gene expression.</abstracttext></p>
</div>',
			'date' => '2015-05-30',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26025256',
			'doi' => '10.1186/s13059-015-0672-7',
			'modified' => '2016-04-14 17:20:03',
			'created' => '2016-04-14 17:20:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 207 => array(
			'id' => '2790',
			'name' => 'Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency.',
			'authors' => 'Chen H, Aksoy I, Gonnot F, Osteil P, Aubry M, Hamela C, Rognard C, Hochard A, Voisin S, Fontaine E, Mure M, Afanassieff M, Cleroux E, Guibert S, Chen J, Vallot C, Acloque H, Genthon C, Donnadieu C, De Vos J, Sanlaville D, Guérin JF, Weber M, Stanton LW, R',
			'description' => 'Leukemia inhibitory factor (LIF)/STAT3 signalling is a hallmark of naive pluripotency in rodent pluripotent stem cells (PSCs), whereas fibroblast growth factor (FGF)-2 and activin/nodal signalling is required to sustain self-renewal of human PSCs in a condition referred to as the primed state. It is unknown why LIF/STAT3 signalling alone fails to sustain pluripotency in human PSCs. Here we show that the forced expression of the hormone-dependent STAT3-ER (ER, ligand-binding domain of the human oestrogen receptor) in combination with 2i/LIF and tamoxifen allows human PSCs to escape from the primed state and enter a state characterized by the activation of STAT3 target genes and long-term self-renewal in FGF2- and feeder-free conditions. These cells acquire growth properties, a gene expression profile and an epigenetic landscape closer to those described in mouse naive PSCs. Together, these results show that temporarily increasing STAT3 activity is sufficient to reprogramme human PSCs to naive-like pluripotent cells.',
			'date' => '2015-05-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25968054',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 208 => array(
			'id' => '2611',
			'name' => 'Opposite expression of CYP51A1 and its natural antisense transcript AluCYP51A1 in adenovirus type 37 infected retinal pigmented epithelial cells.',
			'authors' => 'Pickl JM, Kamel W, Ciftci S, Punga T, Akusjärvi G',
			'description' => 'Cytochrome P450 family member CYP51A1 is a key enzyme in cholesterol biosynthesis whose deregulation is implicated in numerous diseases, including retinal degeneration. Here we describe that HAdV-37 infection leads to downregulation of CYP51A1 expression and overexpression of its antisense non-coding Alu element (AluCYP51A1) in retinal pigment epithelium (RPE) cells. This change in gene expression is associated with a reversed accumulation of a positive histone mark at the CYP51A1 and AluCYP51A1 promoters. Further, transient AluCYP51A1 RNA overexpression correlates with reduced CYP51A1 mRNA accumulation. Collectively, our data suggest that AluCYP51A1 might control CYP51A1 gene expression in HAdV-37-infected RPE cells.',
			'date' => '2015-04-20',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25907535',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 209 => array(
			'id' => '2684',
			'name' => 'A cohesin-OCT4 complex mediates Sox enhancers to prime an early embryonic lineage.',
			'authors' => 'Abboud N, Moore-Morris T, Hiriart E, Yang H, Bezerra H, Gualazzi MG, Stefanovic S, Guénantin AC, Evans SM, Pucéat M',
			'description' => 'Short- and long-scales intra- and inter-chromosomal interactions are linked to gene transcription, but the molecular events underlying these structures and how they affect cell fate decision during embryonic development are poorly understood. One of the first embryonic cell fate decisions (that is, mesendoderm determination) is driven by the POU factor OCT4, acting in concert with the high-mobility group genes Sox-2 and Sox-17. Here we report a chromatin-remodelling mechanism and enhancer function that mediate cell fate switching. OCT4 alters the higher-order chromatin structure at both Sox-2 and Sox-17 loci. OCT4 titrates out cohesin and switches the Sox-17 enhancer from a locked (within an inter-chromosomal Sox-2 enhancer/CCCTC-binding factor CTCF/cohesin loop) to an active (within an intra-chromosomal Sox-17 promoter/enhancer/cohesin loop) state. SALL4 concomitantly mobilizes the polycomb complexes at the Soxs loci. Thus, OCT4/SALL4-driven cohesin- and polycombs-mediated changes in higher-order chromatin structure mediate instruction of early cell fate in embryonic cells.',
			'date' => '2015-04-08',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25851587',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 210 => array(
			'id' => '2625',
			'name' => 'Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1.',
			'authors' => 'Tomazou EM, Sheffield NC, Schmidl C, Schuster M, Schönegger A, Datlinger P, Kubicek S, Bock C, Kovar H',
			'description' => '<p>Transcription factor fusion proteins can transform cells by inducing global changes of the transcriptome, often creating a state of oncogene addiction. Here, we investigate the role of epigenetic mechanisms in this process, focusing on Ewing sarcoma cells that are dependent on the EWS-FLI1 fusion protein. We established reference epigenome maps comprising DNA methylation, seven histone marks, open chromatin states, and RNA levels, and we analyzed the epigenome dynamics upon downregulation of the driving oncogene. Reduced EWS-FLI1 expression led to widespread epigenetic changes in&nbsp;promoters, enhancers, and super-enhancers, and we identified histone H3K27 acetylation as the most strongly affected mark. Clustering of epigenetic promoter signatures defined classes of EWS-FLI1-regulated genes that responded differently to low-dose treatment with histone deacetylase inhibitors. Furthermore, we observed strong and opposing enrichment patterns for&nbsp;E2F and AP-1 among EWS-FLI1-correlated and anticorrelated genes. Our data describe extensive genome-wide rewiring of epigenetic cell states driven by an oncogenic fusion protein.</p>',
			'date' => '2015-02-24',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25704812',
			'doi' => '',
			'modified' => '2017-02-14 12:53:04',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 211 => array(
			'id' => '2575',
			'name' => 'Embryonic stem cell differentiation requires full length Chd1.',
			'authors' => 'Piatti P, Lim CY, Nat R, Villunger A, Geley S, Shue YT, Soratroi C, Moser M, Lusser A',
			'description' => 'The modulation of chromatin dynamics by ATP-dependent chromatin remodeling factors has been recognized as an important mechanism to regulate the balancing of self-renewal and pluripotency in embryonic stem cells (ESCs). Here we have studied the effects of a partial deletion of the gene encoding the chromatin remodeling factor Chd1 that generates an N-terminally truncated version of Chd1 in mouse ESCs in vitro as well as in vivo. We found that a previously uncharacterized serine-rich region (SRR) at the N-terminus is not required for chromatin assembly activity of Chd1 but that it is subject to phosphorylation. Expression of Chd1 lacking this region in ESCs resulted in aberrant differentiation properties of these cells. The self-renewal capacity and ESC chromatin structure, however, were not affected. Notably, we found that newly established ESCs derived from Chd1(Δ2/Δ2) mutant mice exhibited similar differentiation defects as in vitro generated mutant ESCs, even though the N-terminal truncation of Chd1 was fully compatible with embryogenesis and post-natal life in the mouse. These results underscore the importance of Chd1 for the regulation of pluripotency in ESCs and provide evidence for a hitherto unrecognized critical role of the phosphorylated N-terminal SRR for full functionality of Chd1.',
			'date' => '2015-01-26',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25620209',
			'doi' => '',
			'modified' => '2015-07-24 15:39:04',
			'created' => '2015-07-24 15:39:04',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 212 => array(
			'id' => '2552',
			'name' => 'A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus.',
			'authors' => 'Lazorthes S, Vallot C, Briois S, Aguirrebengoa M, Thuret JY, Laurent GS, Rougeulle C, Kapranov P, Mann C, Trouche D, Nicolas E',
			'description' => 'Non-coding RNAs (ncRNAs) play major roles in proper chromatin organization and function. Senescence, a strong anti-proliferative process and a major anticancer barrier, is associated with dramatic chromatin reorganization in heterochromatin foci. Here we analyze strand-specific transcriptome changes during oncogene-induced human senescence. Strikingly, while differentially expressed RNAs are mostly repressed during senescence, ncRNAs belonging to the recently described vlincRNA (very long intergenic ncRNA) class are mainly activated. We show that VAD, a novel antisense vlincRNA strongly induced during senescence, is required for the maintenance of senescence features. VAD modulates chromatin structure in cis and activates gene expression in trans at the INK4 locus, which encodes cell cycle inhibitors important for senescence-associated cell proliferation arrest. Importantly, VAD inhibits the incorporation of the repressive histone variant H2A.Z at INK4 gene promoters in senescent cells. Our data underline the importance of vlincRNAs as sensors of cellular environment changes and as mediators of the correct transcriptional response.',
			'date' => '2015-01-20',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25601475',
			'doi' => '',
			'modified' => '2015-07-24 15:39:04',
			'created' => '2015-07-24 15:39:04',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 213 => array(
			'id' => '2492',
			'name' => 'Cryosectioning the intestinal crypt-villus axis: an ex vivo method to study the dynamics of epigenetic modifications from stem cells to differentiated cells',
			'authors' => 'Vincent A, Kazmierczak C, Duchêne B, Jonckheere N, Leteurtre E, Van Seuningen I',
			'description' => 'The intestinal epithelium is a particularly attractive biological adult model to study epigenetic mechanisms driving adult stem cell renewal and cell differentiation. Since epigenetic modifications are dynamic, we have developed an original ex vivo approach to study the expression and epigenetic profiles of key genes associated with either intestinal cell pluripotency or differentiation by isolating cryosections of the intestinal crypt-villus axis. Gene expression, DNA methylation and histone modifications were studied by qRT-PCR, Methylation Specific-PCR and micro-Chromatin Immunoprecipitation, respectively. Using this approach, it was possible to identify segment-specific methylation and chromatin profiles. We show that (i) expression of intestinal stem cell markers (Lgr5, Ascl2) exclusively in the crypt is associated with active histone marks, (ii) promoters of all pluripotency genes studied and transcription factors involved in intestinal cell fate (Cdx2) harbour a bivalent chromatin pattern in the crypts, (iii) expression of differentiation markers (Muc2, Sox9) along the crypt-villus axis is associated with DNA methylation. Hence, using an original model of cryosectioning along the crypt-villus axis that allows in situ detection of dynamic epigenetic modifications, we demonstrate that regulation of pluripotency and differentiation markers in healthy intestinal mucosa involves different and specific epigenetic mechanisms.',
			'date' => '2014-12-27',
			'pmid' => 'http://www.sciencedirect.com/science/article/pii/S1873506114001585',
			'doi' => '',
			'modified' => '2015-07-24 15:39:04',
			'created' => '2015-07-24 15:39:04',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 214 => array(
			'id' => '2299',
			'name' => 'Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs.',
			'authors' => 'Adoue V, Schiavi A, Light N, Almlöf JC, Lundmark P, Ge B, Kwan T, Caron M, Rönnblom L, Wang C, Chen SH, Goodall AH, Cambien F, Deloukas P, Ouwehand WH, Syvänen AC, Pastinen T',
			'description' => 'Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40-60% of these cis-rSNPs to be shared across cell types. We uncover a new class of cis-rSNPs, which disrupt footprint-derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof-of-principle for a new approach for genome-wide functional validation of transcription factor-SNP interactions. By perturbing NFκB action in lymphoblasts, we identified 489 cis-regulated transcripts with altered AE after NFκB perturbation. Altogether, we perform a comprehensive analysis of cis-variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases. ',
			'date' => '2014-10-16',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/25326100',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 215 => array(
			'id' => '2330',
			'name' => 'Obesity increases histone H3 lysine 9 and 18 acetylation at Tnfa and Ccl2 genes in mouse liver',
			'authors' => 'Mikula M, Majewska A, Ledwon JK, Dzwonek A, Ostrowski J',
			'description' => 'Obesity contributes to the development of non‑alcoholic fatty liver disease (NAFLD), which is characterized by the upregulated expression of two key inflammatory mediators: tumor necrosis factor (Tnfa) and monocyte chemotactic protein 1 (Mcp1; also known as Ccl2). However, the chromatin make-up at these genes in the liver in obese individuals has not been explored. In this study, to identify obesity-mediated epigenetic changes at Tnfa and Ccl2, we used a murine model of obesity induced by a high-fat diet (HFD) and hyperphagic (ob/ob) mice. Chromatin immunoprecipitation (ChIP) assay was used to determine the abundance of permissive histone marks, namely histone H3 lysine 9 and 18 acetylation (H3K9/K18Ac), H3 lysine 4 trimethylation (H3K4me3) and H3 lysine 36 trimethylation (H3K36me3), in conjunction with polymerase 2 RNA (Pol2) and nuclear factor (Nf)-κB recruitment in the liver. Additionally, to correlate the liver tissue‑derived ChIP measurements with a robust in vitro transcriptional response at the Tnfa and Ccl2 genes, we used lipopolysaccharide (LPS) treatment to induce an inflammatory response in Hepa1-6 cells, a cell line derived from murine hepatocytes. ChIP revealed increased H3K9/K18Ac at Tnfa and Ccl2 in the obese mice, although the differences were only statistically significant for Tnfa (p<0.05). Unexpectedly, the levels of H3K4me3 and H3K36me3 marks, as well as Pol2 and Nf-κB recruitment, did not correspond with the increased expression of these two genes in the obese mice. By contrast, the acute treatment of Hepa1-6 cells with LPS significantly increased the H3K9/K18Ac marks, as well as Pol2 and Nf-κB recruitment at both genes, while the levels of H3K4me3 and H3K36me3 marks remained unaltered. These results demonstrate that increased Tnfa and Ccl2 expression in fatty liver at the chromatin level corresponds to changes in the level of histone H3 acetylation.',
			'date' => '2014-10-03',
			'pmid' => 'http://www.spandidos-publications.com/10.3892/ijmm.2014.1958',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 216 => array(
			'id' => '2338',
			'name' => 'The specific alteration of histone methylation profiles by DZNep during early zebrafish development.',
			'authors' => 'Ostrup O, Reiner AH, Aleström P, Collas P',
			'description' => '<p>Early embryo development constitutes a unique opportunity to study acquisition of epigenetic marks, including histone methylation. This study investigates the in vivo function and specificity of 3-deazaneplanocin A (DZNep), a promising anti-cancer drug that targets polycomb complex genes. One- to two-cell stage embryos were cultured with DZNep, and subsequently evaluated at the post-mid blastula transition stage for H3K27me3, H3K4me3 and H3K9me3 occupancy and enrichment at promoters using ChIP-chip microarrays. DZNep affected promoter enrichment of H3K27me3 and H3K9me3, whereas H3K4me3 remained stable. Interestingly, DZNep induced a loss of H3K27me3 and H3K9me3 from a substantial number of promoters but did not prevent de novo acquisition of these marks on others, indicating gene-specific targeting of its action. Loss/gain of H3K27me3 on promoters did not result in changes in gene expression levels until 24h post-fertilization. In contrast, genes gaining H3K9me3 displayed strong and constant down-regulation upon DZNep treatment. H3K9me3 enrichment on these gene promoters was observed not only in the proximal area as expected, but also over the transcription start site. Altered H3K9me3 profiles were associated with severe neuronal and cranial phenotypes at day 4-5 post-fertilization. Thus, DZNep was shown to affect enrichment patterns of H3K27me3 and H3K9me3 at promoters in a gene-specific manner.</p>',
			'date' => '2014-09-28',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25260724',
			'doi' => '',
			'modified' => '2016-04-08 09:43:32',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 217 => array(
			'id' => '2228',
			'name' => 'Interrogation of allelic chromatin states in human cells by high-density ChIP-genotyping.',
			'authors' => 'Light N, Adoue V, Ge B, Chen SH, Kwan T, Pastinen T',
			'description' => 'Allele-specific (AS) assessment of chromatin has the potential to elucidate specific cis-regulatory mechanisms, which are predicted to underlie the majority of the known genetic associations to complex disease. However, development of chromatin landscapes at allelic resolution has been challenging since sites of variable signal strength require substantial read depths not commonly applied in sequencing based approaches. In this study, we addressed this by performing parallel analyses of input DNA and chromatin immunoprecipitates (ChIP) on high-density Illumina genotyping arrays. Allele-specificity for the histone modifications H3K4me1, H3K4me3, H3K27ac, H3K27me3, and H3K36me3 was assessed using ChIP samples generated from 14 lymphoblast and 6 fibroblast cell lines. AS-ChIP SNPs were combined into domains and validated using high-confidence ChIP-seq sites. We observed characteristic patterns of allelic-imbalance for each histone-modification around allele-specifically expressed transcripts. Notably, we found H3K4me1 to be significantly anti-correlated with allelic expression (AE) at transcription start sites, indicating H3K4me1 allelic imbalance as a marker of AE. We also found that allelic chromatin domains exhibit population and cell-type specificity as well as heritability within trios. Finally, we observed that a subset of allelic chromatin domains is regulated by DNase I-sensitive quantitative trait loci and that these domains are significantly enriched for genome-wide association studies hits, with autoimmune disease associated SNPs specifically enriched in lymphoblasts. This study provides the first genome-wide maps of allelic-imbalance for five histone marks. Our results provide new insights into the role of chromatin in cis-regulation and highlight the need for high-depth sequencing in ChIP-seq studies along with the need to improve allele-specificity of ChIP-enrichment.',
			'date' => '2014-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25055051',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 218 => array(
			'id' => '2298',
			'name' => 'Differences among brain tumor stem cell types and fetal neural stem cells in focal regions of histone modifications and DNA methylation, broad regions of modifications, and bivalent promoters.',
			'authors' => 'Yoo S, Bieda MC',
			'description' => 'BACKGROUND: Aberrational epigenetic marks are believed to play a major role in establishing the abnormal features of cancer cells. Rational use and development of drugs aimed at epigenetic processes requires an understanding of the range, extent, and roles of epigenetic reprogramming in cancer cells. Using ChIP-chip and MeDIP-chip approaches, we localized well-established and prevalent epigenetic marks (H3K27me3, H3K4me3, H3K9me3, DNA methylation) on a genome scale in several lines of putative glioma stem cells (brain tumor stem cells, BTSCs) and, for comparison, normal human fetal neural stem cells (fNSCs). RESULTS: We determined a substantial "core" set of promoters possessing each mark in every surveyed BTSC cell type, which largely overlapped the corresponding fNSC sets. However, there was substantial diversity among cell types in mark localization. We observed large differences among cell types in total number of H3K9me3+ positive promoters and peaks and in broad modifications (defined as >50 kb peak length) for H3K27me3 and, to a lesser extent, H3K9me3. We verified that a change in a broad modification affected gene expression of CACNG7. We detected large numbers of bivalent promoters, but most bivalent promoters did not display direct overlap of contrasting epigenetic marks, but rather occupied nearby regions of the proximal promoter. There were significant differences in the sets of promoters bearing bivalent marks in the different cell types and few consistent differences between fNSCs and BTSCs. CONCLUSIONS: Overall, our "core set" data establishes sets of potential therapeutic targets, but the diversity in sets of sites and broad modifications among cell types underscores the need to carefully consider BTSC subtype variation in epigenetic therapy. Our results point toward substantial differences among cell types in the activity of the production/maintenance systems for H3K9me3 and for broad regions of modification (H3K27me3 or H3K9me3). Finally, the unexpected diversity in bivalent promoter sets among these multipotent cells indicates that bivalent promoters may play complex roles in the overall biology of these cells. These results provide key information for forming the basis for future rational drug therapy aimed at epigenetic processes in these cells.',
			'date' => '2014-08-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25163646',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 219 => array(
			'id' => '2201',
			'name' => 'Long Noncoding RNA TARID Directs Demethylation and Activation of the Tumor Suppressor TCF21 via GADD45A.',
			'authors' => 'Arab K, Park YJ, Lindroth AM, Schäfer A, Oakes C, Weichenhan D, Lukanova A, Lundin E, Risch A, Meister M, Dienemann H, Dyckhoff G, Herold-Mende C, Grummt I, Niehrs C, Plass C',
			'description' => 'DNA methylation is a dynamic and reversible process that governs gene expression during development and disease. Several examples of active DNA demethylation have been documented, involving genome-wide and gene-specific DNA demethylation. How demethylating enzymes are targeted to specific genomic loci remains largely unknown. We show that an antisense lncRNA, termed TARID (for TCF21 antisense RNA inducing demethylation), activates TCF21 expression by inducing promoter demethylation. TARID interacts with both the TCF21 promoter and GADD45A (growth arrest and DNA-damage-inducible, alpha), a regulator of DNA demethylation. GADD45A in turn recruits thymine-DNA glycosylase for base excision repair-mediated demethylation involving oxidation of 5-methylcytosine to 5-hydroxymethylcytosine in the TCF21 promoter by ten-eleven translocation methylcytosine dioxygenase proteins. The results reveal a function of lncRNAs, serving as a genomic address label for GADD45A-mediated demethylation of specific target genes.',
			'date' => '2014-08-21',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25087872',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 220 => array(
			'id' => '2063',
			'name' => 'Identification of a large protein network involved in epigenetic transmission in replicating DNA of embryonic stem cells.',
			'authors' => 'Aranda S, Rutishauser D, Ernfors P',
			'description' => 'Pluripotency of embryonic stem cells (ESCs) is maintained by transcriptional activities and chromatin modifying complexes highly organized within the chromatin. Although much effort has been focused on identifying genome-binding sites, little is known on their dynamic association with chromatin across cell divisions. Here, we used a modified version of the iPOND (isolation of proteins at nascent DNA) technology to identify a large protein network enriched at nascent DNA in ESCs. This comprehensive and unbiased proteomic characterization in ESCs reveals that, in addition to the core replication machinery, proteins relevant for pluripotency of ESCs are present at DNA replication sites. In particular, we show that the chromatin remodeller HDAC1-NuRD complex is enriched at nascent DNA. Interestingly, an acute block of HDAC1 in ESCs leads to increased acetylation of histone H3 lysine 9 at nascent DNA together with a concomitant loss of methylation. Consistently, in contrast to what has been described in tumour cell lines, these chromatin marks were found to be stable during cell cycle progression of ESCs. Our results are therefore compatible with a rapid deacetylation-coupled methylation mechanism during the replication of DNA in ESCs that may participate in the preservation of pluripotency of ESCs during replication.',
			'date' => '2014-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24852249',
			'doi' => '',
			'modified' => '2015-07-24 15:39:02',
			'created' => '2015-07-24 15:39:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 221 => array(
			'id' => '2107',
			'name' => 'Seminoma and embryonal carcinoma footprints identified by analysis of integrated genome-wide epigenetic and expression profiles of germ cell cancer cell lines.',
			'authors' => 'van der Zwan YG, Rijlaarsdam MA, Rossello FJ, Notini AJ, de Boer S, Watkins DN, Gillis AJ, Dorssers LC, White SJ, Looijenga LH',
			'description' => 'BACKGROUND: Originating from Primordial Germ Cells/gonocytes and developing via a precursor lesion called Carcinoma In Situ (CIS), Germ Cell Cancers (GCC) are the most common cancer in young men, subdivided in seminoma (SE) and non-seminoma (NS). During physiological germ cell formation/maturation, epigenetic processes guard homeostasis by regulating the accessibility of the DNA to facilitate transcription. Epigenetic deregulation through genetic and environmental parameters (i.e. genvironment) could disrupt embryonic germ cell development, resulting in delayed or blocked maturation. This potentially facilitates the formation of CIS and progression to invasive GCC. Therefore, determining the epigenetic and functional genomic landscape in GCC cell lines could provide insight into the pathophysiology and etiology of GCC and provide guidance for targeted functional experiments. RESULTS: This study aims at identifying epigenetic footprints in SE and EC cell lines in genome-wide profiles by studying the interaction between gene expression, DNA CpG methylation and histone modifications, and their function in the pathophysiology and etiology of GCC. Two well characterized GCC-derived cell lines were compared, one representative for SE (TCam-2) and the other for EC (NCCIT). Data were acquired using the Illumina HumanHT-12-v4 (gene expression) and HumanMethylation450 BeadChip (methylation) microarrays as well as ChIP-sequencing (activating histone modifications (H3K4me3, H3K27ac)). Results indicate known germ cell markers not only to be differentiating between SE and NS at the expression level, but also in the epigenetic landscape. CONCLUSION: The overall similarity between TCam-2/NCCIT support an erased embryonic germ cell arrested in early gonadal development as common cell of origin although the exact developmental stage from which the tumor cells are derived might differ. Indeed, subtle difference in the (integrated) epigenetic and expression profiles indicate TCam-2 to exhibit a more germ cell-like profile, whereas NCCIT shows a more pluripotent phenotype. The results provide insight into the functional genome in GCC cell lines.',
			'date' => '2014-06-02',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24887064',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 222 => array(
			'id' => '2054',
			'name' => 'Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer',
			'authors' => 'Zecchini V, Madhu B, Russell R, Pértega-Gomes N, Warren A, Gaude E, Borlido J, Stark R, Ireland-Zecchini H, Rao R, Scott H, Boren J, Massie C, Asim M, Brindle K, Griffiths J, Frezza C, Neal DE, Mills IG',
			'description' => 'Tumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. Hypoxia-inducible factor 1A (HIF1A) is a major regulator of this process, but its activation under normoxic conditions, termed pseudohypoxia, is not well documented. Here, using an integrative approach combining the first genome-wide mapping of chromatin binding for an endocytic adaptor, ARRB1, both in vitro and in vivo with gene expression profiling, we demonstrate that nuclear ARRB1 contributes to this metabolic shift in prostate cancer cells via regulation of HIF1A transcriptional activity under normoxic conditions through regulation of succinate dehydrogenase A (SDHA) and fumarate hydratase (FH) expression. ARRB1-induced pseudohypoxia may facilitate adaptation of cancer cells to growth in the harsh conditions that are frequently encountered within solid tumours. Our study is the first example of an endocytic adaptor protein regulating metabolic pathways. It implicates ARRB1 as a potential tumour promoter in prostate cancer and highlights the importance of metabolic alterations in prostate cancer.',
			'date' => '2014-05-16',
			'pmid' => 'http://onlinelibrary.wiley.com/doi/10.15252/embj.201386874/full',
			'doi' => '',
			'modified' => '2015-07-24 15:39:02',
			'created' => '2015-07-24 15:39:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 223 => array(
			'id' => '1891',
			'name' => 'Stage-specific control of early B cell development by the transcription factor Ikaros.',
			'authors' => 'Schwickert TA, Tagoh H, Gültekin S, Dakic A, Axelsson E, Minnich M, Ebert A, Werner B, Roth M, Cimmino L, Dickins RA, Zuber J, Jaritz M, Busslinger M',
			'description' => 'The transcription factor Ikaros is an essential regulator of lymphopoiesis. Here we studied its B cell-specific function by conditional inactivation of the gene encoding Ikaros (Ikzf1) in pro-B cells. B cell development was arrested at an aberrant 'pro-B cell' stage characterized by increased cell adhesion and loss of signaling via the pre-B cell signaling complex (pre-BCR). Ikaros activated genes encoding signal transducers of the pre-BCR and repressed genes involved in the downregulation of pre-BCR signaling and upregulation of the integrin signaling pathway. Unexpectedly, derepression of expression of the transcription factor Aiolos did not compensate for the loss of Ikaros in pro-B cells. Ikaros induced or suppressed active chromatin at regulatory elements of activated or repressed target genes. Notably, binding of Ikaros and expression of its target genes were dynamically regulated at distinct stages of early B lymphopoiesis.',
			'date' => '2014-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24509509',
			'doi' => '',
			'modified' => '2015-07-24 15:39:02',
			'created' => '2015-07-24 15:39:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 224 => array(
			'id' => '1793',
			'name' => 'A novel microscopy-based high-throughput screening method to identify proteins that regulate global histone modification levels.',
			'authors' => 'Baas R, Lelieveld D, van Teeffelen H, Lijnzaad P, Castelijns B, van Schaik FM, Vermeulen M, Egan DA, Timmers HT, de Graaf P',
			'description' => '<p>Posttranslational modifications of histones play an important role in the regulation of gene expression and chromatin structure in eukaryotes. The balance between chromatin factors depositing (writers) and removing (erasers) histone marks regulates the steady-state levels of chromatin modifications. Here we describe a novel microscopy-based screening method to identify proteins that regulate histone modification levels in a high-throughput fashion. We named our method CROSS, for Chromatin Regulation Ontology SiRNA Screening. CROSS is based on an siRNA library targeting the expression of 529 proteins involved in chromatin regulation. As a proof of principle, we used CROSS to identify chromatin factors involved in histone H3 methylation on either lysine-4 or lysine-27. Furthermore, we show that CROSS can be used to identify chromatin factors that affect growth in cancer cell lines. Taken together, CROSS is a powerful method to identify the writers and erasers of novel and known chromatin marks and facilitates the identification of drugs targeting epigenetic modifications.</p>',
			'date' => '2014-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24334265',
			'doi' => '',
			'modified' => '2016-04-12 09:46:40',
			'created' => '2015-07-24 15:39:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 225 => array(
			'id' => '1783',
			'name' => 'Pan-histone demethylase inhibitors simultaneously targeting Jumonji C and lysine-specific demethylases display high anticancer activities.',
			'authors' => 'Rotili D, Tomassi S, Conte M, Benedetti R, Tortorici M, Ciossani G, Valente S, Marrocco B, Labella D, Novellino E, Mattevi A, Altucci L, Tumber A, Yapp C, King ON, Hopkinson RJ, Kawamura A, Schofield CJ, Mai A',
			'description' => 'In prostate cancer, two different types of histone lysine demethylases (KDM), LSD1/KDM1 and JMJD2/KDM4, are coexpressed and colocalize with the androgen receptor. We designed and synthesized hybrid LSD1/JmjC or "pan-KDM" inhibitors 1-6 by coupling the skeleton of tranylcypromine 7, a known LSD1 inhibitor, with 4-carboxy-4'-carbomethoxy-2,2'-bipyridine 8 or 5-carboxy-8-hydroxyquinoline 9, two 2-oxoglutarate competitive templates developed for JmjC inhibition. Hybrid compounds 1-6 are able to simultaneously target both KDM families and have been validated as potential antitumor agents in cells. Among them, 2 and 3 increase H3K4 and H3K9 methylation levels in cells and cause growth arrest and substantial apoptosis in LNCaP prostate and HCT116 colon cancer cells. When tested in noncancer mesenchymal progenitor (MePR) cells, 2 and 3 induced little and no apoptosis, respectively, thus showing cancer-selective inhibiting action.',
			'date' => '2014-01-09',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24325601',
			'doi' => '',
			'modified' => '2015-07-24 15:39:01',
			'created' => '2015-07-24 15:39:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 226 => array(
			'id' => '1727',
			'name' => 'Interplay between active chromatin marks and RNA-directed DNA methylation in Arabidopsis thaliana.',
			'authors' => 'Greenberg MV, Deleris A, Hale CJ, Liu A, Feng S, Jacobsen SE',
			'description' => 'DNA methylation is an epigenetic mark that is associated with transcriptional repression of transposable elements and protein-coding genes. Conversely, transcriptionally active regulatory regions are strongly correlated with histone 3 lysine 4 di- and trimethylation (H3K4m2/m3). We previously showed that Arabidopsis thaliana plants with mutations in the H3K4m2/m3 demethylase JUMONJI 14 (JMJ14) exhibit a mild reduction in RNA-directed DNA methylation (RdDM) that is associated with an increase in H3K4m2/m3 levels. To determine whether this incomplete RdDM reduction was the result of redundancy with other demethylases, we examined the genetic interaction of JMJ14 with another class of H3K4 demethylases: lysine-specific demethylase 1-like 1 and lysine-specific demethylase 1-like 2 (LDL1 and LDL2). Genome-wide DNA methylation analyses reveal that both families cooperate to maintain RdDM patterns. ChIP-seq experiments show that regions that exhibit an observable DNA methylation decrease are co-incidental with increases in H3K4m2/m3. Interestingly, the impact on DNA methylation was stronger at DNA-methylated regions adjacent to H3K4m2/m3-marked protein-coding genes, suggesting that the activity of H3K4 demethylases may be particularly crucial to prevent spreading of active epigenetic marks. Finally, RNA sequencing analyses indicate that at RdDM targets, the increase of H3K4m2/m3 is not generally associated with transcriptional de-repression. This suggests that the histone mark itself--not transcription--impacts the extent of RdDM.',
			'date' => '2013-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24244201',
			'doi' => '',
			'modified' => '2015-07-24 15:39:01',
			'created' => '2015-07-24 15:39:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 227 => array(
			'id' => '1581',
			'name' => 'A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis.',
			'authors' => 'Kollmann K, Heller G, Schneckenleithner C, Warsch W, Scheicher R, Ott RG, Schäfer M, Fajmann S, Schlederer M, Schiefer AI, Reichart U, Mayerhofer M, Hoeller C, Zöchbauer-Müller S, Kerjaschki D, Bock C, Kenner L, Hoefler G, Freissmuth M, Green AR, Moriggl ',
			'description' => 'In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185(BCR-ABL+) B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16(INK4a) and the pro-angiogenic factor VEGF-A. This function is independent of CDK6's kinase activity. High CDK6 expression thus suppresses proliferation by upregulating p16(INK4a), providing an internal safeguard. However, in the absence of p16(INK4a), CDK6 can exert its full tumor-promoting function by enhancing proliferation and stimulating angiogenesis. The finding that CDK6 connects cell-cycle progression to angiogenesis confirms CDK6's central role in hematopoietic malignancies and could underlie the selection pressure to upregulate CDK6 and silence p16(INK4a).',
			'date' => '2013-08-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23948297',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 228 => array(
			'id' => '1512',
			'name' => 'Disease-Related Growth Factor and Embryonic Signaling Pathways Modulate an Enhancer of TCF21 Expression at the 6q23.2 Coronary Heart Disease Locus.',
			'authors' => 'Miller CL, Anderson DR, Kundu RK, Raiesdana A, Nürnberg ST, Diaz R, Cheng K, Leeper NJ, Chen CH, Chang IS, Schadt EE, Hsiung CA, Assimes TL, Quertermous T',
			'description' => 'Coronary heart disease (CHD) is the leading cause of mortality in both developed and developing countries worldwide. Genome-wide association studies (GWAS) have now identified 46 independent susceptibility loci for CHD, however, the biological and disease-relevant mechanisms for these associations remain elusive. The large-scale meta-analysis of GWAS recently identified in Caucasians a CHD-associated locus at chromosome 6q23.2, a region containing the transcription factor TCF21 gene. TCF21 (Capsulin/Pod1/Epicardin) is a member of the basic-helix-loop-helix (bHLH) transcription factor family, and regulates cell fate decisions and differentiation in the developing coronary vasculature. Herein, we characterize a cis-regulatory mechanism by which the lead polymorphism rs12190287 disrupts an atypical activator protein 1 (AP-1) element, as demonstrated by allele-specific transcriptional regulation, transcription factor binding, and chromatin organization, leading to altered TCF21 expression. Further, this element is shown to mediate signaling through platelet-derived growth factor receptor beta (PDGFR-β) and Wilms tumor 1 (WT1) pathways. A second disease allele identified in East Asians also appears to disrupt an AP-1-like element. Thus, both disease-related growth factor and embryonic signaling pathways may regulate CHD risk through two independent alleles at TCF21.',
			'date' => '2013-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23874238',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 229 => array(
			'id' => '1465',
			'name' => 'Bivalent chromatin marks developmental regulatory genes in the mouse embryonic germline in vivo.',
			'authors' => 'Sachs M, Onodera C, Blaschke K, Ebata KT, Song JS, Ramalho-Santos M',
			'description' => 'Developmental regulatory genes have both activating (H3K4me3) and repressive (H3K27me3) histone modifications in embryonic stem cells (ESCs). This bivalent configuration is thought to maintain lineage commitment programs in a poised state. However, establishing physiological relevance has been complicated by the high number of cells required for chromatin immunoprecipitation (ChIP). We developed a low-cell-number chromatin immunoprecipitation (low-cell ChIP) protocol to investigate the chromatin of mouse primordial germ cells (PGCs). Genome-wide analysis of embryonic day 11.5 (E11.5) PGCs revealed H3K4me3/H3K27me3 bivalent domains highly enriched at developmental regulatory genes in a manner remarkably similar to ESCs. Developmental regulators remain bivalent and transcriptionally silent through the initiation of sexual differentiation at E13.5. We also identified >2,500 "orphan" bivalent domains that are distal to known genes and expressed in a tissue-specific manner but silent in PGCs. Our results demonstrate the existence of bivalent domains in the germline and raise the possibility that the somatic program is continuously maintained as bivalent, potentially imparting transgenerational epigenetic inheritance.',
			'date' => '2013-06-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23727241',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 230 => array(
			'id' => '1458',
			'name' => 'Integrative analysis of deep sequencing data identifies estrogen receptor early response genes and links ATAD3B to poor survival in breast cancer.',
			'authors' => 'Ovaska K, Matarese F, Grote K, Charapitsa I, Cervera A, Liu C, Reid G, Seifert M, Stunnenberg HG, Hautaniemi S',
			'description' => 'Identification of responsive genes to an extra-cellular cue enables characterization of pathophysiologically crucial biological processes. Deep sequencing technologies provide a powerful means to identify responsive genes, which creates a need for computational methods able to analyze dynamic and multi-level deep sequencing data. To answer this need we introduce here a data-driven algorithm, SPINLONG, which is designed to search for genes that match the user-defined hypotheses or models. SPINLONG is applicable to various experimental setups measuring several molecular markers in parallel. To demonstrate the SPINLONG approach, we analyzed ChIP-seq data reporting PolII, estrogen receptor α (ERα), H3K4me3 and H2A.Z occupancy at five time points in the MCF-7 breast cancer cell line after estradiol stimulus. We obtained 777 ERa early responsive genes and compared the biological functions of the genes having ERα binding within 20 kb of the transcription start site (TSS) to genes without such binding site. Our results show that the non-genomic action of ERα via the MAPK pathway, instead of direct ERa binding, may be responsible for early cell responses to ERα activation. Our results also indicate that the ERα responsive genes triggered by the genomic pathway are transcribed faster than those without ERα binding sites. The survival analysis of the 777 ERα responsive genes with 150 primary breast cancer tumors and in two independent validation cohorts indicated the ATAD3B gene, which does not have ERα binding site within 20 kb of its TSS, to be significantly associated with poor patient survival.',
			'date' => '2013-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23818839',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 231 => array(
			'id' => '1425',
			'name' => 'Expression of a large LINE-1-driven antisense RNA is linked to epigenetic silencing of the metastasis suppressor gene TFPI-2 in cancer.',
			'authors' => 'Cruickshanks HA, Vafadar-Isfahani N, Dunican DS, Lee A, Sproul D, Lund JN, Meehan RR, Tufarelli C',
			'description' => 'LINE-1 retrotransposons are abundant repetitive elements of viral origin, which in normal cells are kept quiescent through epigenetic mechanisms. Activation of LINE-1 occurs frequently in cancer and can enable LINE-1 mobilization but also has retrotransposition-independent consequences. We previously reported that in cancer, aberrantly active LINE-1 promoters can drive transcription of flanking unique sequences giving rise to LINE-1 chimeric transcripts (LCTs). Here, we show that one such LCT, LCT13, is a large transcript (>300 kb) running antisense to the metastasis-suppressor gene TFPI-2. We have modelled antisense RNA expression at TFPI-2 in transgenic mouse embryonic stem (ES) cells and demonstrate that antisense RNA induces silencing and deposition of repressive histone modifications implying a causal link. Consistent with this, LCT13 expression in breast and colon cancer cell lines is associated with silencing and repressive chromatin at TFPI-2. Furthermore, we detected LCT13 transcripts in 56% of colorectal tumours exhibiting reduced TFPI-2 expression. Our findings implicate activation of LINE-1 elements in subsequent epigenetic remodelling of surrounding genes, thus hinting a novel retrotransposition-independent role for LINE-1 elements in malignancy.',
			'date' => '2013-05-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23703216',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 232 => array(
			'id' => '1389',
			'name' => 'The developmental epigenomics toolbox: ChIP-seq and MethylCap-seq profiling of early zebrafish embryos.',
			'authors' => 'Bogdanović O, Fernández-Miñán A, Tena JJ, de la Calle-Mustienes E, Gómez-Skarmeta JL',
			'description' => 'Genome-wide profiling of DNA methylation and histone modifications answered many questions as to how the genes are regulated on a global scale and what their epigenetic makeup is. Yet, little is known about the function of these marks during early vertebrate embryogenesis. Here we provide detailed protocols for ChIP-seq and MethylCap-seq procedures applied to zebrafish (Danio rerio) embryonic material at four developmental stages. As a proof of principle, we have profiled on a global scale a number of post-translational histone modifications including H3K4me1, H3K4me3 and H3K27ac. We demonstrate that these marks are dynamic during early development and that such developmental transitions can be detected by ChIP-seq. In addition, we applied MethylCap-seq to show that developmentally-regulated DNA methylation remodeling can be detected by such a procedure. Our MethylCap-seq data concur with previous DNA methylation studies of early zebrafish development rendering this method highly suitable for the global assessment of DNA methylation in early vertebrate embryos.',
			'date' => '2013-04-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23624103',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 233 => array(
			'id' => '1285',
			'name' => 'Genome-wide analysis of LXRα activation reveals new transcriptional networks in human atherosclerotic foam cells.',
			'authors' => 'Feldmann R, Fischer C, Kodelja V, Behrens S, Haas S, Vingron M, Timmermann B, Geikowski A, Sauer S',
			'description' => 'Increased physiological levels of oxysterols are major risk factors for developing atherosclerosis and cardiovascular disease. Lipid-loaded macrophages, termed foam cells, are important during the early development of atherosclerotic plaques. To pursue the hypothesis that ligand-based modulation of the nuclear receptor LXRα is crucial for cell homeostasis during atherosclerotic processes, we analysed genome-wide the action of LXRα in foam cells and macrophages. By integrating chromatin immunoprecipitation-sequencing (ChIP-seq) and gene expression profile analyses, we generated a highly stringent set of 186 LXRα target genes. Treatment with the nanomolar-binding ligand T0901317 and subsequent auto-regulatory LXRα activation resulted in sequence-dependent sharpening of the genome-binding patterns of LXRα. LXRα-binding loci that correlated with differential gene expression revealed 32 novel target genes with potential beneficial effects, which in part explained the implications of disease-associated genetic variation data. These observations identified highly integrated LXRα ligand-dependent transcriptional networks, including the APOE/C1/C4/C2-gene cluster, which contribute to the reversal of cholesterol efflux and the dampening of inflammation processes in foam cells to prevent atherogenesis.',
			'date' => '2013-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23393188',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 234 => array(
			'id' => '1304',
			'name' => 'Regulation of transcription through acetylation of H3K122 on the lateral surface of the histone octamer.',
			'authors' => 'Tropberger P, Pott S, Keller C, Kamieniarz-Gdula K, Caron M, Richter F, Li G, Mittler G, Liu ET, Bühler M, Margueron R, Schneider R',
			'description' => 'Histone modifications are key regulators of chromatin function. However, little is known to what extent histone modifications can directly impact on chromatin. Here, we address how a modification within the globular domain of histones regulates chromatin function. We demonstrate that H3K122ac can be sufficient to stimulate transcription and that mutation of H3K122 impairs transcriptional activation, which we attribute to a direct effect of H3K122ac on histone-DNA binding. In line with this, we find that H3K122ac defines genome-wide genetic elements and chromatin features associated with active transcription. Furthermore, H3K122ac is catalyzed by the coactivators p300/CBP and can be induced by nuclear hormone receptor signaling. Collectively, this suggests that transcriptional regulators elicit their effects not only via signaling to histone tails but also via direct structural perturbation of nucleosomes by directing acetylation to their lateral surface.',
			'date' => '2013-02-14',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23415232',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 235 => array(
			'id' => '1497',
			'name' => 'Histone lysine trimethylation or acetylation can be modulated by phytoestrogen, estrogen or anti-HDAC in breast cancer cell lines.',
			'authors' => 'Dagdemir A, Durif J, Ngollo M, Bignon YJ, Bernard-Gallon D',
			'description' => '<p>AIM: The isoflavones genistein, daidzein and equol (daidzein metabolite) have been reported to interact with epigenetic modifications, specifically hypermethylation of tumor suppressor genes. The objective of this study was to analyze and understand the mechanisms by which phytoestrogens act on chromatin in breast cancer cell lines. MATERIALS &amp; METHODS: Two breast cancer cell lines, MCF-7 and MDA-MB 231, were treated with genistein (18.5 &micro;M), daidzein (78.5 &micro;M), equol (12.8 &micro;M), 17&beta;-estradiol (10 nM) and suberoylanilide hydroxamic acid (1 &micro;M) for 48 h. A control with untreated cells was performed. 17&beta;-estradiol and an anti-HDAC were used to compare their actions with phytoestrogens. The chromatin immunoprecipitation coupled with quantitative PCR was used to follow soy phytoestrogen effects on H3 and H4 histones on H3K27me3, H3K9me3, H3K4me3, H4K8ac and H3K4ac marks, and we selected six genes (EZH2, BRCA1, ER&alpha;, ER&beta;, SRC3 and P300) for analysis. RESULTS: Soy phytoestrogens induced a decrease in trimethylated marks and an increase in acetylating marks studied at six selected genes. CONCLUSION: We demonstrated that soy phytoestrogens tend to modify transcription through the demethylation and acetylation of histones in breast cancer cell lines.</p>',
			'date' => '2013-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23414320',
			'doi' => '',
			'modified' => '2016-05-03 12:17:35',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 236 => array(
			'id' => '1267',
			'name' => 'Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA.',
			'authors' => 'Fadloun A, Le Gras S, Jost B, Ziegler-Birling C, Takahashi H, Gorab E, Carninci P, Torres-Padilla ME',
			'description' => 'How a more plastic chromatin state is maintained and reversed during development is unknown. Heterochromatin-mediated silencing of repetitive elements occurs in differentiated cells. Here, we used repetitive elements, including retrotransposons, as model loci to address how and when heterochromatin forms during development. RNA sequencing throughout early mouse embryogenesis revealed that repetitive-element expression is dynamic and stage specific, with most repetitive elements becoming repressed before implantation. We show that LINE-1 and IAP retrotransposons become reactivated from both parental genomes after fertilization. Chromatin immunoprecipitation for H3K4me3 and H3K9me3 in 2- and 8-cell embryos indicates that their developmental silencing follows loss of activating marks rather than acquisition of conventional heterochromatic marks. Furthermore, short LINE-1 RNAs regulate LINE-1 transcription in vivo. Our data indicate that reprogramming after mammalian fertilization comprises a robust transcriptional activation of retrotransposons and that repetitive elements are initially regulated through RNA.',
			'date' => '2013-01-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23353788',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 237 => array(
			'id' => '1195',
			'name' => 'Ezh2 maintains a key phase of muscle satellite cell expansion but does not regulate terminal differentiation.',
			'authors' => 'Woodhouse S, Pugazhendhi D, Brien P, Pell JM.',
			'description' => 'Tissue generation and repair requires a stepwise process of cell fate restriction to ensure adult stem cells differentiate in a timely and appropriate manner. A crucial role has been implicated for Polycomb-group (PcG) proteins and the H3K27me3 repressive histone mark, in coordinating the transcriptional programmes necessary for this process, but the targets and developmental timing for this repression remain unclear. To address these questions, we generated novel genome-wide maps of H3K27me3 and H3K4me3 in freshly isolated muscle stem cells. These data, together with the analysis of two conditional Ezh2-null mouse strains, identified a critical proliferation phase in which Ezh2 activity is essential. Mice lacking Ezh2 in satellite cells exhibited decreased muscle growth, severely impaired regeneration and reduced stem cell number, due to a profound failure of the proliferative progenitor population to expand. Surprisingly, deletion of Ezh2 after the onset of terminal differentiation did not impede muscle repair or homeostasis. Using these knockout models, RNA-Seq and the ChIP-Seq datasets we show that Ezh2 does not regulate the muscle differentiation process in vivo. These results emphasise the lineage and cell type specific functions for Ezh2 and the Polycomb repressive complex 2.',
			'date' => '2012-11-30',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/23203812',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 238 => array(
			'id' => '1162',
			'name' => 'Limitations and possibilities of low cell number ChIP-seq.',
			'authors' => 'Gilfillan GD, Hughes T, Sheng Y, Hjorthaug HS, Straub T, Gervin K, Harris JR, Undlien DE, Lyle R',
			'description' => 'ABSTRACT: BACKGROUND: Chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq) offers high resolution, genome-wide analysis of DNA-protein interactions. However, current standard methods require abundant starting material in the range of 1--20 million cells per immunoprecipitation, and remain a bottleneck to the acquisition of biologically relevant epigenetic data. Using a ChIP-seq protocol optimised for low cell numbers (down to 100,000 cells / IP), we examined the performance of the ChIP-seq technique on a series of decreasing cell numbers. RESULTS: We present an enhanced native ChIP-seq method tailored to low cell numbers that represents a 200-fold reduction in input requirements over existing protocols. The protocol was tested over a range of starting cell numbers covering three orders of magnitude, enabling determination of the lower limit of the technique. At low input cell numbers, increased levels of unmapped and duplicate reads reduce the number of unique reads generated, and can drive up sequencing costs and affect sensitivity if ChIP is attempted from too few cells. CONCLUSIONS: The optimised method presented here considerably reduces the input requirements for performing native ChIP-seq. It extends the applicability of the technique to isolated primary cells and rare cell populations (e.g. biobank samples, stem cells), and in many cases will alleviate the need for cell culture and any associated alteration of epigenetic marks. However, this study highlights a challenge inherent to ChIP-seq from low cell numbers: as cell input numbers fall, levels of unmapped sequence reads and PCR-generated duplicate reads rise. We discuss a number of solutions to overcome the effects of reducing cell number that may aid further improvements to ChIP performance.',
			'date' => '2012-11-21',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23171294',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 239 => array(
			'id' => '1143',
			'name' => 'Protein Group Modification and Synergy in the SUMO Pathway as Exemplified in DNA Repair.',
			'authors' => 'Psakhye I, Jentsch S',
			'description' => 'Protein modification by SUMO affects a wide range of protein substrates. Surprisingly, although SUMO pathway mutants display strong phenotypes, the function of individual SUMO modifications is often enigmatic, and SUMOylation-defective mutants commonly lack notable phenotypes. Here, we use DNA double-strand break repair as an example and show that DNA damage triggers a SUMOylation wave, leading to simultaneous multisite modifications of several repair proteins of the same pathway. Catalyzed by a DNA-bound SUMO ligase and triggered by single-stranded DNA, SUMOylation stabilizes physical interactions between the proteins. Notably, only wholesale elimination of SUMOylation of several repair proteins significantly affects the homologous recombination pathway by considerably slowing down DNA repair. Thus, SUMO acts synergistically on several proteins, and individual modifications only add up to efficient repair. We propose that SUMOylation may thus often target a protein group rather than individual proteins, whereas localized modification enzymes and highly specific triggers ensure specificity.',
			'date' => '2012-11-09',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23122649',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 240 => array(
			'id' => '1137',
			'name' => 'IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer.',
			'authors' => 'Baird AM, Leonard J, Naicker KM, Kilmartin L, O'Byrne KJ, Gray SG',
			'description' => 'BACKGROUND: IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC). METHODS: RT-PCR and chromatin immunopreciptiation (ChIP) were used to examine the levels, epigenetic regulation and effects of various drugs (DNA methyltransferase inhibitors, Histone Deacetylase inhibitors and Gemcitabine) on IL-23 expression in NSCLC cells and macrophages. The effects of recombinant IL-23 protein on cellular proliferation were examined by MTT assay. Statistical analysis consisted of Student's t-test or one way analysis of variance (ANOVA) where groups in the experiment were three or more. RESULTS: In a cohort of primary non-small cell lung cancer (NSCLC) tumours, IL-23A expression was significantly elevated in patient tumour samples (p<0.05). IL-23A expression is epigenetically regulated through histone post-translational modifications and DNA CpG methylation. Gemcitabine, a chemotherapy drug indicated for first-line treatment of NSCLC also induced IL-23A expression. Recombinant IL-23 significantly increased cellular proliferation in NSCLC cell lines. CONCLUSIONS: These results may therefore have important implications for treating NSCLC patients with either epigenetic targeted therapies or Gemcitabine.',
			'date' => '2012-10-29',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23116756',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 241 => array(
			'id' => '1078',
			'name' => 'New partners in regulation of gene expression: the enhancer of trithorax and polycomb corto interacts with methylated ribosomal protein l12 via its chromodomain.',
			'authors' => 'Coléno-Costes A, Jang SM, de Vanssay A, Rougeot J, Bouceba T, Randsholt NB, Gibert JM, Le Crom S, Mouchel-Vielh E, Bloyer S, Peronnet F',
			'description' => 'Chromodomains are found in many regulators of chromatin structure, and most of them recognize methylated lysines on histones. Here, we investigate the role of the Drosophila melanogaster protein Corto's chromodomain. The Enhancer of Trithorax and Polycomb Corto is involved in both silencing and activation of gene expression. Over-expression of the Corto chromodomain (CortoCD) in transgenic flies shows that it is a chromatin-targeting module, critical for Corto function. Unexpectedly, mass spectrometry analysis reveals that polypeptides pulled down by CortoCD from nuclear extracts correspond to ribosomal proteins. Furthermore, real-time interaction analyses demonstrate that CortoCD binds with high affinity RPL12 tri-methylated on lysine 3. Corto and RPL12 co-localize with active epigenetic marks on polytene chromosomes, suggesting that both are involved in fine-tuning transcription of genes in open chromatin. RNA-seq based transcriptomes of wing imaginal discs over-expressing either CortoCD or RPL12 reveal that both factors deregulate large sets of common genes, which are enriched in heat-response and ribosomal protein genes, suggesting that they could be implicated in dynamic coordination of ribosome biogenesis. Chromatin immunoprecipitation experiments show that Corto and RPL12 bind hsp70 and are similarly recruited on gene body after heat shock. Hence, Corto and RPL12 could be involved together in regulation of gene transcription. We discuss whether pseudo-ribosomal complexes composed of various ribosomal proteins might participate in regulation of gene expression in connection with chromatin regulators.',
			'date' => '2012-10-11',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23071455',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 242 => array(
			'id' => '831',
			'name' => 'Extensive promoter hypermethylation and hypomethylation is associated with aberrant microRNA expression in chronic lymphocytic leukemia.',
			'authors' => 'Baer C, Claus R, Frenzel LP, Zucknick M, Park YJ, Gu L, Weichenhan D, Fischer M, Pallasch CP, Herpel E, Rehli M, Byrd JC, Wendtner CM, Plass C',
			'description' => '<p>Dysregulated microRNA (miRNA) expression contributes to the pathogenesis of hematopoietic malignancies, including chronic lymphocytic leukemia (CLL). However, an understanding of the mechanisms that cause aberrant miRNA transcriptional control is lacking. In this study, we comprehensively investigated the role and extent of miRNA epigenetic regulation in CLL. Genome-wide profiling performed on 24 CLL and 10 healthy B cell samples revealed global DNA methylation patterns upstream of miRNA sequences that distinguished malignant from healthy cells and identified putative miRNA promoters. Integration of DNA methylation and miRNA promoter data led to the identification of 128 recurrent miRNA targets for aberrant promoter DNA methylation. DNA hypomethylation accounted for over 60% of all aberrant promoter-associated DNA methylation in CLL, and promoter DNA hypomethylation was restricted to well-defined regions. Individual hyper- and hypomethylated promoters allowed discrimination of CLL samples from healthy controls. Promoter DNA methylation patterns were confirmed in an independent patient cohort, with eleven miRNAs consistently demonstrating an inverse correlation between DNA methylation status and expression level. Together, our findings characterize the role of epigenetic changes in the regulation of miRNA transcription and create a repository of disease-specific promoter regions that may provide additional insights into the pathogenesis of CLL.</p>',
			'date' => '2012-06-18',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22710432',
			'doi' => '',
			'modified' => '2016-05-03 12:14:21',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 243 => array(
			'id' => '1204',
			'name' => 'The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells.',
			'authors' => 'Karpiuk O, Najafova Z, Kramer F, Hennion M, Galonska C, König A, Snaidero N, Vogel T, Shchebet A, Begus-Nahrmann Y, Kassem M, Simons M, Shcherbata H, Beissbarth T, Johnsen SA',
			'description' => 'Extensive changes in posttranslational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly understood. We show that histone H2B monoubiquitination (H2Bub1) significantly increases during differentiation of human mesenchymal stem cells (hMSCs) and various lineage-committed precursor cells and in diverse organisms. Furthermore, the H2B ubiquitin ligase RNF40 is required for the induction of differentiation markers and transcriptional reprogramming of hMSCs. This function is dependent upon CDK9 and the WAC adaptor protein, which are required for H2B monoubiquitination. Finally, we show that RNF40 is required for the resolution of the H3K4me3/H3K27me3 bivalent poised state on lineage-specific genes during the transition from an inactive to an active chromatin conformation. Thus, these data indicate that H2Bub1 is required for maintaining multipotency of hMSCs and plays a central role in controlling stem cell differentiation.',
			'date' => '2012-06-08',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22681891',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 244 => array(
			'id' => '792',
			'name' => 'Intronic RNAs mediate EZH2 regulation of epigenetic targets.',
			'authors' => 'Guil S, Soler M, Portela A, Carrère J, Fonalleras E, Gómez A, Villanueva A, Esteller M',
			'description' => 'Epigenetic deregulation at a number of genomic loci is one of the hallmarks of cancer. A role for some RNA molecules in guiding repressive polycomb complex PRC2 to specific chromatin regions has been proposed. Here we use an in vivo cross-linking method to detect and identify direct PRC2-RNA interactions in human cancer cells, revealing a number of intronic RNA sequences capable of binding to the core component EZH2 and regulating the transcriptional output of its genomic counterpart. Overexpression of EZH2-bound intronic RNA for the H3K4 methyltransferase gene SMYD3 is concomitant with an increase in EZH2 occupancy throughout the corresponding genomic fragment and is sufficient to reduce levels of the endogenous transcript and protein, resulting in reduced growth capability in cell culture and animal models. These findings reveal the role of intronic RNAs in fine-tuning gene expression regulation at the level of transcriptional control.',
			'date' => '2012-06-03',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22659877',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 245 => array(
			'id' => '732',
			'name' => 'The transcriptional and epigenomic foundations of ground state pluripotency.',
			'authors' => 'Marks H, Kalkan T, Menafra R, Denissov S, Jones K, Hofemeister H, Nichols J, Kranz A, Francis Stewart A, Smith A, Stunnenberg HG',
			'description' => 'Mouse embryonic stem (ES) cells grown in serum exhibit greater heterogeneity in morphology and expression of pluripotency factors than ES cells cultured in defined medium with inhibitors of two kinases (Mek and GSK3), a condition known as "2i" postulated to establish a naive ground state. We show that the transcriptome and epigenome profiles of serum- and 2i-grown ES cells are distinct. 2i-treated cells exhibit lower expression of lineage-affiliated genes, reduced prevalence at promoters of the repressive histone modification H3K27me3, and fewer bivalent domains, which are thought to mark genes poised for either up- or downregulation. Nonetheless, serum- and 2i-grown ES cells have similar differentiation potential. Precocious transcription of developmental genes in 2i is restrained by RNA polymerase II promoter-proximal pausing. These findings suggest that transcriptional potentiation and a permissive chromatin context characterize the ground state and that exit from it may not require a metastable intermediate or multilineage priming.',
			'date' => '2012-04-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22541430',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 246 => array(
			'id' => '456',
			'name' => 'Control of ground-state pluripotency by allelic regulation of Nanog.',
			'authors' => 'Miyanari Y, Torres-Padilla ME',
			'description' => 'Pluripotency is established through genome-wide reprogramming during mammalian pre-implantation development, resulting in the formation of the naive epiblast. Reprogramming involves both the resetting of epigenetic marks and the activation of pluripotent-cell-specific genes such as Nanog and Oct4 (also known as Pou5f1). The tight regulation of these genes is crucial for reprogramming, but the mechanisms that regulate their expression in vivo have not been uncovered. Here we show that Nanog-but not Oct4-is monoallelically expressed in early pre-implantation embryos. Nanog then undergoes a progressive switch to biallelic expression during the transition towards ground-state pluripotency in the naive epiblast of the late blastocyst. Embryonic stem (ES) cells grown in leukaemia inhibitory factor (LIF) and serum express Nanog mainly monoallelically and show asynchronous replication of the Nanog locus, a feature of monoallelically expressed genes, but ES cells activate both alleles when cultured under 2i conditions, which mimic the pluripotent ground state in vitro. Live-cell imaging with reporter ES cells confirmed the allelic expression of Nanog and revealed allelic switching. The allelic expression of Nanog is regulated through the fibroblast growth factor-extracellular signal-regulated kinase signalling pathway, and it is accompanied by chromatin changes at the proximal promoter but occurs independently of DNA methylation. Nanog-heterozygous blastocysts have fewer inner-cell-mass derivatives and delayed primitive endoderm formation, indicating a role for the biallelic expression of Nanog in the timely maturation of the inner cell mass into a fully reprogrammed pluripotent epiblast. We suggest that the tight regulation of Nanog dose at the chromosome level is necessary for the acquisition of ground-state pluripotency during development. Our data highlight an unexpected role for allelic expression in controlling the dose of pluripotency factors in vivo, adding an extra level to the regulation of reprogramming.',
			'date' => '2012-02-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22327294',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 247 => array(
			'id' => '919',
			'name' => 'Prepatterning of developmental gene expression by modified histones before zygotic genome activation.',
			'authors' => 'Lindeman LC, Andersen IS, Reiner AH, Li N, Aanes H, Østrup O, Winata C, Mathavan S, Müller F, Aleström P, Collas P',
			'description' => 'A hallmark of anamniote vertebrate development is a window of embryonic transcription-independent cell divisions before onset of zygotic genome activation (ZGA). Chromatin determinants of ZGA are unexplored; however, marking of developmental genes by modified histones in sperm suggests a predictive role of histone marks for ZGA. In zebrafish, pre-ZGA development for ten cell cycles provides an opportunity to examine whether genomic enrichment in modified histones is present before initiation of transcription. By profiling histone H3 trimethylation on all zebrafish promoters before and after ZGA, we demonstrate here an epigenetic prepatterning of developmental gene expression. This involves pre-ZGA marking of transcriptionally inactive genes involved in homeostatic and developmental regulation by permissive H3K4me3 with or without repressive H3K9me3 or H3K27me3. Our data suggest that histone modifications are instructive for the developmental gene expression program.',
			'date' => '2011-12-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22137762',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 248 => array(
			'id' => '913',
			'name' => 'IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF.',
			'authors' => 'Baird AM, Gray SG, O'Byrne KJ',
			'description' => 'BACKGROUND: IL-20 is a pleiotrophic member of the IL-10 family and plays a role in skin biology and the development of haematopoietic cells. Recently, IL-20 has been demonstrated to have potential anti-angiogenic effects in non-small cell lung cancer (NSCLC) by down regulating COX-2. METHODS: The expression of IL-20 and its cognate receptors (IL-20RA/B and IL-22R1) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of this family was examined in normal bronchial epithelial and NSCLC cell lines. Furthermore, the effect of IL-20 on VEGF family members was examined. RESULTS: The expression of IL-20 and its receptors are frequently dysregulated in NSCLC. IL-20RB mRNA was significantly elevated in NSCLC tumours (p<0.01). Protein levels of the receptors, IL-20RB and IL-22R1, were significantly increased (p<0.01) in the tumours of NSCLC patients. IL-20 and its receptors were found to be epigenetically regulated through histone post-translational modifications and DNA CpG residue methylation. In addition, treatment with recombinant IL-20 resulted in decreased expression of the VEGF family members at the mRNA level. CONCLUSIONS: This family of genes are dysregulated in NSCLC and are subject to epigenetic regulation. Whilst the anti-angiogenic properties of IL-20 require further clarification, targeting this family via epigenetic means may be a viable therapeutic option in lung cancer treatment.',
			'date' => '2011-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21565488',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 249 => array(
			'id' => '637',
			'name' => 'H3.5 is a novel hominid-specific histone H3 variant that is specifically expressed in the seminiferous tubules of human testes.',
			'authors' => 'Schenk R, Jenke A, Zilbauer M, Wirth S, Postberg J',
			'description' => 'The incorporation of histone variants into chromatin plays an important role for the establishment of particular chromatin states. Six human histone H3 variants are known to date, not counting CenH3 variants: H3.1, H3.2, H3.3 and the testis-specific H3.1t as well as the recently described variants H3.X and H3.Y. We report the discovery of H3.5, a novel non-CenH3 histone H3 variant. H3.5 is encoded on human chromosome 12p11.21 and probably evolved in a common ancestor of all recent great apes (Hominidae) as a consequence of H3F3B gene duplication by retrotransposition. H3.5 mRNA is specifically expressed in seminiferous tubules of human testis. Interestingly, H3.5 has two exact copies of ARKST motifs adjacent to lysine-9 or lysine-27, and lysine-79 is replaced by asparagine. In the Hek293 cell line, ectopically expressed H3.5 is assembled into chromatin and targeted by PTM. H3.5 preferentially colocalizes with euchromatin, and it is associated with actively transcribed genes and can replace an essential function of RNAi-depleted H3.3 in cell growth.',
			'date' => '2011-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21274551',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 250 => array(
			'id' => '256',
			'name' => 'Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer',
			'authors' => 'O'Byrne KJ, Baird AM, Kilmartin L, Leonard J, Sacevich C, Gray SG.',
			'description' => 'Due to their inherently hypoxic environment, cancer cells often resort to glycolysis, or the anaerobic breakdown of glucose to form ATP to provide for their energy needs, known as the Warburg effect. At the same time, overexpression of the insulin receptor in non-small cell lung cancer (NSCLC) is associated with an increased risk of metastasis and decreased survival. The uptake of glucose into cells is carried out via glucose transporters or GLUTs. Of these, GLUT-4 is essential for insulin-stimulated glucose uptake. Following treatment with the epigenetic targeting agents histone deacetylase inhibitors (HDACi), GLUT-3 and GLUT-4 expression were found to be induced in NSCLC cell lines, with minimal responses in transformed normal human bronchial epithelial cells (HBECs). Similar results for GLUT-4 were observed in cells derived from liver, muscle, kidney and pre-adipocytes. Bioinformatic analysis of the promoter for GLUT-4 indicates that it may also be regulated by several chromatin binding factors or complexes including CTCF, SP1 and SMYD3. Chromatin immunoprecipitation studies demonstrate that the promoter for GLUT-4 is dynamically remodeled in response to HDACi. Overall, these results may have value within the clinical setting as (a) it may be possible to use this to enhance fluorodeoxyglucose (18F) positron emission tomography (FDG-PET) imaging sensitivity; (b) it may be possible to target NSCLC through the use of HDACi and insulin mediated uptake of the metabolic targeting drugs such as 2-deoxyglucose (2-DG); or (c) enhance or sensitize NSCLC to chemotherapy. ',
			'date' => '2011-03-25',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/24212773',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 251 => array(
			'id' => '265',
			'name' => 'Characterisation of genome-wide PLZF/RARA target genes.',
			'authors' => 'Spicuglia S, Vincent-Fabert C, Benoukraf T, Tibéri G, Saurin AJ, Zacarias-Cabeza J, Grimwade D, Mills K, Calmels B, Bertucci F, Sieweke M, Ferrier P, Duprez E',
			'description' => 'The PLZF/RARA fusion protein generated by the t(11;17)(q23;q21) translocation in acute promyelocytic leukaemia (APL) is believed to act as an oncogenic transcriptional regulator recruiting epigenetic factors to genes important for its transforming potential. However, molecular mechanisms associated with PLZF/RARA-dependent leukaemogenesis still remain unclear.We searched for specific PLZF/RARA target genes by ChIP-on-chip in the haematopoietic cell line U937 conditionally expressing PLZF/RARA. By comparing bound regions found in U937 cells expressing endogenous PLZF with PLZF/RARA-induced U937 cells, we isolated specific PLZF/RARA target gene promoters. We next analysed gene expression profiles of our identified target genes in PLZF/RARA APL patients and analysed DNA sequences and epigenetic modification at PLZF/RARA binding sites. We identify 413 specific PLZF/RARA target genes including a number encoding transcription factors involved in the regulation of haematopoiesis. Among these genes, 22 were significantly down regulated in primary PLZF/RARA APL cells. In addition, repressed PLZF/RARA target genes were associated with increased levels of H3K27me3 and decreased levels of H3K9K14ac. Finally, sequence analysis of PLZF/RARA bound sequences reveals the presence of both consensus and degenerated RAREs as well as enrichment for tissue-specific transcription factor motifs, highlighting the complexity of targeting fusion protein to chromatin. Our study suggests that PLZF/RARA directly targets genes important for haematopoietic development and supports the notion that PLZF/RARA acts mainly as an epigenetic regulator of its direct target genes.',
			'date' => '2011-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21949697',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 252 => array(
			'id' => '585',
			'name' => 'Tiling histone H3 lysine 4 and 27 methylation in zebrafish using high-density microarrays.',
			'authors' => 'Lindeman LC, Reiner AH, Mathavan S, Aleström P, Collas P',
			'description' => 'BACKGROUND: Uncovering epigenetic states by chromatin immunoprecipitation and microarray hybridization (ChIP-chip) has significantly contributed to the understanding of gene regulation at the genome-scale level. Many studies have been carried out in mice and humans; however limited high-resolution information exists to date for non-mammalian vertebrate species. PRINCIPAL FINDINGS: We report a 2.1-million feature high-resolution Nimblegen tiling microarray for ChIP-chip interrogations of epigenetic states in zebrafish (Danio rerio). The array covers 251 megabases of the genome at 92 base-pair resolution. It includes ∼15 kb of upstream regulatory sequences encompassing all RefSeq promoters, and over 5 kb in the 5' end of coding regions. We identify with high reproducibility, in a fibroblast cell line, promoters enriched in H3K4me3, H3K27me3 or co-enriched in both modifications. ChIP-qPCR and sequential ChIP experiments validate the ChIP-chip data and support the co-enrichment of trimethylated H3K4 and H3K27 on a subset of genes. H3K4me3- and/or H3K27me3-enriched genes are associated with distinct transcriptional status and are linked to distinct functional categories. CONCLUSIONS: We have designed and validated for the scientific community a comprehensive high-resolution tiling microarray for investigations of epigenetic states in zebrafish, a widely used developmental and disease model organism.',
			'date' => '2010-12-20',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21187971',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 253 => array(
			'id' => '413',
			'name' => 'Autonomous silencing of the imprinted Cdkn1c gene in stem cells',
			'authors' => 'Wood MD, Hiura H, Tunster S, Arima T, Shin J-H, Higgins M, John1 RM',
			'description' => 'Parent-of-origin specific expression of imprinted genes relies on the differential DNA methylation of specific genomic regions. Differentially methylated regions (DMRs) acquire DNA methylation either during gametogenesis (primary DMR) or after fertilization when allele-specific expression is established (secondary DMR). Little is known about the function of these secondary DMRs. We investigated the DMR spanning Cdkn1c in mouse embryonic stem cells, androgenetic stem cells and embryonic germ stem cells. In all cases, expression of Cdkn1c was appropriately repressed in in vitro differentiated cells. However, stem cells failed to de novo methylate the silenced gene even after sustained differentiation. In the absence of maintained DNA methylation (Dnmt1-/-), Cdkn1c escapes silencing demonstrating the requirement for DNA methylation in long term silencing in vivo. We propose that post-fertilization differential methylation reflects the importance of retaining single gene dosage of a subset of imprinted loci in the adult.',
			'date' => '2010-04-01',
			'pmid' => 'http://www.pubmed/20372090',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 254 => array(
			'id' => '69',
			'name' => 'The histone variant macroH2A is an epigenetic regulator of key developmental genes.',
			'authors' => 'Buschbeck M, Uribesalgo I, Wibowo I, Rué P, Martin D, Gutierrez A, Morey L, Guigó R, López-Schier H, Di Croce L',
			'description' => 'The histone variants macroH2A1 and macroH2A2 are associated with X chromosome inactivation in female mammals. However, the physiological function of macroH2A proteins on autosomes is poorly understood. Microarray-based analysis in human male pluripotent cells uncovered occupancy of both macroH2A variants at many genes encoding key regulators of development and cell fate decisions. On these genes, the presence of macroH2A1+2 is a repressive mark that overlaps locally and functionally with Polycomb repressive complex 2. We demonstrate that macroH2A1+2 contribute to the fine-tuning of temporal activation of HOXA cluster genes during neuronal differentiation. Furthermore, elimination of macroH2A2 function in zebrafish embryos produced severe but specific phenotypes. Taken together, our data demonstrate that macroH2A variants constitute an important epigenetic mark involved in the concerted regulation of gene expression programs during cellular differentiation and vertebrate development.',
			'date' => '2009-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/19734898',
			'doi' => '',
			'modified' => '2015-07-24 15:38:56',
			'created' => '2015-07-24 15:38:56',
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		(int) 255 => array(
			'id' => '117',
			'name' => 'High-resolution analysis of epigenetic changes associated with X inactivation.',
			'authors' => 'Marks H, Chow JC, Denissov S, Françoijs KJ, Brockdorff N, Heard E, Stunnenberg HG',
			'description' => 'Differentiation of female murine ES cells triggers silencing of one X chromosome through X-chromosome inactivation (XCI). Immunofluorescence studies showed that soon after Xist RNA coating the inactive X (Xi) undergoes many heterochromatic changes, including the acquisition of H3K27me3. However, the mechanisms that lead to the establishment of heterochromatin remain unclear. We first analyze chromatin changes by ChIP-chip, as well as RNA expression, around the X-inactivation center (Xic) in female and male ES cells, and their day 4 and 10 differentiated derivatives. A dynamic epigenetic landscape is observed within the Xic locus. Tsix repression is accompanied by deposition of H3K27me3 at its promoter during differentiation of both female and male cells. However, only in female cells does an active epigenetic landscape emerge at the Xist locus, concomitant with high Xist expression. Several regions within and around the Xic show unsuspected chromatin changes, and we define a series of unusual loci containing highly enriched H3K27me3. Genome-wide ChIP-seq analyses show a female-specific quantitative increase of H3K27me3 across the X chromosome as XCI proceeds in differentiating female ES cells. Using female ES cells with nonrandom XCI and polymorphic X chromosomes, we demonstrate that this increase is specific to the Xi by allele-specific SNP mapping of the ChIP-seq tags. H3K27me3 becomes evenly associated with the Xi in a chromosome-wide fashion. A selective and robust increase of H3K27me3 and concomitant decrease in H3K4me3 is observed over active genes. This indicates that deposition of H3K27me3 during XCI is tightly associated with the act of silencing of individual genes across the Xi.',
			'date' => '2009-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/19581487',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
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		(int) 256 => array(
			'id' => '1435',
			'name' => 'H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming.',
			'authors' => 'Daujat S, Weiss T, Mohn F, Lange UC, Ziegler-Birling C, Zeissler U, Lappe M, Schübeler D, Torres-Padilla ME, Schneider R',
			'description' => 'Histone modifications are central to the regulation of all DNA-dependent processes. Lys64 of histone H3 (H3K64) lies within the globular domain at a structurally important position. We identify trimethylation of H3K64 (H3K64me3) as a modification that is enriched at pericentric heterochromatin and associated with repeat sequences and transcriptionally inactive genomic regions. We show that this new mark is dynamic during the two main epigenetic reprogramming events in mammals. In primordial germ cells, H3K64me3 is present at the time of specification, but it disappears transiently during reprogramming. In early mouse embryos, it is inherited exclusively maternally; subsequently, the modification is rapidly removed, suggesting an important role for H3K64me3 turnover in development. Taken together, our findings establish H3K64me3 as a previously uncharacterized histone modification that is preferentially localized to repressive chromatin. We hypothesize that H3K64me3 helps to 'secure' nucleosomes, and perhaps the surrounding chromatin, in an appropriately repressed state during development.',
			'date' => '2009-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/19561610',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
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		),
		(int) 257 => array(
			'id' => '2600',
			'name' => 'Epigenetic-Mediated Downregulation of μ-Protocadherin in Colorectal Tumours',
			'authors' => 'Bujko M, Kober P, Statkiewicz M, Mikula M, Ligaj M, Zwierzchowski L, Ostrowski J, Siedlecki JA',
			'description' => 'Carcinogenesis involves altered cellular interaction and tissue morphology that partly arise from aberrant expression of cadherins. Mucin-like protocadherin is implicated in intercellular adhesion and its expression was found decreased in colorectal cancer (CRC). This study has compared MUPCDH (CDHR5) expression in three key types of colorectal tissue samples, for normal mucosa, adenoma, and carcinoma. A gradual decrease of mRNA levels and protein expression was observed in progressive stages of colorectal carcinogenesis which are consistent with reports of increasing MUPCDH 5′ promoter region DNA methylation. High MUPCDH methylation was also observed in HCT116 and SW480 CRC cell lines that revealed low gene expression levels compared to COLO205 and HT29 cell lines which lack DNA methylation at the MUPCDH locus. Furthermore, HCT116 and SW480 showed lower levels of RNA polymerase II and histone H3 lysine 4 trimethylation (H3K4me3) as well as higher levels of H3K27 trimethylation at the MUPCDH promoter. MUPCDH expression was however restored in HCT116 and SW480 cells in the presence of 5-Aza-2′-deoxycytidine (DNA methyltransferase inhibitor). Results indicate that μ-protocadherin downregulation occurs during early stages of tumourigenesis and progression into the adenoma-carcinoma sequence. Epigenetic mechanisms are involved in this silencing.',
			'date' => '0000-00-00',
			'pmid' => 'http://www.hindawi.com/journals/grp/2015/317093/',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
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			'id' => '783',
			'name' => 'Analysis of active chromatin modifications in early mammalian embryos reveals uncoupling of H2A.Z acetylation and H3K36 trimethylation from embryonic genome activation',
			'authors' => 'Bošković A, Bender A, Gall L, Ziegler-Birling C, Beaujean N, Torres-Padilla ME',
			'description' => 'Early embryonic development is characterized by dramatic changes in cell potency and chromatin organization. The role of histone variants in the context of chromatin remodeling during embryogenesis remains under investigated. In particular, the nuclear distribution of the histone variant H2A.Z and its modifications have not been examined. Here we investigated the dynamics of acetylation of H2A.Z and two other active chromatin marks, H3K9ac and H3K36me3, throughout murine and bovine pre-implantation development. We show that H2A.Z distribution is dynamic during the earliest stages of mouse development, with protein levels significantly varying across stages and lowest at the 2-cell stage. When present, H2A.Z localizes preferentially to euchromatin at all stages analyzed. H2A.Z is acetylated in preimplantation blastomeres and is preferentially localized to euchromatin, in line with the known role of H2A.Zac in transcriptional activation. Interestingly, however, H2A.Zac is undetectable in mouse embryos at the 2-cell stage, the time of major embryonic genome activation (EGA). Similarly, H3K36me3 is present exclusively in the maternal chromatin immediately after fertilization but becomes undetectable in interphase nuclei at the 2-cell stage, suggesting uncoupling of these active marks with global embryonic transcription activation. In bovine embryos, which undergo EGA at the 8-cell stage, H2A.Zac can be detected in zygotes, 4-, 8- and 16-cell stage embryos as well as in blastocysts, indicating that the dynamics of H2A.Zac is not conserved in mammals. In contrast, H3K36me3 displays mostly undetectable and heterogeneous localization pattern throughout bovine pre-implantation development. Thus, our results suggest that ‘canonical’ active chromatin marks exhibit a dynamic behavior in embryonic nuclei, which is both stage- and speciesspecific. We hypothesize that chromatin of early embryonic nuclei is subject to fine-tuning through differential acquisition of histone marks, allowing for proper chromatin remodeling and developmental progression in a species-specific fashion.',
			'date' => '0000-00-00',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/22647320',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
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			'description' => '<p>I have used Diagenode's antibodies for my ChIP&ndash;qPCR experiments in HK-2 cells. The antibodies performed very well in our experiments with specific signal, and good signal to noise ratio in the promoter of the gapdh gene.</p>
<center><img src="../../img/categories/antibodies/H3K4me3-hk2.png" /></center>
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong> ChIP assays were performed using human HK-2 cells, the Diagenode antibody against H3K4me3 (Cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with standard fixation and sonication protocol, using sheared chromatin from 4 million cells. A total amount of 4 ug of antibody were used per ChIP experiment, normal mouse IgG (4 &mu;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). These results are in accordance with the observation that trimethylation of K4 at histone H3 is associated with the promoters of active genes.</small></p>',
			'author' => 'Claudio Cappelli PhD. Post-Doc. Investigator, Laboratory of Molecular Pathology, Institute of Biochemestry and Microbiology, University Austral of Chile, about H3K4me3 polyclonal antibody Premium, 50 μl size.',
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			'description' => '<p>In life sciences, epigenetics is nowadays the most rapid developing field with new astonishing discoveries made every day. To keep pace with this field, we are in need of reliable tools to foster our research - tools Diagenode provides us with. From <strong>antibodies</strong> to <strong>automated solutions</strong> - all from one source and with robust support. Antibodies used in our lab: H3K27me3 polyclonal antibody &ndash; Premium, H3K4me3 polyclonal antibody &ndash; Premium, H3K9me3 polyclonal antibody &ndash; Premium, H3K4me1 polyclonal antibody &ndash; Premium, CTCF polyclonal antibody &ndash; Classic, Rabbit IgG.</p>',
			'author' => 'Dr. Florian Uhle, Dept. of Anesthesiology, Heidelberg University Hospital, Germany',
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			'description' => '<p>We use the <strong>Bioruptor</strong> sonication device and the antibody against the histone modification H3K4me3 in our lab. The Bioruptor device is used for the shearing of chromatin in ChIP-Seq experiments and for generation of protein lysates (whole cell extracts). Thanks to the Bioruptor device we achieve excellent and reproducible results in both applications. The <strong>H3K4me3 antibody</strong> is used in our ChIP-Seq experiments as well as Western Blotting. With this antibody we are able to generate highly enriched ChIP-Seq samples with extremely low background. In Western Blot we can detect one specific, strong band with the H3K4me3 antibody.</p>
<p>Diagenode provides not only very good products for research but also an excellent customer support.</p>',
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			'description' => '<p><span>I work with Diagenode&rsquo;s <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> and shear the DNA on the <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a> for the last year and I have to say that these two products saved my PhD project! Some time ago, our well-established ChIP protocol suddenly stopped to work and after long time of figuring out the reason, we invested into <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a>. </span><span>I am very satisfied from the way it works, plus it&rsquo;s super quiet! Combining the sonicator with the <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> we finally got things working.&nbsp;</span><span>I have also decided to try the <a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns">Microplex Library Prep kit</a>, which is amazing. I have been working with other kits and I find this one efficient and very easy to use. </span><span>Recently, I have tested one of the epigenetics antibody (<a href="../products/search?keyword=H3K4me3">H3K4me3</a>) and it works very well on the plant tissue, together with the ChIP-seq kit and Bioruptor. </span></p>
<p>Thanks Diagenode for saving my PhD!</p>',
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		'id' => '2173',
		'antibody_id' => '115',
		'name' => 'H3K4me3 Antibody',
		'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
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<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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	'name' => 'H3K4me3 polyclonal antibody  (sample size)',
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<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
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<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
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<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
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<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
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<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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$testimonials = '<blockquote><p>I have used Diagenode's antibodies for my ChIP&ndash;qPCR experiments in HK-2 cells. The antibodies performed very well in our experiments with specific signal, and good signal to noise ratio in the promoter of the gapdh gene.</p>
<center><img src="../../img/categories/antibodies/H3K4me3-hk2.png" /></center>
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong> ChIP assays were performed using human HK-2 cells, the Diagenode antibody against H3K4me3 (Cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with standard fixation and sonication protocol, using sheared chromatin from 4 million cells. A total amount of 4 ug of antibody were used per ChIP experiment, normal mouse IgG (4 &mu;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). These results are in accordance with the observation that trimethylation of K4 at histone H3 is associated with the promoters of active genes.</small></p><cite>Claudio Cappelli PhD. Post-Doc. Investigator, Laboratory of Molecular Pathology, Institute of Biochemestry and Microbiology, University Austral of Chile, about H3K4me3 polyclonal antibody Premium, 50 μl size.</cite></blockquote>
<blockquote><p>In life sciences, epigenetics is nowadays the most rapid developing field with new astonishing discoveries made every day. To keep pace with this field, we are in need of reliable tools to foster our research - tools Diagenode provides us with. From <strong>antibodies</strong> to <strong>automated solutions</strong> - all from one source and with robust support. Antibodies used in our lab: H3K27me3 polyclonal antibody &ndash; Premium, H3K4me3 polyclonal antibody &ndash; Premium, H3K9me3 polyclonal antibody &ndash; Premium, H3K4me1 polyclonal antibody &ndash; Premium, CTCF polyclonal antibody &ndash; Classic, Rabbit IgG.</p><cite>Dr. Florian Uhle, Dept. of Anesthesiology, Heidelberg University Hospital, Germany</cite></blockquote>
<blockquote><p>We use the <strong>Bioruptor</strong> sonication device and the antibody against the histone modification H3K4me3 in our lab. The Bioruptor device is used for the shearing of chromatin in ChIP-Seq experiments and for generation of protein lysates (whole cell extracts). Thanks to the Bioruptor device we achieve excellent and reproducible results in both applications. The <strong>H3K4me3 antibody</strong> is used in our ChIP-Seq experiments as well as Western Blotting. With this antibody we are able to generate highly enriched ChIP-Seq samples with extremely low background. In Western Blot we can detect one specific, strong band with the H3K4me3 antibody.</p>
<p>Diagenode provides not only very good products for research but also an excellent customer support.</p><cite>Dr Lora Dimitrova, Charité-Universitätsmedizin Berlin, Germany</cite></blockquote>
<blockquote><p><span>I work with Diagenode&rsquo;s <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> and shear the DNA on the <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a> for the last year and I have to say that these two products saved my PhD project! Some time ago, our well-established ChIP protocol suddenly stopped to work and after long time of figuring out the reason, we invested into <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a>. </span><span>I am very satisfied from the way it works, plus it&rsquo;s super quiet! Combining the sonicator with the <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> we finally got things working.&nbsp;</span><span>I have also decided to try the <a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns">Microplex Library Prep kit</a>, which is amazing. I have been working with other kits and I find this one efficient and very easy to use. </span><span>Recently, I have tested one of the epigenetics antibody (<a href="../products/search?keyword=H3K4me3">H3K4me3</a>) and it works very well on the plant tissue, together with the ChIP-seq kit and Bioruptor. </span></p>
<p>Thanks Diagenode for saving my PhD!</p><cite>Kamila Kwasniewska, Plant Developmental Genetics, Smurfit Institute, Trinity College, Dublin</cite></blockquote>
<blockquote><p>I am working with the <a href="../p/true-microchip-kit-x16-16-rxns">True MicroChIP</a> &amp; <a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns">Microplex Library Preparation</a> Kits and several histone modification antibodies like H3K27ac, H3K4me3, H3K36me3, and H3K27me3.&nbsp;I got always very good and reproducible results for my ChIP-seq experiments.</p><cite>Andrea Thiesen, ZMB, Developmental Biology, Prof. Dr. Andrea Vortkamp´s lab, University Duisburg-Essen, Germany</cite></blockquote>
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'
$related = array(
	'id' => '2173',
	'antibody_id' => '115',
	'name' => 'H3K4me3 Antibody',
	'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
	'label1' => 'Validation data',
	'info1' => '<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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</div>
<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
</div>
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	'label2' => 'Target Description',
	'info2' => '<p>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called "histone code". Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Methylation of histone H3K4 is associated with activation of gene transcription.</p>
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	'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
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<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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</div>
<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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<p>Read more:</p>
<p><a href="https://www.diagenode.com/en/categories/cutandtag">Products for CUT&amp;Tag assay</a></p>
<p><a href="https://www.diagenode.com/en/pages/cut-and-tag">Performance of Diagenode's antibodies in CUT&amp;Tag</a></p>
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<p><a href="https://www.diagenode.com/en/pages/cut-and-tag">Performance of Diagenode's antibodies in CUT&amp;Tag</a></p>
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<p><a href="https://www.diagenode.com/en/categories/cutandtag">Products for CUT&amp;Tag assay</a></p>
<p><a href="https://www.diagenode.com/en/pages/cut-and-tag">Performance of Diagenode's antibodies in CUT&amp;Tag</a></p>
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	'authors' => 'Bošković A, Bender A, Gall L, Ziegler-Birling C, Beaujean N, Torres-Padilla ME',
	'description' => 'Early embryonic development is characterized by dramatic changes in cell potency and chromatin organization. The role of histone variants in the context of chromatin remodeling during embryogenesis remains under investigated. In particular, the nuclear distribution of the histone variant H2A.Z and its modifications have not been examined. Here we investigated the dynamics of acetylation of H2A.Z and two other active chromatin marks, H3K9ac and H3K36me3, throughout murine and bovine pre-implantation development. We show that H2A.Z distribution is dynamic during the earliest stages of mouse development, with protein levels significantly varying across stages and lowest at the 2-cell stage. When present, H2A.Z localizes preferentially to euchromatin at all stages analyzed. H2A.Z is acetylated in preimplantation blastomeres and is preferentially localized to euchromatin, in line with the known role of H2A.Zac in transcriptional activation. Interestingly, however, H2A.Zac is undetectable in mouse embryos at the 2-cell stage, the time of major embryonic genome activation (EGA). Similarly, H3K36me3 is present exclusively in the maternal chromatin immediately after fertilization but becomes undetectable in interphase nuclei at the 2-cell stage, suggesting uncoupling of these active marks with global embryonic transcription activation. In bovine embryos, which undergo EGA at the 8-cell stage, H2A.Zac can be detected in zygotes, 4-, 8- and 16-cell stage embryos as well as in blastocysts, indicating that the dynamics of H2A.Zac is not conserved in mammals. In contrast, H3K36me3 displays mostly undetectable and heterogeneous localization pattern throughout bovine pre-implantation development. Thus, our results suggest that ‘canonical’ active chromatin marks exhibit a dynamic behavior in embryonic nuclei, which is both stage- and speciesspecific. We hypothesize that chromatin of early embryonic nuclei is subject to fine-tuning through differential acquisition of histone marks, allowing for proper chromatin remodeling and developmental progression in a species-specific fashion.',
	'date' => '0000-00-00',
	'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/22647320',
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			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone H3 containing the trimethylated lysine 4 (H3K4me3), using a KLH-conjugated synthetic peptide.</span></p>
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<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
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<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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			'format' => '10 µg',
			'catalog_number' => 'C15410003-10',
			'old_catalog_number' => 'pAb-003-010',
			'sf_code' => 'C15410003-D001-000582',
			'type' => 'FRE',
			'search_order' => '03-Antibody',
			'price_EUR' => '125',
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			'slug' => 'h3k4me3-polyclonal-antibody-premium-sample-size-10-ug',
			'meta_title' => 'H3K4me3 polyclonal antibody - Premium (sample size)',
			'meta_keywords' => '',
			'meta_description' => 'H3K4me3 polyclonal antibody - Premium (sample size)',
			'modified' => '2022-06-29 14:43:38',
			'created' => '2015-06-29 14:08:20',
			'locale' => 'jpn'
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			'host' => '*****',
			'id' => '115',
			'name' => 'H3K4me3 polyclonal antibody',
			'description' => 'Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called “histone code”. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Methylation of histone H3K4 is associated with activation of gene transcription.',
			'clonality' => '',
			'isotype' => '',
			'lot' => 'A8034D',
			'concentration' => '1.3 &micro;g/&micro;l',
			'reactivity' => 'Human, mouse, pig, zebrafish, trout, Daphnia, Arabidopsis, rice, tomato, maize, poplar, silena latifolia, wide range expected.',
			'type' => 'Polyclonal, <strong>ChIP grade, ChIP-seq grade</strong>',
			'purity' => 'Affinity purified polyclonal antibody.',
			'classification' => 'Premium',
			'application_table' => '<table>
<thead>
<tr>
<th>Applications</th>
<th>Suggested dilution</th>
<th>References</th>
</tr>
</thead>
<tbody>
<tr>
<td>ChIP/ChIP-seq<sup>*</sup></td>
<td><span style="font-family: Helvetica;">0.5 - 1&nbsp;&micro;g</span></td>
<td>Fig 1, 2</td>
</tr>
<tr>
<td>CUT&amp;Tag</td>
<td>0.5 &micro;g</td>
<td>Fig 3</td>
</tr>
<tr>
<td>ELISA</td>
<td>1:2,000</td>
<td>Fig 4</td>
</tr>
<tr>
<td>Dot Blotting</td>
<td>1:1000</td>
<td>Fig 5</td>
</tr>
<tr>
<td>Western Blotting</td>
<td>1:1,000</td>
<td>Fig 6</td>
</tr>
<tr>
<td>Immunofluorescence</td>
<td>1:200</td>
<td>Fig 7</td>
</tr>
</tbody>
</table>
<p></p>
<p><small><sup>*</sup> Please note that the optimal antibody amount per IP should be determined by the end-user. We recommend testing 0.5-5 &micro;g per IP.</small></p>',
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			'precautions' => 'This product is for research use only. Not for use in diagnostic or therapeutic procedures.',
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			'slug' => '',
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			'modified' => '2022-08-17 11:57:06',
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		'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone H3 containing the trimethylated lysine 4 (H3K4me3), using a KLH-conjugated synthetic peptide.</span></p>
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
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<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
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<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
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<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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		'meta_description' => 'H3K4me3 polyclonal antibody - Premium (sample size)',
		'modified' => '2022-06-29 14:43:38',
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		'host' => '*****',
		'id' => '115',
		'name' => 'H3K4me3 polyclonal antibody',
		'description' => 'Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called “histone code”. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Methylation of histone H3K4 is associated with activation of gene transcription.',
		'clonality' => '',
		'isotype' => '',
		'lot' => 'A8034D',
		'concentration' => '1.3 &micro;g/&micro;l',
		'reactivity' => 'Human, mouse, pig, zebrafish, trout, Daphnia, Arabidopsis, rice, tomato, maize, poplar, silena latifolia, wide range expected.',
		'type' => 'Polyclonal, <strong>ChIP grade, ChIP-seq grade</strong>',
		'purity' => 'Affinity purified polyclonal antibody.',
		'classification' => 'Premium',
		'application_table' => '<table>
<thead>
<tr>
<th>Applications</th>
<th>Suggested dilution</th>
<th>References</th>
</tr>
</thead>
<tbody>
<tr>
<td>ChIP/ChIP-seq<sup>*</sup></td>
<td><span style="font-family: Helvetica;">0.5 - 1&nbsp;&micro;g</span></td>
<td>Fig 1, 2</td>
</tr>
<tr>
<td>CUT&amp;Tag</td>
<td>0.5 &micro;g</td>
<td>Fig 3</td>
</tr>
<tr>
<td>ELISA</td>
<td>1:2,000</td>
<td>Fig 4</td>
</tr>
<tr>
<td>Dot Blotting</td>
<td>1:1000</td>
<td>Fig 5</td>
</tr>
<tr>
<td>Western Blotting</td>
<td>1:1,000</td>
<td>Fig 6</td>
</tr>
<tr>
<td>Immunofluorescence</td>
<td>1:200</td>
<td>Fig 7</td>
</tr>
</tbody>
</table>
<p></p>
<p><small><sup>*</sup> Please note that the optimal antibody amount per IP should be determined by the end-user. We recommend testing 0.5-5 &micro;g per IP.</small></p>',
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		'precautions' => 'This product is for research use only. Not for use in diagnostic or therapeutic procedures.',
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		'Master' => array(
			'id' => '2173',
			'antibody_id' => '115',
			'name' => 'H3K4me3 Antibody',
			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
			'label1' => 'Validation data',
			'info1' => '<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
</div>
</div>
<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
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<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
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<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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			'label2' => 'Target Description',
			'info2' => '<p>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called "histone code". Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Methylation of histone H3K4 is associated with activation of gene transcription.</p>
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			'format' => '50 µg',
			'catalog_number' => 'C15410003',
			'old_catalog_number' => 'pAb-003-050',
			'sf_code' => 'C15410003-D001-000581',
			'type' => 'FRE',
			'search_order' => '03-Antibody',
			'price_EUR' => '480',
			'price_USD' => '470',
			'price_GBP' => '430',
			'price_JPY' => '75190',
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			'price_AUD' => '1175',
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			'last_datasheet_update' => 'January 8, 2021',
			'slug' => 'h3k4me3-polyclonal-antibody-premium-50-ug-50-ul',
			'meta_title' => 'H3K4me3 Antibody - ChIP-seq Grade (C15410003) | Diagenode',
			'meta_keywords' => '',
			'meta_description' => 'H3K4me3 (Histone H3 trimethylated at lysine 4) Polyclonal Antibody validated  in ChIP-seq, ChIP-qPCR, CUT&Tag, ELISA, DB, WB and IF. Specificity confirmed by Peptide array. Batch-specific data available on the website. Sample size available.',
			'modified' => '2024-11-19 16:51:19',
			'created' => '2015-06-29 14:08:20'
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			'id' => '1836',
			'antibody_id' => null,
			'name' => 'iDeal ChIP-seq kit for Histones',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/ideal-chipseq-for-histones-complete-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<p>Don&rsquo;t risk wasting your precious sequencing samples. Diagenode&rsquo;s validated <strong>iDeal ChIP-seq kit for Histones</strong> has everything you need for a successful start-to-finish <strong>ChIP of histones prior to Next-Generation Sequencing</strong>. The complete kit contains all buffers and reagents for cell lysis, chromatin shearing, immunoprecipitation and DNA purification. In addition, unlike competing solutions, the kit contains positive and negative control antibodies (H3K4me3 and IgG, respectively) as well as positive and negative control PCR primers pairs (GAPDH TSS and Myoglobin exon 2, respectively) for your convenience and a guarantee of optimal results. The kit has been validated on multiple histone marks.</p>
<p>&nbsp;The &nbsp;iDeal ChIP-seq kit for Histones<strong> </strong>is perfect for <strong>cells</strong> (<strong>100,000 cells</strong> to <strong>1,000,000 cells</strong> per IP) and has been validated for <strong>tissues</strong> (<strong>1.5 mg</strong> to <strong>5 mg</strong> of tissue per IP).</p>
<p>&nbsp;The iDeal ChIP-seq kit is the only kit on the market validated for the major sequencing systems. Our expertise in ChIP-seq tools allows reproducible and efficient results every time.</p>
<p></p>
<p>&nbsp;<strong></strong></p>
<p></p>',
			'label1' => 'Characteristics',
			'info1' => '<ul style="list-style-type: disc;">
<li>Highly <strong>optimized</strong> protocol for ChIP-seq from cells and tissues</li>
<li><strong>Validated</strong> for ChIP-seq with multiple histones marks</li>
<li>Most <strong>complete</strong> kit available (covers all steps, including the control antibodies and primers)</li>
<li>Optimized chromatin preparation in combination with the Bioruptor ensuring the best <strong>epitope integrity</strong></li>
<li>Magnetic beads make ChIP easy, fast and more <strong>reproducible</strong></li>
<li>Combination with Diagenode ChIP-seq antibodies provides high yields with excellent <strong>specificity</strong> and <strong>sensitivity</strong></li>
<li>Purified DNA suitable for any downstream application</li>
<li>Easy-to-follow protocol</li>
</ul>
<p>Note: to obtain optimal results, this kit should be used in combination with the DiaMag1.5 - magnetic rack.</p>
<h3>ChIP-seq on cells</h3>
<p><img src="https://www.diagenode.com/img/product/kits/iDeal-kit-C01010053-figure-1.jpg" alt="Figure 1A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1A. The high consistency of the iDeal ChIP-seq kit on the Ion Torrent&trade; PGM&trade; (Life Technologies) and GAIIx (Illumina<sup>&reg;</sup>)</strong><br /> ChIP was performed on sheared chromatin from 1 million HelaS3 cells using the iDeal ChIP-seq kit and 1 &micro;g of H3K4me3 positive control antibody. Two different biological samples have been analyzed using two different sequencers - GAIIx (Illumina<sup>&reg;</sup>) and PGM&trade; (Ion Torrent&trade;). The expected ChIP-seq profile for H3K4me3 on the GAPDH promoter region has been obtained.<br /> Image A shows a several hundred bp along chr12 with high similarity of read distribution despite the radically different sequencers. Image B is a close capture focusing on the GAPDH that shows that even the peak structure is similar.</p>
<p class="text-center"><strong>Perfect match between ChIP-seq data obtained with the iDeal ChIP-seq workflow and reference dataset</strong></p>
<p><img src="https://www.diagenode.com/img/product/kits/perfect-match-between-chipseq-data.png" alt="Figure 1B" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>
<p><img src="https://www.diagenode.com/img/product/kits/iDeal-kit-C01010053-figure-2.jpg" alt="Figure 2" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 2. Efficient and easy chromatin shearing using the Bioruptor<sup>&reg;</sup> and Shearing buffer iS1 from the iDeal ChIP-seq kit</strong><br /> Chromatin from 1 million of Hela cells was sheared using the Bioruptor<sup>&reg;</sup> combined with the Bioruptor<sup>&reg;</sup> Water cooler (Cat No. BioAcc-cool) during 3 rounds of 10 cycles of 30 seconds &ldquo;ON&rdquo; / 30 seconds &ldquo;OFF&rdquo; at HIGH power setting (position H). Diagenode 1.5 ml TPX tubes (Cat No. M-50001) were used for chromatin shearing. Samples were gently vortexed before and after performing each sonication round (rounds of 10 cycles), followed by a short centrifugation at 4&deg;C to recover the sample volume at the bottom of the tube. The sheared chromatin was then decross-linked as described in the kit manual and analyzed by agarose gel electrophoresis.</p>
<p><img src="https://www.diagenode.com/img/product/kits/iDeal-kit-C01010053-figure-3.jpg" alt="Figure 3" style="display: block; margin-left: auto; margin-right: auto;" width="264" height="320" /></p>
<p><strong>Figure 3. Validation of ChIP by qPCR: reliable results using Diagenode&rsquo;s ChIP-seq grade H3K4me3 antibody, isotype control and sets of validated primers</strong><br /> Specific enrichment on positive loci (GAPDH, EIF4A2, c-fos promoter regions) comparing to no enrichment on negative loci (TSH2B promoter region and Myoglobin exon 2) was detected by qPCR. Samples were prepared using the Diagenode iDeal ChIP-seq kit. Diagenode ChIP-seq grade antibody against H3K4me3 and the corresponding isotype control IgG were used for immunoprecipitation. qPCR amplification was performed with sets of validated primers.</p>
<h3>ChIP-seq on tissue</h3>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-figure-h3k4me3.jpg" alt="Figure 4A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 4A.</strong> Chromatin Immunoprecipitation has been performed using chromatin from mouse liver tissue, the iDeal ChIP-seq kit for Histones and the Diagenode ChIP-seq-grade H3K4me3 (Cat. No. C15410003) antibody. The IP'd DNA was subsequently analysed on an Illumina&reg; HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in a region surrounding the GAPDH positive control gene.</p>
<p><img src="https://www.diagenode.com/img/product/kits/match-of-the-top40-peaks-2.png" alt="Figure 4B" caption="false" style="display: block; margin-left: auto; margin-right: auto;" width="700" height="280" /></p>
<p><strong>Figure 4B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>',
			'label2' => 'Species, cell lines, tissues tested',
			'info2' => '<p>The iDeal ChIP-seq Kit for Histones is compatible with a broad variety of cell lines, tissues and species - some examples are shown below. Other species / cell lines / tissues can be used with this kit.</p>
<p><u>Cell lines:</u></p>
<p>Human: A549, A673, CD8+ T, Blood vascular endothelial cells, Lymphatic endothelial cells, fibroblasts, K562, MDA-MB231</p>
<p>Pig: Alveolar macrophages</p>
<p>Mouse: C2C12, primary HSPC, synovial fibroblasts, HeLa-S3, FACS sorted cells from embryonic kidneys, macrophages, mesodermal cells, myoblasts, NPC, salivary glands, spermatids, spermatocytes, skeletal muscle stem cells, stem cells, Th2</p>
<p>Hamster: CHO</p>
<p>Other cell lines / species: compatible, not tested</p>
<p><u>Tissues</u></p>
<p>Bee &ndash; brain</p>
<p>Daphnia &ndash; whole animal</p>
<p>Horse &ndash; brain, heart, lamina, liver, lung, skeletal muscles, ovary</p>
<p>Human &ndash; Erwing sarcoma tumor samples</p>
<p>Other tissues: compatible, not tested</p>
<p>Did you use the iDeal ChIP-seq for Histones Kit on other cell line / tissue / species? <a href="mailto:agnieszka.zelisko@diagenode.com?subject=Species, cell lines, tissues tested with the iDeal ChIP-seq Kit for TF&amp;body=Dear Customer,%0D%0A%0D%0APlease, leave below your feedback about the iDeal ChIP-seq for Transcription Factors (cell / tissue type, species, other information...).%0D%0A%0D%0AThank you for sharing with us your experience !%0D%0A%0D%0ABest regards,%0D%0A%0D%0AAgnieszka Zelisko-Schmidt, PhD">Let us know!</a></p>',
			'label3' => '  Additional solutions compatible with iDeal ChIP-seq Kit for Histones',
			'info3' => '<p><a href="../p/chromatin-shearing-optimization-kit-low-sds-100-million-cells">Chromatin EasyShear Kit - Ultra Low SDS </a>optimizes chromatin shearing, a critical step for ChIP.</p>
<p>&nbsp;The <a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq">MicroPlex Library Preparation Kit </a>provides easy and optimal &nbsp;library preparation of ChIPed samples.</p>
<p><a href="../categories/chip-seq-grade-antibodies">ChIP-seq grade anti-histone antibodies</a> provide high yields with excellent specificity and sensitivity.</p>
<p>&nbsp;Plus, for our IP-Star Automation users for automated ChIP, check out our <a href="../p/auto-ideal-chip-seq-kit-for-histones-x24-24-rxns">automated</a> version of this kit.</p>',
			'format' => '4 chrom. prep./24 IPs',
			'catalog_number' => 'C01010051',
			'old_catalog_number' => 'AB-001-0024',
			'sf_code' => 'C01010051-',
			'type' => 'RFR',
			'search_order' => '04-undefined',
			'price_EUR' => '915',
			'price_USD' => '1130',
			'price_GBP' => '840',
			'price_JPY' => '143335',
			'price_CNY' => '',
			'price_AUD' => '2825',
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			'slug' => 'ideal-chip-seq-kit-x24-24-rxns',
			'meta_title' => 'iDeal ChIP-seq kit x24',
			'meta_keywords' => '',
			'meta_description' => 'iDeal ChIP-seq kit x24',
			'modified' => '2023-04-20 16:00:20',
			'created' => '2015-06-29 14:08:20',
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		(int) 1 => array(
			'id' => '1839',
			'antibody_id' => null,
			'name' => 'iDeal ChIP-seq kit for Transcription Factors',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/ideal-chipseq-transcription-factors-x10-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<div class="row">
<div class="small-12 medium-8 large-8 columns"><br />
<p><span style="font-weight: 400;">Diagenode&rsquo;s <strong>iDeal ChIP-seq Kit for Transcription Factors</strong> is a highly validated solution for robust transcription factor and other non-histone proteins ChIP-seq results and contains everything you need for start-to-finish </span><b>ChIP </b><span style="font-weight: 400;">prior to </span><b>Next-Generation Sequencing</b><span style="font-weight: 400;">. This complete solution contains all buffers and reagents for cell lysis, chromatin shearing, immunoprecipitation, and DNA purification. In addition, unlike competing solutions, the kit contains positive and negative control antibodies (CTCF and IgG, respectively) as well as positive and negative control PCR primers pairs (H19 and Myoglobin exon 2, respectively) for your convenience and a guarantee of optimal results. <br /></span></p>
</div>
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<p><span style="font-weight: 400;">The </span><b>&nbsp;iDeal ChIP-seq kit for Transcription Factors </b><span style="font-weight: 400;">is compatible for cells or tissues:</span></p>
<table style="width: 419px; margin-left: auto; margin-right: auto;">
<tbody>
<tr>
<td style="width: 144px;"></td>
<td style="width: 267px; text-align: center;"><span style="font-weight: 400;">Amount per IP</span></td>
</tr>
<tr>
<td style="width: 144px;">Cells</td>
<td style="width: 267px; text-align: center;"><strong>4,000,000</strong></td>
</tr>
<tr>
<td style="width: 144px;">Tissues</td>
<td style="width: 267px; text-align: center;"><strong>30 mg</strong></td>
</tr>
</tbody>
</table>
<p><span style="font-weight: 400;">The iDeal ChIP-seq kit is the only kit on the market validated for major sequencing systems. Our expertise in ChIP-seq tools allows reproducible and efficient results every time. </span></p>
<p></p>
<p></p>',
			'label1' => 'Characteristics',
			'info1' => '<ul>
<li><span style="font-weight: 400;"><strong>Highly optimized protocol</strong> for ChIP-seq from cells and tissues</span></li>
<li><span style="font-weight: 400;"><strong>Validated</strong> for <strong>ChIP-seq</strong> with multiple transcription factors and non-histone targets<br /></span></li>
<li><span style="font-weight: 400;"><strong>Most complete kit</strong> available (covers all steps, including the control antibodies and primers)<br /></span></li>
<li><span style="font-weight: 400;"><strong>Magnetic beads</strong> make ChIP <strong>easy</strong>, <strong>fast</strong> and more <strong>reproducible</strong></span></li>
<li><span style="font-weight: 400;">Combination with Diagenode ChIP-seq antibodies provides <strong>high yields</strong> with excellent <strong>specificity</strong> and <strong>sensitivity</strong><br /></span></li>
<li><span style="font-weight: 400;">Purified DNA suitable for any downstream application</span></li>
<li><span style="font-weight: 400;">Easy-to-follow protocol</span></li>
</ul>
<p><span style="font-weight: 400;"></span></p>
<p>&nbsp;</p>
<h3>ChIP-seq on cells</h3>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-ctcf-diagenode.jpg" alt="CTCF Diagenode" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1.</strong> (A) Chromatin Immunoprecipitation has been performed using chromatin from HeLa cells, the iDeal ChIP-seq kit for Transcription Factors and the Diagenode ChIP-seq-grade CTCF antibody. The IP'd DNA was subsequently analysed on an Illumina<sup>&reg;</sup> HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in a region surrounding the GAPDH positive control gene.</p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-figure-b-total-diagendoe-peaks.png" alt="CTCF Diagenode" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 1B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>
<p>&nbsp;</p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-TF-chip-seq-A.png" alt="ChIP-seq figure A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-TF-chip-seq-B.png" alt="ChIP-seq figure B" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-TF-chip-seq-C.png" alt="ChIP-seq figure C" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 2.</strong> Chromatin Immunoprecipitation has been performed using chromatin from HeLa cells, the iDeal ChIP-seq kit for Transcription Factors and the Diagenode ChIP-seq-grade HDAC1 (A), LSD1 (B) and p53 antibody (C). The IP'd DNA was subsequently analysed on an Illumina<sup>&reg;</sup> Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in regions of chromosome 3 (A), chromosome 12 (B) and chromosome 6 (C) respectively.</p>
<p>&nbsp;</p>
<h3>ChIP-seq on tissue</h3>
<p><img src="https://www.diagenode.com/img/product/kits/ideal-figure-3a.jpg" alt="ChIP-seq figure A" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 3A.</strong> Chromatin Immunoprecipitation has been performed using chromatin from mouse liver tissue, the iDeal ChIP-seq kit for Transcription Factors and the Diagenode ChIP-seq-grade CTCF antibody. The IP'd DNA was subsequently analysed on an Illumina&reg; HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. This figure shows the peak distribution in a region surrounding the Vwf positive control gene.</p>
<p><img src="https://www.diagenode.com/img/product/kits/match-of-the-top40-peaks.png" alt="Match of the Top40 peaks" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure 3B.</strong> The ChIP-seq dataset from this experiment has been compared with a reference dataset from the Broad Institute. We observed a perfect match between the top 40% of Diagenode peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>',
			'label2' => 'Species, cell lines, tissues tested',
			'info2' => '<p>The iDeal ChIP-seq Kit for Transcription Factors is compatible with a broad variety of cell lines, tissues and species - some examples are shown below. Other species / cell lines / tissues can be used with this kit.</p>
<p><span style="text-decoration: underline;">Cell lines:</span></p>
<p>Human: A549, A673, BT-549, CD4 T, HCC1806, HeLa, HepG2, HFF, HK-GFP-MR, ILC,&nbsp;K562, KYSE-180, LapC4, M14, MCF7, MDA-MB-231, MDA-MB-436, RDES, SKNO1, VCaP, U2-OS, ZR-75-1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;</p>
<p>Mouse: ESC, NPCs, BZ, GT1-7, acinar cells, HSPCs, Th2 cells, keratinocytes</p>
<p>Cattle: pbMEC, <span>MAC-T</span></p>
<p><span>Other cell lines / species: compatible, not tested</span></p>
<p><span style="text-decoration: underline;">Tissues:</span></p>
<p>Mouse: kidney, heart, brain, iris, liver, limbs from E10.5 embryos</p>
<p><span>Horse: l</span>iver, brain, heart, lung, skeletal muscle, lamina, ovary</p>
<p>Other tissues: compatible, not tested</p>
<p><span style="text-decoration: underline;">ChIP on yeast</span></p>
<p>The iDeal ChIP-seq kit for TF is compatible with yeast samples. Check out our <strong><a href="https://www.diagenode.com/files/products/kits/Application_Note-ChIP_on_Yeast.pdf">Application Note</a></strong>&nbsp;presenting an optimized detailed protocol for ChIP on yeast.</p>
<p></p>
<p>Did you use the iDeal ChIP-seq for Transcription Factors Kit on other cell line / tissue / species? <a href="mailto:agnieszka.zelisko@diagenode.com?subject=Species, cell lines, tissues tested with the iDeal ChIP-seq Kit for TF&amp;body=Dear Customer,%0D%0A%0D%0APlease, leave below your feedback about the iDeal ChIP-seq for Transcription Factors (cell / tissue type, species, other information...).%0D%0A%0D%0AThank you for sharing with us your experience !%0D%0A%0D%0ABest regards,%0D%0A%0D%0AAgnieszka Zelisko-Schmidt, PhD">Let us know!</a></p>',
			'label3' => 'Additional solutions compatible with iDeal ChIP-seq kit for Transcription Factors',
			'info3' => '<p><span style="font-weight: 400;">The</span> <a href="https://www.diagenode.com/en/p/chromatin-shearing-optimization-kit-low-sds-for-tfs-25-rxns"><span style="font-weight: 400;">Chromatin EasyShear Kit &ndash; Low SDS </span></a><span style="font-weight: 400;">is the kit compatible with the iDeal ChIP-seq kit for TF, recommended for the optimization of chromatin shearing, a critical step for ChIP.</span></p>
<p><a href="https://www.diagenode.com/en/p/chip-cross-link-gold-600-ul"><span style="font-weight: 400;">ChIP Cross-link Gold</span></a> <span style="font-weight: 400;">should be used in combination with formaldehyde when working with higher order and/or dynamic interactions, for efficient protein-protein fixation.</span></p>
<p><span style="font-weight: 400;">For library preparation of immunoprecipitated samples we recommend to use the </span><b>&nbsp;</b><a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq"><span style="font-weight: 400;">MicroPlex Library Preparation Kit</span></a><span style="font-weight: 400;"> - validated for library preparation from picogram inputs.</span></p>
<p><a href="https://www.diagenode.com/en/categories/chip-seq-grade-antibodies"><span style="font-weight: 400;">ChIP-seq grade antibodies</span></a><span style="font-weight: 400;"> provide high yields with excellent specificity and sensitivity.</span></p>
<p><span style="font-weight: 400;">Check the list of available </span><a href="https://www.diagenode.com/en/categories/primer-pairs"><span style="font-weight: 400;">Primer pairs</span></a><span style="font-weight: 400;"> designed for high specificity to specific genomic regions.</span></p>
<p><span style="font-weight: 400;">Plus, for our <a href="https://www.diagenode.com/en/categories/ip-star">IP-Star Automation</a> users for automated ChIP, check out our <a href="https://www.diagenode.com/en/p/auto-ideal-chip-seq-kit-for-transcription-factors-x24-24-rxns">automated version</a> of this kit.</span></p>',
			'format' => '4 chrom. prep./24 IPs',
			'catalog_number' => 'C01010055',
			'old_catalog_number' => '',
			'sf_code' => 'C01010055-',
			'type' => 'RFR',
			'search_order' => '04-undefined',
			'price_EUR' => '915',
			'price_USD' => '1130',
			'price_GBP' => '840',
			'price_JPY' => '143335',
			'price_CNY' => '',
			'price_AUD' => '2825',
			'country' => 'ALL',
			'except_countries' => 'None',
			'quote' => false,
			'in_stock' => false,
			'featured' => true,
			'no_promo' => false,
			'online' => true,
			'master' => true,
			'last_datasheet_update' => '0000-00-00',
			'slug' => 'ideal-chip-seq-kit-for-transcription-factors-x24-24-rxns',
			'meta_title' => 'iDeal ChIP-seq kit for Transcription Factors x24',
			'meta_keywords' => '',
			'meta_description' => 'iDeal ChIP-seq kit for Transcription Factors x24',
			'modified' => '2023-06-20 18:27:37',
			'created' => '2015-06-29 14:08:20',
			'ProductsRelated' => array(
				[maximum depth reached]
			),
			'Image' => array(
				[maximum depth reached]
			)
		),
		(int) 2 => array(
			'id' => '1856',
			'antibody_id' => null,
			'name' => 'True MicroChIP-seq Kit',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/truemicrochipseq-kit-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<p>The <b>True </b><b>MicroChIP-seq</b><b> kit </b>provides a robust ChIP protocol suitable for the investigation of histone modifications within chromatin from as few as <b>10 000 cells</b>, including <b>FACS sorted cells</b>. The kit can be used for chromatin preparation for downstream ChIP-qPCR or ChIP-seq analysis. The <b>complete kit</b> contains everything you need for start-to-finish ChIP including all validated buffers and reagents for chromatin shearing, immunoprecipitation and DNA purification for exceptional <strong>ChIP-qPCR</strong> or <strong>ChIP-seq</strong> results. In addition, positive control antibodies and negative control PCR primers are included for your convenience and assurance of result sensitivity and specificity.</p>
<p>The True MicroChIP-seq kit offers unique benefits:</p>
<ul>
<li>An <b>optimized chromatin preparation </b>protocol compatible with low number of cells (<b>10.000</b>) in combination with the Bioruptor&trade; shearing device</li>
<li>Most <b>complete kit </b>available (covers all steps and includes control antibodies and primers)</li>
<li><b>Magnetic beads </b>make ChIP easy, fast, and more reproducible</li>
<li>MicroChIP DiaPure columns (included in the kit) enable the <b>maximum recovery </b>of immunoprecipitation DNA suitable for any downstream application</li>
<li><b>Excellent </b><b>ChIP</b><b>-seq </b>result when combined with <a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq">MicroPlex</a><a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq"> Library Preparation kit </a>adapted for low input</li>
</ul>
<p>For fast ChIP-seq on low input &ndash; check out Diagenode&rsquo;s <a href="https://www.diagenode.com/en/p/uchipmentation-for-histones-24-rxns">&micro;</a><a href="https://www.diagenode.com/en/p/uchipmentation-for-histones-24-rxns">ChIPmentation</a><a href="https://www.diagenode.com/en/p/uchipmentation-for-histones-24-rxns"> for histones</a>.</p>
<p><sub>The True MicroChIP-seq kit, Cat. No. C01010132 is an upgraded version of the kit True MicroChIP, Cat. No. C01010130, with the new validated protocols (e.g. FACS sorted cells) and MicroChIP DiaPure columns included in the kit.</sub></p>',
			'label1' => 'Characteristics',
			'info1' => '<ul>
<li><b>Revolutionary:</b> Only 10,000 cells needed for complete ChIP-seq procedure</li>
<li><b>Validated on</b> studies for histone marks</li>
<li><b>Automated protocol </b>for the IP-Star<sup>&reg;</sup> Compact Automated Platform available</li>
</ul>
<p></p>
<p>The True MicroChIP-seq kit protocol has been optimized for the use of 10,000 - 100,000 cells per immunoprecipitation reaction. Regarding chromatin immunoprecipitation, three protocol variants have been optimized:<br />starting with a batch, starting with an individual sample and starting with the FACS-sorted cells.</p>
<div><button id="readmorebtn" style="background-color: #b02736; color: white; border-radius: 5px; border: none; padding: 5px;">Show Workflow</button></div>
<p><br /> <img src="https://www.diagenode.com/img/product/kits/workflow-microchip.png" id="workflowchip" class="hidden" width="600px" /></p>
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</p>
<div class="extra-spaced" align="center"></div>
<div class="row">
<div class="carrousel" style="background-position: center;">
<div class="container">
<div class="row" style="background: rgba(255,255,255,0.1);">
<div class="large-12 columns truemicro-slider" id="truemicro-slider">
<div>
<h3>High efficiency ChIP on 10,000 cells</h3>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><img src="https://www.diagenode.com/img/product/kits/true-micro-chip-histone-results.png" width="800px" /></div>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><center>
<p><small><strong>Figure 1.&nbsp;</strong>ChIP efficiency on 10,000 cells. ChIP was performed on human Hela cells using the Diagenode antibodies <a href="https://www.diagenode.com/en/p/h3k4me3-polyclonal-antibody-premium-50-ug-50-ul">H3K4me3</a> (Cat. No. C15410003), <a href="https://www.diagenode.com/en/p/h3k27ac-polyclonal-antibody-classic-50-mg-42-ml">H3K27ac</a> (C15410174), <a href="https://www.diagenode.com/en/p/h3k9me3-polyclonal-antibody-classic-50-ug">H3K9me3</a> (C15410056) and <a href="https://www.diagenode.com/en/p/h3k27me3-polyclonal-antibody-classic-50-mg-34-ml">H3K27me3</a> (C15410069). Sheared chromatin from 10,000 cells and 0.1 &micro;g (H3K27ac), 0.25 &micro;g (H3K4me3 and H3K27me3) or 0.5 &micro;g (H3K9me3) of the antibody were used per IP. Corresponding amount of IgG was used as control. Quantitative PCR was performed with primers for corresponding positive and negative loci. Figure shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
</center></div>
</div>
<div>
<h3>True MicroChIP-seq protocol in a combination with MicroPlex library preparation kit results in reliable and accurate sequencing data</h3>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><img src="https://www.diagenode.com/img/product/kits/fig2-truemicro.jpg" alt="True MicroChip results" width="800px" /></div>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><center>
<p><small><strong>Figure 2.</strong> Integrative genomics viewer (IGV) visualization of ChIP-seq experiments using 50.000 of K562 cells. ChIP has been performed accordingly to True MicroChIP protocol followed by the library preparation using MicroPlex Library Preparation Kit (C05010001). The above figure shows the peaks from ChIP-seq experiments using the following antibodies: H3K4me1 (C15410194), H3K9/14ac (C15410200), H3K27ac (C15410196) and H3K36me3 (C15410192).</small></p>
</center></div>
</div>
<div>
<h3>Successful chromatin profiling from 10.000 of FACS-sorted cells</h3>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><img src="https://www.diagenode.com/img/product/kits/fig3ab-truemicro.jpg" alt="small non coding RNA" width="800px" /></div>
<div class="large-10 small-12 medium-10 large-centered medium-centered small-centered columns"><center>
<p><small><strong>Figure 3.</strong> (A) Integrative genomics viewer (IGV) visualization of ChIP-seq experiments and heatmap 3kb upstream and downstream of the TSS (B) for H3K4me3. ChIP has been performed using 10.000 of FACS-sorted cells (K562) and H3K4me3 antibody (C15410003) accordingly to True MicroChIP protocol followed by the library preparation using MicroPlex Library Preparation Kit (C05010001). Data were compared to ENCODE standards.</small></p>
</center></div>
</div>
</div>
</div>
</div>
</div>
</div>
<p>
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			'label2' => 'Additional solutions compatible with the True MicroChIP-seq Kit',
			'info2' => '<p><span style="font-weight: 400;">The <a href="https://www.diagenode.com/en/p/chromatin-shearing-optimization-kit-high-sds-100-million-cells">Chromatin EasyShear Kit &ndash; High SDS</a></span><span style="font-weight: 400;">&nbsp;Recommended for the optimizing chromatin shearing.</span></p>
<p><a href="https://www.diagenode.com/en/categories/chip-seq-grade-antibodies"><span style="font-weight: 400;">ChIP-seq grade antibodies</span></a><span style="font-weight: 400;"> for high yields, specificity, and sensitivity.</span></p>
<p><span style="font-weight: 400;">Check the list of available </span><a href="https://www.diagenode.com/en/categories/primer-pairs"><span style="font-weight: 400;">primer pairs</span></a><span style="font-weight: 400;"> designed for high specificity to specific genomic regions.</span></p>
<p><span style="font-weight: 400;">For library preparation of immunoprecipitated samples we recommend to use the </span><b>&nbsp;</b><a href="https://www.diagenode.com/en/categories/library-preparation-for-ChIP-seq"><span style="font-weight: 400;">MicroPlex Library Preparation Kit</span></a><span style="font-weight: 400;"> - validated for library preparation from picogram inputs.</span></p>
<p><span style="font-weight: 400;">For IP-Star Automation users, check out the </span><a href="https://www.diagenode.com/en/p/auto-true-microchip-kit-16-rxns"><span style="font-weight: 400;">automated version</span></a><span style="font-weight: 400;"> of this kit.</span></p>
<p><span style="font-weight: 400;">Application note: </span><a href="https://www.diagenode.com/files/application_notes/Diagenode_AATI_Joint.pdf"><span style="font-weight: 400;">Best Workflow Practices for ChIP-seq Analysis with Small Samples</span></a></p>
<p></p>',
			'label3' => 'Species, cell lines, tissues tested',
			'info3' => '<p>The True MicroChIP-seq kit is compatible with a broad variety of cell lines, tissues and species - some examples are shown below. Other species / cell lines / tissues can be used with this kit.</p>
<p><strong>Cell lines:</strong></p>
<p>Bovine: blastocysts,<br />Drosophila: embryos, salivary glands<br />Human: EndoC-ẞH1 cells, HeLa cells, PBMC, urothelial cells<br />Mouse: adipocytes, B cells, blastocysts, pre-B cells, BMDM cells, chondrocytes, embryonic stem cells, KH2 cells, LSK cells, macrophages, MEP cells, microglia, NK cells, oocytes, pancreatic cells, P19Cl6 cells, RPE cells,</p>
<p>Other cell lines / species: compatible, not tested</p>
<p><strong>Tissues:</strong></p>
<p>Horse: adipose tissue</p>
<p>Mice: intestine tissue</p>
<p>Other tissues: not tested</p>',
			'format' => '20 rxns',
			'catalog_number' => 'C01010132',
			'old_catalog_number' => 'C01010130',
			'sf_code' => 'C01010132-',
			'type' => 'RFR',
			'search_order' => '04-undefined',
			'price_EUR' => '625',
			'price_USD' => '680',
			'price_GBP' => '575',
			'price_JPY' => '97905',
			'price_CNY' => '',
			'price_AUD' => '1700',
			'country' => 'ALL',
			'except_countries' => 'None',
			'quote' => false,
			'in_stock' => false,
			'featured' => true,
			'no_promo' => false,
			'online' => true,
			'master' => true,
			'last_datasheet_update' => '0000-00-00',
			'slug' => 'true-microchip-kit-x16-16-rxns',
			'meta_title' => 'True MicroChIP-seq Kit | Diagenode C01010132',
			'meta_keywords' => '',
			'meta_description' => 'True MicroChIP-seq Kit provides a robust ChIP protocol suitable for the investigation of histone modifications within chromatin from as few as 10 000 cells, including FACS sorted cells. Compatible with ChIP-qPCR as well as ChIP-seq.',
			'modified' => '2023-04-20 16:06:10',
			'created' => '2015-06-29 14:08:20',
			'ProductsRelated' => array(
				[maximum depth reached]
			),
			'Image' => array(
				[maximum depth reached]
			)
		),
		(int) 3 => array(
			'id' => '1927',
			'antibody_id' => null,
			'name' => 'MicroPlex Library Preparation Kit v2 (12 indexes)',
			'description' => '<p><a href="https://www.diagenode.com/files/products/kits/MicroPlex-Libary-Prep-Kit-v2-manual.pdf"><img src="https://www.diagenode.com/img/buttons/bt-manual.png" /></a></p>
<p><span><strong>Specifically optimized for ChIP-seq</strong></span><br /><br /><span>The MicroPlex Library Preparation&trade; kit is the only kit on the market which is validated for ChIP-seq and which allows the preparation of indexed libraries from just picogram inputs. In combination with the&nbsp;</span><a href="./true-microchip-kit-x16-16-rxns">True MicroChIP kit</a><span>, it allows for performing ChIP-seq on as few as 10,000 cells. Less input, fewer steps, fewer supplies, faster time to results!&nbsp;</span></p>
<p>The MicroPlex v2 kit (Cat. No. C05010012) contains all necessary reagents including single indexes for multiplexing up to 12 samples using single barcoding. For higher multiplexing (using dual indexes) check <a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns">MicroPlex Library Preparation Kits v3</a>.</p>',
			'label1' => 'Characteristics',
			'info1' => '<ul>
<li><strong>1 tube, 2 hours, 3 steps</strong> protocol</li>
<li><strong>Input: </strong>50 pg &ndash; 50 ng</li>
<li><strong>Reduce potential bias</strong> - few PCR amplification cycles needed</li>
<li><strong>High sensitivity ChIP-seq</strong> - low PCR duplication rate</li>
<li><strong>Great multiplexing flexibility</strong> with 12 barcodes (8 nt) included</li>
<li><strong>Validated with the <a href="https://www.diagenode.com/p/sx-8g-ip-star-compact-automated-system-1-unit" title="IP-Star Automated System">IP-Star<sup>&reg;</sup> Automated Platform</a></strong></li>
</ul>
<h3>How it works</h3>
<center><img src="https://www.diagenode.com/img/product/kits/microplex-method-overview-v2.png" /></center>
<p style="margin-bottom: 0;"><small><strong>Microplex workflow - protocol with single indexes</strong><br />An input of 50 pg to 50 ng of fragmented dsDNA is converted into sequencing-ready libraries for Illumina&reg; NGS platforms using a fast and simple 3-step protocol</small></p>
<ul class="accordion" data-accordion="" id="readmore" style="margin-left: 0;">
<li class="accordion-navigation"><a href="#first" style="background: #ffffff; padding: 0rem; margin: 0rem; color: #13b2a2;"><small>Read more about MicroPlex workflow</small></a>
<div id="first" class="content">
<p><small><strong>Step 1. Template Preparation</strong> provides efficient repair of the fragmented double-stranded DNA input.</small></p>
<p><small>In this step, the DNA is repaired and yields molecules with blunt ends.</small></p>
<p><small><strong>Step 2. Library Synthesis.</strong> enables ligation of MicroPlex patented stem- loop adapters.</small></p>
<p><small>In the next step, stem-loop adaptors with blocked 5&rsquo; ends are ligated with high efficiency to the 5&rsquo; end of the genomic DNA, leaving a nick at the 3&rsquo; end. The adaptors cannot ligate to each other and do not have single- strand tails, both of which contribute to non-specific background found with many other NGS preparations.</small></p>
<p><small><strong>Step 3. Library Amplification</strong> enables extension of the template, cleavage of the stem-loop adaptors, and amplification of the library. Illumina- compatible indexes are also introduced using a high-fidelity, highly- processive, low-bias DNA polymerase.</small></p>
<p><small>In the final step, the 3&rsquo; ends of the genomic DNA are extended to complete library synthesis and Illumina-compatible indexes are added through a high-fidelity amplification. Any remaining free adaptors are destroyed. Hands-on time and the risk of contamination are minimized by using a single tube and eliminating intermediate purifications.</small></p>
<p><small>Obtained libraries are purified, quantified and sized. The libraries pooling can be performed as well before sequencing.</small></p>
</div>
</li>
</ul>
<p></p>
<h3>Reliable detection of enrichments in ChIP-seq</h3>
<p><img src="https://www.diagenode.com/img/product/kits/microplex-library-prep-kit-figure-a.png" alt="Reliable detection of enrichments in ChIP-seq figure 1" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure A.</strong> ChIP has been peformed with H3K4me3 antibody, amplification of 17 pg of DNA ChIP'd from 10.000 cells and amplification of 35 pg of DNA ChIP'd from 100.000 cells (control experiment). The IP'd DNA was amplified and transformed into a sequencing-ready preparation for the Illumina plateform with the MicroPlex Library Preparation kit. The library was then analysed on an Illumina<sup>&reg;</sup> Genome Analyzer. Cluster generation and sequencing were performed according to the manufacturer's instructions.</p>
<p><img src="https://www.diagenode.com/img/product/kits/microplex-library-prep-kit-figure-b.png" alt="Reliable detection of enrichments in ChIP-seq figure 2" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p><strong>Figure B.</strong> We observed a perfect match between the top 40% of True MicroChIP peaks and the reference dataset. Based on the NIH Encode project criterion, ChIP-seq results are considered reproducible between an original and reproduced dataset if the top 40% of peaks have at least an 80% overlap ratio with the compared dataset.</p>',
			'label2' => '',
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			'format' => '12 rxns',
			'catalog_number' => 'C05010012',
			'old_catalog_number' => 'C05010010',
			'sf_code' => 'C05010012-',
			'type' => 'FRE',
			'search_order' => '04-undefined',
			'price_EUR' => '935',
			'price_USD' => '1215',
			'price_GBP' => '835',
			'price_JPY' => '146470',
			'price_CNY' => '',
			'price_AUD' => '3038',
			'country' => 'ALL',
			'except_countries' => 'None',
			'quote' => false,
			'in_stock' => false,
			'featured' => false,
			'no_promo' => false,
			'online' => true,
			'master' => true,
			'last_datasheet_update' => '0000-00-00',
			'slug' => 'microplex-library-preparation-kit-v2-x12-12-indices-12-rxns',
			'meta_title' => 'MicroPlex Library Preparation Kit v2 x12 (12 indices)',
			'meta_keywords' => '',
			'meta_description' => 'MicroPlex Library Preparation Kit v2 x12 (12 indices)',
			'modified' => '2023-04-20 15:01:16',
			'created' => '2015-06-29 14:08:20',
			'ProductsRelated' => array(
				[maximum depth reached]
			),
			'Image' => array(
				[maximum depth reached]
			)
		),
		(int) 4 => array(
			'id' => '2264',
			'antibody_id' => '121',
			'name' => 'H3K9me3 Antibody',
			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone<strong> H3 containing the trimethylated lysine 9</strong> (<strong>H3K9me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
			'label1' => 'Validation Data',
			'info1' => '<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig1.png" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K9me3</strong><br />ChIP assays were performed using human HeLa cells, the Diagenode antibody against H3K9me3 (cat. No. C15410193) and optimized PCR primer sets for qPCR. ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using the &ldquo;iDeal ChIP-seq&rdquo; kit (cat. No. C01010051). A titration of the antibody consisting of 0.5, 1, 2, and 5 &micro;g per ChIP experiment was analysed. IgG (1 &micro;g/IP) was used as negative IP control. QPCR was performed with primers for the heterochromatin marker Sat2 and for the ZNF510 gene, used as positive controls, and for the promoters of the active EIF4A2 and GAPDH genes, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2a.png" width="700" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2b.png" width="700" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2c.png" width="700" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-ChIP-Fig2d.png" width="700" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K9me3</strong><br />ChIP was performed with 0.5 &micro;g of the Diagenode antibody against H3K9me3 (cat. No. C15410193) on sheared chromatin from 1,000,000 HeLa cells using the &ldquo;iDeal ChIP-seq&rdquo; kit as described above. The IP'd DNA was subsequently analysed on an Illumina HiSeq 2000. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 50 bp tags were aligned to the human genome using the BWA algorithm. Figure 2A shows the signal distribution along the long arm of chromosome 19 and a zoomin to an enriched region containing several ZNF repeat genes. The arrows indicate two satellite repeat regions which exhibit a stronger signal. Figures 2B, 2C and 2D show the enrichment along the ZNF510 positive control target and at the H19 and KCNQ1 imprinted genes.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-CT-Fig3a.png" width="700" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410193-CT-Fig3b.png" width="700" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K9me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 1 &micro;g of the Diagenode antibody against H3K9me3 (cat. No. C15410193) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in a genomic regions on chromosome 1 containing several ZNF repeat genes and in a genomic region surrounding the KCNQ1 imprinting control gene on chromosome 11 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-Elisa-Fig4.png" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the antibody directed against human H3K9me3 (cat. No. C15410193) in antigen coated wells. The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:87,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-DB-Fig5.png" /></center></div>
<div class="small-8 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K9me3</strong><br />A Dot Blot analysis was performed to test the cross reactivity of the Diagenode antibody against H3K9me3 (cat. No. C15410193) with peptides containing other modifications and unmodified sequences of histone H3 and H4. One hundred to 0.2 pmol of the peptide containing the respective histone modification were spotted on a membrane. The antibody was used at a dilution of 1:20,000. Figure 5 shows a high specificity of the antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-4 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-WB-Fig6.png" /></center></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K9me3</strong><br />Western blot was performed on whole cell (25 &micro;g, lane 1) and histone extracts (15 &micro;g, lane 2) from HeLa cells, and on 1 &micro;g of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K9me3 (cat. No. C15410193). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410193-IF-Fig7.png" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K9me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K9me3 (cat. No. C15410193) and with DAPI. Cells were fixed with 4% formaldehyde for 10&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labelled with the H3K9me3 antibody (middle) diluted 1:500 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The left panel shows staining of the nuclei with DAPI. A merge of both stainings is shown on the right.</small></p>
</div>
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			'label2' => 'Target Description',
			'info2' => '<p>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called &ldquo;histone code&rdquo;. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Trimethylation of histone H3K9 is associated with inactive genomic regions, satellite repeats and ZNF gene repeats.</p>',
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			'format' => '50 μg',
			'catalog_number' => 'C15410193',
			'old_catalog_number' => 'pAb-193-050',
			'sf_code' => 'C15410193-D001-000581',
			'type' => 'FRE',
			'search_order' => '03-Antibody',
			'price_EUR' => '480',
			'price_USD' => '470',
			'price_GBP' => '430',
			'price_JPY' => '75190',
			'price_CNY' => '0',
			'price_AUD' => '1175',
			'country' => 'ALL',
			'except_countries' => 'None',
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			'slug' => 'h3k9me3-polyclonal-antibody-premium-50-mg',
			'meta_title' => 'H3K9me3 Antibody - ChIP-seq Grade (C15410193) | Diagenode',
			'meta_keywords' => '',
			'meta_description' => 'H3K9me3  (Histone H3 trimethylated at lysine 9) Polyclonal Antibody validated  in ChIP-seq, ChIP-qPCR, CUT&Tag, ELISA, DB, WB and IF. Specificity confirmed by Peptide array assay. Batch-specific data available on the website. Sample size available.',
			'modified' => '2021-10-20 09:55:53',
			'created' => '2015-06-29 14:08:20',
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		(int) 5 => array(
			'id' => '2268',
			'antibody_id' => '70',
			'name' => 'H3K27me3 Antibody',
			'description' => '<p>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 27</strong> (<strong>H3K27me3</strong>), using a KLH-conjugated synthetic peptide.</p>',
			'label1' => 'Validation Data',
			'info1' => '<div class="row">
<div class="small-6 columns">
<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig1.png" alt="H3K27me3 Antibody ChIP Grade" /></p>
<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2.png" alt="H3K27me3 Antibody for ChIP" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K27me3</strong><br />ChIP assays were performed using human HeLa cells, the Diagenode antibody against H3K27me3 (Cat. No. C15410195) and optimized PCR primer pairs for qPCR. ChIP was performed with the &ldquo;iDeal ChIP-seq&rdquo; kit (Cat. No. C01010051), using sheared chromatin from 1 million cells. The chromatin was spiked with a panel of in vitro assembled nucleosomes, each containing a specific lysine methylation. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control.</small></p>
<p><small><strong>Figure 1A.</strong> Quantitative PCR was performed with primers specific for the promoter of the active GAPDH and EIF4A2 genes, used as negative controls, and for the inactive TSH2B and MYT1 genes, used as positive controls. The graph shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
<p><small><strong>Figure 1B.</strong> Recovery of the nucleosomes carrying the H3K27me1, H3K27me2, H3K27me3, H3K4me3, H3K9me3 and H3K36me3 modifications and the unmodified H3K27 as determined by qPCR. The figure clearly shows the antibody is very specific in ChIP for the H3K27me3 modification.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2a.png" alt="H3K27me3 Antibody ChIP-seq Grade" /></p>
</div>
</div>
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<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2b.png" alt="H3K27me3 Antibody for ChIP-seq" /></p>
<p>C. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2c.png" alt="H3K27me3 Antibody for ChIP-seq assay" /></p>
<p>D. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-ChIP-Fig2d.png" alt="H3K27me3 Antibody validated in ChIP-seq" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K27me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLa cells using 1 &micro;g of the Diagenode antibody against H3K27me3 (Cat. No. C15410195) as described above. The IP'd DNA was subsequently analysed on an Illumina HiSeq. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 50 bp tags were aligned to the human genome using the BWA algorithm. Figure 2 shows the enrichment in genomic regions of chromosome 6 and 20, surrounding the TSH2B and MYT1 positive control genes (fig 2A and 2B, respectively), and in two genomic regions of chromosome 1 and X (figure 2C and D).</small></p>
</div>
</div>
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<div class="extra-spaced"></div>
<div class="extra-spaced"></div>
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<div class="small-12 columns">
<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-CUTTAG-Fig3A.png" /></p>
<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410195-CUTTAG-Fig3B.png" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K27me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 1 &micro;g of the Diagenode antibody against H3K27me3 (cat. No. C15410195) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions on chromosome and 13 and 20 (figure 3A and B, respectively).</small></p>
</div>
</div>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-ELISA-Fig4.png" alt="H3K27me3 Antibody ELISA Validation " /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody directed against H3K27me3 (Cat. No. C15410195). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:3,000.</small></p>
</div>
</div>
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<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-DB-Fig5a.png" alt="H3K27me3 Antibody Dot Blot Validation " /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K27me3</strong><br />A Dot Blot analysis was performed to test the cross reactivity of the Diagenode antibody against H3K27me3 (Cat. No. C15410195) with peptides containing other modifications of histone H3 and H4 and the unmodified H3K27 sequence. One hundred to 0.2 pmol of the peptide containing the respective histone modification were spotted on a membrane. The antibody was used at a dilution of 1:5,000. Figure 5 shows a high specificity of the antibody for the modification of interest. Please note that the antibody also recognizes the modification if S28 is phosphorylated.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-WB-Fig6.png" alt="H3K27me3 Antibody validated in Western Blot" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K27me3</strong><br />Western blot was performed on whole cell (25 &micro;g, lane 1) and histone extracts (15 &micro;g, lane 2) from HeLa cells, and on 1 &micro;g of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K27me3 (cat. No. C15410195) diluted 1:500 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410195-IF-Fig7.png" alt="H3K27me3 Antibody validated for Immunofluorescence" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K27me3</strong><br />Human HeLa cells were stained with the Diagenode antibody against H3K27me3 (Cat. No. C15410195) and with DAPI. Cells were fixed with 4% formaldehyde for 10&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labelled with the H3K27me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The middle panel shows staining of the nuclei with DAPI. A merge of the two stainings is shown on the right.</small></p>
</div>
</div>',
			'label2' => 'Target Description',
			'info2' => '<p><small>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which alter chromatin structure to facilitate transcriptional activation, repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called &ldquo;histone code&rdquo;. Histone methylation and demethylation is regulated by histone methyl transferases and histone demethylases. Methylation of histone H3K27 is associated with inactive genomic regions.</small></p>',
			'label3' => '',
			'info3' => '',
			'format' => '50 μg',
			'catalog_number' => 'C15410195',
			'old_catalog_number' => 'pAb-195-050',
			'sf_code' => 'C15410195-D001-000581',
			'type' => 'FRE',
			'search_order' => '03-Antibody',
			'price_EUR' => '480',
			'price_USD' => '470',
			'price_GBP' => '430',
			'price_JPY' => '75190',
			'price_CNY' => '',
			'price_AUD' => '1175',
			'country' => 'ALL',
			'except_countries' => 'None',
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			'last_datasheet_update' => 'January 14, 2021',
			'slug' => 'h3k27me3-polyclonal-antibody-premium-50-mg-27-ml',
			'meta_title' => 'H3K27me3 Antibody - ChIP-seq Grade (C15410195) | Diagenode',
			'meta_keywords' => '',
			'meta_description' => 'H3K27me3 (Histone H3 trimethylated at lysine 27) Polyclonal Antibody validated  in ChIP-seq, ChIP-qPCR, CUT&Tag, ELISA, DB, WB and IF. Specificity confirmed by Peptide array assay. Batch-specific data available on the website. Sample size available.',
			'modified' => '2024-01-17 13:55:58',
			'created' => '2015-06-29 14:08:20',
			'ProductsRelated' => array(
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		(int) 6 => array(
			'id' => '2262',
			'antibody_id' => '74',
			'name' => 'H3K36me3 Antibody',
			'description' => '<p>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 36</strong> (<strong>H3K36me3</strong>), using a KLH-conjugated synthetic peptide.</p>',
			'label1' => 'Validation Data',
			'info1' => '<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig1.png" alt="H3K36me3 Antibody ChIP Grade" caption="false" width="432" height="674" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K36me3</strong><br /> <strong>Figure 1A</strong> ChIP assays were performed using human HeLa cells, the Diagenode antibody against H3K36me3 (Cat. No. C15410192) and optimized PCR primer pairs for qPCR. ChIP was performed with the &ldquo;Auto Histone ChIP-seq&rdquo; kit (Cat. No. C01010022) on the IP-Star automated system, using sheared chromatin from 1,000,000 cells. A titration consisting of 1, 2, 5 and 10 &micro;g of antibody per ChIP experiment was analyzed. IgG (2 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers for the coding region of the active GAPDH and ACTB genes, used as positive controls, and for the promoter and a region located 1 kb upstream of the promoter of the GAPDH gene, used as negative controls.<br /><br /> <strong>Figure 1B</strong> ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K36me3 (Cat. No. C15410192) and optimized PCR primer pairs for qPCR. ChIP was performed with the &ldquo;iDeal ChIP-seq&rdquo; kit (Cat. No. C01010051), using sheared chromatin from 100,000 cells. A titration consisting of 0.2, 0.5, 1 and 2 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers for the coding region of the active GAPDH and ACTB genes, used as positive controls, and for the coding region of the inactive MB gene and the Sat satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
</div>
</div>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig2-2.jpg" alt="H3K36me3 Antibody SNAP-ChIP validation" caption="false" width="432" height="298" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 2. ChIP results obtained with the Diagenode antibody directed against H3K36me3</strong><br /> ChIP assays were performed on sheared chromatin from 1 million human HeLa cells as described above. The chromatin was spiked with a panel of in vitro assembled nucleosomes, each containing a specific lysine methylation (SNAP-ChIP K-MetStat Panel, Epicypher). A titration consisting of 0.2, 0.5, 1 and 2 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the nucleosomes carrying the H3K36me1, H3K36me2, H3K36me3, H3K4me3, H3K9me3, H3K27me3 and H4K20me3 modifications and the unmodified H3K4. The graph shows the recovery, expressed as a % of input. These results demonstrate a high specificity of the H3K36me3 antibody for the modification of interest.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig2.png" alt="H3K36me3 Antibody for ChIP-seq" caption="false" width="893" height="702" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. ChIP-seq results obtained with the Diagenode antibody directed against H3K36me3</strong><br /> ChIP was performed on sheared chromatin from 100,000 K562 cells with the &ldquo;iDeal ChIP-seq&rdquo; kit (Cat. No. C01010051) using 0.5 &micro;g of the Diagenode antibody against H3K36me3 (Cat. No. C15410192) as described above. The IP&rsquo;d DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer&rsquo;s instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 3 shows the H3K36me3 signal distribution along the complete sequence and a zoomin of human chromosome 12 (figure 2A and B) and in 2 genomic regions containing the GAPDH and ACTB positive control genes (figure 3C and D).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig3.png" alt="H3K36me3 Antibody ELISA validation" caption="false" width="432" height="328" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K36me3 (Cat. No. C15410192). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:132,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns">
<p>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig4-a.png" alt="H3K36me3 Antibody Dot Blot Validation" caption="false" width="432" height="162" /></p>
<p>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig4-b.png" alt="H3K36me3 Antibody Peptide Array validation" caption="false" width="432" height="257" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K36me3</strong><br /> <strong>Figure 5A.</strong> To test the cross reactivity of the Diagenode antibody against H3K36me3 (Cat. No. C15410192), a Dot Blot analysis was performed with peptides containing other modifications or unmodified sequences of histone H3 and H4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:20,000. Figure 5A shows a high specificity of the antibody for the modification of interest. <strong>Figure 5B.</strong> The specificity of the antibody was further demonstrated by peptide array analyses on an array containing 384 peptides with different combinations of modifications from histone H3, H4, H2A and H2B. The antibody was used at a dilution of 1:10,000. Figure 5B shows the specificity factor, calculated as the ratio of the average intensity of all spots containing the mark, divided by the average intensity of all spots not containing the mark. The peptide array analysis shows a slight cross reaction with H4K20me3 that was not observed in dot blot.</small></p>
</div>
</div>
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<div class="extra-spaced"></div>
<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig5.png" alt="H3K36me3 Antibody for Western Blot" caption="false" width="432" height="346" /></p>
</div>
<div class="small-6 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K36me3</strong><br /> Western blot was performed on whole cell (25 &micro;g, lane 1) and histone extracts (15 &micro;g, lane 2) from HeLa cells, and on 1 &micro;g of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K36me3 (Cat. No. C15410192). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is shown on the right, the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410192-fig6.png" alt="H3K36me3 Antibody for Immunofluorescence " caption="false" width="893" height="232" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K36me3</strong><br /> HeLa cells were stained with the Diagenode antibody against H3K36me3 (Cat. C15410192) and with DAPI. Cells were fixed with 4% formaldehyde for 10&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labeled with the H3K36me3 antibody (left) diluted 1:500 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The middle panel shows staining of the nuclei with DAPI. A merge of the two stainings is shown on the right.</small></p>
</div>
</div>',
			'label2' => 'Target Description',
			'info2' => '<p>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called &ldquo;histone code&rdquo;. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Trimethylation of histone H3K36 is associated with active genes.</p>',
			'label3' => '',
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			'slug' => 'h3k36me3-polyclonal-antibody-premium-50-mg',
			'meta_title' => 'H3K36me3 Antibody - ChIP-seq Grade (C15410192) | Diagenode',
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			'meta_description' => 'H3K36me3 (Histone H3 trimethylated at lysine 36) Polyclonal Antibody validated  in ChIP-seq, ChIP-grade, ELISA, DB, WB and IF. Specificity confirmed by Peptide array. Batch-specific data available on the website. Sample size available. ',
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			'id' => '2173',
			'antibody_id' => '115',
			'name' => 'H3K4me3 Antibody',
			'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
			'label1' => 'Validation data',
			'info1' => '<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" /></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<p></p>
<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="row">
<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
<div class="small-8 columns">
<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
</div>
</div>
<div class="row">
<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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			'info2' => '<p>Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called "histone code". Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Methylation of histone H3K4 is associated with activation of gene transcription.</p>
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			'meta_title' => 'H3K4me3 Antibody - ChIP-seq Grade (C15410003) | Diagenode',
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			'meta_description' => 'H3K4me3 (Histone H3 trimethylated at lysine 4) Polyclonal Antibody validated  in ChIP-seq, ChIP-qPCR, CUT&Tag, ELISA, DB, WB and IF. Specificity confirmed by Peptide array. Batch-specific data available on the website. Sample size available.',
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			'description' => '<p><strong>Western blot</strong> : The quality of antibodies used in this technique is crucial for correct and specific protein identification. Diagenode offers huge selection of highly sensitive and specific western blot-validated antibodies.</p>
<p>Learn more about: <a href="https://www.diagenode.com/applications/western-blot">Loading control, MW marker visualization</a><em>. <br /></em></p>
<p><em></em>Check our selection of antibodies validated in Western blot.</p>',
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<p>Diagenode offers huge selection of highly sensitive antibodies validated in IF.</p>
<p><img src="https://www.diagenode.com/img/product/antibodies/C15200229-IF.jpg" alt="" height="245" width="256" /></p>
<p><sup><strong>Immunofluorescence using the Diagenode monoclonal antibody directed against CRISPR/Cas9</strong></sup></p>
<p><sup>HeLa cells transfected with a Cas9 expression vector (left) or untransfected cells (right) were fixed in methanol at -20&deg;C, permeabilized with acetone at -20&deg;C and blocked with PBS containing 2% BSA. The cells were stained with the Cas9 C-terminal antibody (Cat. No. C15200229) diluted 1:400, followed by incubation with an anti-mouse secondary antibody coupled to AF488. The bottom images show counter-staining of the nuclei with Hoechst 33342.</sup></p>
<h5><sup>Check our selection of antibodies validated in IF.</sup></h5>',
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			'meta_description' => 'Diagenode offers a wide range of antibodies and technical support for ChIP-qPCR applications',
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<p>Read more:</p>
<p><a href="https://www.diagenode.com/en/categories/cutandtag">Products for CUT&amp;Tag assay</a></p>
<p><a href="https://www.diagenode.com/en/pages/cut-and-tag">Performance of Diagenode's antibodies in CUT&amp;Tag</a></p>
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			'description' => '<p><b>Unparalleled ChIP-Seq results with the most rigorously validated antibodies</b></p>
<p><span style="font-weight: 400;">Diagenode provides leading solutions for epigenetic research. Because ChIP-seq is a widely-used technique, we validate our antibodies in ChIP and ChIP-seq experiments (in addition to conventional methods like Western blot, Dot blot, ELISA, and immunofluorescence) to provide the highest quality antibody. We standardize our validation and production to guarantee high product quality without technical bias. Diagenode guarantees ChIP-seq grade antibody performance under our suggested conditions.</span></p>
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<div class="small-12 medium-9 large-9 columns">
<p><strong>ChIP-seq profile</strong> of active (H3K4me3 and H3K36me3) and inactive (H3K27me3) marks using Diagenode antibodies.</p>
<img src="https://www.diagenode.com/img/categories/antibodies/chip-seq-grade-antibodies.png" /></div>
<div class="small-12 medium-3 large-3 columns">
<p><small> ChIP was performed on sheared chromatin from 100,000 K562 cells using iDeal ChIP-seq kit for Histones (cat. No. C01010051) with 1 &micro;g of the Diagenode antibodies against H3K27me3 (cat. No. C15410195) and H3K4me3 (cat. No. C15410003), and 0.5 &micro;g of the antibody against H3K36me3 (cat. No. C15410192). The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. The figure shows the signal distribution along the complete sequence of human chromosome 3, a zoomin to a 10 Mb region and a further zoomin to a 1.5 Mb region. </small></p>
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<p>Diagenode&rsquo;s highly validated antibodies:</p>
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<li>Highly sensitive and specific</li>
<li>Cost-effective (requires less antibody per reaction)</li>
<li>Batch-specific data is available on the website</li>
<li>Expert technical support</li>
<li>Sample sizes available</li>
<li>100% satisfaction guarantee</li>
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			'name' => 'Histone antibodies',
			'description' => '<p>Histones are the main protein components of chromatin involved in the compaction of DNA into nucleosomes, the basic units of chromatin. A <strong>nucleosome</strong> consists of one pair of each of the core histones (<strong>H2A</strong>, <strong>H2B</strong>, <strong>H3</strong> and <strong>H4</strong>) forming an octameric structure wrapped by 146 base pairs of DNA. The different nucleosomes are linked by the linker histone<strong> H1, </strong>allowing for further condensation of chromatin.</p>
<p>The core histones have a globular structure with large unstructured N-terminal tails protruding from the nucleosome.&nbsp; They can undergo to multiple post-translational modifications (PTM), mainly at the N-terminal tails. These <strong>post-translational modifications </strong>include&nbsp; methylation, acetylation, phosphorylation, ubiquitinylation, citrullination, sumoylation, deamination and crotonylation.&nbsp; The most well characterized PTMs are <strong>methylation,</strong> <strong>acetylation and phosphorylation</strong>. Histone methylation occurs mainly on lysine (K) residues, which can be mono-, di- or tri-methylated, and on arginines (R), which can be mono-methylated and symmetrically or asymmetrically di-methylated. Histone acetylation occurs on lysines and histone phosphorylation mainly on serines (S), threonines (T) and tyrosines (Y).</p>
<p>The PTMs of the different residues are involved in numerous processes such as DNA repair, DNA replication and chromosome condensation. They influence the chromatin organization and can be positively or negatively associated with gene expression. Trimethylation of H3K4, H3K36 and H3K79, and lysine acetylation generally result in an open chromatin configuration (figure below) and are therefore associated with <strong>euchromatin</strong> and gene activation. Trimethylation of H3K9, K3K27 and H4K20, on the other hand, is enriched in <strong>heterochromatin </strong>and associated with gene silencing. The combination of different histone modifications is called the "<strong>histone code</strong>&rdquo;, analogous to the genetic code.</p>
<p><img src="https://www.diagenode.com/img/categories/antibodies/histone-marks-illustration.png" /></p>
<p>Diagenode is proud to offer a large range of antibodies against histones and histone modifications. Our&nbsp; antibodies are highly specific and have been validated in many applications, including <strong>ChIP</strong> and <strong>ChIP-seq</strong>.</p>
<p>Diagenode&rsquo;s collection includes antibodies recognizing:</p>
<ul>
<li><strong>Histone H1 variants</strong></li>
<li><strong>Histone H2A, H2A variants and histone H2A</strong> <strong>modifications</strong> (serine phosphorylation, lysine acetylation, lysine ubiquitinylation)</li>
<li><strong>Histone H2B and H2B</strong> <strong>modifications </strong>(serine phosphorylation, lysine acetylation)</li>
<li><strong>Histone H3 and H3 modifications </strong>(lysine methylation (mono-, di- and tri-methylated), lysine acetylation, serine phosphorylation, threonine phosphorylation, arginine methylation (mono-methylated, symmetrically and asymmetrically di-methylated))</li>
<li><strong>Histone H4 and H4 modifications (</strong>lysine methylation (mono-, di- and tri-methylated), lysine acetylation, arginine methylation (mono-methylated and symmetrically di-methylated), serine phosphorylation )</li>
</ul>
<p><span style="font-weight: 400;"><strong>HDAC's HAT's, HMT's and other</strong> <strong>enzymes</strong> which modify histones can be found in the category <a href="../categories/chromatin-modifying-proteins-histone-transferase">Histone modifying enzymes</a><br /></span></p>
<p><span style="font-weight: 400;"> Diagenode&rsquo;s highly validated antibodies:</span></p>
<ul>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Highly sensitive and specific</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Cost-effective (requires less antibody per reaction)</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Batch-specific data is available on the website</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Expert technical support</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Sample sizes available</span></li>
<li><span style="font-weight: 400;"> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 100% satisfaction guarantee</span></li>
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			'description' => '<h1><strong>Validated epigenetics antibodies</strong>&nbsp;&ndash; care for a sample?<br />&nbsp;</h1>
<p>Diagenode has partnered with leading epigenetics experts and numerous epigenetics consortiums to bring to you a validated and comprehensive collection of epigenetic antibodies. As an expert in epigenetics, we are committed to offering highly-specific antibodies validated for ChIP/ChIP-seq and many other applications. All batch-specific validation data is available on our website.<br /><a href="../categories/antibodies">Read about our expertise in antibody production</a>.</p>
<ul>
<li><strong>Focused</strong> -&nbsp;Diagenode's selection of antibodies is exclusively dedicated for epigenetic research. <a title="See the full collection." href="../categories/all-antibodies">See the full collection.</a></li>
<li><strong>Strict quality standards</strong>&nbsp;with rigorous QC and validation</li>
<li><strong>Classified</strong>&nbsp;based on level of validation for flexibility of application</li>
</ul>
<p>Existing sample sizes are listed below. We will soon expand our collection. &nbsp;Are you looking for a sample size of another antibody? Just <a href="mailto:agnieszka.zelisko@diagenode.com?Subject=Sample%20Size%20Request" target="_top">Contact us</a>.</p>',
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			'name' => 'All antibodies',
			'description' => '<p><span style="font-weight: 400;">All Diagenode&rsquo;s antibodies are listed below. Please, use our Quick search field to find the antibody of interest by target name, application, purity.</span></p>
<p><span style="font-weight: 400;">Diagenode&rsquo;s highly validated antibodies:</span></p>
<ul>
<li>Highly sensitive and specific</li>
<li>Cost-effective (requires less antibody per reaction)</li>
<li>Batch-specific data is available on the website</li>
<li>Expert technical support</li>
<li>Sample sizes available</li>
<li>100% satisfaction guarantee</li>
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			'meta_description' => 'Diagenode Offers Strict quality standards with Rigorous QC and validated Antibodies. Classified based on level of validation for flexibility of Application. Comprehensive selection of histone and non-histone Antibodies',
			'meta_title' => 'Diagenode's selection of Antibodies is exclusively dedicated for Epigenetic Research | Diagenode',
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			'name' => 'ChIP-grade antibodies',
			'description' => '<div class="row">
<div class="small-12 columns"><center></center>
<p><br />Chromatin immunoprecipitation (<b>ChIP</b>) is a technique to study the associations of proteins with the specific genomic regions in intact cells. One of the most important steps of this protocol is the immunoprecipitation of targeted protein using the antibody specifically recognizing it. The quality of antibodies used in ChIP is essential for the success of the experiment. Diagenode offers extensively validated ChIP-grade antibodies, confirmed for their specificity, and high level of performance in ChIP. Each batch is validated, and batch-specific data are available on the website.</p>
<p></p>
</div>
</div>
<p><strong>ChIP results</strong> obtained with the antibody directed against H3K4me3 (Cat. No. <a href="../p/h3k4me3-polyclonal-antibody-premium-50-ug-50-ul">C15410003</a>).&nbsp;</p>
<div class="row">
<div class="small-12 medium-6 large-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" alt="" width="400" height="315" />&nbsp;</div>
<div class="small-12 medium-6 large-6 columns">
<p></p>
<p></p>
<p></p>
</div>
</div>
<p></p>
<p>Our aim at Diagenode is to offer the largest collection of highly specific <strong>ChIP-grade antibodies</strong>. We add new antibodies monthly. Find your ChIP-grade antibody in the list below and check more information about tested applications, extensive validation data, and product information.</p>',
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			'meta_description' => 'Diagenode Offers Extensively Validated ChIP-Grade Antibodies, Confirmed for their Specificity, and high level of Performance in Chromatin Immunoprecipitation ChIP',
			'meta_title' => 'Chromatin immunoprecipitation ChIP-grade antibodies | Diagenode',
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			'id' => '149',
			'position' => '42',
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			'name' => 'CUT&Tag Antibodies',
			'description' => '<p>&nbsp; &nbsp; &nbsp; &nbsp;&nbsp;</p>',
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		(int) 0 => array(
			'id' => '725',
			'name' => 'Datasheet H3K4me3 C15410003',
			'description' => '<p>Datasheet description</p>',
			'image_id' => null,
			'type' => 'Datasheet',
			'url' => 'files/products/antibodies/Datasheet_H3K4me3_C15410003.pdf',
			'slug' => 'datasheet-h3k4me3-C15410003',
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		),
		(int) 1 => array(
			'id' => '11',
			'name' => 'Antibodies you can trust',
			'description' => '<p style="text-align: justify;"><span>Epigenetic research tools have evolved over time from endpoint PCR to qPCR to the analyses of large sets of genome-wide sequencing data. ChIP sequencing (ChIP-seq) has now become the gold standard method for chromatin studies, given the accuracy and coverage scale of the approach over other methods. Successful ChIP-seq, however, requires a higher level of experimental accuracy and consistency in all steps of ChIP than ever before. Particularly crucial is the quality of ChIP antibodies. </span></p>',
			'image_id' => null,
			'type' => 'Poster',
			'url' => 'files/posters/Antibodies_you_can_trust_Poster.pdf',
			'slug' => 'antibodies-you-can-trust-poster',
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			'created' => '2015-07-03 16:05:15',
			'ProductsDocument' => array(
				[maximum depth reached]
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		),
		(int) 2 => array(
			'id' => '38',
			'name' => 'Epigenetic Antibodies Brochure',
			'description' => '<p>More than in any other immuoprecipitation assays, quality antibodies are critical tools in many epigenetics experiments. Since 10 years, Diagenode has developed the most stringent quality production available on the market for antibodies exclusively focused on epigenetic uses. All our antibodies have been qualified to work in epigenetic applications.</p>',
			'image_id' => null,
			'type' => 'Brochure',
			'url' => 'files/brochures/Epigenetic_Antibodies_Brochure.pdf',
			'slug' => 'epigenetic-antibodies-brochure',
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			'created' => '2015-07-03 16:05:27',
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			'id' => '1815',
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	'Publication' => array(
		(int) 0 => array(
			'id' => '5000',
			'name' => 'Claudin-1 as a potential marker of stress-induced premature senescence in vascular smooth muscle cells',
			'authors' => 'Agnieszka Gadecka et al.',
			'description' => '<p><span>Cellular senescence, a permanent state of cell cycle arrest, can result either from external stress and is then called stress-induced premature senescence (SIPS), or from the exhaustion of cell division potential giving rise to replicative senescence (RS). Despite numerous biomarkers distinguishing SIPS from RS remains challenging. We propose claudin-1 (CLDN1) as a potential cell-specific marker of SIPS in vascular smooth muscle cells (VSMCs). In our study, VSMCs subjected to RS or SIPS exhibited significantly higher levels of CLDN1 expression exclusively in SIPS. Moreover, nuclear accumulation of this protein was also characteristic only of prematurely senescent cells. ChIP-seq results suggest that higher CLDN1 expression in SIPS might be a result of a more open chromatin state, as evidenced by a broader H3K4me3 peak in the gene promoter region. However, the broad H3K4me3 peak and relatively high&nbsp;</span><em>CLDN1</em><span><span>&nbsp;</span>expression in RS did not translate into protein level, which implies a different regulatory mechanism in this type of senescence. Elevated CLDN1 levels were also observed in VSMCs isolated from atherosclerotic plaques, although this was highly donor dependent. These findings indicate that increased CLDN1 level in prematurely senescent cells may serve as a promising cell-specific marker of SIPS in VSMCs, both in vitro and ex vivo.</span></p>',
			'date' => '2024-11-07',
			'pmid' => 'https://www.researchsquare.com/article/rs-5192437/v1',
			'doi' => 'https://doi.org/10.21203/rs.3.rs-5192437/v1',
			'modified' => '2024-11-12 09:27:24',
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		),
		(int) 1 => array(
			'id' => '4965',
			'name' => 'Trained immunity is regulated by T cell-induced CD40-TRAF6 signaling',
			'authors' => 'Jacobs M.M.E. et al.',
			'description' => '<p><span>Trained immunity is characterized by histone modifications and metabolic changes in innate immune cells following exposure to inflammatory signals, leading to heightened responsiveness to secondary stimuli. Although our understanding of the molecular regulation of trained immunity has increased, the role of adaptive immune cells herein remains largely unknown. Here, we show that T&nbsp;cells modulate trained immunity via cluster of differentiation 40-tissue necrosis factor receptor-associated factor 6 (CD40-TRAF6) signaling. CD40-TRAF6 inhibition modulates functional, transcriptomic, and metabolic reprogramming and modifies histone 3 lysine 4 trimethylation associated with trained immunity. Besides&nbsp;</span><i>in&nbsp;vitro</i><span><span>&nbsp;</span>studies, we reveal that single-nucleotide polymorphisms in the proximity of<span>&nbsp;</span></span><i>CD40</i><span><span>&nbsp;</span>are linked to trained immunity responses<span>&nbsp;</span></span><i>in&nbsp;vivo</i><span><span>&nbsp;</span>and that combining CD40-TRAF6 inhibition with cytotoxic T lymphocyte antigen 4-immunoglobulin (CTLA4-Ig)-mediated co-stimulatory blockade induces long-term graft acceptance in a murine heart transplantation model. Combined, our results reveal that trained immunity is modulated by CD40-TRAF6 signaling between myeloid and adaptive immune cells and that this can be leveraged for therapeutic purposes.</span></p>',
			'date' => '2024-09-24',
			'pmid' => 'https://www.cell.com/cell-reports/fulltext/S2211-1247(24)01015-5',
			'doi' => '',
			'modified' => '2024-09-02 10:23:11',
			'created' => '2024-09-02 10:23:11',
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				[maximum depth reached]
			)
		),
		(int) 2 => array(
			'id' => '4958',
			'name' => 'Legionella pneumophila modulates macrophage functions through epigenetic reprogramming via the C-type lectin receptor Mincle',
			'authors' => 'Stegmann F. et al.',
			'description' => '<p><em>Legionella pneumophila</em><span><span>&nbsp;</span>is a pathogen which can lead to a severe form of pneumonia in humans known as Legionnaires disease after replication in alveolar macrophages. Viable<span>&nbsp;</span></span><em>L.&nbsp;pneumophila</em><span><span>&nbsp;</span>actively secrete effector molecules to modulate the host&rsquo;s immune response. Here, we report that<span>&nbsp;</span></span><em>L.&nbsp;pneumophila</em><span>-derived factors reprogram macrophages into a tolerogenic state, a process to which the C-type lectin receptor Mincle (CLEC4E) markedly contributes. The underlying epigenetic state is characterized by increases of the closing mark H3K9me3 and decreases of the opening mark H3K4me3, subsequently leading to the reduced secretion of the cytokines TNF, IL-6, IL-12, the production of reactive oxygen species, and cell-surface expression of MHC-II and CD80 upon re-stimulation. In summary, these findings provide important implications for our understanding of Legionellosis and the contribution of Mincle to reprogramming of macrophages by<span>&nbsp;</span></span><em>L.&nbsp;pneumophila</em><span>.</span></p>',
			'date' => '2024-09-20',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S2589004224019254#:~:text=L.,crucial%20for%20mediating%20tolerance%20induction.',
			'doi' => 'https://doi.org/10.1016/j.isci.2024.110700',
			'modified' => '2024-09-02 10:06:00',
			'created' => '2024-09-02 10:06:00',
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		(int) 3 => array(
			'id' => '4974',
			'name' => 'Systematic prioritization of functional variants and effector genes underlying colorectal cancer risk',
			'authors' => 'Law P.J. et al.',
			'description' => '<p><span>Genome-wide association studies of colorectal cancer (CRC) have identified 170 autosomal risk loci. However, for most of these, the functional variants and their target genes are unknown. Here, we perform statistical fine-mapping incorporating tissue-specific epigenetic annotations and massively parallel reporter assays to systematically prioritize functional variants for each CRC risk locus. We identify plausible causal variants for the 170 risk loci, with a single variant for 40. We link these variants to 208 target genes by analyzing colon-specific quantitative trait loci and implementing the activity-by-contact model, which integrates epigenomic features and Micro-C data, to predict enhancer&ndash;gene connections. By deciphering CRC risk loci, we identify direct links between risk variants and target genes, providing further insight into the molecular basis of CRC susceptibility and highlighting potential pharmaceutical targets for prevention and treatment.</span></p>',
			'date' => '2024-09-16',
			'pmid' => 'https://www.nature.com/articles/s41588-024-01900-w',
			'doi' => 'https://doi.org/10.1038/s41588-024-01900-w',
			'modified' => '2024-09-23 10:14:18',
			'created' => '2024-09-23 10:14:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 4 => array(
			'id' => '4971',
			'name' => 'Bivalent chromatin accommodates survivin and BRG1/SWI complex to activate DNA damage response in CD4+ cells',
			'authors' => 'Chandrasekaran V. et al.',
			'description' => '<section aria-labelledby="Abs1" data-title="Abstract" lang="en">
<div class="c-article-section" id="Abs1-section">
<div class="c-article-section__content" id="Abs1-content">
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Background</h3>
<p>Bivalent regions of chromatin (BvCR) are characterized by trimethylated lysine 4 (H3K4me3) and lysine 27 on histone H3 (H3K27me3) deposition which aid gene expression control during cell differentiation. The role of BvCR in post-transcriptional DNA damage response remains unidentified. Oncoprotein survivin binds chromatin and mediates IFN&gamma; effects in CD4<sup>+</sup><span>&nbsp;</span>cells. In this study, we explored the role of BvCR in DNA damage response of autoimmune CD4<sup>+</sup><span>&nbsp;</span>cells in rheumatoid arthritis (RA).</p>
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Methods</h3>
<p>We performed deep sequencing of the chromatin bound to survivin, H3K4me3, H3K27me3, and H3K27ac, in human CD4<sup>+</sup><span>&nbsp;</span>cells and identified BvCR, which possessed all three histone H3 modifications. Protein partners of survivin on chromatin were predicted by integration of motif enrichment analysis, computational machine-learning, and structural modeling, and validated experimentally by mass spectrometry and peptide binding array. Survivin-dependent change in BvCR and transcription of genes controlled by the BvCR was studied in CD4<sup>+</sup><span>&nbsp;</span>cells treated with survivin inhibitor, which revealed survivin-dependent biological processes. Finally, the survivin-dependent processes were mapped to the transcriptome of CD4<sup>+</sup><span>&nbsp;</span>cells in blood and in synovial tissue of RA patients and the effect of modern immunomodulating drugs on these processes was explored.</p>
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Results</h3>
<p>We identified that BvCR dominated by H3K4me3 (H3K4me3-BvCR) accommodated survivin within<span>&nbsp;</span><i>cis</i>-regulatory elements of the genes controlling DNA damage. Inhibition of survivin or JAK-STAT signaling enhanced H3K4me3-BvCR dominance, which improved DNA damage recognition and arrested cell cycle progression in cultured CD4<sup>+</sup><span>&nbsp;</span>cells. Specifically, BvCR accommodating survivin aided sequence-specific anchoring of the BRG1/SWI chromatin-remodeling complex coordinating DNA damage response. Mapping survivin interactome to BRG1/SWI complex demonstrated interaction of survivin with the subunits anchoring the complex to chromatin. Co-expression of BRG1, survivin and IFN&gamma; in CD4<sup>+</sup><span>&nbsp;</span>cells rendered complete deregulation of DNA damage response in RA. Such cells possessed strong ability of homing to RA joints. Immunomodulating drugs inhibited the anchoring subunits of BRG1/SWI complex, which affected arthritogenic profile of CD4<sup>+</sup><span>&nbsp;</span>cells.</p>
<h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Conclusions</h3>
<p>BvCR execute DNA damage control to maintain genome fidelity in IFN-activated CD4<sup>+</sup><span>&nbsp;</span>cells. Survivin anchors the BRG1/SWI complex to BvCR to repress DNA damage response. These results offer a platform for therapeutic interventions targeting survivin and BRG1/SWI complex in autoimmunity.</p>
</div>
</div>
</section>
<section data-title="Background">
<div class="c-article-section" id="Sec1-section">
<h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec1"></h2>
</div>
</section>',
			'date' => '2024-09-11',
			'pmid' => 'https://biosignaling.biomedcentral.com/articles/10.1186/s12964-024-01814-4',
			'doi' => 'https://doi.org/10.1186/s12964-024-01814-4',
			'modified' => '2024-09-16 10:02:18',
			'created' => '2024-09-16 10:02:18',
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		),
		(int) 5 => array(
			'id' => '4951',
			'name' => 'LL37/self-DNA complexes mediate monocyte reprogramming',
			'authors' => 'Aman Damara et al.',
			'description' => '<p><span>LL37 alone and in complex with self-DNA triggers inflammatory responses in myeloid cells and plays a crucial role in the development of systemic autoimmune diseases, like psoriasis and systemic lupus erythematosus. We demonstrated that LL37/self-DNA complexes induce long-term metabolic and epigenetic changes in monocytes, enhancing their responsiveness to subsequent stimuli. Monocytes trained with LL37/self-DNA complexes and those derived from psoriatic patients exhibited heightened glycolytic and oxidative phosphorylation rates, elevated release of proinflammatory cytokines, and affected na&iuml;ve CD4</span><sup>+</sup><span><span>&nbsp;</span>T cells. Additionally, KDM6A/B, a demethylase of lysine 27 on histone 3, was upregulated in psoriatic monocytes and monocytes treated with LL37/self-DNA complexes. Inhibition of KDM6A/B reversed the trained immune phenotype by reducing proinflammatory cytokine production, metabolic activity, and the induction of IL-17-producing T cells by LL37/self-DNA-treated monocytes. Our findings highlight the role of LL37/self-DNA-induced innate immune memory in psoriasis pathogenesis, uncovering its impact on monocyte and T cell dynamics.</span></p>',
			'date' => '2024-08-01',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S1521661624003966',
			'doi' => 'https://doi.org/10.1016/j.clim.2024.110287',
			'modified' => '2024-07-04 15:53:17',
			'created' => '2024-07-04 15:53:17',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 6 => array(
			'id' => '4968',
			'name' => 'Innate immune training restores pro-reparative myeloid functions to promote remyelination in the aged central nervous system',
			'authors' => 'Tiwari V. et al.',
			'description' => '<p><span>The reduced ability of the central nervous system to regenerate with increasing age limits functional recovery following demyelinating injury. Previous work has shown that myelin debris can overwhelm the metabolic capacity of microglia, thereby impeding tissue regeneration in aging, but the underlying mechanisms are unknown. In a model of demyelination, we found that a substantial number of genes that were not effectively activated in aged myeloid cells displayed epigenetic modifications associated with restricted chromatin accessibility. Ablation of two class I histone deacetylases in microglia was sufficient to restore the capacity of aged mice to remyelinate lesioned tissue. We used Bacillus Calmette-Guerin (BCG), a live-attenuated vaccine, to train the innate immune system and detected epigenetic reprogramming of brain-resident myeloid cells and functional restoration of myelin debris clearance and lesion recovery. Our results provide insight into aging-associated decline in myeloid function and how this decay can be prevented by innate immune reprogramming.</span></p>',
			'date' => '2024-07-24',
			'pmid' => 'https://www.cell.com/immunity/fulltext/S1074-7613(24)00348-0',
			'doi' => '',
			'modified' => '2024-09-02 17:05:54',
			'created' => '2024-09-02 17:05:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 7 => array(
			'id' => '4954',
			'name' => 'A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment',
			'authors' => 'Perez R. F. at al. ',
			'description' => '<p><span>Aging involves the deterioration of organismal function, leading to the emergence of multiple pathologies. Environmental stimuli, including lifestyle, can influence the trajectory of this process and may be used as tools in the pursuit of healthy aging. To evaluate the role of epigenetic mechanisms in this context, we have generated bulk tissue and single cell multi-omic maps of the male mouse dorsal hippocampus in young and old animals exposed to environmental stimulation in the form of enriched environments. We present a molecular atlas of the aging process, highlighting two distinct axes, related to inflammation and to the dysregulation of mRNA metabolism, at the functional RNA and protein level. Additionally, we report the alteration of heterochromatin domains, including the loss of bivalent chromatin and the uncovering of a heterochromatin-switch phenomenon whereby constitutive heterochromatin loss is partially mitigated through gains in facultative heterochromatin. Notably, we observed the multi-omic reversal of a great number of aging-associated alterations in the context of environmental enrichment, which was particularly linked to glial and oligodendrocyte pathways. In conclusion, our work describes the epigenomic landscape of environmental stimulation in the context of aging and reveals how lifestyle intervention can lead to the multi-layered reversal of aging-associated decline.</span></p>',
			'date' => '2024-07-16',
			'pmid' => 'https://www.nature.com/articles/s41467-024-49608-z',
			'doi' => 'https://doi.org/10.1038/s41467-024-49608-z',
			'modified' => '2024-07-29 11:33:49',
			'created' => '2024-07-29 11:33:49',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 8 => array(
			'id' => '4946',
			'name' => 'The landscape of RNA-chromatin interaction reveals small non-coding RNAs as essential mediators of leukemia maintenance',
			'authors' => 'Haiyang Yun et al.',
			'description' => '<p><span>RNA constitutes a large fraction of chromatin. Spatial distribution and functional relevance of most of RNA-chromatin interactions remain unknown. We established a landscape analysis of RNA-chromatin interactions in human acute myeloid leukemia (AML). In total more than 50 million interactions were captured in an AML cell line. Protein-coding mRNAs and long non-coding RNAs exhibited a substantial number of interactions with chromatin in&nbsp;</span><i>cis</i><span><span>&nbsp;</span>suggesting transcriptional activity. In contrast, small nucleolar RNAs (snoRNAs) and small nuclear RNAs (snRNAs) associated with chromatin predominantly in<span>&nbsp;</span></span><i>trans</i><span><span>&nbsp;</span>suggesting chromatin specific functions. Of note, snoRNA-chromatin interaction was associated with chromatin modifications and occurred independently of the classical snoRNA-RNP complex. Two C/D box snoRNAs, namely<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span>, displayed high frequency of<span>&nbsp;</span></span><i>trans</i><span>-association with chromatin. The transcription of<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span><span>&nbsp;</span>was increased upon leukemia transformation and enriched in leukemia stem cells, but decreased during myeloid differentiation. Suppression of<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span><span>&nbsp;</span>impaired leukemia cell proliferation and colony forming capacity in AML cell lines and primary patient samples. Notably, this effect was leukemia specific with less impact on healthy CD34+ hematopoietic stem and progenitor cells. These findings highlight the functional importance of chromatin-associated RNAs overall and in particular of<span>&nbsp;</span></span><i>SNORD118</i><span><span>&nbsp;</span>and<span>&nbsp;</span></span><i>SNORD3A</i><span><span>&nbsp;</span>in maintaining leukemia propagation.</span></p>',
			'date' => '2024-06-28',
			'pmid' => 'https://www.nature.com/articles/s41375-024-02322-7',
			'doi' => 'https://doi.org/10.1038/s41375-024-02322-7',
			'modified' => '2024-07-04 14:32:41',
			'created' => '2024-07-04 14:32:41',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 9 => array(
			'id' => '4948',
			'name' => 'Single-cell epigenomic reconstruction of developmental trajectories from pluripotency in human neural organoid systems',
			'authors' => 'Fides Zenk et al.',
			'description' => '<p><span>Cell fate progression of pluripotent progenitors is strictly regulated, resulting in high human cell diversity. Epigenetic modifications also orchestrate cell fate restriction. Unveiling the epigenetic mechanisms underlying human cell diversity has been difficult. In this study, we use human brain and retina organoid models and present single-cell profiling of H3K27ac, H3K27me3 and H3K4me3 histone modifications from progenitor to differentiated neural fates to reconstruct the epigenomic trajectories regulating cell identity acquisition. We capture transitions from pluripotency through neuroepithelium to retinal and brain region and cell type specification. Switching of repressive and activating epigenetic modifications can precede and predict cell fate decisions at each stage, providing a temporal census of gene regulatory elements and transcription factors. Removing H3K27me3 at the neuroectoderm stage disrupts fate restriction, resulting in aberrant cell identity acquisition. Our single-cell epigenome-wide map of human neural organoid development serves as a blueprint to explore human cell fate determination.</span></p>',
			'date' => '2024-06-24',
			'pmid' => 'https://www.nature.com/articles/s41593-024-01652-0',
			'doi' => 'https://doi.org/10.1038/s41593-024-01652-0',
			'modified' => '2024-07-04 14:54:14',
			'created' => '2024-07-04 14:54:14',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 10 => array(
			'id' => '4924',
			'name' => 'SURVIVIN IN SYNERGY WITH BAF/SWI COMPLEX BINDS BIVALENT CHROMATIN REGIONS AND ACTIVATES DNA DAMAGE RESPONSE IN CD4+ T CELLS',
			'authors' => 'Chandrasekaran V. et al.',
			'description' => '<p id="p-2">This study explores a regulatory role of oncoprotein survivin on the bivalent regions of chromatin (BvCR) characterized by concomitant deposition of trimethylated lysine of histone H3 at position 4 (H3K4me3) and 27 (H3K27me3).</p>
<p id="p-3">Intersect between BvCR and chromatin sequences bound to survivin demonstrated their co-localization on<span>&nbsp;</span><em>cis</em>-regulatory elements of genes which execute DNA damage control in primary human CD4<sup>+</sup><span>&nbsp;</span>cells. Survivin anchored BRG1-complex to BvCR to repress DNA damage repair genes in IFN&gamma;-stimulated CD4<sup>+</sup><span>&nbsp;</span>cells. In contrast, survivin inhibition shifted the functional balance of BvCR in favor of H3K4me3, which activated DNA damage recognition and repair. Co-expression of BRG1, survivin and IFN&gamma; in CD4<sup>+</sup><span>&nbsp;</span>cells of patients with rheumatoid arthritis identified arthritogenic BRG1<sup>hi</sup><span>&nbsp;</span>cells abundant in autoimmune synovia. Immunomodulating drugs inhibited the subunits anchoring BRG1-complex to BvCR, which changed the arthritogenic profile.</p>
<p id="p-4">Together, this study demonstrates the function of BvCR in DNA damage control of CD4<sup>+</sup><span>&nbsp;</span>cells offering an epigenetic platform for survivin and BRG1-complex targeting interventions to combat autoimmunity.</p>
<div id="sec-1" class="subsection">
<p id="p-5"><strong>Summary</strong><span>&nbsp;</span>This study shows that bivalent chromatin regions accommodate survivin which represses DNA repair enzymes in IFN&gamma;-stimulated CD4<sup>+</sup><span>&nbsp;</span>T cells. Survivin anchors BAF/SWI complex to these regions and supports autoimmune profile of T cells, providing novel targets for therapeutic intervention.</p>
</div>',
			'date' => '2024-03-10',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/2024.03.05.583464v1',
			'doi' => 'https://doi.org/10.1101/2024.03.05.583464',
			'modified' => '2024-03-13 17:07:31',
			'created' => '2024-03-13 17:07:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 11 => array(
			'id' => '4911',
			'name' => 'Multiomics uncovers the epigenomic and transcriptomic response to viral and bacterial stimulation in turbot',
			'authors' => 'Aramburu O. et al.',
			'description' => '<p><span>Uncovering the epigenomic regulation of immune responses is essential for a comprehensive understanding of host defence mechanisms but remains poorly described in farmed fish. Here, we report the first annotation of the innate immune regulatory response in the genome of turbot (</span><em>Scophthalmus maximus</em><span>), a farmed flatfish. We integrated RNA-Seq with ATAC-Seq and ChIP-Seq (histone marks H3K4me3, H3K27ac and H3K27me3) using samples from head kidney. Sampling was performed 24 hours post-stimulation with viral (poly I:C) and bacterial (inactivate<span>&nbsp;</span></span><em>Vibrio anguillarum</em><span>) mimics<span>&nbsp;</span></span><em>in vivo</em><span><span>&nbsp;</span>and<span>&nbsp;</span></span><em>in vitro</em><span><span>&nbsp;</span>(primary leukocyte cultures). Among the 8,797 differentially expressed genes (DEGs), we observed enrichment of transcriptional activation pathways in response to<span>&nbsp;</span></span><em>Vibrio</em><span><span>&nbsp;</span>and immune response pathways - including interferon stimulated genes - for poly I:C. Meanwhile, metabolic and cell cycle were downregulated by both mimics. We identified notable differences in chromatin accessibility (20,617<span>&nbsp;</span></span><em>in vitro</em><span>, 59,892<span>&nbsp;</span></span><em>in vivo</em><span>) and H3K4me3 bound regions (11,454<span>&nbsp;</span></span><em>in vitro</em><span>, 10,275<span>&nbsp;</span></span><em>in viv</em><span>o) - i.e. marking active promoters - between stimulations and controls. Overlaps of DEGs with promoters showing differential accessibility or histone mark binding revealed a significant coupling of the transcriptome and chromatin state. DEGs with activation marks in their promoters were enriched for similar functions to the global DEG set, but not in all cases, suggesting key regulatory genes were in poised or bivalent states. Active promoters and putative enhancers were differentially enriched in transcription factor binding motifs, many of them common to viral and bacterial responses. Finally, an in-depth analysis of immune response changes in chromatin state surrounding key DEGs encoding transcription factors was performed. This comprehensive multi-omics investigation provides an improved understanding of the epigenomic basis for the turbot immune responses and provides novel functional genomic information that can be leveraged in selective breeding towards enhanced disease resistance.</span></p>',
			'date' => '2024-02-15',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/2024.02.15.580452v1',
			'doi' => 'https://doi.org/10.1101/2024.02.15.580452',
			'modified' => '2024-02-22 11:41:27',
			'created' => '2024-02-22 11:41:27',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 12 => array(
			'id' => '4842',
			'name' => 'Alterations in the hepatocyte epigenetic landscape in steatosis.',
			'authors' => 'Maji  Ranjan K. et al.',
			'description' => '<p>Fatty liver disease or the accumulation of fat in the liver, has been reported to affect the global population. This comes with an increased risk for the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Yet, little is known about the effects of a diet containing high fat and alcohol towards epigenetic aging, with respect to changes in transcriptional and epigenomic profiles. In this study, we took up a multi-omics approach and integrated gene expression, methylation signals, and chromatin signals to study the epigenomic effects of a high-fat and alcohol-containing diet on mouse hepatocytes. We identified four relevant gene network clusters that were associated with relevant pathways that promote steatosis. Using a machine learning approach, we predict specific transcription factors that might be responsible to modulate the functionally relevant clusters. Finally, we discover four additional CpG loci and validate aging-related differential CpG methylation. Differential CpG methylation linked to aging showed minimal overlap with altered methylation in steatosis.</p>',
			'date' => '2023-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37415213',
			'doi' => '10.1186/s13072-023-00504-8',
			'modified' => '2023-08-01 14:08:16',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 13 => array(
			'id' => '4859',
			'name' => 'Sexual differentiation in human malaria parasites is regulated bycompetition between phospholipid metabolism and histone methylation.',
			'authors' => 'Harris  C. T. et al.',
			'description' => '<p>For Plasmodium falciparum, the most widespread and virulent malaria parasite that infects humans, persistence depends on continuous asexual replication in red blood cells, while transmission to their mosquito vector requires asexual blood-stage parasites to differentiate into non-replicating gametocytes. This decision is controlled by stochastic derepression of a heterochromatin-silenced locus encoding AP2-G, the master transcription factor of sexual differentiation. The frequency of ap2-g derepression was shown to be responsive to extracellular phospholipid precursors but the mechanism linking these metabolites to epigenetic regulation of ap2-g was unknown. Through a combination of molecular genetics, metabolomics and chromatin profiling, we show that this response is mediated by metabolic competition for the methyl donor S-adenosylmethionine between histone methyltransferases and phosphoethanolamine methyltransferase, a critical enzyme in the parasite's pathway for de novo phosphatidylcholine synthesis. When phosphatidylcholine precursors are scarce, increased consumption of SAM for de novo phosphatidylcholine synthesis impairs maintenance of the histone methylation responsible for silencing ap2-g, increasing the frequency of derepression and sexual differentiation. This provides a key mechanistic link that explains how LysoPC and choline availability can alter the chromatin status of the ap2-g locus controlling sexual differentiation.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37277533',
			'doi' => '10.1038/s41564-023-01396-w',
			'modified' => '2023-08-01 14:48:21',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 14 => array(
			'id' => '4862',
			'name' => 'Mutant FUS induces chromatin reorganization in the hippocampus andalters memory processes.',
			'authors' => 'Tzeplaeff  L. et al.',
			'description' => '<p>Cytoplasmic mislocalization of the nuclear Fused in Sarcoma (FUS) protein is associated to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cytoplasmic FUS accumulation is recapitulated in the frontal cortex and spinal cord of heterozygous Fus mice. Yet, the mechanisms linking FUS mislocalization to hippocampal function and memory formation are still not characterized. Herein, we show that in these mice, the hippocampus paradoxically displays nuclear FUS accumulation. Multi-omic analyses showed that FUS binds to a set of genes characterized by the presence of an ETS/ELK-binding motifs, and involved in RNA metabolism, transcription, ribosome/mitochondria and chromatin organization. Importantly, hippocampal nuclei showed a decompaction of the neuronal chromatin at highly expressed genes and an inappropriate transcriptomic response was observed after spatial training of Fus mice. Furthermore, these mice lacked precision in a hippocampal-dependent spatial memory task and displayed decreased dendritic spine density. These studies shows that mutated FUS affects epigenetic regulation of the chromatin landscape in hippocampal neurons, which could participate in FTD/ALS pathogenic events. These data call for further investigation in the neurological phenotype of FUS-related diseases and open therapeutic strategies towards epigenetic drugs.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37327984',
			'doi' => '10.1016/j.pneurobio.2023.102483',
			'modified' => '2023-08-01 14:55:49',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 15 => array(
			'id' => '4820',
			'name' => 'The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cellfate.',
			'authors' => 'Lackner  A. et al.',
			'description' => '<p><span>Placental development relies on coordinated cell fate decisions governed by signalling inputs. However, little is known about how signalling cues are transformed into repressive mechanisms triggering lineage-specific transcriptional signatures. Here, we demonstrate that upon inhibition of the Fgf/Erk pathway in mouse trophoblast stem cells (TSCs), the Ets2 repressor factor (Erf) interacts with the Nuclear Receptor Co-Repressor Complex 1 and 2 (NCoR1/2) and recruits it to key trophoblast genes. Genetic ablation of Erf or Tbl1x (a component of the NCoR1/2 complex) abrogates the Erf/NCoR1/2 interaction. This leads to mis-expression of Erf/NCoR1/2 target genes, resulting in a TSC differentiation defect. Mechanistically, Erf regulates expression of these genes by recruiting the NCoR1/2 complex and decommissioning their H3K27ac-dependent enhancers. Our findings uncover how the Fgf/Erf/NCoR1/2 repressive axis governs cell fate and placental development, providing a paradigm for Fgf-mediated transcriptional control.</span></p>',
			'date' => '2023-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37137875',
			'doi' => '10.1038/s41467-023-38101-8',
			'modified' => '2023-06-19 10:10:38',
			'created' => '2023-06-13 21:11:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 16 => array(
			'id' => '4778',
			'name' => 'Comprehensive epigenomic profiling reveals the extent of disease-specificchromatin states and informs target discovery in ankylosing spondylitis',
			'authors' => 'Brown  A.C. et al.',
			'description' => '<p>Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterized by enthesitis of the spine and sacroiliac joints. Genome-wide association studies (GWASs) have revealed more than 100 genetic associations whose functional effects remain largely unresolved. Here, we present a comprehensive transcriptomic and epigenomic map of disease-relevant blood immune cell subsets from AS patients and healthy controls.We find that, while CD14+ monocytes and CD4+ and CD8+ T cells show disease-specific differences at the RNA level, epigenomic differences are only apparent upon multi-omics integration. The latter reveals enrichment at disease-associated loci in monocytes. We link putative functional SNPs to genes using high-resolution Capture-C at 10 loci, including PTGER4 and ETS1, and show how disease-specific functional genomic data can be integrated with GWASs to enhance therapeutic target discovery. This study combines epigenetic and transcriptional analysis with GWASs to identify disease-relevant cell types and gene regulation of likely pathogenic relevance and prioritize drug targets.</p>',
			'date' => '2023-04-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.xgen.2023.100306',
			'doi' => '10.1016/j.xgen.2023.100306',
			'modified' => '2023-06-13 09:14:26',
			'created' => '2023-05-05 12:34:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 17 => array(
			'id' => '4763',
			'name' => 'Chromatin profiling identifies transcriptional readthrough as a conservedmechanism for piRNA biogenesis in mosquitoes.',
			'authors' => 'Qu  J. et al.',
			'description' => '<p>The piRNA pathway in mosquitoes differs substantially from other model organisms, with an expanded PIWI gene family and functions in antiviral defense. Here, we define core piRNA clusters as genomic loci that show ubiquitous piRNA expression in both somatic and germline tissues. These core piRNA clusters are enriched for non-retroviral endogenous viral elements (nrEVEs) in antisense orientation and depend on key biogenesis factors, Veneno, Tejas, Yb, and Shutdown. Combined transcriptome and chromatin state analyses identify transcriptional readthrough as a conserved mechanism for cluster-derived piRNA biogenesis in the vector mosquitoes Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and Anopheles gambiae. Comparative analyses between the two Aedes species suggest that piRNA clusters function as traps for nrEVEs, allowing adaptation to environmental challenges such as virus infection. Our systematic transcriptome and chromatin state analyses lay the foundation for studies of gene regulation, genome evolution, and piRNA function in these important vector species.</p>',
			'date' => '2023-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36930642',
			'doi' => '10.1016/j.celrep.2023.112257',
			'modified' => '2023-04-17 09:12:37',
			'created' => '2023-04-14 13:41:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 18 => array(
			'id' => '4765',
			'name' => 'Epigenetic dosage identifies two major and functionally distinct beta cells ubtypes.',
			'authors' => 'Dror  E.et al.',
			'description' => '<p>The mechanisms that specify and stabilize cell subtypes remain poorly understood. Here, we identify two major subtypes of pancreatic &Icirc;&sup2; cells based on histone mark heterogeneity (beta HI and beta LO). Beta HI cells exhibit 4-fold higher levels of H3K27me3, distinct chromatin organization and compaction, and a specific transcriptional pattern. B<span>eta HI and beta LO</span> cells also differ in size, morphology, cytosolic and nuclear ultrastructure, epigenomes, cell surface marker expression, and function, and can be FACS separated into CD24 and CD24 fractions. Functionally, &Icirc;&sup2; cells have increased mitochondrial mass, activity, and insulin secretion in vivo and ex vivo. Partial loss of function indicates that H3K27me3 dosage regulates <span>beta HI/beta LO&nbsp;</span>ratio in vivo, suggesting that control of <span>beta HI&nbsp;</span>cell subtype identity and ratio is at least partially uncoupled. Both subtypes are conserved in humans, with <span>beta HI</span> cells enriched in humans with type 2 diabetes. Thus, epigenetic dosage is a novel regulator of cell subtype specification and identifies two functionally distinct&nbsp;beta cell subtypes.</p>',
			'date' => '2023-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36948185',
			'doi' => '10.1016/j.cmet.2023.03.008',
			'modified' => '2023-04-17 09:26:02',
			'created' => '2023-04-14 13:41:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 19 => array(
			'id' => '4667',
			'name' => 'Detailed molecular and epigenetic characterization of the Pig IPECJ2and Chicken SL-29 cell lines',
			'authors' => 'de Vos  J. et al.',
			'description' => '<p>The pig IPECJ2 and chicken SL-29 cell lines are of interest because of their untransformed nature and wide use in functional studies. Molecular characterization of these cell lines is important to gain insight into possible molecular aberrations. The aims of this paper are providing a molecular and epigenetic characterization of the IPEC-J2 and SL-29 cell lines and providing a cell-line reference for the FAANG community, and future biomedical research. Whole genome sequencing , gene expression, DNA methylation , chromatin accessibility and ChIP-seq of four histone marks (H3K4me1, H3K4me3, H3K27ac, H3K27me3) and an insulator (CTCF) are used to achieve these aims. Heteroploidy (aneuploidy) of various chromosomes was observed from whole genome sequencing analysis in both cell lines. Furthermore, higher gene expression for genes located on chromosomes with aneuploidy in comparison to diploid chromosomes was observed. Regulatory complexity of gene expression, DNA methylation and chromatin accessibility was investigated through an integrative approach.</p>',
			'date' => '2023-02-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.isci.2023.106252',
			'doi' => '10.1016/j.isci.2023.106252',
			'modified' => '2023-04-07 16:52:26',
			'created' => '2023-02-28 12:19:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 20 => array(
			'id' => '4669',
			'name' => 'Histone remodeling reflects conserved mechanisms of bovine and humanpreimplantation development.',
			'authors' => 'Zhou  C. et al.',
			'description' => '<p>How histone modifications regulate changes in gene expression during preimplantation development in any species remains poorly understood. Using CUT\&amp;Tag to overcome limiting amounts of biological material, we profiled two activating (H3K4me3 and H3K27ac) and two repressive (H3K9me3 and H3K27me3) marks in bovine oocytes, 2-, 4-, and 8-cell embryos, morula, blastocysts, inner cell mass, and trophectoderm. In oocytes, broad bivalent domains mark developmental genes, and prior to embryonic genome activation (EGA), H3K9me3 and H3K27me3 co-occupy gene bodies, suggesting a global mechanism for transcription repression. During EGA, chromatin accessibility is established before canonical H3K4me3 and H3K27ac signatures. Embryonic transcription is required for this remodeling, indicating that maternally provided products alone are insufficient for reprogramming. Last, H3K27me3 plays a major role in restriction of cellular potency, as blastocyst lineages are defined by differential polycomb repression and transcription factor activity. Notably, inferred regulators of EGA and blastocyst formation strongly resemble those described in humans, as opposed to mice. These similarities suggest that cattle are a better model than rodents to investigate the molecular basis of human preimplantation development.</p>',
			'date' => '2023-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36779365',
			'doi' => '10.15252/embr.202255726',
			'modified' => '2023-04-14 09:34:12',
			'created' => '2023-02-28 12:19:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 21 => array(
			'id' => '4605',
			'name' => 'Gene Regulatory Interactions at Lamina-Associated Domains',
			'authors' => 'Madsen-Østerbye  J. et al.',
			'description' => '<p>The nuclear lamina provides a repressive chromatin environment at the nuclear periphery. However, whereas most genes in lamina-associated domains (LADs) are inactive, over ten percent reside in local euchromatic contexts and are expressed. How these genes are regulated and whether they are able to interact with regulatory elements remain unclear. Here, we integrate publicly available enhancer-capture Hi-C data with our own chromatin state and transcriptomic datasets to show that inferred enhancers of active genes in LADs are able to form connections with other enhancers within LADs and outside LADs. Fluorescence in situ hybridization analyses show proximity changes between differentially expressed genes in LADs and distant enhancers upon the induction of adipogenic differentiation. We also provide evidence of involvement of lamin A/C, but not lamin B1, in repressing genes at the border of an in-LAD active region within a topological domain. Our data favor a model where the spatial topology of chromatin at the nuclear lamina is compatible with gene expression in this dynamic nuclear compartment.</p>',
			'date' => '2023-01-01',
			'pmid' => 'https://doi.org/10.3390%2Fgenes14020334',
			'doi' => '10.3390/genes14020334',
			'modified' => '2023-04-04 08:57:32',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 22 => array(
			'id' => '4802',
			'name' => 'Analyzing the Genome-Wide Distribution of Histone Marks byCUT\&Tag in Drosophila Embryos.',
			'authors' => 'Zenk  F. et al.',
			'description' => '<p><span>CUT&amp;Tag is a method to map the genome-wide distribution of histone modifications and some chromatin-associated proteins. CUT&amp;Tag relies on antibody-targeted chromatin tagmentation and can easily be scaled up or automatized. This protocol provides clear experimental guidelines and helpful considerations when planning and executing CUT&amp;Tag experiments.</span></p>',
			'date' => '2023-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37212984',
			'doi' => '10.1007/978-1-0716-3143-0_1',
			'modified' => '2023-06-15 08:43:40',
			'created' => '2023-06-13 21:11:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 23 => array(
			'id' => '4545',
			'name' => 'Histone Deacetylases 1 and 2 target gene regulatory networks of nephronprogenitors to control nephrogenesis.',
			'authors' => 'Liu  Hongbing et al.',
			'description' => '<p>Our studies demonstrated the critical role of Histone deacetylases (HDACs) in the regulation of nephrogenesis. To better understand the key pathways regulated by HDAC1/2 in early nephrogenesis, we performed chromatin immunoprecipitation sequencing (ChIP-Seq) of Hdac1/2 on isolated nephron progenitor cells (NPCs) from mouse E16.5 kidneys. Our analysis revealed that 11802 (40.4\%) of Hdac1 peaks overlap with Hdac2 peaks, further demonstrates the redundant role of Hdac1 and Hdac2 during nephrogenesis. Common Hdac1/2 peaks are densely concentrated close to the transcriptional start site (TSS). GREAT Gene Ontology analysis of overlapping Hdac1/2 peaks reveals that Hdac1/2 are associated with metanephric nephron morphogenesis, chromatin assembly or disassembly, as well as other DNA checkpoints. Pathway analysis shows that negative regulation of Wnt signaling pathway is one of Hdac1/2's most significant function in NPCs. Known motif analysis indicated that Hdac1 is enriched in motifs for Six2, Hox family, and Tcf family members, which are essential for self-renewal and differentiation of nephron progenitors. Interestingly, we found the enrichment of HDAC1/2 at the enhancer and promoter regions of actively transcribed genes, especially those concerned with NPC self-renewal. HDAC1/2 simultaneously activate or repress the expression of different genes to maintain the cellular state of nephron progenitors. We used the Integrative Genomics Viewer to visualize these target genes associated with each function and found that Hdac1/2 co-bound to the enhancers or/and promoters of genes associated with nephron morphogenesis, differentiation, and cell cycle control. Taken together, our ChIP-Seq analysis demonstrates that Hdac1/2 directly regulate the molecular cascades essential for nephrogenesis.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36356658',
			'doi' => '10.1016/j.bcp.2022.115341',
			'modified' => '2022-11-24 10:24:07',
			'created' => '2022-11-24 08:49:52',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 24 => array(
			'id' => '4658',
			'name' => 'Balance between autophagy and cell death is maintained byPolycomb-mediated regulation during stem cell differentiation.',
			'authors' => 'Puri  Deepika et al.',
			'description' => '<p>Autophagy is a conserved cytoprotective process, aberrations in which lead to numerous degenerative disorders. While the cytoplasmic components of autophagy have been extensively studied, the epigenetic regulation of autophagy genes, especially in stem cells, is less understood. Deciphering the epigenetic regulation of autophagy genes becomes increasingly relevant given the therapeutic benefits of small-molecule epigenetic inhibitors in novel treatment modalities. We observe that, during retinoic acid-mediated differentiation of mouse embryonic stem cells (mESCs), autophagy is induced, and identify the Polycomb group histone methyl transferase EZH2 as a regulator of this process. In mESCs, EZH2 represses several autophagy genes, including the autophagy regulator DNA damage-regulated autophagy modulator protein 1 (Dram1). EZH2 facilitates the formation of a bivalent chromatin domain at the Dram1 promoter, allowing gene expression and autophagy induction during differentiation while retaining the repressive H3K27me3 mark. EZH2 inhibition leads to loss of the bivalent domain, with consequent "hyper-expression" of Dram1, accompanied by extensive cell death. This study shows that Polycomb group proteins help maintain a balance between autophagy and cell death during stem cell differentiation, in part by regulating the expression of the Dram1 gene.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36380631',
			'doi' => '10.1111/febs.16656',
			'modified' => '2023-03-07 08:59:36',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 25 => array(
			'id' => '4788',
			'name' => 'Dietary methionine starvation impairs acute myeloid leukemia progression.',
			'authors' => 'Cunningham  A. et al.',
			'description' => '<p>Targeting altered tumor cell metabolism might provide an attractive opportunity for patients with acute myeloid leukemia (AML). An amino acid dropout screen on primary leukemic stem cells and progenitor populations revealed a number of amino acid dependencies, of which methionine was one of the strongest. By using various metabolite rescue experiments, nuclear magnetic resonance-based metabolite quantifications and 13C-tracing, polysomal profiling, and chromatin immunoprecipitation sequencing, we identified that methionine is used predominantly for protein translation and to provide methyl groups to histones via S-adenosylmethionine for epigenetic marking. H3K36me3 was consistently the most heavily impacted mark following loss of methionine. Methionine depletion also reduced total RNA levels, enhanced apoptosis, and induced a cell cycle block. Reactive oxygen species levels were not increased following methionine depletion, and replacement of methionine with glutathione or N-acetylcysteine could not rescue phenotypes, excluding a role for methionine in controlling redox balance control in AML. Although considered to be an essential amino acid, methionine can be recycled from homocysteine. We uncovered that this is primarily performed by the enzyme methionine synthase and only when methionine availability becomes limiting. In&Acirc;&nbsp;vivo, dietary methionine starvation was not only tolerated by mice, but also significantly delayed both cell line and patient-derived AML progression. Finally, we show that inhibition of the H3K36-specific methyltransferase SETD2 phenocopies much of the cytotoxic effects of methionine depletion, providing a more targeted therapeutic approach. In conclusion, we show that methionine depletion is a vulnerability in AML that can be exploited therapeutically, and we provide mechanistic insight into how cells metabolize and recycle methionine.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://doi.org/10.33612%2Fdiss.205032978',
			'doi' => '10.1182/blood.2022017575',
			'modified' => '2023-06-12 09:01:21',
			'created' => '2023-05-05 12:34:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 26 => array(
			'id' => '4499',
			'name' => 'Trained Immunity Provides Long-Term Protection againstBacterial Infections in Channel Catfish.',
			'authors' => 'Petrie-Hanson  L. et al.',
			'description' => '<p>Beta glucan exposure induced trained immunity in channel catfish that conferred long-term protection against and infections one month post exposure. Flow cytometric analyses demonstrated that isolated macrophages and neutrophils phagocytosed higher amounts of and . Beta glucan induced changes in the distribution of histone modifications in the monomethylation and trimethylation of H3K4 and modifications in the acetylation and trimethylation of H3K27. KEGG pathway analyses revealed that these modifications affected expressions of genes controlling phagocytosis, phagosome functions and enhanced immune cell signaling. These analyses correlate the histone modifications with gene functions and to the observed enhanced phagocytosis and to the increased survival following bacterial challenge in channel catfish. These data suggest the chromatin reconfiguration that directs trained immunity as demonstrated in mammals also occurs in channel catfish. Understanding the mechanisms underlying trained immunity can help us design prophylactic and non-antibiotic based therapies and develop broad-based vaccines to limit bacterial disease outbreaks in catfish production.</p>',
			'date' => '2022-10-01',
			'pmid' => 'https://doi.org/10.3390%2Fpathogens11101140',
			'doi' => '10.3390/pathogens11101140',
			'modified' => '2022-11-21 10:31:12',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 27 => array(
			'id' => '4451',
			'name' => 'bESCs from cloned embryos do not retain transcriptomic or epigenetic memory from somatic donor cells.',
			'authors' => 'Navarro  M. et al.',
			'description' => '<p>Embryonic stem cells (ESC) indefinitely maintain the pluripotent state of the blastocyst epiblast. Stem cells are invaluable for studying development and lineage commitment, and in livestock they constitute a useful tool for genomic improvement and in vitro breeding programs. Although these cells have been recently derived from bovine blastocysts, a detailed characterization of their molecular state is still lacking. Here, we apply cutting-edge technologies to analyze the transcriptomic and epigenomic landscape of bovine ESC (bESC) obtained from in vitro fertilized (IVF) and somatic cell nuclear transfer (SCNT) embryos. Bovine ESC were efficiently derived from SCNT and IVF embryos and expressed pluripotency markers while retaining genome stability. Transcriptome analysis revealed that only 46 genes were differentially expressed between IVF- and SCNT-derived bESC, which did not reflect significant deviation in cellular function. Interrogating the histone marks H3K4me3, H3K9me3 and H3K27me3 with CUT\&amp;Tag, we found that the epigenomes of both bESC groups were virtually indistinguishable. Minor epigenetic differences were randomly distributed throughout the genome and were not associated with differentially expressed or developmentally important genes. Finally, categorization of genomic regions according to their combined histone mark signal demonstrated that all bESC shared the same epigenomic signatures, especially at promoters. Overall, we conclude that bESC derived from SCNT and IVF are transcriptomically and epigenetically analogous, allowing for the production of an unlimited source of pluripotent cells from high genetic merit organisms without resorting to genome editing techniques.</p>',
			'date' => '2022-08-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/35951478/',
			'doi' => '10.1530/REP-22-0063',
			'modified' => '2022-10-21 09:31:32',
			'created' => '2022-09-28 09:53:13',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 28 => array(
			'id' => '4416',
			'name' => 'Large-scale manipulation of promoter DNA methylation revealscontext-specific transcriptional responses and stability.',
			'authors' => 'de Mendoza  A. et al. ',
			'description' => '<p>BACKGROUND: Cytosine DNA methylation is widely described as a transcriptional repressive mark with the capacity to silence promoters. Epigenome engineering techniques enable direct testing of the effect of induced DNA methylation on endogenous promoters; however, the downstream effects have not yet been comprehensively assessed. RESULTS: Here, we simultaneously induce methylation at thousands of promoters in human cells using an engineered zinc finger-DNMT3A fusion protein, enabling us to test the effect of forced DNA methylation upon transcription, chromatin accessibility, histone modifications, and DNA methylation persistence after the removal of the fusion protein. We find that transcriptional responses to DNA methylation are highly context-specific, including lack of repression, as well as cases of increased gene expression, which appears to be driven by the eviction of methyl-sensitive transcriptional repressors. Furthermore, we find that some regulatory networks can override DNA methylation and that promoter methylation can cause alternative promoter usage. DNA methylation deposited at promoter and distal regulatory regions is rapidly erased after removal of the zinc finger-DNMT3A fusion protein, in a process combining passive and TET-mediated demethylation. Finally, we demonstrate that induced DNA methylation can exist simultaneously on promoter nucleosomes that possess the active histone modification H3K4me3, or DNA bound by the initiated form of RNA polymerase II. CONCLUSIONS: These findings have important implications for epigenome engineering and demonstrate that the response of promoters to DNA methylation is more complex than previously appreciated.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35883107',
			'doi' => '10.1186/s13059-022-02728-5',
			'modified' => '2022-09-15 09:01:24',
			'created' => '2022-09-08 16:32:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 29 => array(
			'id' => '4417',
			'name' => 'HOTAIR interacts with PRC2 complex regulating the regional preadipocytetranscriptome and human fat distribution.',
			'authors' => 'Kuo  Feng-Chih et al.',
			'description' => '<p>Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA HOTAIR (HOX transcript antisense RNA) is exclusively expressed in gluteofemoral AT, where it is essential for adipocyte development. We find that HOTAIR interacts with polycomb repressive complex 2 (PRC2) and we identify core HOTAIR-PRC2 target genes involved in adipocyte lineage determination. Repression of target genes coincides with PRC2 promoter occupancy and H3K27 trimethylation. HOTAIR is also involved in modifying the gluteal adipocyte transcriptome through alternative splicing. Gluteal-specific expression of HOTAIR is maintained by defined regions of open chromatin across the HOTAIR promoter. HOTAIR expression levels can be modified by hormonal (estrogen, glucocorticoids) and genetic variation (rs1443512 is a HOTAIR eQTL associated with reduced gynoid fat mass). These data identify HOTAIR as a dynamic regulator of the gluteal adipocyte transcriptome and epigenome with functional importance for human regional AT development.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35905723',
			'doi' => '10.1016/j.celrep.2022.111136',
			'modified' => '2022-09-27 14:41:23',
			'created' => '2022-09-08 16:32:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 30 => array(
			'id' => '4458',
			'name' => 'Epiblast inducers capture mouse trophectoderm stem cells in vitro andpattern blastoids for implantation in utero.',
			'authors' => 'Seong  Jinwoo et al.',
			'description' => '<p>The embryo instructs the allocation of cell states to spatially regulate functions. In the blastocyst, patterning of trophoblast (TR) cells ensures successful implantation and placental development. Here, we defined an optimal set of molecules secreted by the epiblast (inducers) that captures in&nbsp;vitro stable, highly self-renewing mouse trophectoderm stem cells (TESCs) resembling the blastocyst stage. When exposed to suboptimal inducers, these stem cells fluctuate to form interconvertible subpopulations with reduced self-renewal and facilitated differentiation, resembling peri-implantation cells, known as TR stem cells (TSCs). TESCs have enhanced capacity to form blastoids that implant more efficiently in utero due to inducers maintaining not only local TR proliferation and self-renewal, but also WNT6/7B secretion that stimulates uterine decidualization. Overall, the epiblast maintains sustained growth and decidualization potential of abutting TR cells, while, as known, distancing imposed by the blastocyst cavity differentiates TR cells for uterus adhesion, thus patterning the essential functions of implantation.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35803228',
			'doi' => '10.1016/j.stem.2022.06.002',
			'modified' => '2022-10-21 09:44:00',
			'created' => '2022-09-28 09:53:13',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 31 => array(
			'id' => '4386',
			'name' => 'Epigenomic analysis reveals a dynamic and context-specific macrophageenhancer landscape associated with innate immune activation and tolerance.',
			'authors' => 'Zhang  P. et al.',
			'description' => '<p>BACKGROUND: Chromatin states and enhancers associate gene expression, cell identity and disease. Here, we systematically delineate the acute innate immune response to endotoxin in terms of human macrophage enhancer activity and contrast with endotoxin tolerance, profiling the coding and non-coding transcriptome, chromatin accessibility and epigenetic modifications. RESULTS: We describe the spectrum of enhancers under acute and tolerance conditions and the regulatory networks between these enhancers and biological processes including gene expression, splicing regulation, transcription factor binding and enhancer RNA signatures. We demonstrate that the vast majority of differentially regulated enhancers on acute stimulation are subject to tolerance and that expression quantitative trait loci, disease-risk variants and eRNAs are enriched in these regulatory regions and related to context-specific gene expression. We find enrichment for context-specific eQTL involving endotoxin response and specific infections and delineate specific differential regions informative for GWAS variants in inflammatory bowel disease and multiple sclerosis, together with a context-specific enhancer involving a bacterial infection eQTL for KLF4. We show enrichment in differential enhancers for tolerance involving transcription factors NF&kappa;B-p65, STATs and IRFs and prioritize putative causal genes directly linking genetic variants and disease risk enhancers. We further delineate similarities and differences in epigenetic landscape between stem cell-derived macrophages and primary cells and characterize the context-specific enhancer activities for key innate immune response genes KLF4, SLAMF1 and IL2RA. CONCLUSIONS: Our study demonstrates the importance of context-specific macrophage enhancers in gene regulation and utility for interpreting disease associations, providing a roadmap to link genetic variants with molecular and cellular functions.</p>',
			'date' => '2022-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35751107',
			'doi' => '10.1186/s13059-022-02702-1',
			'modified' => '2022-08-11 14:07:03',
			'created' => '2022-08-11 12:14:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 32 => array(
			'id' => '4221',
			'name' => 'Epigenetic Mechanisms Mediating Cell State Transitions in Chondrocytes',
			'authors' => 'Wuelling M. et al.',
			'description' => '<p><span>Epigenetic modifications play critical roles in regulating cell lineage differentiation, but the epigenetic mechanisms guiding specific differentiation steps within a cell lineage have rarely been investigated. To decipher such mechanisms, we used the defined transition from proliferating (PC) into hypertrophic chondrocytes (HC) during endochondral ossification as a model. We established a map of activating and repressive histone modifications for each cell type. ChromHMM state transition analysis and Pareto-based integration of differential levels of mRNA and epigenetic marks revealed that differentiation-associated gene repression is initiated by the addition of H3K27me3 to promoters still carrying substantial levels of activating marks. Moreover, the integrative analysis identified genes specifically expressed in cells undergoing the transition into hypertrophy. Investigation of enhancer profiles detected surprising differences in enhancer number, location, and transcription factor binding sites between the two closely related cell types. Furthermore, cell type-specific upregulation of gene expression was associated with increased numbers of H3K27ac peaks. Pathway analysis identified PC-specific enhancers associated with chondrogenic genes, whereas HC-specific enhancers mainly control metabolic pathways linking epigenetic signature to biological functions. Since HC-specific enhancers show a higher conservation in postnatal tissues, the switch to metabolic pathways seems to be a hallmark of differentiated tissues. Surprisingly, the analysis of H3K27ac levels at super-enhancers revealed a rapid adaption of H3K27ac occupancy to changes in gene expression, supporting the importance of enhancer modulation for acute alterations in gene expression. &copy; 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).</span></p>',
			'date' => '2022-05-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/33534175/',
			'doi' => '10.1002/jbmr.4263',
			'modified' => '2022-04-25 11:46:32',
			'created' => '2022-04-21 12:00:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 33 => array(
			'id' => '4446',
			'name' => 'Variation in PU.1 binding and chromatin looping at neutrophil enhancersinfluences autoimmune disease susceptibility',
			'authors' => 'Watt  S. et al. ',
			'description' => '<p>Neutrophils play fundamental roles in innate inflammatory response, shape adaptive immunity1, and have been identified as a potentially causal cell type underpinning genetic associations with immune system traits and diseases2,3 The majority of these variants are non-coding and the underlying mechanisms are not fully understood. Here, we profiled the binding of one of the principal myeloid transcriptional regulators, PU.1, in primary neutrophils across nearly a hundred volunteers, and elucidate the coordinated genetic effects of PU.1 binding variation, local chromatin state, promoter-enhancer interactions and gene expression. We show that PU.1 binding and the associated chain of molecular changes underlie genetically-driven differences in cell count and autoimmune disease susceptibility. Our results advance interpretation for genetic loci associated with neutrophil biology and immune disease.</p>',
			'date' => '2022-05-01',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/620260v1.abstract',
			'doi' => '10.1101/620260',
			'modified' => '2022-10-14 16:39:03',
			'created' => '2022-09-28 09:53:13',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 34 => array(
			'id' => '4402',
			'name' => 'The CpG Island-Binding Protein SAMD1 Contributes to anUnfavorable Gene Signature in HepG2 Hepatocellular CarcinomaCells.',
			'authors' => 'Simon  C. et al.',
			'description' => '<p>The unmethylated CpG island-binding protein SAMD1 is upregulated in many human cancer types, but its cancer-related role has not yet been investigated. Here, we used the hepatocellular carcinoma cell line HepG2 as a cancer model and investigated the cellular and transcriptional roles of SAMD1 using ChIP-Seq and RNA-Seq. SAMD1 targets several thousand gene promoters, where it acts predominantly as a transcriptional repressor. HepG2 cells with SAMD1 deletion showed slightly reduced proliferation, but strongly impaired clonogenicity. This phenotype was accompanied by the decreased expression of pro-proliferative genes, including MYC target genes. Consistently, we observed a decrease in the active H3K4me2 histone mark at most promoters, irrespective of SAMD1 binding. Conversely, we noticed an increase in interferon response pathways and a gain of H3K4me2 at a subset of enhancers that were enriched for IFN-stimulated response elements (ISREs). We identified key transcription factor genes, such as , , and , that were directly repressed by SAMD1. Moreover, SAMD1 deletion also led to the derepression of the PI3K-inhibitor , contributing to diminished mTOR signaling and ribosome biogenesis pathways. Our work suggests that SAMD1 is involved in establishing a pro-proliferative setting in hepatocellular carcinoma cells. Inhibiting SAMD1's function in liver cancer cells may therefore lead to a more favorable gene signature.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35453756',
			'doi' => '10.3390/biology11040557',
			'modified' => '2022-08-11 14:45:43',
			'created' => '2022-08-11 12:14:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 35 => array(
			'id' => '4524',
			'name' => 'Local euchromatin enrichment in lamina-associated domains anticipatestheir repositioning in the adipogenic lineage.',
			'authors' => 'Madsen-Østerbye  J. et al.',
			'description' => '<p>BACKGROUND: Interactions of chromatin with the nuclear lamina via lamina-associated domains (LADs) confer structural stability to the genome. The dynamics of positioning of LADs during differentiation, and how LADs impinge on developmental gene expression, remains, however, elusive. RESULTS: We examined changes in the association of lamin B1 with the genome in the first 72 h of differentiation of adipose stem cells into adipocytes. We demonstrate a repositioning of entire stand-alone LADs and of LAD edges as a prominent nuclear structural feature of early adipogenesis. Whereas adipogenic genes are released from LADs, LADs sequester downregulated or repressed genes irrelevant for the adipose lineage. However, LAD repositioning only partly concurs with gene expression changes. Differentially expressed genes in LADs, including LADs conserved throughout differentiation, reside in local euchromatic and lamin-depleted sub-domains. In these sub-domains, pre-differentiation histone modification profiles correlate with the LAD versus inter-LAD outcome of these genes during adipogenic commitment. Lastly, we link differentially expressed genes in LADs to short-range enhancers which overall co-partition with these genes in LADs versus inter-LADs during differentiation. CONCLUSIONS: We conclude that LADs are predictable structural features of adipose nuclear architecture that restrain non-adipogenic genes in a repressive environment.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35410387',
			'doi' => '10.1186/s13059-022-02662-6',
			'modified' => '2022-11-24 09:08:01',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 36 => array(
			'id' => '4528',
			'name' => 'ZWC complex-mediated SPT5 phosphorylation suppresses divergentantisense RNA transcription at active gene promoters.',
			'authors' => 'Park  K. et al.',
			'description' => '<p>The human genome encodes large numbers of non-coding RNAs, including divergent antisense transcripts at transcription start sites (TSSs). However, molecular mechanisms by which divergent antisense transcription is regulated have not been detailed. Here, we report a novel ZWC complex composed of ZC3H4, WDR82&nbsp;and CK2 that suppresses divergent antisense transcription. The ZWC complex preferentially localizes at TSSs of active genes through direct interactions of ZC3H4 and WDR82 subunits with the S5p RNAPII C-terminal domain. ZC3H4 depletion leads to increased divergent antisense transcription, especially at genes that naturally produce divergent antisense transcripts. We further demonstrate that the ZWC complex phosphorylates the previously uncharacterized N-terminal acidic domain of SPT5, a subunit of the transcription-elongation factor DSIF, and that this phosphorylation is responsible for suppressing divergent antisense transcription. Our study provides evidence that the newly identified ZWC-DSIF axis regulates the direction of transcription during the transition from early to productive elongation.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35325203',
			'doi' => '10.1093/nar/gkac193',
			'modified' => '2022-11-24 09:24:05',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 37 => array(
			'id' => '4857',
			'name' => 'Broad domains of histone marks in the highly compact  macronucleargenome.',
			'authors' => 'Drews  F. et al.',
			'description' => '<p>The unicellular ciliate contains a large vegetative macronucleus with several unusual characteristics, including an extremely high coding density and high polyploidy. As macronculear chromatin is devoid of heterochromatin, our study characterizes the functional epigenomic organization necessary for gene regulation and proper Pol II activity. Histone marks (H3K4me3, H3K9ac, H3K27me3) reveal no narrow peaks but broad domains along gene bodies, whereas intergenic regions are devoid of nucleosomes. Our data implicate H3K4me3 levels inside ORFs to be the main factor associated with gene expression, and H3K27me3 appears in association with H3K4me3 in plastic genes. Silent and lowly expressed genes show low nucleosome occupancy, suggesting that gene inactivation does not involve increased nucleosome occupancy and chromatin condensation. Because of a high occupancy of Pol II along highly expressed ORFs, transcriptional elongation appears to be quite different from that of other species. This is supported by missing heptameric repeats in the C-terminal domain of Pol II and a divergent elongation system. Our data imply that unoccupied DNA is the default state, whereas gene activation requires nucleosome recruitment together with broad domains of H3K4me3. In summary, gene activation and silencing in run counter to the current understanding of chromatin biology.</p>',
			'date' => '2022-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35264449',
			'doi' => '10.1101/gr.276126.121',
			'modified' => '2023-08-01 14:45:37',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 38 => array(
			'id' => '4367',
			'name' => 'Cell-type specific transcriptional networks in root xylem adjacent celllayers',
			'authors' => 'Asensi Fabado  Maria Amparo et al.',
			'description' => '<p>Transport of water, ions and signals from roots to leaves via the xylem vessels is essential for plant life and needs to be tightly regulated. The final composition of the transpiration stream before passage into the shoots is controlled by the xylem-adjacent cell layers, namely xylem parenchyma and pericycle, in the upper part of the root. To unravel regulatory networks in this strategically important location, we generated Arabidopsis lines expressing a nuclear tag under the control of the HKT1 promoter. HKT1 retrieves sodium from the xylem to prevent toxic levels in the shoot, and this function depends on its specific expression in upper root xylem-adjacent tissues. Based on FACS RNA-sequencing and INTACT ChIP-sequencing, we identified the gene repertoire that is preferentially expressed in the tagged cell types and discovered transcription factors experiencing cell-type specific loss of H3K27me3 demethylation. For one of these, ZAT6, we show that H3K27me3-demethylase REF6 is required for de-repression. Analysis of zat6 mutants revealed that ZAT6 activates a suite of cell-type specific downstream genes and restricts Na+ accumulation in the shoots. The combined Files open novel opportunities for &lsquo;bottom-up&rsquo; causal dissection of cell-type specific regulatory networks that control root-to-shoot communication under environmental challenge.</p>',
			'date' => '2022-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2022.02.04.479129',
			'doi' => '10.1101/2022.02.04.479129',
			'modified' => '2022-08-04 16:17:32',
			'created' => '2022-08-04 14:55:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 39 => array(
			'id' => '4214',
			'name' => 'Comprehensive characterization of the epigenetic landscape in Multiple Myeloma',
			'authors' => 'Elina Alaterre et al.',
			'description' => '<p>Background: Human multiple myeloma (MM) cell lines (HMCLs) have been widely used to understand the<br />molecular processes that drive MM biology. Epigenetic modifications are involved in MM development,<br />progression, and drug resistance. A comprehensive characterization of the epigenetic landscape of MM would<br />advance our understanding of MM pathophysiology and may attempt to identify new therapeutic targets.<br />Methods: We performed chromatin immunoprecipitation sequencing to analyze histone mark changes<br />(H3K4me1, H3K4me3, H3K9me3, H3K27ac, H3K27me3 and H3K36me3) on 16 HMCLs.<br />Results: Differential analysis of histone modification profiles highlighted links between histone modifications<br />and cytogenetic abnormalities or recurrent mutations. Using histone modifications associated to enhancer<br />regions, we identified super-enhancers (SE) associated with genes involved in MM biology. We also identified<br />promoters of genes enriched in H3K9me3 and H3K27me3 repressive marks associated to potential tumor<br />suppressor functions. The prognostic value of genes associated with repressive domains and SE was used to<br />build two distinct scores identifying high-risk MM patients in two independent cohorts (CoMMpass cohort; n =<br />674 and Montpellier cohort; n = 69). Finally, we explored H3K4me3 marks comparing drug-resistant and<br />-sensitive HMCLs to identify regions involved in drug resistance. From these data, we developed epigenetic<br />biomarkers based on the H3K4me3 modification predicting MM cell response to lenalidomide and histone<br />deacetylase inhibitors (HDACi).<br />Conclusions: The epigenetic landscape of MM cells represents a unique resource for future biological studies.<br />Furthermore, risk-scores based on SE and repressive regions together with epigenetic biomarkers of drug<br />response could represent new tools for precision medicine in MM.</p>',
			'date' => '2022-01-16',
			'pmid' => 'https://www.thno.org/v12p1715',
			'doi' => '10.7150/thno.54453',
			'modified' => '2022-01-27 13:17:28',
			'created' => '2022-01-27 13:14:17',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 40 => array(
			'id' => '4225',
			'name' => 'Comprehensive characterization of the epigenetic landscape in Multiple
Myeloma',
			'authors' => 'Alaterre, Elina and Ovejero, Sara and Herviou, Laurie and de
Boussac, Hugues and Papadopoulos, Giorgio and Kulis, Marta and
Boireau, Stéphanie and Robert, Nicolas and Requirand, Guilhem
and Bruyer, Angélique and Cartron, Guillaume and Vincent,
Laure and M',
			'description' => 'Background: Human multiple myeloma (MM) cell lines (HMCLs) have
been widely used to understand the molecular processes that drive MM
biology. Epigenetic modifications are involved in MM development,
progression, and drug resistance. A comprehensive characterization of the
epigenetic landscape of MM would advance our understanding of MM
pathophysiology and may attempt to identify new therapeutic
targets.

Methods: We performed chromatin immunoprecipitation
sequencing to analyze histone mark changes (H3K4me1, H3K4me3,
H3K9me3, H3K27ac, H3K27me3 and H3K36me3) on 16
HMCLs.

Results: Differential analysis of histone modification
profiles highlighted links between histone modifications and cytogenetic
abnormalities or recurrent mutations. Using histone modifications
associated to enhancer regions, we identified super-enhancers (SE)
associated with genes involved in MM biology. We also identified
promoters of genes enriched in H3K9me3 and H3K27me3 repressive
marks associated to potential tumor suppressor functions. The prognostic
value of genes associated with repressive domains and SE was used to
build two distinct scores identifying high-risk MM patients in two
independent cohorts (CoMMpass cohort; n = 674 and Montpellier cohort;
n = 69). Finally, we explored H3K4me3 marks comparing drug-resistant
and -sensitive HMCLs to identify regions involved in drug resistance.
From these data, we developed epigenetic biomarkers based on the
H3K4me3 modification predicting MM cell response to lenalidomide and
histone deacetylase inhibitors (HDACi).

Conclusions: The epigenetic
landscape of MM cells represents a unique resource for future biological
studies. Furthermore, risk-scores based on SE and repressive regions
together with epigenetic biomarkers of drug response could represent new
tools for precision medicine in MM.',
			'date' => '2022-01-01',
			'pmid' => 'https://www.thno.org/v12p1715.htm',
			'doi' => '10.7150/thno.54453',
			'modified' => '2022-05-19 10:41:50',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 41 => array(
			'id' => '4326',
			'name' => 'Loss of KMT2C reprograms the epigenomic landscape in hPSCsresulting in NODAL overexpression and a failure of hemogenic endotheliumspecification.',
			'authors' => 'Maurya Shailendra et al.',
			'description' => '<p>Germline or somatic variation in the family of KMT2 lysine methyltransferases have been associated with a variety of congenital disorders and cancers. Notably, -fusions are prevalent in 70\% of infant leukaemias but fail to phenocopy short latency leukaemogenesis in mammalian models, suggesting additional factors are necessary for transformation. Given the lack of additional somatic mutation, the role of epigenetic regulation in cell specification, and our prior results of germline variation in infant leukaemia patients, we hypothesized that germline dysfunction of KMT2C altered haematopoietic specification. In isogenic KO hPSCs, we found genome-wide differences in histone modifications at active and poised enhancers, leading to gene expression profiles akin to mesendoderm rather than mesoderm highlighted by a significant increase in NODAL expression and WNT inhibition, ultimately resulting in a lack of hemogenic endothelium specification. These unbiased multi-omic results provide new evidence for germline mechanisms increasing risk of early leukaemogenesis.</p>',
			'date' => '2022-01-01',
			'pmid' => 'https://doi.org/10.1080%2F15592294.2021.1954780',
			'doi' => '10.1080/15592294.2021.1954780',
			'modified' => '2022-06-20 09:27:45',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 42 => array(
			'id' => '4238',
			'name' => 'The long noncoding RNA H19 regulates tumor plasticity inneuroendocrine prostate cancer',
			'authors' => 'Singh N. et al.',
			'description' => '<p>Neuroendocrine (NE) prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (PCa) arising either de novo or from transdifferentiated prostate adenocarcinoma following androgen deprivation therapy (ADT). Extensive computational analysis has identified a high degree of association between the long noncoding RNA (lncRNA) H19 and NEPC, with the longest isoform highly expressed in NEPC. H19 regulates PCa lineage plasticity by driving a bidirectional cell identity of NE phenotype (H19 overexpression) or luminal phenotype (H19 knockdown). It contributes to treatment resistance, with the knockdown of H19 re-sensitizing PCa to ADT. It is also essential for the proliferation and invasion of NEPC. H19 levels are negatively regulated by androgen signaling via androgen receptor (AR). When androgen is absent SOX2 levels increase, driving H19 transcription and facilitating transdifferentiation. H19 facilitates the PRC2 complex in regulating methylation changes at H3K27me3/H3K4me3 histone sites of AR-driven and NEPC-related genes. Additionally, this lncRNA induces alterations in genome-wide DNA methylation on CpG sites, further regulating genes associated with the NEPC phenotype. Our clinical data identify H19 as a candidate diagnostic marker and predictive marker of NEPC with elevated H19 levels associated with an increased probability of biochemical recurrence and metastatic disease in patients receiving ADT. Here we report H19 as an early upstream regulator of cell fate, plasticity, and treatment resistance in NEPC that can reverse/transform cells to a treatable form of PCa once therapeutically deactivated.</p>',
			'date' => '2021-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34934057',
			'doi' => '10.1038/s41467-021-26901-9',
			'modified' => '2022-05-19 17:06:50',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 43 => array(
			'id' => '4239',
			'name' => 'Epromoters function as a hub to recruit key transcription factorsrequired for the inflammatory response',
			'authors' => 'Santiago-Algarra D. et al. ',
			'description' => '<p>Gene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. Our previous results demonstrated that a subset of gene promoters, termed Epromoters, work as bona fide enhancers and regulate distal gene expression. Here, we hypothesized that Epromoters play a key role in the coordination of rapid gene induction during the inflammatory response. Using a high-throughput reporter assay we explored the function of Epromoters in response to type I interferon. We find that clusters of IFNa-induced genes are frequently associated with Epromoters and that these regulatory elements preferentially recruit the STAT1/2 and IRF transcription factors and distally regulate the activation of interferon-response genes. Consistently, we identified and validated the involvement of Epromoter-containing clusters in the regulation of LPS-stimulated macrophages. Our findings suggest that Epromoters function as a local hub recruiting the key TFs required for coordinated regulation of gene clusters during the inflammatory response.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34795220',
			'doi' => '10.1038/s41467-021-26861-0',
			'modified' => '2022-05-19 17:10:30',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 44 => array(
			'id' => '4251',
			'name' => 'Comparing the epigenetic landscape in myonuclei purified with a PCM1antibody from a fast/glycolytic and a slow/oxidative muscle.',
			'authors' => 'Bengtsen Mads et al.',
			'description' => '<p>Muscle cells have different phenotypes adapted to different usage, and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of the epigenetic landscape by ChIP-Seq in two muscle extremes, the fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where up to 60\% of the nuclei can be of a different origin. Since cellular homogeneity is critical in epigenome-wide association studies we developed a new method for purifying skeletal muscle nuclei from whole tissue, based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labelling and a magnetic-assisted sorting approach, we were able to sort out myonuclei with 95\% purity in muscles from mice, rats and humans. The sorting eliminated influence from the other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the differences in the functional properties of the two muscles, and revealed distinct regulatory programs involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles were also regulated by different sets of transcription factors; e.g. in soleus, binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SIX1 binding sites were found to be overrepresented. In addition, more novel transcription factors for muscle regulation such as members of the MAF family, ZFX and ZBTB14 were identified.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/34752468/',
			'doi' => '10.1371/journal.pgen.1009907',
			'modified' => '2022-05-20 09:39:35',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 45 => array(
			'id' => '4241',
			'name' => 'Rhesus macaques self-curing from a schistosome infection can displaycomplete immunity to challenge',
			'authors' => 'Amaral MS et al.  ',
			'description' => '<p>The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict \&gt;200 million people worldwide. By monitoring bloodstream levels of parasite-gut-derived antigen, we show that from week 10 onwards an established infection with Schistosoma mansoni is cleared in an exponential manner, eliciting resistance to reinfection. Secondary challenge at week 42 demonstrates that protection is strong in all animals and complete in some. Antibody profiles suggest that antigens mediating protection are the released products of developing schistosomula. In culture they are killed by addition of rhesus plasma, collected from week 8 post-infection onwards, and even more efficiently with post-challenge plasma. Furthermore, cultured schistosomula lose chromatin activating marks at the transcription start site of genes related to worm development and show decreased expression of genes related to lysosomes and lytic vacuoles involved with autophagy. Overall, our results indicate that enhanced antibody responses against the challenge migrating larvae mediate the naturally acquired protective immunity and will inform the route to an effective vaccine.</p>',
			'date' => '2021-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34702841',
			'doi' => '10.1038/s41467-021-26497-0',
			'modified' => '2022-05-19 17:15:53',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 46 => array(
			'id' => '4268',
			'name' => 'p300 suppresses the transition of myelodysplastic syndromes to acutemyeloid leukemia',
			'authors' => 'Man Na et al.',
			'description' => '<p>Myelodysplastic syndromes (MDS) are hematopoietic stem and progenitor cell (HSPC) malignancies characterized by ineffective hematopoiesis and an increased risk of leukemia transformation. Epigenetic regulators are recurrently mutated in MDS, directly implicating epigenetic dysregulation in MDS pathogenesis. Here, we identified a tumor suppressor role of the acetyltransferase p300 in clinically relevant MDS models driven by mutations in the epigenetic regulators TET2, ASXL1, and SRSF2. The loss of p300 enhanced the proliferation and self-renewal capacity of Tet2-deficient HSPCs, resulting in an increased HSPC pool and leukemogenicity in primary and transplantation mouse models. Mechanistically, the loss of p300 in Tet2-deficient HSPCs altered enhancer accessibility and the expression of genes associated with differentiation, proliferation, and leukemia development. Particularly, p300 loss led to an increased expression of Myb, and the depletion of Myb attenuated the proliferation of HSPCs and improved the survival of leukemia-bearing mice. Additionally, we show that chemical inhibition of p300 acetyltransferase activity phenocopied Ep300 deletion in Tet2-deficient HSPCs, whereas activation of p300 activity with a small molecule impaired the self-renewal and leukemogenicity of Tet2-deficient cells. This suggests a potential therapeutic application of p300 activators in the treatment of MDS with TET2 inactivating mutations.</p>',
			'date' => '2021-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34622806',
			'doi' => '10.1172/jci.insight.138478',
			'modified' => '2022-05-23 09:44:16',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 47 => array(
			'id' => '4231',
			'name' => 'Differential contribution to gene expression prediction of histonemodifications at enhancers or promoters.',
			'authors' => 'González-Ramírez M. et al.',
			'description' => '<p>The ChIP-seq signal of histone modifications at promoters is a good predictor of gene expression in different cellular contexts, but whether this is also true at enhancers is not clear. To address this issue, we develop quantitative models to characterize the relationship of gene expression with histone modifications at enhancers or promoters. We use embryonic stem cells (ESCs), which contain a full spectrum of active and repressed (poised) enhancers, to train predictive models. As many poised enhancers in ESCs switch towards an active state during differentiation, predictive models can also be trained on poised enhancers throughout differentiation and in development. Remarkably, we determine that histone modifications at enhancers, as well as promoters, are predictive of gene expression in ESCs and throughout differentiation and development. Importantly, we demonstrate that their contribution to the predictive models varies depending on their location in enhancers or promoters. Moreover, we use a local regression (LOESS) to normalize sequencing data from different sources, which allows us to apply predictive models trained in a specific cellular context to a different one. We conclude that the relationship between gene expression and histone modifications at enhancers is universal and different from promoters. Our study provides new insight into how histone modifications relate to gene expression based on their location in enhancers or promoters.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/34473698/',
			'doi' => '10.1371/journal.pcbi.1009368',
			'modified' => '2022-05-19 16:50:59',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 48 => array(
			'id' => '4294',
			'name' => 'DOT1L O-GlcNAcylation promotes its protein stability andMLL-fusion leukemia cell proliferation.',
			'authors' => 'Song Tanjing et al.',
			'description' => '<p>Histone lysine methylation functions at the interface of the extracellular environment and intracellular gene expression. DOT1L is a versatile histone H3K79 methyltransferase with a prominent role in MLL-fusion leukemia, yet little is known about how DOT1L responds to extracellular stimuli. Here, we report that DOT1L protein stability is regulated by the extracellular glucose level through the hexosamine biosynthetic pathway (HBP). Mechanistically, DOT1L is O-GlcNAcylated at evolutionarily conserved S1511 in its C terminus. We identify UBE3C as a DOT1L E3 ubiquitin ligase promoting DOT1L degradation whose interaction with DOT1L is susceptible to O-GlcNAcylation. Consequently, HBP enhances H3K79 methylation and expression of critical DOT1L target genes such as HOXA9/MEIS1, promoting cell proliferation in MLL-fusion leukemia. Inhibiting HBP or O-GlcNAc transferase (OGT) increases cellular sensitivity to DOT1L inhibitor. Overall, our work uncovers O-GlcNAcylation and UBE3C as critical determinants of DOT1L protein abundance, revealing a mechanism by which glucose metabolism affects malignancy progression through histone methylation.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34551297',
			'doi' => '10.1016/j.celrep.2021.109739',
			'modified' => '2022-05-24 09:20:37',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 49 => array(
			'id' => '4297',
			'name' => 'INTS11 regulates hematopoiesis by promoting PRC2 function.',
			'authors' => 'Zhang Peng et al.',
			'description' => '<p>INTS11, the catalytic subunit of the Integrator (INT) complex, is crucial for the biogenesis of small nuclear RNAs and enhancer RNAs. However, the role of INTS11 in hematopoietic stem and progenitor cell (HSPC) biology is unknown. Here, we report that INTS11 is required for normal hematopoiesis and hematopoietic-specific genetic deletion of leads to cell cycle arrest and impairment of fetal and adult HSPCs. We identified a novel INTS11-interacting protein complex, Polycomb repressive complex 2 (PRC2), that maintains HSPC functions. Loss of INTS11 destabilizes the PRC2 complex, decreases the level of histone H3 lysine 27 trimethylation (H3K27me3), and derepresses PRC2 target genes. Reexpression of INTS11 or PRC2 proteins in -deficient HSPCs restores the levels of PRC2 and H3K27me3 as well as HSPC functions. Collectively, our data demonstrate that INTS11 is an essential regulator of HSPC homeostasis through the INTS11-PRC2 axis.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34516911',
			'doi' => '10.1126/sciadv.abh1684',
			'modified' => '2022-05-30 09:31:00',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 50 => array(
			'id' => '4282',
			'name' => 'Enhanced targeted DNA methylation of the CMV and endogenous promoterswith dCas9-DNMT3A3L entails distinct subsequent histonemodification changes in CHO cells.',
			'authors' => 'Marx Nicolas et al. ',
			'description' => '<p>With the emergence of new CRISPR/dCas9 tools that enable site specific modulation of DNA methylation and histone modifications, more detailed investigations of the contribution of epigenetic regulation to the precise phenotype of cells in culture, including recombinant production subclones, is now possible. These also allow a wide range of applications in metabolic engineering once the impact of such epigenetic modifications on the chromatin state is available. In this study, enhanced DNA methylation tools were targeted to a recombinant viral promoter (CMV), an endogenous promoter that is silenced in its native state in CHO cells, but had been reactivated previously (&beta;-galactoside &alpha;-2,6-sialyltransferase 1) and an active endogenous promoter (&alpha;-1,6-fucosyltransferase), respectively. Comparative ChIP-analysis of histone modifications revealed a general loss of active promoter histone marks and the acquisition of distinct repressive heterochromatin marks after targeted methylation. On the other hand, targeted demethylation resulted in autologous acquisition of active promoter histone marks and loss of repressive heterochromatin marks. These data suggest that DNA methylation directs the removal or deposition of specific histone marks associated with either active, poised or silenced chromatin. Moreover, we show that de novo methylation of the CMV promoter results in reduced transgene expression in CHO cells. Although targeted DNA methylation is not efficient, the transgene is repressed, thus offering an explanation for seemingly conflicting reports about the source of CMV promoter instability in CHO cells. Importantly, modulation of epigenetic marks enables to nudge the cell into a specific gene expression pattern or phenotype, which is stabilized in the cell by autologous addition of further epigenetic marks. Such engineering strategies have the added advantage of being reversible and potentially tunable to not only turn on or off a targeted gene, but also to achieve the setting of a desirable expression level.</p>',
			'date' => '2021-07-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.ymben.2021.04.014',
			'doi' => '10.1016/j.ymben.2021.04.014',
			'modified' => '2022-05-23 10:09:24',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 51 => array(
			'id' => '4118',
			'name' => 'ChIP-seq protocol for sperm cells and embryos to assess environmentalimpacts and epigenetic inheritance',
			'authors' => 'Lismer, Ariane and Lambrot, Romain and Lafleur, Christine and Dumeaux,Vanessa and Kimmins, Sarah',
			'description' => '<p>In the field of epigenetic inheritance, delineating molecular mechanisms implicated in the transfer of paternal environmental conditions to descendants has been elusive. This protocol details how to track sperm chromatin intergenerationally. We describe mouse model design to probe chromatin states in single mouse sperm and techniques to assess pre-implantation embryo chromatin and gene expression. We place emphasis on how to obtain high-quality and quantifiable data sets in sperm and embryos, as well as highlight the limitations of working with low input.</p>',
			'date' => '2021-06-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.xpro.2021.100602',
			'doi' => '10.1016/j.xpro.2021.100602',
			'modified' => '2021-12-06 17:59:57',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 52 => array(
			'id' => '4318',
			'name' => 'E2F6 initiates stable epigenetic silencing of germline genes duringembryonic development',
			'authors' => 'Dahlet T. et al.',
			'description' => '<p>In mouse development, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes; however, the molecular mechanisms of this specificity remain unclear. Here, we demonstrate that the transcription factor E2F6, a member of the polycomb repressive complex 1.6 (PRC1.6), is critical to target and initiate epigenetic silencing at germline genes in early embryogenesis. Genome-wide, E2F6 binds preferentially to CpG islands in embryonic cells. E2F6 cooperates with MGA to silence a subgroup of germline genes in mouse embryonic stem cells and in embryos, a function that critically depends on the E2F6 marked box domain. Inactivation of E2f6 leads to a failure to deposit CpG island DNA methylation at these genes during implantation. Furthermore, E2F6 is required to initiate epigenetic silencing in early embryonic cells but becomes dispensable for the maintenance in differentiated cells. Our findings elucidate the mechanisms of epigenetic targeting of germline genes and provide a paradigm for how transient repression signals by DNA-binding factors in early embryonic cells are translated into long-term epigenetic silencing during mouse development.</p>',
			'date' => '2021-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34117224',
			'doi' => '10.1038/s41467-021-23596-w',
			'modified' => '2022-08-02 16:53:03',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 53 => array(
			'id' => '4349',
			'name' => 'Lasp1 regulates adherens junction dynamics and fibroblast transformationin destructive arthritis',
			'authors' => 'Beckmann D. et al.',
			'description' => '<p>The LIM and SH3 domain protein 1 (Lasp1) was originally cloned from metastatic breast cancer and characterised as an adaptor molecule associated with tumourigenesis and cancer cell invasion. However, the regulation of Lasp1 and its function in the aggressive transformation of cells is unclear. Here we use integrative epigenomic profiling of invasive fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and from mouse models of the disease, to identify Lasp1 as an epigenomically co-modified region in chronic inflammatory arthritis and a functionally important binding partner of the Cadherin-11/&beta;-Catenin complex in zipper-like cell-to-cell contacts. In vitro, loss or blocking of Lasp1 alters pathological tissue formation, migratory behaviour and platelet-derived growth factor response of arthritic FLS. In arthritic human TNF transgenic mice, deletion of Lasp1 reduces arthritic joint destruction. Therefore, we show a function of Lasp1 in cellular junction formation and inflammatory tissue remodelling and identify Lasp1 as a potential target for treating inflammatory joint disorders associated with aggressive cellular transformation.</p>',
			'date' => '2021-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34131132',
			'doi' => '10.1038/s41467-021-23706-8',
			'modified' => '2022-08-03 17:02:30',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 54 => array(
			'id' => '4143',
			'name' => 'Placental uptake and metabolism of 25(OH)Vitamin D determines itsactivity within the fetoplacental unit',
			'authors' => 'Ashley, B. et al.',
			'description' => '<p>Pregnancy 25-hydroxyvitamin D (25(OH)D) concentrations are associated with maternal and fetal health outcomes, but the underlying mechanisms have not been elucidated. Using physiological human placental perfusion approaches and intact villous explants we demonstrate a role for the placenta in regulating the relationships between maternal 25(OH)D concentrations and fetal physiology. Here, we demonstrate active placental uptake of 25(OH)D3 by endocytosis and placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the fetal and maternal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than solely the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer, including transcriptional activation and inflammatory responses. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta; with widespread effects on the placenta itself. These data show complex and synergistic interplay between vitamin D and the placenta, and inform possible interventions to optimise placental function to better support fetal growth and the maternal adaptations to pregnancy.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.03.01.431439',
			'doi' => '10.1101/2021.03.01.431439',
			'modified' => '2021-12-13 09:29:25',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 55 => array(
			'id' => '4160',
			'name' => 'Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.',
			'authors' => 'Pettinato, Anthony M. et al. ',
			'description' => '<p>Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization by unclear mechanisms. To study this process, we engineer a human cardiomyocyte model to track replication and polyploidization using fluorescently tagged cyclin B1 and cardiac troponin T. Using time-lapse imaging, in&nbsp;vitro cardiomyocyte replication patterns recapitulate the progressive mononuclear polyploidization and replicative arrest observed in&nbsp;vivo. Single-cell transcriptomics and chromatin state analyses reveal that polyploidization is preceded by sarcomere assembly, enhanced oxidative metabolism, a DNA damage response, and p53 activation. CRISPR knockout screening reveals p53 as a driver of cell-cycle arrest and polyploidization. Inhibiting sarcomere function, or scavenging ROS, inhibits cell-cycle arrest and polyploidization. Finally, we show that cardiomyocyte engraftment in infarcted rat hearts is enhanced 4-fold by the increased proliferation of troponin-knockout cardiomyocytes. Thus, the sarcomere inhibits cell division through a DNA damage response that can be targeted to improve cardiomyocyte replacement strategies.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33951429',
			'doi' => '10.1016/j.celrep.2021.109088',
			'modified' => '2021-12-16 10:58:59',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 56 => array(
			'id' => '4343',
			'name' => 'The SAM domain-containing protein 1 (SAMD1) acts as a repressivechromatin regulator at unmethylated CpG islands',
			'authors' => 'Stielow B. et al. ',
			'description' => '<p>CpG islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here, we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 has an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. The absence of SAMD1 impairs ES cell differentiation processes, leading to misregulation of key biological pathways. Together, our work establishes SAMD1 as a newly identified chromatin regulator acting at unmethylated CGIs.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33980486',
			'doi' => '10.1126/sciadv.abf2229',
			'modified' => '2022-08-03 16:34:24',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 57 => array(
			'id' => '4350',
			'name' => 'Simplification of culture conditions and feeder-free expansion of bovineembryonic stem cells',
			'authors' => 'Soto D. A. et al. ',
			'description' => '<p>Bovine embryonic stem cells (bESCs) extend the lifespan of the transient pluripotent bovine inner cell mass in vitro. After years of research, derivation of stable bESCs was only recently reported. Although successful, bESC culture relies on complex culture conditions that require a custom-made base medium and mouse embryonic fibroblasts (MEF) feeders, limiting the widespread use of bESCs. We report here simplified bESC culture conditions based on replacing custom base medium with a commercially available alternative and eliminating the need for MEF feeders by using a chemically-defined substrate. bESC lines were cultured and derived using a base medium consisting of N2B27 supplements and 1\% BSA (NBFR-bESCs). Newly derived bESC lines were easy to establish, simple to propagate and stable after long-term culture. These cells expressed pluripotency markers and actively proliferated for more than 35 passages while maintaining normal karyotype and the ability to differentiate into derivatives of all three germ lineages in embryoid bodies and teratomas. In addition, NBFR-bESCs grew for multiple passages in a feeder-free culture system based on vitronectin and Activin A medium supplementation while maintaining pluripotency. Simplified conditions will facilitate the use of bESCs for gene editing applications and pluripotency and lineage commitment studies.</p>',
			'date' => '2021-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34040070',
			'doi' => '10.1038/s41598-021-90422-0',
			'modified' => '2022-08-03 16:38:27',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 58 => array(
			'id' => '4161',
			'name' => 'The anti-inflammatory cytokine interleukin-37 is an inhibitor of trainedimmunity.',
			'authors' => 'Cavalli, Giulio and Tengesdal, Isak W and Gresnigt, Mark and Nemkov, Travisand Arts, Rob J W and Domínguez-Andrés, Jorge and Molteni, Raffaella andStefanoni, Davide and Cantoni, Eleonora and Cassina, Laura and Giugliano,Silvia and Schraa, Kiki and Mill',
			'description' => '<p>Trained immunity (TI) is a de facto innate immune memory program induced in monocytes/macrophages by exposure to pathogens or vaccines, which evolved as protection against infections. TI is characterized by immunometabolic changes and histone post-translational modifications, which enhance production of pro-inflammatory cytokines. As aberrant activation of TI is implicated in inflammatory diseases, tight regulation is critical; however, the mechanisms responsible for this modulation remain elusive. Interleukin-37 (IL-37) is an anti-inflammatory cytokine that curbs inflammation and modulates metabolic pathways. In this study, we show that administration of recombinant IL-37 abrogates the protective effects of TI in&nbsp;vivo, as revealed by reduced host pro-inflammatory responses and survival to disseminated candidiasis. Mechanistically, IL-37 reverses the immunometabolic changes and histone post-translational modifications characteristic of TI in monocytes, thus suppressing cytokine production in response to infection. IL-37 thereby emerges as an inhibitor of TI and as a potential therapeutic target in immune-mediated pathologies.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33826894',
			'doi' => '10.1016/j.celrep.2021.108955',
			'modified' => '2021-12-21 15:16:27',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 59 => array(
			'id' => '4178',
			'name' => 'Comparative analysis of histone H3K4me3 modifications between blastocystsand somatic tissues in cattle.',
			'authors' => 'Ishibashi, Mao et al.',
			'description' => '<p>Epigenetic changes induced in the early developmental stages by the surrounding environment can have not only short-term but also long-term consequences throughout life. This concept constitutes the "Developmental Origins of Health and Disease" (DOHaD) hypothesis and encompasses the possibility of controlling livestock health and diseases by epigenetic regulation during early development. As a preliminary step for examining changes of epigenetic modifications in early embryos and their long-lasting effects in fully differentiated somatic tissues, we aimed to obtain high-throughput genome-wide histone H3 lysine 4 trimethylation (H3K4me3) profiles of bovine blastocysts and to compare these data with those from adult somatic tissues in order to extract common and typical features between these tissues in terms of H3K4me3 modifications. Bovine blastocysts were produced in vitro and subjected to chromatin immunoprecipitation-sequencing analysis of H3K4me3. Comparative analysis of the blastocyst-derived H3K4me3 profile with publicly available data from adult liver and muscle tissues revealed that the blastocyst profile could be used as a "sieve" to extract somatic tissue-specific modifications in genes closely related to tissue-specific functions. Furthermore, principal component analysis of the level of common modifications between blastocysts and somatic tissues in meat production-related and imprinted genes well characterized inter- and intra-tissue differences. The results of this study produced a referential genome-wide H3K4me3 profile of bovine blastocysts within the limits of their in vitro source and revealed its common and typical features in relation to the profiles of adult tissues.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33859293',
			'doi' => '10.1038/s41598-021-87683-0',
			'modified' => '2021-12-21 16:40:41',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 60 => array(
			'id' => '4181',
			'name' => 'Genetic perturbation of PU.1 binding and chromatin looping at neutrophilenhancers associates with autoimmune disease.',
			'authors' => 'Watt, Stephen et al.',
			'description' => '<p>Neutrophils play fundamental roles in innate immune response, shape adaptive immunity, and are a potentially causal cell type underpinning genetic associations with immune system traits and diseases. Here, we profile the binding of myeloid master regulator PU.1 in primary neutrophils across nearly a hundred volunteers. We show that variants associated with differential PU.1 binding underlie genetically-driven differences in cell count and susceptibility to autoimmune and inflammatory diseases. We integrate these results with other multi-individual genomic readouts, revealing coordinated effects of PU.1 binding variants on the local chromatin state, enhancer-promoter contacts and downstream gene expression, and providing a functional interpretation for 27 genes underlying immune traits. Collectively, these results demonstrate the functional role of PU.1 and its target enhancers in neutrophil transcriptional control and immune disease susceptibility.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33863903',
			'doi' => '10.1038/s41467-021-22548-8',
			'modified' => '2021-12-21 16:50:30',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 61 => array(
			'id' => '4138',
			'name' => 'Loss of SETD1B results in the redistribution of genomic H3K4me3 in theoocyte',
			'authors' => 'Hanna, C. W. et al. ',
			'description' => '<p>Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransferases SETD1B and MLL2 are essential for oogenesis. We investigated changes in H3K4me3 in Setd1b conditional knockout (cKO) GV oocytes using ultra-low input ChIP-seq, in conjunction with DNA methylation and gene expression analysis. Setd1b cKO oocytes showed a redistribution of H3K4me3, with a marked loss at active gene promoters associated with downregulated gene expression. Remarkably, many regions gained H3K4me3 in Setd1b cKOs, in particular those that were DNA hypomethylated, transcriptionally inactive and CpGrich - hallmarks of MLL2 targets. Thus, loss of SETD1B appears to enable enhanced MLL2 activity. Our work reveals two distinct, complementary mechanisms of genomic targeting of H3K4me3 in oogenesis, with SETD1B linked to gene expression in the oogenic program and MLL2 to CpG content.</p>',
			'date' => '2021-03-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.03.11.434836',
			'doi' => '10.1101/2021.03.11.434836',
			'modified' => '2021-12-13 09:15:06',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 62 => array(
			'id' => '4162',
			'name' => 'Epigenomic tensor predicts disease subtypes and reveals constrained tumorevolution.',
			'authors' => 'Leistico, Jacob R et al.',
			'description' => '<p>Understanding the epigenomic evolution and specificity of disease subtypes from complex patient data remains a major biomedical problem. We here present DeCET (decomposition and classification of epigenomic tensors), an integrative computational approach for simultaneously analyzing hierarchical heterogeneous data, to identify robust epigenomic differences among tissue types, differentiation states, and disease subtypes. Applying DeCET to our own data from 21 uterine benign tumor (leiomyoma) patients identifies distinct epigenomic features discriminating normal myometrium and leiomyoma subtypes. Leiomyomas possess preponderant alterations in distal enhancers and long-range histone modifications confined to chromatin contact domains that constrain the evolution of pathological epigenomes. Moreover, we demonstrate the power and advantage of DeCET on multiple publicly available epigenomic datasets representing different cancers and cellular states. Epigenomic features extracted by DeCET can thus help improve our understanding of disease states, cellular development, and differentiation, thereby facilitating future therapeutic, diagnostic, and prognostic strategies.</p>',
			'date' => '2021-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33789109',
			'doi' => '10.1016/j.celrep.2021.108927',
			'modified' => '2021-12-21 15:19:13',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 63 => array(
			'id' => '4196',
			'name' => 'Functional annotations of three domestic animal genomes provide vitalresources for comparative and agricultural research.',
			'authors' => 'Kern C. et al.',
			'description' => '<p>Gene regulatory elements are central drivers of phenotypic variation and thus of critical importance towards understanding the genetics of complex traits. The Functional Annotation of Animal Genomes consortium was formed to collaboratively annotate the functional elements in animal genomes, starting with domesticated animals. Here we present an expansive collection of datasets from eight diverse tissues in three important agricultural species: chicken (Gallus gallus), pig (Sus scrofa), and cattle (Bos taurus). Comparative analysis of these datasets and those from the human and mouse Encyclopedia of DNA Elements projects reveal that a core set of regulatory elements are functionally conserved independent of divergence between species, and that tissue-specific transcription factor occupancy at regulatory elements and their predicted target genes are also conserved. These datasets represent a unique opportunity for the emerging field of comparative epigenomics, as well as the agricultural research community, including species that are globally important food resources.</p>',
			'date' => '2021-03-01',
			'pmid' => 'https://doi.org/10.1038%2Fs41467-021-22100-8',
			'doi' => '10.1038/s41467-021-22100-8',
			'modified' => '2022-01-06 14:30:41',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 64 => array(
			'id' => '4127',
			'name' => 'The histone modification H3K4me3 is altered at the  locus in Alzheimer'sdisease brain.',
			'authors' => 'Smith, Adam et al.',
			'description' => '<p>Several epigenome-wide association studies of DNA methylation have highlighted altered DNA methylation in the gene in Alzheimer's disease (AD) brain samples. However, no study has specifically examined histone modifications in the disease. We use chromatin immunoprecipitation-qPCR to quantify tri-methylation at histone 3 lysine 4 (H3K4me3) and 27 (H3K27me3) in the gene in entorhinal cortex from donors with high (n&nbsp;=&nbsp;59) or low (n&nbsp;=&nbsp;29) Alzheimer's disease&nbsp;pathology. We demonstrate decreased levels of H3K4me3, a marker of active gene transcription, with no change in H3K27me3, a marker of inactive genes. H3K4me3 is negatively correlated with DNA methylation in specific regions of the gene. Our study suggests that the gene shows altered epigenetic marks indicative of reduced gene activation in Alzheimer's disease.</p>',
			'date' => '2021-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33815817',
			'doi' => '10.2144/fsoa-2020-0161',
			'modified' => '2021-12-07 10:16:08',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 65 => array(
			'id' => '4146',
			'name' => 'The G2-phase enriched lncRNA SNHG26 is necessary for proper cell cycleprogression and proliferation',
			'authors' => 'Samdal, H. et al.',
			'description' => '<p>Long noncoding RNAs (lncRNAs) are involved in the regulation of cell cycle, although only a few have been functionally characterized. By combining RNA sequencing and ChIP sequencing of cell cycle synchronized HaCaT cells we have previously identified lncRNAs highly enriched for cell cycle functions. Based on a cyclic expression profile and an overall high correlation to histone 3 lysine 4 trimethylation (H3K4me3) and RNA polymerase II (Pol II) signals, the lncRNA SNHG26 was identified as a top candidate. In the present study we report that downregulation of SNHG26 affects mitochondrial stress, proliferation, cell cycle phase distribution, and gene expression in cis- and in trans, and that this effect is reversed by upregulation of SNHG26. We also find that the effect on cell cycle phase distribution is cell type specific and stable over time. Results indicate an oncogenic role of SNHG26, possibly by affecting cell cycle progression through the regulation of downstream MYC-responsive genes.</p>',
			'date' => '2021-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.02.22.432245',
			'doi' => '10.1101/2021.02.22.432245',
			'modified' => '2021-12-14 09:21:27',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 66 => array(
			'id' => '4151',
			'name' => 'The epigenetic landscape in purified myonuclei from fast and slow muscles',
			'authors' => 'Bengtsen, M. et al.',
			'description' => '<p>Muscle cells have different phenotypes adapted to different usage and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of chromatin environment by ChIP-Seq in two muscle extremes, the almost completely fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where less than 60\% of the nuclei are inside muscle fibers. Since cellular homogeneity is critical in epigenome-wide association studies we devised a new method for purifying skeletal muscle nuclei from whole tissue based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labeling and a magnetic-assisted sorting approach we were able to sort out myonuclei with 95\% purity. The sorting eliminated influence from other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the functional properties of the two muscles each with a distinct regulatory program involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles are also regulated by different sets of transcription factors; e.g. in soleus binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SOX1 binding sites were found to be overrepresented. In addition, novel factors for muscle regulation such as MAF, ZFX and ZBTB14 were identified.</p>',
			'date' => '2021-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.02.04.429545',
			'doi' => '10.1101/2021.02.04.429545',
			'modified' => '2021-12-14 09:40:02',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 67 => array(
			'id' => '4198',
			'name' => 'WAPL maintains a cohesin loading cycle to preserve cell-type-specificdistal gene regulation.',
			'authors' => 'Liu N. Q.et al.',
			'description' => '<p>The cohesin complex has an essential role in maintaining genome organization. However, its role in gene regulation remains largely unresolved. Here we report that the cohesin release factor WAPL creates a pool of free cohesin, in a process known as cohesin turnover, which reloads it to cell-type-specific binding sites. Paradoxically, stabilization of cohesin binding, following WAPL ablation, results in depletion of cohesin from these cell-type-specific regions, loss of gene expression and differentiation. Chromosome conformation capture experiments show that cohesin turnover is important for maintaining promoter-enhancer loops. Binding of cohesin to cell-type-specific sites is dependent on the pioneer transcription factors OCT4 (POU5F1) and SOX2, but not NANOG. We show the importance of cohesin turnover in controlling transcription and propose that a cycle of cohesin loading and off-loading, instead of static cohesin binding, mediates promoter and enhancer interactions critical for gene regulation.</p>',
			'date' => '2020-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33318687',
			'doi' => '10.1038/s41588-020-00744-4',
			'modified' => '2022-01-06 14:38:26',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 68 => array(
			'id' => '4061',
			'name' => 'Dissecting Herpes Simplex Virus 1-Induced Host Shutoff at the RNA Level.',
			'authors' => 'Friedel, Caroline C and Whisnant, Adam W and Djakovic, Lara and Rutkowski,Andrzej J and Friedl, Marie-Sophie and Kluge, Michael and Williamson, JamesC and Sai, Somesh and Vidal, Ramon Oliveira and Sauer, Sascha and Hennig,Thomas and Grothey, Arnhild an',
			'description' => '<p>Herpes simplex virus 1 (HSV-1) induces a profound host shut-off during lytic infection. The virion host shut-off () protein plays a key role in this process by efficiently cleaving host and viral mRNAs. Furthermore, the onset of viral DNA replication is accompanied by a rapid decline in host transcriptional activity. To dissect relative contributions of both mechanisms and elucidate gene-specific host transcriptional responses throughout the first 8h of lytic HSV-1 infection, we employed RNA-seq of total, newly transcribed (4sU-labelled) and chromatin-associated RNA in wild-type (WT) and &Delta; infection of primary human fibroblasts. Following virus entry, v activity rapidly plateaued at an elimination rate of around 30\% of cellular mRNAs per hour until 8h p.i. In parallel, host transcriptional activity dropped to 10-20\%. While the combined effects of both phenomena dominated infection-induced changes in total RNA, extensive gene-specific transcriptional regulation was observable in chromatin-associated RNA and was surprisingly concordant between WT and &Delta; infection. Both induced strong transcriptional up-regulation of a small subset of genes that were poorly expressed prior to infection but already primed by H3K4me3 histone marks at their promoters. Most interestingly, analysis of chromatin-associated RNA revealed -nuclease-activity-dependent transcriptional down-regulation of at least 150 cellular genes, in particular of many integrin adhesome and extracellular matrix components. This was accompanied by a -dependent reduction in protein levels by 8h p.i. for many of these genes. In summary, our study provides a comprehensive picture of the molecular mechanisms that govern cellular RNA metabolism during the first 8h of lytic HSV-1 infection. The HSV-1 virion host shut-off () protein efficiently cleaves both host and viral mRNAs in a translation-dependent manner. In this study, we model and quantify changes in activity as well as virus-induced global loss of host transcriptional activity during productive HSV-1 infection. In general, HSV-1-induced alterations in total RNA levels were dominated by these two global effects. In contrast, chromatin-associated RNA depicted gene-specific transcriptional changes. This revealed highly concordant transcriptional changes in WT and infection, confirmed DUX4 as a key transcriptional regulator in HSV-1 infection and depicted -dependent, transcriptional down-regulation of the integrin adhesome and extracellular matrix components. The latter explained seemingly gene-specific effects previously attributed to -mediated mRNA degradation and resulted in a concordant loss in protein levels by 8h p.i. for many of the respective genes.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33148793',
			'doi' => '10.1128/JVI.01399-20',
			'modified' => '2021-02-19 17:31:53',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 69 => array(
			'id' => '4069',
			'name' => 'Increased H3K4me3 methylation and decreased miR-7113-5p expression lead toenhanced Wnt/β-catenin signaling in immune cells from PTSD patientsleading to inflammatory phenotype.',
			'authors' => 'Bam, Marpe and Yang, Xiaoming and Busbee, Brandon P and Aiello, Allison Eand Uddin, Monica and Ginsberg, Jay P and Galea, Sandro and Nagarkatti,Prakash S and Nagarkatti, Mitzi',
			'description' => '<p>BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric disorder accompanied by chronic peripheral inflammation. What triggers inflammation in PTSD is currently unclear. In the present study, we identified potential defects in signaling pathways in peripheral blood mononuclear cells (PBMCs) from individuals with PTSD. METHODS: RNAseq (5 samples each for controls and PTSD), ChIPseq (5 samples each) and miRNA array (6 samples each) were used in combination with bioinformatics tools to identify dysregulated genes in PBMCs. Real time qRT-PCR (24 samples each) and in vitro assays were employed to validate our primary findings and hypothesis. RESULTS: By RNA-seq analysis of PBMCs, we found that Wnt signaling pathway was upregulated in PTSD when compared to normal controls. Specifically, we found increased expression of WNT10B in the PTSD group when compared to controls. Our findings were confirmed using NCBI's GEO database involving a larger sample size. Additionally, in vitro activation studies revealed that activated but not na&iuml;ve PBMCs from control individuals expressed more IFN&gamma; in the presence of recombinant WNT10B suggesting that Wnt signaling played a crucial role in exacerbating inflammation. Next, we investigated the mechanism of induction of WNT10B and found that increased expression of WNT10B may result from epigenetic modulation involving downregulation of hsa-miR-7113-5p which targeted WNT10B. Furthermore, we also observed that WNT10B overexpression was linked to higher expression of H3K4me3 histone modification around the promotor of WNT10B. Additionally, knockdown of histone demethylase specific to H3K4me3, using siRNA, led to increased expression of WNT10B providing conclusive evidence that H3K4me3 indeed controlled WNT10B expression. CONCLUSIONS: In summary, our data demonstrate for the first time that Wnt signaling pathway is upregulated in PBMCs of PTSD patients resulting from epigenetic changes involving microRNA dysregulation and histone modifications, which in turn may promote the inflammatory phenotype in such cells.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33189141',
			'doi' => '10.1186/s10020-020-00238-3',
			'modified' => '2021-02-19 17:54:52',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 70 => array(
			'id' => '4084',
			'name' => 'BCG Vaccination Induces Long-Term Functional Reprogramming of HumanNeutrophils.',
			'authors' => 'Moorlag, Simone J C F M and Rodriguez-Rosales, Yessica Alina and Gillard,Joshua and Fanucchi, Stephanie and Theunissen, Kate and Novakovic, Borisand de Bont, Cynthia M and Negishi, Yutaka and Fok, Ezio T and Kalafati,Lydia and Verginis, Panayotis and M',
			'description' => '<p>The tuberculosis vaccine bacillus Calmette-Gu&eacute;rin (BCG) protects against some heterologous infections, probably via induction of non-specific innate immune memory in monocytes and natural killer (NK) cells, a process known as trained immunity. Recent studies have revealed that the induction of trained immunity is associated with a bias toward granulopoiesis in bone marrow hematopoietic progenitor cells, but it is unknown whether BCG vaccination also leads to functional reprogramming of mature neutrophils. Here, we show that BCG vaccination of healthy humans induces long-lasting changes in neutrophil phenotype, characterized by increased expression of activation markers and antimicrobial function. The enhanced function of human neutrophils persists for at least 3&nbsp;months after vaccination and is associated with genome-wide epigenetic modifications in trimethylation at histone 3 lysine 4. Functional reprogramming of neutrophils by the induction of trained immunity might offer novel therapeutic strategies in clinical conditions that could benefit from modulation of neutrophil effector function.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33207187',
			'doi' => '10.1016/j.celrep.2020.108387',
			'modified' => '2021-03-15 17:07:29',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 71 => array(
			'id' => '4095',
			'name' => 'ZNF354C is a transcriptional repressor that inhibits endothelialangiogenic sprouting.',
			'authors' => 'Oo, James A and Irmer, Barnabas and Günther, Stefan and Warwick, Timothyand Pálfi, Katalin and Izquierdo Ponce, Judit and Teichmann, Tom andPflüger-Müller, Beatrice and Gilsbach, Ralf and Brandes, Ralf P andLeisegang, Matthias S',
			'description' => '<p>Zinc finger proteins (ZNF) are a large group of transcription factors with diverse functions. We recently discovered that endothelial cells harbour a specific mechanism to limit the action of ZNF354C, whose function in endothelial cells is unknown. Given that ZNF354C&nbsp;has so far only been studied in bone and tumour, its function was determined in endothelial cells. ZNF354C is expressed in vascular cells and localises to the nucleus and cytoplasm. Overexpression of ZNF354C in human endothelial cells results in a marked inhibition of endothelial sprouting. RNA-sequencing of human microvascular endothelial cells with and without overexpression of ZNF354C revealed that the protein is a potent transcriptional repressor. ZNF354C contains an active KRAB domain which mediates this suppression as shown by mutagenesis analysis. ZNF354C interacts with dsDNA, TRIM28 and histones, as observed by proximity ligation and immunoprecipitation. Moreover, chromatin immunoprecipitation revealed that the ZNF binds to specific endothelial-relevant target-gene promoters. ZNF354C suppresses these genes as shown by CRISPR/Cas knockout and RNAi. Inhibition of endothelial sprouting by ZNF354C is dependent on the amino acids DV and MLE of the KRAB domain. These results demonstrate that ZNF354C is a repressive transcription factor which acts through a KRAB domain to inhibit endothelial angiogenic sprouting.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33154469',
			'doi' => '10.1038/s41598-020-76193-0',
			'modified' => '2021-03-17 17:19:53',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 72 => array(
			'id' => '4197',
			'name' => 'Derivation of Intermediate Pluripotent Stem Cells Amenable to PrimordialGerm Cell Specification.',
			'authors' => 'Yu L. et al.',
			'description' => '<p>Dynamic pluripotent stem cell (PSC) states are in&nbsp;vitro adaptations of pluripotency continuum in&nbsp;vivo. Previous studies have generated a number of PSCs with distinct properties. To date, however, no known PSCs have demonstrated dual competency for chimera formation and direct responsiveness to primordial germ cell (PGC) specification, a unique functional feature of formative pluripotency. Here, by modulating fibroblast growth factor (FGF), transforming growth factor &beta; (TGF-&beta;), and WNT pathways, we derived PSCs from mice, horses, and humans (designated as XPSCs) that are permissive for direct PGC-like cell induction in&nbsp;vitro and are capable of contributing to intra- or inter-species chimeras in&nbsp;vivo. XPSCs represent a pluripotency state between naive and primed pluripotency and harbor molecular, cellular, and phenotypic features characteristic of formative pluripotency. XPSCs open new avenues for studying mammalian pluripotency and dissecting the molecular mechanisms governing PGC specification. Our method may be broadly applicable for the derivation of analogous stem cells from other mammalian species.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33271070',
			'doi' => '10.1016/j.stem.2020.11.003',
			'modified' => '2022-01-06 14:35:44',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 73 => array(
			'id' => '4201',
			'name' => 'The epigenetic regulator RINF (CXXC5) maintains SMAD7 expression in human immature erythroid cells and sustains red blood cellsexpansion.',
			'authors' => 'Astori A. et al.',
			'description' => '<p>The gene CXXC5, encoding a Retinoid-Inducible Nuclear Factor (RINF), is located within a region at 5q31.2 commonly deleted in myelodysplastic syndrome (MDS) and adult acute myeloid leukemia (AML). RINF may act as an epigenetic regulator and has been proposed as a tumor suppressor in hematopoietic malignancies. However, functional studies in normal hematopoiesis are lacking, and its mechanism of action is unknow. Here, we evaluated the consequences of RINF silencing on cytokineinduced erythroid differentiation of human primary CD34+ progenitors. We found that RINF is expressed in immature erythroid cells and that RINF-knockdown accelerated erythropoietin-driven maturation, leading to a significant reduction (~45\%) in the number of red blood cells (RBCs), without affecting cell viability. The phenotype induced by RINF-silencing was TGF&beta;-dependent and mediated by SMAD7, a TGF&beta;- signaling inhibitor. RINF upregulates SMAD7 expression by direct binding to its promoter and we found a close correlation between RINF and SMAD7 mRNA levels both in CD34+ cells isolated from bone marrow of healthy donors and MDS patients with del(5q). Importantly, RINF knockdown attenuated SMAD7 expression in primary cells and ectopic SMAD7 expression was sufficient to prevent the RINF knockdowndependent erythroid phenotype. Finally, RINF silencing affects 5&rsquo;-hydroxymethylation of human erythroblasts, in agreement with its recently described role as a Tet2- anchoring platform in mouse. Altogether, our data bring insight into how the epigenetic factor RINF, as a transcriptional regulator of SMAD7, may fine-tune cell sensitivity to TGF&beta; superfamily cytokines and thus play an important role in both normal and pathological erythropoiesis.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33241676',
			'doi' => '10.3324/haematol.2020.263558',
			'modified' => '2022-01-06 14:46:32',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 74 => array(
			'id' => '4052',
			'name' => 'StE(z)2, a Polycomb group methyltransferase and deposition of H3K27me3 andH3K4me3 regulate the expression of tuberization genes in potato.',
			'authors' => 'Kumar, Amit and Kondhare, Kirtikumar R and Malankar, Nilam N and Banerjee,Anjan K',
			'description' => '<p>Polycomb Repressive Complex (PRC) group proteins regulate various developmental processes in plants by repressing the target genes via H3K27 trimethylation, whereas their function is antagonized by Trithorax group proteins-mediated H3K4 trimethylation. Tuberization in potato is widely studied, but the role of histone modifications in this process is unknown. Recently, we showed that overexpression of StMSI1 (a PRC2 member) alters the expression of tuberization genes in potato. As MSI1 lacks histone-modification activity, we hypothesized that this altered expression could be caused by another PRC2 member, StE(z)2 (a potential H3K27 methyltransferase in potato). Here, we demonstrate that short-day photoperiod influences StE(z)2 expression in leaf and stolon. Moreover, StE(z)2 overexpression alters plant architecture and reduces tuber yield, whereas its knockdown enhanced the yield. ChIP-sequencing using short-day induced stolons revealed that several tuberization and phytohormone-related genes, such as StBEL5/11/29, StSWEET11B, StGA2OX1 and StPIN1 carry H3K4me3 or H3K27me3 marks and/or are StE(z)2 targets. Interestingly, we noticed that another important tuberization gene, StSP6A is targeted by StE(z)2 in leaves and had increased deposition of H3K27me3 under non-induced (long-day) conditions compared to SD. Overall, we show that StE(z)2 and deposition of H3K27me3 and/or H3K4me3 marks could regulate the expression of key tuberization genes in potato.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33048134',
			'doi' => '10.1093/jxb/eraa468',
			'modified' => '2021-02-19 14:55:34',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 75 => array(
			'id' => '4053',
			'name' => 'Priming for enhanced ARGONAUTE2 activation accompanies induced resistanceto cucumber mosaic virus in Arabidopsis thaliana.',
			'authors' => 'Ando, Sugihiro and Jaskiewicz, Michal and Mochizuki, Sei and Koseki, Saekoand Miyashita, Shuhei and Takahashi, Hideki and Conrath, Uwe',
			'description' => '<p>Systemic acquired resistance (SAR) is a broad-spectrum disease resistance response that can be induced upon infection from pathogens or by chemical treatment, such as with benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH). SAR involves priming for more robust activation of defence genes upon pathogen attack. Whether priming for SAR would involve components of RNA silencing remained unknown. Here, we show that upon leaf infiltration of water, BTH-primed Arabidopsis thaliana plants accumulate higher amounts of mRNA of ARGONAUTE (AGO)2 and AGO3, key components of RNA silencing. The enhanced AGO2 expression is associated with prior-to-activation trimethylation of lysine 4 in histone H3 and acetylation of histone H3 in the AGO2 promoter and with induced resistance to the yellow strain of cucumber mosaic virus (CMV[Y]). The results suggest that priming A.&nbsp;thaliana for enhanced defence involves modification of histones in the AGO2 promoter that condition AGO2 for enhanced activation, associated with resistance to CMV(Y). Consistently, the fold-reduction in CMV(Y) coat protein accumulation by BTH pretreatment was lower in ago2 than in wild type, pointing to reduced capacity of ago2 to activate BTH-induced CMV(Y) resistance. A role of AGO2 in pathogen-induced SAR is suggested by the enhanced activation of AGO2 after infiltrating systemic leaves of plants expressing a localized hypersensitive response upon CMV(Y) infection. In addition, local inoculation of SAR-inducing Pseudomonas syringae pv. maculicola causes systemic priming for enhanced AGO2 expression. Together our results indicate that defence priming targets the AGO2 component of RNA silencing whose enhanced expression is likely to contribute to SAR.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33073913',
			'doi' => '10.1111/mpp.13005',
			'modified' => '2021-02-19 14:57:21',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 76 => array(
			'id' => '4062',
			'name' => 'Digging Deeper into Breast Cancer Epigenetics: Insights from ChemicalInhibition of Histone Acetyltransferase TIP60 .',
			'authors' => 'Idrissou, Mouhamed and Lebert, Andre and Boisnier, Tiphanie and Sanchez,Anna and Houfaf Khoufaf, Fatma Zohra and Penault-Llorca, Frédérique andBignon, Yves-Jean and Bernard-Gallon, Dominique',
			'description' => '<p>Breast cancer is often sporadic due to several factors. Among them, the deregulation of epigenetic proteins may be involved. TIP60 or KAT5 is an acetyltransferase that regulates gene transcription through the chromatin structure. This pleiotropic protein acts in several cellular pathways by acetylating proteins. RNA and protein expressions of TIP60 were shown to decrease in some breast cancer subtypes, particularly in triple-negative breast cancer (TNBC), where a low expression of TIP60 was exhibited compared with luminal subtypes. In this study, the inhibition of the residual activity of TIP60 in breast cancer cell lines was investigated by using two chemical inhibitors, TH1834 and NU9056, first on the acetylation of the specific target, lysine 4 of histone 3 (H3K4) by immunoblotting, and second, by chromatin immunoprecipitation (ChIP)-qPCR (-quantitative Polymerase Chain Reaction). Subsequently, significant decreases or a trend toward decrease of H3K4ac in the different chromatin compartments were observed. In addition, the expression of 48 human nuclear receptors was studied with TaqMan Low-Density Array in these breast cancer cell lines treated with TIP60 inhibitors. The statistical analysis allowed us to comprehensively characterize the androgen receptor and receptors in TNBC cell lines after TH1834 or NU9056 treatment. The understanding of the residual activity of TIP60 in the evolution of breast cancer might be a major asset in the fight against this disease, and could allow TIP60 to be used as a biomarker or therapeutic target for breast cancer progression in the future.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32960142',
			'doi' => '10.1089/omi.2020.0104',
			'modified' => '2021-02-19 17:39:52',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 77 => array(
			'id' => '4073',
			'name' => 'NSD1-deposited H3K36me2 directs de novo methylation in the mouse malegermline and counteracts Polycomb-associated silencing.',
			'authors' => 'Shirane, Kenjiro and Miura, Fumihito and Ito, Takashi and Lorincz, MatthewC',
			'description' => '<p>De novo DNA methylation (DNAme) in mammalian germ cells is dependent on DNMT3A and DNMT3L. However, oocytes and spermatozoa show distinct patterns of DNAme. In mouse oocytes, de novo DNAme requires the lysine methyltransferase (KMTase) SETD2, which deposits H3K36me3. We show here that SETD2 is dispensable for de novo DNAme in the male germline. Instead, the lysine methyltransferase NSD1, which broadly deposits H3K36me2 in euchromatic regions, plays a critical role in de novo DNAme in prospermatogonia, including at imprinted genes. However, males deficient in germline NSD1 show a more severe defect in spermatogenesis than Dnmt3l males. Notably, unlike DNMT3L, NSD1 safeguards a subset of genes against H3K27me3-associated transcriptional silencing. In contrast, H3K36me2 in oocytes is predominantly dependent on SETD2 and coincides with H3K36me3. Furthermore, females with NSD1-deficient oocytes are fertile. Thus, the sexually dimorphic pattern of DNAme in mature mouse gametes is orchestrated by distinct profiles of H3K36 methylation.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32929285',
			'doi' => '10.1038/s41588-020-0689-z',
			'modified' => '2021-02-19 18:02:40',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 78 => array(
			'id' => '4078',
			'name' => 'Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth andPotentiates Checkpoint Inhibition.',
			'authors' => 'Priem, Bram and van Leent, Mandy M T and Teunissen, Abraham J P and Sofias,Alexandros Marios and Mourits, Vera P and Willemsen, Lisa and Klein, Emma Dand Oosterwijk, Roderick S and Meerwaldt, Anu E and Munitz, Jazz andPrévot, Geoffrey and Vera Verschuu',
			'description' => '<p>Trained immunity, a functional state of myeloid cells, has been proposed as a compelling immune-oncological target. Its efficient induction requires direct engagement of myeloid progenitors in the bone marrow. For this purpose, we developed a bone marrow-avid nanobiologic platform designed specifically to induce trained immunity. We established the potent anti-tumor capabilities of our lead candidate MTP-HDL in a B16F10 mouse melanoma model. These anti-tumor effects result from trained immunity-induced myelopoiesis caused by epigenetic rewiring of multipotent progenitors in the bone marrow, which overcomes the immunosuppressive tumor microenvironment. Furthermore, MTP-HDL nanotherapy potentiates checkpoint inhibition in this melanoma model refractory to anti-PD-1 and anti-CTLA-4 therapy. Finally, we determined MTP-HDL's favorable biodistribution and safety profile in non-human primates. In conclusion, we show that rationally designed nanobiologics can promote trained immunity and elicit a durable anti-tumor response either as a monotherapy or in combination with checkpoint inhibitor drugs.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33125893',
			'doi' => '10.1016/j.cell.2020.09.059',
			'modified' => '2021-03-15 16:51:03',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 79 => array(
			'id' => '4092',
			'name' => 'Formation of the CenH3-Deficient Holocentromere in Lepidoptera AvoidsActive Chromatin.',
			'authors' => 'Senaratne, Aruni P and Muller, Héloïse and Fryer, Kelsey A and Kawamoto,Munetaka and Katsuma, Susumu and Drinnenberg, Ines A',
			'description' => '<p>Despite the essentiality for faithful chromosome segregation, centromere architectures are diverse among eukaryotes and embody two main configurations: mono- and holocentromeres, referring, respectively, to localized or unrestricted distribution of centromeric activity. Of the two, some holocentromeres offer the curious condition of having arisen independently in multiple insects, most of which have lost the otherwise essential centromere-specifying factor CenH3 (first described as CENP-A in humans). The loss of CenH3 raises intuitive questions about how holocentromeres are organized and regulated in CenH3-lacking insects. Here, we report the first chromatin-level description of CenH3-deficient holocentromeres by leveraging recently identified centromere components and genomics approaches to map and characterize the holocentromeres of the silk moth Bombyx mori, a representative lepidopteran insect lacking CenH3. This uncovered a robust correlation between the distribution of centromere sites and regions of low chromatin activity along B.&nbsp;mori chromosomes. Transcriptional perturbation experiments recapitulated the exclusion of B.&nbsp;mori centromeres from active chromatin. Based on reciprocal centromere occupancy patterns observed along differentially expressed orthologous genes of Lepidoptera, we further found that holocentromere formation in a manner that is recessive to chromatin dynamics is evolutionarily conserved. Our results help us discuss the plasticity of centromeres in the context of a role for the chromosome-wide chromatin landscape in conferring centromere identity rather than the presence of CenH3. Given the co-occurrence of CenH3 loss and holocentricity in insects, we further propose that the evolutionary establishment of holocentromeres in insects was facilitated through the loss of a CenH3-specified centromere.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33125865',
			'doi' => '10.1016/j.cub.2020.09.078',
			'modified' => '2021-03-17 17:13:50',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 80 => array(
			'id' => '4091',
			'name' => 'Epigenetic regulation of the lineage specificity of primary human dermallymphatic and blood vascular endothelial cells.',
			'authors' => 'Tacconi, Carlotta and He, Yuliang and Ducoli, Luca and Detmar, Michael',
			'description' => '<p>Lymphatic and blood vascular endothelial cells (ECs) share several molecular and developmental features. However, these two cell types possess distinct phenotypic signatures, reflecting their different biological functions. Despite significant advances in elucidating how the specification of lymphatic and blood vascular ECs is regulated at the transcriptional level during development, the key molecular mechanisms governing their lineage identity under physiological or pathological conditions remain poorly understood. To explore the epigenomic signatures in the maintenance of EC lineage specificity, we compared the transcriptomic landscapes, histone composition (H3K4me3 and H3K27me3) and DNA methylomes of cultured matched human primary dermal lymphatic and blood vascular ECs. Our findings reveal that blood vascular lineage genes manifest a more 'repressed' histone composition in lymphatic ECs, whereas DNA methylation at promoters is less linked to the differential transcriptomes of lymphatic versus blood vascular ECs. Meta-analyses identified two transcriptional regulators, BCL6 and MEF2C, which potentially govern endothelial lineage specificity. Notably, the blood vascular endothelial lineage markers CD34, ESAM and FLT1 and the lymphatic endothelial lineage markers PROX1, PDPN and FLT4 exhibited highly differential epigenetic profiles and responded in distinct manners to epigenetic drug treatments. The perturbation of histone and DNA methylation selectively promoted the expression of blood vascular endothelial markers in lymphatic endothelial cells, but not vice versa. Overall, our study reveals that the fine regulation of lymphatic and blood vascular endothelial transcriptomes is maintained via several epigenetic mechanisms, which are crucial to the maintenance of endothelial cell identity.</p>',
			'date' => '2020-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32918672',
			'doi' => '10.1007/s10456-020-09743-9',
			'modified' => '2021-03-17 17:09:36',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 81 => array(
			'id' => '3978',
			'name' => 'OxLDL-mediated immunologic memory in endothelial cells.',
			'authors' => 'Sohrabi Y, Lagache SMM, Voges VC, Semo D, Sonntag G, Hanemann I, Kahles F, Waltenberger J, Findeisen HM',
			'description' => '<p>Trained innate immunity describes the metabolic reprogramming and long-term proinflammatory activation of innate immune cells in response to different pathogen or damage associated molecular patterns, such as oxidized low-density lipoprotein (oxLDL). Here, we have investigated whether the regulatory networks of trained innate immunity also control endothelial cell activation following oxLDL treatment. Human aortic endothelial cells (HAECs) were primed with oxLDL for 24 h. After a resting time of 4 days, cells were restimulated with the TLR2-agonist PAM3cys4. OxLDL priming induced a proinflammatory memory with increased production of inflammatory cytokines such as IL-6, IL-8 and MCP-1 in response to PAM3cys4 restimulation. This memory formation was dependent on TLR2 activation. Furthermore, oxLDL priming of HAECs caused characteristic metabolic and epigenetic reprogramming, including activated mTOR-HIF1&alpha;-signaling with increases in glucose consumption and lactate production, as well as epigenetic modifications in inflammatory gene promoters. Inhibition of mTOR-HIF1&alpha;-signaling or histone methyltransferases blocked the observed phenotype. Furthermore, primed HAECs showed epigenetic activation of ICAM-1 and increased ICAM-1 expression in a HIF1&alpha;-dependent manner. Accordingly, live cell imaging revealed increased monocyte adhesion and transmigration following oxLDL priming. In summary, we demonstrate that oxLDL-mediated endothelial cell activation represents an immunologic event, which triggers metabolic and epigenetic reprogramming. Molecular mechanisms regulating trained innate immunity in innate immune cells also regulate this sustained proinflammatory phenotype in HAECs with enhanced atheroprone cell functions. Further research is necessary to elucidate the detailed metabolic regulation and the functional relevance for atherosclerosis formation in vivo.</p>',
			'date' => '2020-07-26',
			'pmid' => 'http://www.pubmed.gov/32726647',
			'doi' => '10.1016/j.yjmcc.2020.07.006',
			'modified' => '2020-08-10 13:08:21',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 82 => array(
			'id' => '3997',
			'name' => 'The Human Integrator Complex Facilitates Transcriptional Elongation by Endonucleolytic Cleavage of Nascent Transcripts.',
			'authors' => 'Beckedorff F, Blumenthal E, daSilva LF, Aoi Y, Cingaram PR, Yue J, Zhang A, Dokaneheifard S, Valencia MG, Gaidosh G, Shilatifard A, Shiekhattar R',
			'description' => '<p>Transcription by RNA polymerase II (RNAPII) is pervasive in the human genome. However, the mechanisms controlling transcription at promoters and enhancers remain enigmatic. Here, we demonstrate that Integrator subunit 11 (INTS11), the catalytic subunit of the Integrator complex, regulates transcription at these loci through its endonuclease activity. Promoters of genes require INTS11 to cleave nascent transcripts associated with paused RNAPII and induce their premature termination in the proximity of the&nbsp;+1 nucleosome. The turnover of RNAPII permits the subsequent recruitment of an elongation-competent RNAPII complex, leading to productive elongation. In contrast, enhancers require INTS11 catalysis not to evict paused RNAPII but rather to terminate enhancer RNA transcription beyond the&nbsp;+1 nucleosome. These findings are supported by the differential occupancy of negative elongation factor (NELF), SPT5, and tyrosine-1-phosphorylated RNAPII. This study elucidates the role of Integrator in mediating transcriptional elongation at human promoters through the endonucleolytic cleavage of nascent transcripts and the dynamic turnover of RNAPII.</p>',
			'date' => '2020-07-21',
			'pmid' => 'http://www.pubmed.gov/32697989',
			'doi' => '10.1016/j.celrep.2020.107917',
			'modified' => '2020-09-01 14:44:33',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 83 => array(
			'id' => '3996',
			'name' => 'Prostate cancer reactivates developmental epigenomic programs during metastatic progression.',
			'authors' => 'Pomerantz MM, Qiu X, Zhu Y, Takeda DY, Pan W, Baca SC, Gusev A, Korthauer KD, Severson TM, Ha G, Viswanathan SR, Seo JH, Nguyen HM, Zhang B, Pasaniuc B, Giambartolomei C, Alaiwi SA, Bell CA, O'Connor EP, Chabot MS, Stillman DR, Lis R, Font-Tello A, Li L, ',
			'description' => '<p>Epigenetic processes govern prostate cancer (PCa) biology, as evidenced by the dependency of PCa cells on the androgen receptor (AR), a prostate master transcription factor. We generated 268 epigenomic datasets spanning two state transitions-from normal prostate epithelium to localized PCa to metastases-in specimens derived from human tissue. We discovered that reprogrammed AR sites in metastatic PCa are not created de novo; rather, they are prepopulated by the transcription factors FOXA1 and HOXB13 in normal prostate epithelium. Reprogrammed regulatory elements commissioned in metastatic disease hijack latent developmental programs, accessing sites that are implicated in prostate organogenesis. Analysis of reactivated regulatory elements enabled the identification and functional validation of previously unknown metastasis-specific enhancers at HOXB13, FOXA1 and NKX3-1. Finally, we observed that prostate lineage-specific regulatory elements were strongly associated with PCa risk heritability and somatic mutation density. Examining prostate biology through an epigenomic lens is fundamental for understanding the mechanisms underlying tumor progression.</p>',
			'date' => '2020-07-20',
			'pmid' => 'http://www.pubmed.gov/32690948',
			'doi' => '10.1038/s41588-020-0664-8',
			'modified' => '2020-09-01 14:45:54',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 84 => array(
			'id' => '3987',
			'name' => 'The hypomethylation of imprinted genes in IVF/ICSI placenta samples is associated with concomitant changes in histone modifications.',
			'authors' => 'Choux C, Petazzi P, Sanchez-Delgado M, Hernandez Mora JR, Monteagudo A, Sagot P, Monk D, Fauque P',
			'description' => '<p>Although more and more children are born by Assisted Reproductive Technologies (ART), ART safety has not fully been demonstrated. Notably, ART could disturb the delicate step of implantation, and trigger placenta-related adverse outcomes with potential long-term effects, through disrupted epigenetic regulation. We have previously demonstrated that placental DNA methylation was significantly lower after IVF/ICSI than following natural conception at two differentially methylated regions (DMRs) associated with imprinted genes (IGs): and . As histone modifications are critical for placental physiology, the aim of this study was to profile permissive and repressive histone marks in placenta biopsies to reveal a better understanding of the epigenetic changes in the context of ART. Utilizing chromatin immunoprecipitation (ChIP) coupled with quantitative PCR, permissive (H3K4me3, H3K4me2, and H3K9ac) and repressive (H3K9me3 and H3K9me2) post-translational histone modifications were quantified. The analyses revealed a significantly higher quantity of H3K4me2 precipitation in the IVF/ICSI group than in the natural conception group for and DMRs (P&nbsp;=&nbsp;0.016 and 0.003, respectively). Conversely, the quantity of both repressive marks at and DMRs was significantly lower in the IVF/ICSI group than in the natural conception group (P&nbsp;=&nbsp;0.011 and 0.027 for ; and P&nbsp;=&nbsp;0.010 and 0.035 for ). These novel findings highlight that DNA hypomethylation at imprinted DMRs following ART is linked with increased permissive/decreased repressive histone marks, altogether promoting a more permissive chromatin conformation. This concomitant change in epigenetic state at IGs at birth might be an important developmental event because of ART manipulations.</p>',
			'date' => '2020-06-23',
			'pmid' => 'http://www.pubmed.gov/32573317',
			'doi' => '10.1080/15592294.2020.1783168',
			'modified' => '2020-09-01 15:10:37',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 85 => array(
			'id' => '3986',
			'name' => 'Epigenetic priming by Dppa2 and 4 in pluripotency facilitates multi-lineage commitment.',
			'authors' => 'Eckersley-Maslin MA, Parry A, Blotenburg M, Krueger C, Ito Y, Franklin VNR, Narita M, D'Santos CS, Reik W',
			'description' => '<p>How the epigenetic landscape is established in development is still being elucidated. Here, we uncover developmental pluripotency associated 2 and 4 (DPPA2/4) as epigenetic priming factors that establish a permissive epigenetic landscape at a subset of developmentally important bivalent promoters characterized by low expression and poised RNA-polymerase. Differentiation assays reveal that Dppa2/4 double knockout mouse embryonic stem cells fail to exit pluripotency and differentiate efficiently. DPPA2/4 bind both H3K4me3-marked and bivalent gene promoters and associate with COMPASS- and Polycomb-bound chromatin. Comparing knockout and inducible knockdown systems, we find that acute depletion of DPPA2/4 results in rapid loss of H3K4me3 from key bivalent genes, while H3K27me3 is initially more stable but lost following extended culture. Consequently, upon DPPA2/4 depletion, these promoters gain DNA methylation and are unable to be activated upon differentiation. Our findings uncover a novel epigenetic priming mechanism at developmental promoters, poising them for future lineage-specific activation.</p>',
			'date' => '2020-06-22',
			'pmid' => 'http://www.pubmed.gov/32572255',
			'doi' => '10.1038/s41594-020-0443-3',
			'modified' => '2020-09-01 15:12:03',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 86 => array(
			'id' => '3982',
			'name' => 'Genomic deregulation of PRMT5 supports growth and stress tolerance in chronic lymphocytic leukemia.',
			'authors' => 'Schnormeier AK, Pommerenke C, Kaufmann M, Drexler HG, Koeppel M',
			'description' => '<p>Patients suffering from chronic lymphocytic leukemia (CLL) display highly diverse clinical courses ranging from indolent cases to aggressive disease, with genetic and epigenetic features resembling this diversity. Here, we developed a comprehensive approach combining a variety of molecular and clinical data to pinpoint translocation events disrupting long-range chromatin interactions and causing cancer-relevant transcriptional deregulation. Thereby, we discovered a B cell specific cis-regulatory element restricting the expression of genes in the associated locus, including PRMT5 and DAD1, two factors with oncogenic potential. Experimental PRMT5 inhibition identified transcriptional programs similar to those in patients with differences in PRMT5 abundance, especially MYC-driven and stress response pathways. In turn, such inhibition impairs factors involved in DNA repair, sensitizing cells for apoptosis. Moreover, we show that artificial deletion of the regulatory element from its endogenous context resulted in upregulation of corresponding genes, including PRMT5. Furthermore, such disruption renders PRMT5 transcription vulnerable to additional stimuli and subsequently alters the expression of downstream PRMT5 targets. These studies provide a mechanism of PRMT5 deregulation in CLL and the molecular dependencies identified might have therapeutic implementations.</p>',
			'date' => '2020-06-17',
			'pmid' => 'http://www.pubmed.gov/32555249',
			'doi' => '10.1038/s41598-020-66224-1',
			'modified' => '2020-09-01 15:17:40',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 87 => array(
			'id' => '4360',
			'name' => 'The hypomethylation of imprinted genes in IVF/ICSI placenta samplesis associated with concomitant changes in histone modifications.',
			'authors' => 'Choux C. et al. ',
			'description' => '<p>Although more and more children are born by Assisted Reproductive Technologies (ART), ART safety has not fully been demonstrated. Notably, ART could disturb the delicate step of implantation, and trigger placenta-related adverse outcomes with potential long-term effects, through disrupted epigenetic regulation. We have previously demonstrated that placental DNA methylation was significantly lower after IVF/ICSI than following natural conception at two differentially methylated regions (DMRs) associated with imprinted genes (IGs): and . As histone modifications are critical for placental physiology, the aim of this study was to profile permissive and repressive histone marks in placenta biopsies to reveal a better understanding of the epigenetic changes in the context of ART. Utilizing chromatin immunoprecipitation (ChIP) coupled with quantitative PCR, permissive (H3K4me3, H3K4me2, and H3K9ac) and repressive (H3K9me3 and H3K9me2) post-translational histone modifications were quantified. The analyses revealed a significantly higher quantity of H3K4me2 precipitation in the IVF/ICSI group than in the natural conception group for and DMRs (P = 0.016 and 0.003, respectively). Conversely, the quantity of both repressive marks at and DMRs was significantly lower in the IVF/ICSI group than in the natural conception group (P = 0.011 and 0.027 for ; and P = 0.010 and 0.035 for ). These novel findings highlight that DNA hypomethylation at imprinted DMRs following ART is linked with increased permissive/decreased repressive histone marks, altogether promoting a more permissive chromatin conformation. This concomitant change in epigenetic state at IGs at birth might be an important developmental event because of ART manipulations.</p>',
			'date' => '2020-06-01',
			'pmid' => 'http://www.pubmed.gov/32573317',
			'doi' => '10.1080/15592294.2020.1783168',
			'modified' => '2022-08-03 17:14:32',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 88 => array(
			'id' => '4005',
			'name' => 'Measuring Histone Modifications in the Human Parasite Schistosoma mansoni ',
			'authors' => 'de Carvalho Augusto R, Roquis D, Al Picard M, Chaparro C, Cosseau C, Grunau C.',
			'description' => '<p>DNA-binding proteins play critical roles in many major processes such as development and sexual biology of Schistosoma mansoni and are important for the pathogenesis of schistosomiasis. Chromatin immunoprecipitation (ChIP) experiments followed by sequencing (ChIP-seq) are useful to characterize the association of genomic regions with posttranslational chemical modifications of histone proteins. Challenges in the standard ChIP protocol have motivated recent enhancements in this approach, such as reducing the number of cells required and increasing the resolution. In this chapter, we describe the latest advances made by our group in the ChIP methods to improve the standard ChIP protocol to reduce the number of input cells required and to increase the resolution and robustness of ChIP in S. mansoni.</p>',
			'date' => '2020-05-26',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/32451999/',
			'doi' => '10.1007/978-1-0716-0635-3_9 ',
			'modified' => '2020-09-11 15:31:21',
			'created' => '2020-09-11 15:25:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 89 => array(
			'id' => '3965',
			'name' => 'Histone post-translational modifications in Silene latifolia X and Y chromosomes suggest a mammal-like dosage compensation system',
			'authors' => 'Luis Rodríguez Lorenzo José, Hubinský Marcel, Vyskot Boris, Hobza Roman',
			'description' => '<p>Silene latifolia is a model organism to study evolutionary young heteromorphic sex chromosome evolution in plants. Previous research indicates a Y-allele gene degeneration and a dosage compensation system already operating. Here, we propose an epigenetic approach based on analysis of several histone post-translational modifications (PTMs) to find the first epigenetic hints of the X:Y sex chromosome system regulation in S. latifolia. Through chromatin immunoprecipitation we interrogated six genes from X and Y alleles. Several histone PTMS linked to DNA methylation and transcriptional repression (H3K27me3, H3K23me, H3K9me2 and H3K9me3) and to transcriptional activation (H3K4me3 and H4K5, 8, 12, 16ac) were used. DNA enrichment (Immunoprecipitated DNA/input DNA) was analyzed and showed three main results: i) promoters of the Y allele are associated with heterochromatin marks, ii) promoters of the X allele in males are associated with activation of transcription marks and finally, iii) promoters of X alleles in females are associated with active and repressive marks. Our finding indicates a transcription activation of X allele and transcription repression of Y allele in males. In females we found a possible differential regulation (up X1, down X2) of each female X allele. These results agree with the mammal-like epigenetic dosage compensation regulation.</p>',
			'date' => '2020-05-24',
			'pmid' => 'https://www.sciencedirect.com/science/article/abs/pii/S0168945220301333',
			'doi' => '10.1016/j.plantsci.2020.110528',
			'modified' => '2020-08-12 09:42:21',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 90 => array(
			'id' => '3952',
			'name' => 'TET3 controls the expression of the H3K27me3 demethylase Kdm6b during neural commitment.',
			'authors' => 'Montibus B, Cercy J, Bouschet T, Charras A, Maupetit-Méhouas S, Nury D, Gonthier-Guéret C, Chauveau S, Allegre N, Chariau C, Hong CC, Vaillant I, Marques CJ, Court F, Arnaud P',
			'description' => '<p>The acquisition of cell identity is associated with developmentally regulated changes in the cellular histone methylation signatures. For instance, commitment to neural differentiation relies on the tightly controlled gain or loss of H3K27me3, a hallmark of polycomb-mediated transcriptional gene silencing, at specific gene sets. The KDM6B demethylase, which removes H3K27me3 marks at defined promoters and enhancers, is a key factor in neurogenesis. Therefore, to better understand the epigenetic regulation of neural fate acquisition, it is important to determine how Kdm6b expression is regulated. Here, we investigated the molecular mechanisms involved in the induction of Kdm6b expression upon neural commitment of mouse embryonic stem cells. We found that the increase in Kdm6b expression is linked to a rearrangement between two 3D configurations defined by the promoter contact with two different regions in the Kdm6b locus. This is associated with changes in 5-hydroxymethylcytosine (5hmC) levels at these two regions, and requires a functional ten-eleven-translocation (TET) 3 protein. Altogether, our data support a model whereby Kdm6b induction upon neural commitment relies on an intronic enhancer the activity of which is defined by its TET3-mediated 5-hmC level. This original observation reveals an unexpected interplay between the 5-hmC and H3K27me3 pathways during neural lineage commitment in mammals. It also questions to which extent KDM6B-mediated changes in H3K27me3 level account for the TET-mediated effects on gene expression.</p>',
			'date' => '2020-05-14',
			'pmid' => 'http://www.pubmed.gov/32405722',
			'doi' => '10.1007/s00018-020-03541-8',
			'modified' => '2020-08-17 09:53:08',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 91 => array(
			'id' => '3951',
			'name' => 'In vitro capture and characterization of embryonic rosette-stage pluripotency between naive and primed states.',
			'authors' => 'Neagu A, van Genderen E, Escudero I, Verwegen L, Kurek D, Lehmann J, Stel J, Dirks RAM, van Mierlo G, Maas A, Eleveld C, Ge Y, den Dekker AT, Brouwer RWW, van IJcken WFJ, Modic M, Drukker M, Jansen JH, Rivron NC, Baart EB, Marks H, Ten Berge D',
			'description' => '<p>Following implantation, the naive pluripotent epiblast of the mouse blastocyst generates a rosette, undergoes lumenogenesis and forms the primed pluripotent egg cylinder, which is able to generate the embryonic tissues. How pluripotency progression and morphogenesis are linked and whether intermediate pluripotent states exist remain controversial. We identify here a rosette pluripotent state defined by the co-expression of naive factors with the transcription factor OTX2. Downregulation of blastocyst WNT signals drives the transition into rosette pluripotency by inducing OTX2. The rosette then activates MEK signals that induce lumenogenesis and drive progression to primed pluripotency. Consequently, combined WNT and MEK inhibition supports rosette-like stem cells, a self-renewing naive-primed intermediate. Rosette-like stem cells erase constitutive heterochromatin marks and display a primed chromatin landscape, with bivalently marked primed pluripotency genes. Nonetheless, WNT induces reversion to naive pluripotency. The rosette is therefore a reversible pluripotent intermediate whereby control over both pluripotency progression and morphogenesis pivots from WNT to MEK signals.</p>',
			'date' => '2020-05-01',
			'pmid' => 'http://www.pubmed.gov/32367046',
			'doi' => '10.1038/s41556-020-0508-x',
			'modified' => '2020-08-17 09:55:37',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 92 => array(
			'id' => '3929',
			'name' => 'The TGF-β profibrotic cascade targets ecto-5'-nucleotidase gene in proximal tubule epithelial cells and is a traceable marker of progressive diabetic kidney disease.',
			'authors' => 'Cappelli C, Tellez A, Jara C, Alarcón S, Torres A, Mendoza P, Podestá L, Flores C, Quezada C, Oyarzún C, Martín RS',
			'description' => '<p>Progressive diabetic nephropathy (DN) and loss of renal function correlate with kidney fibrosis. Crosstalk between TGF-&beta; and adenosinergic signaling contributes to the phenotypic transition of cells and to renal fibrosis in DN models. We evaluated the role of TGF-&beta; on NT5E gene expression coding for the ecto-5`-nucleotidase CD73, the limiting enzyme in extracellular adenosine production. We showed that high d-glucose may predispose HK-2 cells towards active transcription of the proximal promoter region of the NT5E gene while additional TGF-&beta; results in full activation. The epigenetic landscape of the NT5E gene promoter was modified by concurrent TGF-&beta; with occupancy by the p300 co-activator and the phosphorylated forms of the Smad2/3 complex and RNA Pol II. Transcriptional induction at NT5E in response to TGF-&beta; was earlier compared to the classic responsiveness genes PAI-1 and Fn1. CD73 levels and AMPase activity were concomitantly increased by TGF-&beta; in HK-2 cells. Interestingly, we found increased CD73 content in urinary extracellular vesicles only in diabetic patients with renal repercussions. Further, CD73-mediated AMPase activity was increased in the urinary sediment of DN patients. We conclude that the NT5E gene is a target of the profibrotic TGF-&beta; cascade and is a traceable marker of progressive DN.</p>',
			'date' => '2020-04-11',
			'pmid' => 'http://www.pubmed.gov/32289379',
			'doi' => '10.1016/j.bbadis.2020.165796',
			'modified' => '2020-08-17 10:46:30',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 93 => array(
			'id' => '3889',
			'name' => 'LXR Activation Induces a Proinflammatory Trained Innate Immunity-Phenotype in Human Monocytes',
			'authors' => 'Sohrabi Yahya, Sonntag Glenn V. H., Braun Laura C., Lagache Sina M. M., Liebmann Marie, Klotz Luisa, Godfrey Rinesh, Kahles Florian, Waltenberger Johannes, Findeisen Hannes M.',
			'description' => '<p>The concept of trained innate immunity describes a long-term proinflammatory memory in innate immune cells. Trained innate immunity is regulated through reprogramming of cellular metabolic pathways including cholesterol and fatty acid synthesis. Here, we have analyzed the role of Liver X Receptor (LXR), a key regulator of cholesterol and fatty acid homeostasis, in trained innate immunity.</p>',
			'date' => '2020-03-10',
			'pmid' => 'https://www.frontiersin.org/articles/10.3389/fimmu.2020.00353/full',
			'doi' => '10.3389/ﬁmmu.2020.00353',
			'modified' => '2020-03-20 17:19:37',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 94 => array(
			'id' => '3884',
			'name' => 'A MORC-driven transcriptional switch controls Toxoplasma developmental trajectories and sexual commitment.',
			'authors' => 'Farhat DC, Swale C, Dard C, Cannella D, Ortet P, Barakat M, Sindikubwabo F, Belmudes L, De Bock PJ, Couté Y, Bougdour A, Hakimi MA',
			'description' => '<p>Toxoplasma gondii has a complex life cycle that is typified by asexual development that takes place in vertebrates, and sexual reproduction, which occurs exclusively in felids and is therefore less studied. The developmental transitions rely on changes in the patterns of gene expression, and recent studies have assigned roles for chromatin shapers, including histone modifications, in establishing specific epigenetic programs for each given stage. Here, we identified the T. gondii microrchidia (MORC) protein as an upstream transcriptional repressor of sexual commitment. MORC, in a complex with Apetala 2 (AP2) transcription factors, was shown to recruit the histone deacetylase HDAC3, thereby impeding the accessibility of chromatin at the genes that are exclusively expressed during sexual stages. We found that MORC-depleted cells underwent marked transcriptional changes, resulting in the expression of a specific repertoire of genes, and revealing a shift from asexual proliferation to sexual differentiation. MORC acts as a master regulator that directs the hierarchical expression of secondary AP2 transcription factors, and these transcription factors potentially contribute to the unidirectionality of the life cycle. Thus, MORC plays a cardinal role in the T. gondii life cycle, and its conditional depletion offers a method to study the sexual development of the parasite in vitro, and is proposed as an alternative to the requirement of T. gondii infections in cats.</p>',
			'date' => '2020-02-24',
			'pmid' => 'http://www.pubmed.gov/32094587',
			'doi' => '10.1038/s41564-020-0674-4',
			'modified' => '2020-03-20 17:27:25',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 95 => array(
			'id' => '3874',
			'name' => 'Recombination may occur in the absence of transcription in the immunoglobulin heavy chain recombination centre.',
			'authors' => 'Oudinet C, Braikia FZ, Dauba A, Khamlichi AA',
			'description' => '<p>Developing B cells undergo V(D)J recombination to generate a vast repertoire of Ig molecules. V(D)J recombination is initiated by the RAG1/RAG2 complex in recombination centres (RCs), where gene segments become accessible to the complex. Whether transcription is the causal factor of accessibility or whether it is a side product of other processes that generate accessibility remains a controversial issue. At the IgH locus, V(D)J recombination is controlled by E&mu; enhancer, which directs the transcriptional, epigenetic and recombinational events in the IgH RC. Deletion of E&mu; enhancer affects both transcription and recombination, making it difficult to conclude if E&mu; controls the two processes through the same or different mechanisms. By using a mouse line carrying a CpG-rich sequence upstream of E&mu; enhancer and analyzing transcription and recombination at the single-cell level, we found that recombination could occur in the RC in the absence of detectable transcription, suggesting that E&mu; controls transcription and recombination through distinct mechanisms. Moreover, while the normally E&mu;-dependent transcription and demethylating activities were impaired, recruitment of chromatin remodeling complexes was unaffected. RAG1 was efficiently recruited, thus compensating for the defective transcription-associated recruitment of RAG2, and providing a mechanistic basis for RAG1/RAG2 assembly to initiate V(D)J recombination.</p>',
			'date' => '2020-02-22',
			'pmid' => 'http://www.pubmed.gov/32086526',
			'doi' => '10.1093/nar/gkaa108',
			'modified' => '2020-03-20 17:40:41',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 96 => array(
			'id' => '3873',
			'name' => 'Inhibition of methyltransferase activity of enhancer of zeste 2 leads to enhanced lipid accumulation and altered chromatin status in zebrafish.',
			'authors' => 'den Broeder MJ, Ballangby J, Kamminga LM, Aleström P, Legler J, Lindeman LC, Kamstra JH',
			'description' => '<p>BACKGROUND: Recent studies indicate that exposure to environmental chemicals may increase susceptibility to developing metabolic diseases. This susceptibility may in part be caused by changes to the epigenetic landscape which consequently affect gene expression and lead to changes in lipid metabolism. The epigenetic modifier enhancer of zeste 2 (Ezh2) is a histone H3K27 methyltransferase implicated to play a role in lipid metabolism and adipogenesis. In this study, we used the zebrafish (Danio rerio) to investigate the role of Ezh2 on lipid metabolism and chromatin status following developmental exposure to the Ezh1/2 inhibitor PF-06726304 acetate. We used the environmental chemical tributyltin (TBT) as a positive control, as this chemical is known to act on lipid metabolism via EZH-mediated pathways in mammals. RESULTS: Zebrafish embryos (0-5&nbsp;days post-fertilization, dpf) exposed to non-toxic concentrations of PF-06726304 acetate (5&nbsp;&mu;M) and TBT (1&nbsp;nM) exhibited increased lipid accumulation. Changes in chromatin were analyzed by the assay for transposase-accessible chromatin sequencing (ATAC-seq) at 50% epiboly (5.5 hpf). We observed 349 altered chromatin regions, predominantly located at H3K27me3 loci and mostly more open chromatin in the exposed samples. Genes associated to these loci were linked to metabolic pathways. In addition, a selection of genes involved in lipid homeostasis, adipogenesis and genes specifically targeted by PF-06726304 acetate via altered chromatin accessibility were differentially expressed after TBT and PF-06726304 acetate exposure at 5 dpf, but not at 50% epiboly stage. One gene, cebpa, did not show a change in chromatin, but did show a change in gene expression at 5 dpf. Interestingly, underlying H3K27me3 marks were significantly decreased at this locus at 50% epiboly. CONCLUSIONS: Here, we show for the first time the applicability of ATAC-seq as a tool to investigate toxicological responses in zebrafish. Our analysis indicates that Ezh2 inhibition leads to a partial primed state of chromatin linked to metabolic pathways which results in gene expression changes later in development, leading to enhanced lipid accumulation. Although ATAC-seq seems promising, our in-depth assessment of the cebpa locus indicates that we need to consider underlying epigenetic marks as well.</p>',
			'date' => '2020-02-12',
			'pmid' => 'http://www.pubmed.gov/32051014',
			'doi' => '10.1186/s13072-020-0329-y',
			'modified' => '2020-03-20 17:42:02',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 97 => array(
			'id' => '3883',
			'name' => 'Targeting Macrophage Histone H3 Modification as a Leishmania Strategy to Dampen the NF-κB/NLRP3-Mediated Inflammatory Response.',
			'authors' => 'Lecoeur H, Prina E, Rosazza T, Kokou K, N'Diaye P, Aulner N, Varet H, Bussotti G, Xing Y, Milon G, Weil R, Meng G, Späth GF',
			'description' => '<p>Aberrant macrophage activation during intracellular infection generates immunopathologies that can cause severe human morbidity. A better understanding of immune subversion strategies and macrophage phenotypic and functional responses is necessary to design host-directed intervention strategies. Here, we uncover a fine-tuned transcriptional response that is induced in primary and lesional macrophages infected by the parasite Leishmania amazonensis and dampens NF-&kappa;B and NLRP3 inflammasome activation. Subversion is amastigote-specific and characterized by a decreased expression of activating and increased expression of de-activating components of these pro-inflammatory pathways, thus revealing a regulatory dichotomy that abrogates the anti-microbial response. Changes in transcript abundance correlate with histone H3K9/14 hypoacetylation and H3K4 hypo-trimethylation in infected primary and lesional macrophages at promoters of NF-&kappa;B-related, pro-inflammatory genes. Our results reveal a Leishmania immune subversion strategy targeting host cell epigenetic regulation to establish conditions beneficial for parasite survival and open avenues for host-directed, anti-microbial drug discovery.</p>',
			'date' => '2020-02-11',
			'pmid' => 'http://www.pubmed.gov/32049017',
			'doi' => '10.1016/j.celrep.2020.01.030',
			'modified' => '2020-03-20 17:29:47',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 98 => array(
			'id' => '3868',
			'name' => 'Replicational Dilution of H3K27me3 in Mammalian Cells and the Role of Poised Promoters.',
			'authors' => 'Jadhav U, Manieri E, Nalapareddy K, Madha S, Chakrabarti S, Wucherpfennig K, Barefoot M, Shivdasani RA',
			'description' => '<p>Polycomb repressive complex 2 (PRC2) places H3K27me3 at developmental genes and is causally implicated in keeping bivalent genes silent. It is unclear if that silence requires minimum H3K27me3 levels and how the mark transmits faithfully across mammalian somatic cell generations. Mouse intestinal cells lacking EZH2 methyltransferase reduce H3K27me3 proportionately at all PRC2 target sites, but &sim;40% uniform residual levels keep target genes inactive. These genes, derepressed in PRC2-null villus cells, remain silent in intestinal stem cells (ISCs). Quantitative chromatin immunoprecipitation and computational modeling indicate that because unmodified histones dilute H3K27me3 by 50% each time DNA replicates, PRC2-deficient ISCs initially retain sufficient H3K27me3 to avoid gene derepression. EZH2 mutant human lymphoma cells also require multiple divisions before H3K27me3 dilution relieves gene silencing. In both cell types, promoters with high basal H3K4me2/3 activate in spite of some residual H3K27me3, compared to less-poised promoters. These findings have implications for PRC2 inhibition in cancer therapy.</p>',
			'date' => '2020-01-29',
			'pmid' => 'http://www.pubmed.gov/32027840',
			'doi' => '10.1016/j.molcel.2020.01.017',
			'modified' => '2020-03-20 17:46:30',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 99 => array(
			'id' => '3848',
			'name' => 'A comprehensive epigenomic analysis of phenotypically distinguishable, genetically identical female and male Daphnia pulex.',
			'authors' => 'Kvist J, Athanàsio CG, Pfrender ME, Brown JB, Colbourne JK, Mirbahai L',
			'description' => '<p>BACKGROUND: Daphnia species reproduce by cyclic parthenogenesis involving both sexual and asexual reproduction. The sex of the offspring is environmentally determined and mediated via endocrine signalling by the mother. Interestingly, male and female Daphnia can be genetically identical, yet display large differences in behaviour, morphology, lifespan and metabolic activity. Our goal was to integrate multiple omics datasets, including gene expression, splicing, histone modification and DNA methylation data generated from genetically identical female and male Daphnia pulex under controlled laboratory settings with the aim of achieving a better understanding of the underlying epigenetic factors that may contribute to the phenotypic differences observed between the two genders. RESULTS: In this study we demonstrate that gene expression level is positively correlated with increased DNA methylation, and histone H3 trimethylation at lysine&thinsp;4 (H3K4me3) at predicted promoter regions. Conversely, elevated histone H3 trimethylation at lysine&thinsp;27 (H3K27me3), distributed across the entire transcript length, is negatively correlated with gene expression level. Interestingly, male Daphnia are dominated with epigenetic modifications that globally promote elevated gene expression, while female Daphnia are dominated with epigenetic modifications that reduce gene expression globally. For examples, CpG methylation (positively correlated with gene expression level) is significantly higher in almost all differentially methylated sites in male compared to female Daphnia. Furthermore, H3K4me3 modifications are higher in male compared to female Daphnia in more than 3/4 of the differentially regulated promoters. On the other hand, H3K27me3 is higher in female compared to male Daphnia in more than 5/6 of differentially modified sites. However, both sexes demonstrate roughly equal number of genes that are up-regulated in one gender compared to the other sex. Since, gene expression analyses typically assume that most genes are expressed at equal level among samples and different conditions, and thus cannot detect global changes affecting most genes. CONCLUSIONS: The epigenetic differences between male and female in Daphnia pulex are vast and dominated by changes that promote elevated gene expression in male Daphnia. Furthermore, the differences observed in both gene expression changes and epigenetic modifications between the genders relate to pathways that are physiologically relevant to the observed phenotypic differences.</p>',
			'date' => '2020-01-06',
			'pmid' => 'http://www.pubmed.gov/31906859',
			'doi' => '10.1186/s12864-019-6415-5',
			'modified' => '2020-02-20 11:34:47',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 100 => array(
			'id' => '3802',
			'name' => 'Analysis of Histone Modifications in Rodent Pancreatic Islets by Native Chromatin Immunoprecipitation.',
			'authors' => 'Sandovici I, Nicholas LM, O'Neill LP',
			'description' => '<p>The islets of Langerhans are clusters of cells dispersed throughout the pancreas that produce several hormones essential for controlling a variety of metabolic processes, including glucose homeostasis and lipid metabolism. Studying the transcriptional control of pancreatic islet cells has important implications for understanding the mechanisms that control their normal development, as well as the pathogenesis of metabolic diseases such as diabetes. Histones represent the main protein components of the chromatin and undergo diverse covalent modifications that are very important for gene regulation. Here we describe the isolation of pancreatic islets from rodents and subsequently outline the methods used to immunoprecipitate and analyze the native chromatin obtained from these cells.</p>',
			'date' => '2020-01-01',
			'pmid' => 'http://www.pubmed.gov/31586329',
			'doi' => '10.1007/978-1-4939-9882-1',
			'modified' => '2019-12-05 11:28:01',
			'created' => '2019-12-02 15:25:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 101 => array(
			'id' => '4096',
			'name' => 'Changes in H3K27ac at Gene Regulatory Regions in Porcine AlveolarMacrophages Following LPS or PolyIC Exposure.',
			'authors' => 'Herrera-Uribe, Juber and Liu, Haibo and Byrne, Kristen A and Bond, Zahra Fand Loving, Crystal L and Tuggle, Christopher K',
			'description' => '<p>Changes in chromatin structure, especially in histone modifications (HMs), linked with chromatin accessibility for transcription machinery, are considered to play significant roles in transcriptional regulation. Alveolar macrophages (AM) are important immune cells for protection against pulmonary pathogens, and must readily respond to bacteria and viruses that enter the airways. Mechanism(s) controlling AM innate response to different pathogen-associated molecular patterns (PAMPs) are not well defined in pigs. By combining RNA sequencing (RNA-seq) with chromatin immunoprecipitation and sequencing (ChIP-seq) for four histone marks (H3K4me3, H3K4me1, H3K27ac and H3K27me3), we established a chromatin state map for AM stimulated with two different PAMPs, lipopolysaccharide (LPS) and Poly(I:C), and investigated the potential effect of identified histone modifications on transcription factor binding motif (TFBM) prediction and RNA abundance changes in these AM. The integrative analysis suggests that the differential gene expression between non-stimulated and stimulated AM is significantly associated with changes in the H3K27ac level at active regulatory regions. Although global changes in chromatin states were minor after stimulation, we detected chromatin state changes for differentially expressed genes involved in the TLR4, TLR3 and RIG-I signaling pathways. We found that regions marked by H3K27ac genome-wide were enriched for TFBMs of TF that are involved in the inflammatory response. We further documented that TF whose expression was induced by these stimuli had TFBMs enriched within H3K27ac-marked regions whose chromatin state changed by these same stimuli. Given that the dramatic transcriptomic changes and minor chromatin state changes occurred in response to both stimuli, we conclude that regulatory elements (i.e. active promoters) that contain transcription factor binding motifs were already active/poised in AM for immediate inflammatory response to PAMPs. In summary, our data provides the first chromatin state map of porcine AM in response to bacterial and viral PAMPs, contributing to the Functional Annotation of Animal Genomes (FAANG) project, and demonstrates the role of HMs, especially H3K27ac, in regulating transcription in AM in response to LPS and Poly(I:C).</p>',
			'date' => '2020-01-01',
			'pmid' => 'https://www.frontiersin.org/articles/10.3389/fgene.2020.00817/full',
			'doi' => '10.3389/fgene.2020.00817',
			'modified' => '2021-03-17 17:22:56',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 102 => array(
			'id' => '3839',
			'name' => 'Functionally Annotating Regulatory Elements in the Equine Genome Using Histone Mark ChIP-Seq.',
			'authors' => 'Kingsley NB, Kern C, Creppe C, Hales EN, Zhou H, Kalbfleisch TS, MacLeod JN, Petersen JL, Finno CJ, Bellone RR',
			'description' => '<p>One of the primary aims of the Functional Annotation of ANimal Genomes (FAANG) initiative is to characterize tissue-specific regulation within animal genomes. To this end, we used chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to map four histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me3) in eight prioritized tissues collected as part of the FAANG equine biobank from two thoroughbred mares. Data were generated according to optimized experimental parameters developed during quality control testing. To ensure that we obtained sufficient ChIP and successful peak-calling, data and peak-calls were assessed using six quality metrics, replicate comparisons, and site-specific evaluations. Tissue specificity was explored by identifying binding motifs within unique active regions, and motifs were further characterized by gene ontology (GO) and protein-protein interaction analyses. The histone marks identified in this study represent some of the first resources for tissue-specific regulation within the equine genome. As such, these publicly available annotation data can be used to advance equine studies investigating health, performance, reproduction, and other traits of economic interest in the horse.</p>',
			'date' => '2019-12-18',
			'pmid' => 'http://www.pubmed.gov/31861495',
			'doi' => '10.3390/genes11010003',
			'modified' => '2020-02-20 11:20:25',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 103 => array(
			'id' => '3837',
			'name' => 'H3K4me1 Supports Memory-like NK Cells Induced by Systemic Inflammation.',
			'authors' => 'Rasid O, Chevalier C, Camarasa TM, Fitting C, Cavaillon JM, Hamon MA',
			'description' => '<p>Natural killer (NK) cells are unique players in innate immunity and, as such, an attractive target for immunotherapy. NK cells display immune memory properties in certain models, but the long-term status of NK cells following systemic inflammation is unknown. Here we show that following LPS-induced endotoxemia in mice, NK cells acquire cell-intrinsic memory-like properties, showing increased production of IFN&gamma; upon specific secondary stimulation. The NK cell memory response is detectable for at least 9&nbsp;weeks and contributes to protection from E.&nbsp;coli infection upon adoptive transfer. Importantly, we reveal a mechanism essential for NK cell memory, whereby an H3K4me1-marked latent enhancer is uncovered at the ifng locus. Chemical inhibition of histone methyltransferase activity erases the enhancer and abolishes NK cell memory. Thus, NK cell memory develops after endotoxemia in a histone methylation-dependent manner, ensuring a heightened response to secondary stimulation.</p>',
			'date' => '2019-12-17',
			'pmid' => 'http://www.pubmed.gov/31851924',
			'doi' => '10.1016/j.celrep.2019.11.043',
			'modified' => '2020-02-20 11:24:10',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 104 => array(
			'id' => '3830',
			'name' => 'Trained immunity modulates inflammation-induced fibrosis.',
			'authors' => 'Jeljeli M, Riccio LGC, Doridot L, Chêne C, Nicco C, Chouzenoux S, Deletang Q, Allanore Y, Kavian N, Batteux F',
			'description' => '<p>Chronic inflammation and fibrosis can result from inappropriately activated immune responses that are mediated by macrophages. Macrophages can acquire memory-like characteristics in response to antigen exposure. Here, we show the effect of BCG or low-dose LPS stimulation on macrophage phenotype, cytokine production, chromatin and metabolic modifications. Low-dose LPS training alleviates fibrosis and inflammation in a mouse model of systemic sclerosis (SSc), whereas BCG-training exacerbates disease in this model. Adoptive transfer of low-dose LPS-trained or BCG-trained macrophages also has beneficial or harmful effects, respectively. Furthermore, coculture with low-dose LPS trained macrophages reduces the fibro-inflammatory profile of fibroblasts from mice and patients with SSc, indicating that trained immunity might be a phenomenon that can be targeted to treat SSc and other autoimmune and inflammatory fibrotic disorders.</p>',
			'date' => '2019-12-11',
			'pmid' => 'http://www.pubmed.gov/31827093',
			'doi' => '10.1038/s41467-019-13636-x',
			'modified' => '2020-02-25 13:32:01',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 105 => array(
			'id' => '3826',
			'name' => 'MicroRNA-708 is a novel regulator of the Hoxa9 program in myeloid cells.',
			'authors' => 'Schneider E, Pochert N, Ruess C, MacPhee L, Escano L, Miller C, Krowiorz K, Delsing Malmberg E, Heravi-Moussavi A, Lorzadeh A, Ashouri A, Grasedieck S, Sperb N, Kumar Kopparapu P, Iben S, Staffas A, Xiang P, Rösler R, Kanduri M, Larsson E, Fogelstrand L, ',
			'description' => '<p>MicroRNAs (miRNAs) are commonly deregulated in acute myeloid leukemia (AML), affecting critical genes not only through direct targeting, but also through modulation of downstream effectors. Homeobox (Hox) genes balance self-renewal, proliferation, cell death, and differentiation in many tissues and aberrant Hox gene expression can create a predisposition to leukemogenesis in hematopoietic cells. However, possible linkages between the regulatory pathways of Hox genes and miRNAs are not yet fully resolved. We identified miR-708 to be upregulated in Hoxa9/Meis1 AML inducing cell lines as well as in AML patients. We further showed Meis1 directly targeting miR-708 and modulating its expression through epigenetic transcriptional regulation. CRISPR/Cas9 mediated knockout of miR-708 in Hoxa9/Meis1 cells delayed disease onset in vivo, demonstrating for the first time a pro-leukemic contribution of miR-708 in this context. Overexpression of miR-708 however strongly impeded Hoxa9 mediated transformation and homing capacity in vivo through modulation of adhesion factors and induction of myeloid differentiation. Taken together, we reveal miR-708, a putative tumor suppressor miRNA and direct target of Meis1, as a potent antagonist of the Hoxa9 phenotype but an effector of transformation in Hoxa9/Meis1. This unexpected finding highlights the yet unexplored role of miRNAs as indirect regulators of the Hox program during normal and aberrant hematopoiesis.</p>',
			'date' => '2019-11-25',
			'pmid' => 'http://www.pubmed.gov/31768018',
			'doi' => '10.1038/s41375-019-0651-1',
			'modified' => '2020-02-25 13:36:10',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 106 => array(
			'id' => '3807',
			'name' => 'Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.',
			'authors' => 'Aloia L, McKie MA, Vernaz G, Cordero-Espinoza L, Aleksieva N, van den Ameele J, Antonica F, Font-Cunill B, Raven A, Aiese Cigliano R, Belenguer G, Mort RL, Brand AH, Zernicka-Goetz M, Forbes SJ, Miska EA, Huch M',
			'description' => '<p>Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal cells. However, the molecular mechanisms by which adult ductal-committed cells acquire cellular plasticity, initiate organoids and regenerate the damaged tissue remain largely unknown. Here, we describe that ductal cells undergo a transient, genome-wide, remodelling of their transcriptome and epigenome during organoid initiation and in vivo following tissue damage. TET1-mediated hydroxymethylation licences differentiated ductal cells to initiate organoids and activate the regenerative programme through the transcriptional regulation of stem-cell genes and regenerative pathways including the YAP-Hippo signalling. Our results argue in favour of the remodelling of genomic methylome/hydroxymethylome landscapes as a general mechanism by which differentiated cells exit a committed state in response to tissue damage.</p>',
			'date' => '2019-11-04',
			'pmid' => 'http://www.pubmed.gov/31685987',
			'doi' => '10.1038/s41556-019-0402-6',
			'modified' => '2019-12-05 11:19:34',
			'created' => '2019-12-02 15:25:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 107 => array(
			'id' => '3824',
			'name' => 'Transcriptional alterations in glioma result primarily from DNA methylation-independent mechanisms.',
			'authors' => 'Court F, Le Boiteux E, Fogli A, Müller-Barthélémy M, Vaurs-Barrière C, Chautard E, Pereira B, Biau J, Kemeny JL, Khalil T, Karayan-Tapon L, Verrelle P, Arnaud P',
			'description' => '<p>In cancer cells, aberrant DNA methylation is commonly associated with transcriptional alterations, including silencing of tumor suppressor genes. However, multiple epigenetic mechanisms, including polycomb repressive marks, contribute to gene deregulation in cancer. To dissect the relative contribution of DNA methylation-dependent and -independent mechanisms to transcriptional alterations at CpG island/promoter-associated genes in cancer, we studied 70 samples of adult glioma, a widespread type of brain tumor, classified according to their isocitrate dehydrogenase () mutation status. We found that most transcriptional alterations in tumor samples were DNA methylation-independent. Instead, altered histone H3 trimethylation at lysine 27 (H3K27me3) was the predominant molecular defect at deregulated genes. Our results also suggest that the presence of a bivalent chromatin signature at CpG island promoters in stem cells predisposes not only to hypermethylation, as widely documented, but more generally to all types of transcriptional alterations in transformed cells. In addition, the gene expression strength in healthy brain cells influences the choice between DNA methylation- and H3K27me3-associated silencing in glioma. Highly expressed genes were more likely to be repressed by H3K27me3 than by DNA methylation. Our findings support a model in which altered H3K27me3 dynamics, more specifically defects in the interplay between polycomb protein complexes and the brain-specific transcriptional machinery, is the main cause of transcriptional alteration in glioma cells. Our study provides the first comprehensive description of epigenetic changes in glioma and their relative contribution to transcriptional changes. It may be useful for the design of drugs targeting cancer-related epigenetic defects.</p>',
			'date' => '2019-10-01',
			'pmid' => 'http://www.pubmed.gov/31533980',
			'doi' => '10.1101/gr.249219.119.',
			'modified' => '2020-02-25 13:41:40',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 108 => array(
			'id' => '3781',
			'name' => 'Functional analyses of a low-penetrance risk variant rs6702619/1p21.2 associating with colorectal cancer in Polish population.',
			'authors' => 'Statkiewicz M, Maryan N, Kulecka M, Kuklinska U, Ostrowski J, Mikula M',
			'description' => '<p>Several studies employed the genome-wide association (GWA) analysis of single-nucleotide polymorphisms (SNPs) to identify susceptibility regions in colorectal cancer (CRC). However, the functional studies exploring the role of associating SNPs with cancer biology are limited. Herein, using chromatin immunoprecipitation assay (ChIP), reporter assay and chromosome conformation capture sequencing (3C-Seq) augmented with publically available genomic and epigenomic databases we aimed to define the function of rs6702619/1p21.2 region associated with CRC in the Polish population. Using ChIP we confirmed that rs6702619 region is occupied by a CTCF, a master regulator of long-range genomic interactions, and is decorated with enhancer-like histone modifications. The enhancer blocking assay revealed that rs6702619 region acts as an insulator with activity dependent on the SNP genotype. Finally, a 3C-Seq survey indicated more than a hundred loci in the rs6702619 locus interactome, including GNAS gene that is frequently amplified in CRC. Taken together, we showed that the CRC-associated rs6702619 region has in vitro and in vivo properties of an insulator that demonstrates long-range physical interactions with CRC-relevant loci.</p>',
			'date' => '2019-09-17',
			'pmid' => 'http://www.pubmed.gov/31531420',
			'doi' => '10.1093/nar/gkm875.',
			'modified' => '2019-10-02 16:51:42',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 109 => array(
			'id' => '3776',
			'name' => 'β-Glucan-Induced Trained Immunity Protects against Leishmania braziliensis Infection: a Crucial Role for IL-32.',
			'authors' => 'Dos Santos JC, Barroso de Figueiredo AM, Teodoro Silva MV, Cirovic B, de Bree LCJ, Damen MSMA, Moorlag SJCFM, Gomes RS, Helsen MM, Oosting M, Keating ST, Schlitzer A, Netea MG, Ribeiro-Dias F, Joosten LAB',
			'description' => '<p>American tegumentary leishmaniasis is a vector-borne parasitic disease caused by Leishmania protozoans. Innate immune cells undergo long-term functional reprogramming in response to infection or Bacillus Calmette-Gu&eacute;rin (BCG) vaccination via a process called trained immunity, conferring non-specific protection from secondary infections. Here, we demonstrate that monocytes trained with the fungal cell wall component &beta;-glucan confer enhanced protection against infections caused by Leishmania braziliensis through the enhanced production of proinflammatory cytokines. Mechanistically, this augmented immunological response is dependent on increased expression of interleukin 32 (IL-32). Studies performed using a humanized IL-32 transgenic mouse highlight the clinical implications of these findings in&nbsp;vivo. This study represents a definitive characterization of the role of IL-32&gamma; in the trained phenotype induced by &beta;-glucan or BCG, the results of which improve our understanding of the molecular mechanisms governing trained immunity and Leishmania infection control.</p>',
			'date' => '2019-09-03',
			'pmid' => 'http://www.pubmed.gov/31484076',
			'doi' => '10.1016/j.celrep.2019.08.004',
			'modified' => '2019-10-02 17:00:49',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 110 => array(
			'id' => '3774',
			'name' => 'Reactivation of super-enhancers by KLF4 in human Head and Neck Squamous Cell Carcinoma.',
			'authors' => 'Tsompana M, Gluck C, Sethi I, Joshi I, Bard J, Nowak NJ, Sinha S, Buck MJ',
			'description' => '<p>Head and neck squamous cell carcinoma (HNSCC) is a disease of significant morbidity and mortality and rarely diagnosed in early stages. Despite extensive genetic and genomic characterization, targeted therapeutics and diagnostic markers of HNSCC are lacking due to the inherent heterogeneity and complexity of the disease. Herein, we have generated the global histone mark based epigenomic and transcriptomic cartogram of SCC25, a representative cell type of mesenchymal HNSCC and its normal oral keratinocyte counterpart. Examination of genomic regions marked by differential chromatin states and associated with misregulated gene expression led us to identify SCC25 enriched regulatory sequences and transcription factors (TF) motifs. These findings were further strengthened by ATAC-seq based open chromatin and TF footprint analysis which unearthed Kr&uuml;ppel-like Factor 4 (KLF4) as a potential key regulator of the SCC25 cistrome. We reaffirm the results obtained from in silico and chromatin studies in SCC25 by ChIP-seq of KLF4 and identify &Delta;Np63 as a co-oncogenic driver of the cancer-specific gene expression milieu. Taken together, our results lead us to propose a model where elevated KLF4 levels sustains the oncogenic state of HNSCC by reactivating repressed chromatin domains at key downstream genes, often by targeting super-enhancers.</p>',
			'date' => '2019-09-02',
			'pmid' => 'http://www.pubmed.gov/31477832',
			'doi' => '10.1038/s41388-019-0990-4',
			'modified' => '2019-10-02 17:05:36',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 111 => array(
			'id' => '3777',
			'name' => 'Nucleome Dynamics during Retinal Development.',
			'authors' => 'Norrie JL, Lupo MS, Xu B, Al Diri I, Valentine M, Putnam D, Griffiths L, Zhang J, Johnson D, Easton J, Shao Y, Honnell V, Frase S, Miller S, Stewart V, Zhou X, Chen X, Dyer MA',
			'description' => '<p>More than 8,000 genes are turned on or off as progenitor cells produce the 7 classes of retinal cell types during development. Thousands of enhancers are also active in the developing retinae, many having features of cell- and developmental stage-specific activity. We studied dynamic changes in the 3D chromatin landscape important for precisely orchestrated changes in gene expression during retinal development by ultra-deep in situ Hi-C analysis on murine retinae. We identified developmental-stage-specific changes in chromatin compartments and enhancer-promoter interactions. We developed a machine learning-based algorithm to map euchromatin and heterochromatin domains genome-wide and overlaid it with chromatin compartments identified by Hi-C. Single-cell ATAC-seq and RNA-seq were integrated with our Hi-C and previous ChIP-seq data to identify cell- and developmental-stage-specific super-enhancers (SEs). We identified a bipolar neuron-specific core regulatory circuit SE upstream of Vsx2, whose deletion in mice led to the loss of bipolar neurons.</p>',
			'date' => '2019-08-21',
			'pmid' => 'http://www.pubmed.gov/31493975',
			'doi' => '10.1016/j.neuron.2019.08.002',
			'modified' => '2019-10-02 16:58:50',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 112 => array(
			'id' => '3742',
			'name' => 'Development and epigenetic plasticity of murine Müller glia.',
			'authors' => 'Dvoriantchikova G, Seemungal RJ, Ivanov D',
			'description' => '<p>The ability to regenerate the entire retina and restore lost sight after injury is found in some species and relies mostly on the epigenetic plasticity of M&uuml;ller glia. To understand the role of mammalian M&uuml;ller glia as a source of progenitors for retinal regeneration, we investigated changes in gene expression during differentiation of retinal progenitor cells (RPCs) into M&uuml;ller glia. We also analyzed the global epigenetic profile of adult M&uuml;ller glia. We observed significant changes in gene expression during differentiation of RPCs into M&uuml;ller glia in only a small group of genes. We found a high similarity between RPCs and M&uuml;ller glia on the transcriptomic and epigenomic levels. Our findings also indicate that M&uuml;ller glia are epigenetically very close to late-born retinal neurons, but not early-born retinal neurons. Importantly, we found that key genes required for phototransduction were highly methylated. Thus, our data suggest that M&uuml;ller glia are epigenetically very similar to late RPCs. Meanwhile, obstacles for regeneration of the entire mammalian retina from M&uuml;ller glia may consist of repressive chromatin and highly methylated DNA in the promoter regions of many genes required for the development of early-born retinal neurons. In addition, DNA demethylation may be required for proper reprogramming and differentiation of M&uuml;ller glia into rod photoreceptors.</p>
<div id="ConnectiveDocSignExtentionInstalled" data-extension-version="1.0.4"></div>
<div id="ConnectiveDocSignExtentionInstalled" data-extension-version="1.0.4"></div>',
			'date' => '2019-07-02',
			'pmid' => 'http://www.pubmed.gov/31276697',
			'doi' => '10.1016/j.bbamcr.2019.06.019',
			'modified' => '2019-08-13 10:50:24',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 113 => array(
			'id' => '3754',
			'name' => 'The alarmin S100A9 hampers osteoclast differentiation from human circulating precursors by reducing the expression of RANK.',
			'authors' => 'Di Ceglie I, Blom AB, Davar R, Logie C, Martens JHA, Habibi E, Böttcher LM, Roth J, Vogl T, Goodyear CS, van der Kraan PM, van Lent PL, van den Bosch MH',
			'description' => '<p>The alarmin S100A8/A9 is implicated in sterile inflammation-induced bone resorption and has been shown to increase the bone-resorptive capacity of mature osteoclasts. Here, we investigated the effects of S100A9 on osteoclast differentiation from human CD14 circulating precursors. Hereto, human CD14 monocytes were isolated and differentiated toward osteoclasts with M-CSF and receptor activator of NF-&kappa;B (RANK) ligand (RANKL) in the presence or absence of S100A9. Tartrate-resistant acid phosphatase staining showed that exposure to S100A9 during monocyte-to-osteoclast differentiation strongly decreased the numbers of multinucleated osteoclasts. This was underlined by a decreased resorption of a hydroxyapatite-like coating. The thus differentiated cells showed a high mRNA and protein production of proinflammatory factors after 16 h of exposure. In contrast, at d 4, the cells showed a decreased production of the osteoclast-promoting protein TNF-&alpha;. Interestingly, S100A9 exposure during the first 16 h of culture only was sufficient to reduce osteoclastogenesis. Using fluorescently labeled RANKL, we showed that, within this time frame, S100A9 inhibited the M-CSF-mediated induction of RANK. Chromatin immunoprecipitation showed that this was associated with changes in various histone marks at the epigenetic level. This S100A9-induced reduction in RANK was in part recovered by blocking TNF-&alpha; but not IL-1. Together, our data show that S100A9 impedes monocyte-to-osteoclast differentiation, probably a reduction in RANK expression.-Di Ceglie, I., Blom, A. B., Davar, R., Logie, C., Martens, J. H. A., Habibi, E., B&ouml;ttcher, L.-M., Roth, J., Vogl, T., Goodyear, C. S., van der Kraan, P. M., van Lent, P. L., van den Bosch, M. H. The alarmin S100A9 hampers osteoclast differentiation from human circulating precursors by reducing the expression of RANK.</p>',
			'date' => '2019-06-14',
			'pmid' => 'http://www.pubmed.gov/31199668',
			'doi' => '10.1096/fj.201802691RR',
			'modified' => '2019-10-03 12:20:02',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 114 => array(
			'id' => '3737',
			'name' => 'Probing the Tumor Suppressor Function of BAP1 in CRISPR-Engineered Human Liver Organoids.',
			'authors' => 'Artegiani B, van Voorthuijsen L, Lindeboom RGH, Seinstra D, Heo I, Tapia P, López-Iglesias C, Postrach D, Dayton T, Oka R, Hu H, van Boxtel R, van Es JH, Offerhaus J, Peters PJ, van Rheenen J, Vermeulen M, Clevers H',
			'description' => '<p>The deubiquitinating enzyme BAP1 is a tumor suppressor, among others involved in cholangiocarcinoma. BAP1 has many proposed molecular targets, while its Drosophila homolog is known to deubiquitinate histone H2AK119. We introduce BAP1 loss-of-function by CRISPR/Cas9 in normal human cholangiocyte organoids. We find that BAP1 controls&nbsp;the expression of junctional and cytoskeleton components by regulating chromatin accessibility. Consequently, we observe loss of multiple epithelial characteristics while motility increases. Importantly, restoring the catalytic activity of BAP1 in the nucleus rescues these cellular and molecular changes. We engineer human liver organoids to combine four common cholangiocarcinoma mutations (TP53, PTEN, SMAD4, and NF1). In this genetic background, BAP1 loss results in acquisition of malignant features upon xenotransplantation. Thus, control of epithelial identity through the regulation of chromatin accessibility appears to be a key aspect of BAP1's tumor suppressor function. Organoid technology combined with CRISPR/Cas9 provides an experimental platform for mechanistic studies of cancer gene function in a human context.</p>',
			'date' => '2019-06-06',
			'pmid' => 'http://www.pubmed.gov/31130514',
			'doi' => '10.1016/j.stem.2019.04.017',
			'modified' => '2019-08-06 16:58:50',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 115 => array(
			'id' => '3713',
			'name' => 'Complementary Activity of ETV5, RBPJ, and TCF3 Drives Formative Transition from Naive Pluripotency.',
			'authors' => 'Kalkan T, Bornelöv S, Mulas C, Diamanti E, Lohoff T, Ralser M, Middelkamp S, Lombard P, Nichols J, Smith A',
			'description' => '<p>The gene regulatory network (GRN) of naive mouse embryonic stem cells (ESCs) must be reconfigured to enable lineage commitment. TCF3 sanctions rewiring by suppressing components of the ESC transcription factor circuitry. However, TCF3 depletion only delays and does not prevent transition to formative pluripotency. Here, we delineate additional contributions of the ETS-family transcription factor ETV5 and the repressor RBPJ. In response to ERK signaling, ETV5 switches activity from supporting self-renewal and undergoes genome relocation linked to commissioning of enhancers activated in formative epiblast. Independent upregulation of RBPJ prevents re-expression of potent naive factors, TBX3 and NANOG, to secure exit from the naive state. Triple deletion of Etv5, Rbpj, and Tcf3 disables ESCs, such that they remain largely undifferentiated and locked in self-renewal, even in the presence of differentiation stimuli. Thus, genetic elimination of three complementary drivers of network transition stalls developmental progression, emulating environmental insulation by small-molecule inhibitors.</p>',
			'date' => '2019-05-02',
			'pmid' => 'http://www.pubmed.gov/31031137',
			'doi' => '10.1016/j.stem.2019.03.017',
			'modified' => '2019-07-05 14:28:38',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 116 => array(
			'id' => '3692',
			'name' => 'PML modulates H3.3 targeting to telomeric and centromeric repeats in mouse fibroblasts.',
			'authors' => 'Spirkoski J, Shah A, Reiner AH, Collas P, Delbarre E',
			'description' => '<p>Targeted deposition of histone variant H3.3 into chromatin is paramount for proper regulation of chromatin integrity, particularly in heterochromatic regions including repeats. We have recently shown that the promyelocytic leukemia (PML) protein prevents H3.3 from being deposited in large heterochromatic PML-associated domains (PADs). However, to what extent PML modulates H3.3 loading on chromatin in other areas of the genome remains unexplored. Here, we examined the impact of PML on targeting of H3.3 to genes and repeat regions that reside outside PADs. We show that loss of PML increases H3.3 deposition in subtelomeric, telomeric, pericentric and centromeric repeats in mouse embryonic fibroblasts, while other repeat classes are not affected. Expression of major satellite, minor satellite and telomeric non-coding transcripts is altered in Pml-null cells. In particular, telomeric Terra transcripts are strongly upregulated, in concordance with a marked reduction in H4K20me3 at these sites. Lastly, for most genes H3.3 enrichment or gene expression outcomes are independent of PML. Our data argue towards the importance of a PML-H3.3 axis in preserving a heterochromatin state at centromeres and telomeres.</p>',
			'date' => '2019-04-16',
			'pmid' => 'http://www.pubmed.gov/30850162',
			'doi' => '10.1016/j.bbrc.2019.02.087',
			'modified' => '2019-06-28 13:50:40',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 117 => array(
			'id' => '3711',
			'name' => 'Long intergenic non-coding RNAs regulate human lung fibroblast function: Implications for idiopathic pulmonary fibrosis.',
			'authors' => 'Hadjicharalambous MR, Roux BT, Csomor E, Feghali-Bostwick CA, Murray LA, Clarke DL, Lindsay MA',
			'description' => '<p>Phenotypic changes in lung fibroblasts are believed to contribute to the development of Idiopathic Pulmonary Fibrosis (IPF), a progressive and fatal lung disease. Long intergenic non-coding RNAs (lincRNAs) have been identified as novel regulators of gene expression and protein activity. In non-stimulated cells, we observed reduced proliferation and inflammation but no difference in the fibrotic response of IPF fibroblasts. These functional changes in non-stimulated cells were associated with changes in the expression of the histone marks, H3K4me1, H3K4me3 and H3K27ac indicating a possible involvement of epigenetics. Following activation with TGF-&beta;1 and IL-1&beta;, we demonstrated an increased fibrotic but reduced inflammatory response in IPF fibroblasts. There was no significant difference in proliferation following PDGF exposure. The lincRNAs, LINC00960 and LINC01140 were upregulated in IPF fibroblasts. Knockdown studies showed that LINC00960 and LINC01140 were positive regulators of proliferation in both control and IPF fibroblasts but had no effect upon the fibrotic response. Knockdown of LINC01140 but not LINC00960 increased the inflammatory response, which was greater in IPF compared to control fibroblasts. Overall, these studies demonstrate for the first time that lincRNAs are important regulators of proliferation and inflammation in human lung fibroblasts and that these might mediate the reduced inflammatory response observed in IPF-derived fibroblasts.</p>',
			'date' => '2019-04-15',
			'pmid' => 'http://www.pubmed.gov/30988425',
			'doi' => '10.1038/s41598-019-42292-w',
			'modified' => '2019-07-05 14:31:28',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 118 => array(
			'id' => '3702',
			'name' => 'Identification of ADGRE5 as discriminating MYC target between Burkitt lymphoma and diffuse large B-cell lymphoma.',
			'authors' => 'Kleo K, Dimitrova L, Oker E, Tomaszewski N, Berg E, Taruttis F, Engelmann JC, Schwarzfischer P, Reinders J, Spang R, Gronwald W, Oefner PJ, Hummel M',
			'description' => '<p>BACKGROUND: MYC is a heterogeneously expressed transcription factor that plays a multifunctional role in many biological processes such as cell proliferation and differentiation. It is also associated with many types of cancer including the malignant lymphomas. There are two types of aggressive B-cell lymphoma, namely Burkitt lymphoma (BL) and a subgroup of diffuse large cell lymphoma (DLBCL), which both carry MYC translocations and overexpress MYC but both differ significantly in their clinical outcome. In DLBCL, MYC translocations are associated with an aggressive behavior and poor outcome, whereas MYC-positive BL show a superior outcome. METHODS: To shed light on this phenomenon, we investigated the different modes of actions of MYC in aggressive B-cell lymphoma cell lines subdivided into three groups: (i) MYC-positive BL, (ii) DLBCL with MYC translocation (DLBCLpos) and (iii) DLBCL without MYC translocation (DLBCLneg) for control. In order to identify genome-wide MYC-DNA binding sites a chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) was performed. In addition, ChIP-Seq for H3K4me3 was used for determination of genomic regions accessible for transcriptional activity. These data were supplemented with gene expression data derived from RNA-Seq. RESULTS: Bioinformatics integration of all data sets revealed different MYC-binding patterns and transcriptional profiles in MYC-positive BL and DLBCL cell lines indicating different functional roles of MYC for gene regulation in aggressive B-cell lymphomas. Based on this multi-omics analysis we identified ADGRE5 (alias CD97) - a member of the EGF-TM7 subfamily of adhesion G protein-coupled receptors - as a MYC target gene, which is specifically expressed in BL but not in DLBCL regardless of MYC translocation. CONCLUSION: Our study describes a diverse genome-wide MYC-DNA binding pattern in BL and DLBCL cell lines with and without MYC translocations. Furthermore, we identified ADREG5 as a MYC target gene able to discriminate between BL and DLBCL irrespectively of the presence of MYC breaks in DLBCL. Since ADGRE5 plays an important role in tumor cell formation, metastasis and invasion, it might also be instrumental to better understand the different pathobiology of BL and DLBCL and help to explain discrepant clinical characteristics of BL and DLBCL.</p>',
			'date' => '2019-04-05',
			'pmid' => 'http://www.pubmed.gov/30953469',
			'doi' => '10.1186/s12885-019-5537-0',
			'modified' => '2019-07-05 14:41:38',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 119 => array(
			'id' => '3732',
			'name' => 'Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis.',
			'authors' => 'Mallaney C, Ostrander EL, Celik H, Kramer AC, Martens A, Kothari A, Koh WK, Haussler E, Iwamori N, Gontarz P, Zhang B, Challen GA',
			'description' => '<p>The histone demethylase KDM6B (JMJD3) is upregulated in blood disorders, suggesting that it may have important pathogenic functions. Here we examined the function of Kdm6b in hematopoietic stem cells (HSC) to evaluate its potential as a therapeutic target. Loss of Kdm6b lead to depletion of phenotypic and functional HSCs in adult mice, and Kdm6b is necessary for HSC self-renewal in response to inflammatory and proliferative stress. Loss of Kdm6b leads to a pro-differentiation poised state in HSCs due to the increased expression of the AP-1 transcription factor complex (Fos and Jun) and immediate early response (IER) genes. These gene expression changes occurred independently of chromatin modifications. Targeting AP-1 restored function of Kdm6b-deficient HSCs, suggesting that Kdm6b regulates this complex during HSC stress response. We also show Kdm6b supports developmental context-dependent leukemogenesis for T-cell acute lymphoblastic leukemia (T-ALL) and M5 acute myeloid leukemia (AML). Kdm6b is required for effective fetal-derived T-ALL and adult-derived AML, but not vice versa. These studies identify a crucial role for Kdm6b in regulating HSC self-renewal in different contexts, and highlight the potential of KDM6B as a therapeutic target in different hematopoietic malignancies.</p>',
			'date' => '2019-04-01',
			'pmid' => 'http://www.pubmed.gov/30936419',
			'doi' => '10.1038/s41375-019-0462-4',
			'modified' => '2019-08-07 09:14:05',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 120 => array(
			'id' => '3700',
			'name' => 'A critical regulator of Bcl2 revealed by systematic transcript discovery of lncRNAs associated with T-cell differentiation.',
			'authors' => 'Saadi W, Kermezli Y, Dao LTM, Mathieu E, Santiago-Algarra D, Manosalva I, Torres M, Belhocine M, Pradel L, Loriod B, Aribi M, Puthier D, Spicuglia S',
			'description' => '<p>Normal T-cell differentiation requires a complex regulatory network which supports a series of maturation steps, including lineage commitment, T-cell receptor (TCR) gene rearrangement, and thymic positive and negative selection. However, the underlying molecular mechanisms are difficult to assess due to limited T-cell models. Here we explore the use of the pro-T-cell line P5424 to study early T-cell differentiation. Stimulation of P5424 cells by the calcium ionophore ionomycin together with PMA resulted in gene regulation of T-cell differentiation and activation markers, partially mimicking the CD4CD8 double negative (DN) to double positive (DP) transition and some aspects of subsequent T-cell maturation and activation. Global analysis of gene expression, along with kinetic experiments, revealed a significant association between the dynamic expression of coding genes and neighbor lncRNAs including many newly-discovered transcripts, thus suggesting potential co-regulation. CRISPR/Cas9-mediated genetic deletion of Robnr, an inducible lncRNA located downstream of the anti-apoptotic gene Bcl2, demonstrated a critical role of the Robnr locus in the induction of Bcl2. Thus, the pro-T-cell line P5424 is a powerful model system to characterize regulatory networks involved in early T-cell differentiation and maturation.</p>',
			'date' => '2019-03-18',
			'pmid' => 'http://www.pubmed.gov/30886319',
			'doi' => '10.1038/s41598-019-41247-5',
			'modified' => '2019-07-05 14:43:51',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 121 => array(
			'id' => '3571',
			'name' => 'The role of TCF3 as potential master regulator in blastemal Wilms tumors.',
			'authors' => 'Kehl T, Schneider L, Kattler K, Stöckel D, Wegert J, Gerstner N, Ludwig N, Distler U, Tenzer S, Gessler M, Walter J, Keller A, Graf N, Meese E, Lenhof HP',
			'description' => '<p>Wilms tumors are the most common type of pediatric kidney tumors. While the overall prognosis for patients is favorable, especially tumors that exhibit a blastemal subtype after preoperative chemotherapy have a poor prognosis. For an improved risk assessment and therapy stratification, it is essential to identify the driving factors that are distinctive for this aggressive subtype. In our study, we compared gene expression profiles of 33 tumor biopsies (17 blastemal and 16 other tumors) after neoadjuvant chemotherapy. The analysis of this dataset using the Regulator Gene Association Enrichment algorithm successfully identified several biomarkers and associated molecular mechanisms that distinguish between blastemal and nonblastemal Wilms tumors. Specifically, regulators involved in embryonic development and epigenetic processes like chromatin remodeling and histone modification play an essential role in blastemal tumors. In this context, we especially identified TCF3 as the central regulatory element. Furthermore, the comparison of ChIP-Seq data of Wilms tumor cell cultures from a blastemal mouse xenograft and a stromal tumor provided further evidence that the chromatin states of blastemal cells share characteristics with embryonic stem cells that are not present in the stromal tumor cell line. These stem-cell like characteristics could potentially add to the increased malignancy and chemoresistance of the blastemal subtype. Along with TCF3, we detected several additional biomarkers that are distinctive for blastemal Wilms tumors after neoadjuvant chemotherapy and that may provide leads for new therapeutic regimens.</p>',
			'date' => '2019-03-15',
			'pmid' => 'http://www.pubmed.gov/30155889',
			'doi' => '10.1002/ijc.31834',
			'modified' => '2019-03-21 17:10:17',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 122 => array(
			'id' => '3611',
			'name' => 'Extensive Recovery of Embryonic Enhancer and Gene Memory Stored in Hypomethylated Enhancer DNA.',
			'authors' => 'Jadhav U, Cavazza A, Banerjee KK, Xie H, O'Neill NK, Saenz-Vash V, Herbert Z, Madha S, Orkin SH, Zhai H, Shivdasani RA',
			'description' => '<p>Developing and adult tissues use different cis-regulatory elements. Although DNA at some decommissioned embryonic enhancers is hypomethylated in adult cells, it is unknown whether this putative epigenetic memory is complete and recoverable. We find that, in adult mouse cells, hypomethylated CpG dinucleotides preserve a nearly complete archive of tissue-specific developmental enhancers. Sites that carry the active histone mark H3K4me1, and are therefore considered "primed," are mainly cis elements that act late in organogenesis. In contrast, sites decommissioned early in development retain hypomethylated DNA as a singular property. In adult intestinal and blood cells, sustained absence of polycomb repressive complex 2 indirectly reactivates most-and only-hypomethylated developmental enhancers. Embryonic and fetal transcriptional programs re-emerge as a result, in reverse chronology to cis element inactivation during development. Thus, hypomethylated DNA in adult cells preserves a "fossil record" of tissue-specific developmental enhancers, stably marking decommissioned sites and enabling recovery of this epigenetic memory.</p>',
			'date' => '2019-03-15',
			'pmid' => 'http://www.pubmed.gov/30905509',
			'doi' => '10.1016/j.molcel.2019.02.024',
			'modified' => '2019-04-17 14:46:15',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 123 => array(
			'id' => '3569',
			'name' => 'The epigenetic basis for the impaired ability of adult murine retinal pigment epithelium cells to regenerate retinal tissue.',
			'authors' => 'Dvoriantchikova G, Seemungal RJ, Ivanov D',
			'description' => '<p>The epigenetic plasticity of amphibian retinal pigment epithelium (RPE) allows them to regenerate the entire retina, a trait known to be absent in mammals. In this study, we investigated the epigenetic plasticity of adult murine RPE to identify possible mechanisms that prevent mammalian RPE from regenerating retinal tissue. RPE were analyzed using microarray, ChIP-seq, and whole-genome bisulfite sequencing approaches. We found that the majority of key genes required for progenitor phenotypes were in a permissive chromatin state and unmethylated in RPE. We observed that the majority of non-photoreceptor genes had promoters in a repressive chromatin state, but these promoters were in unmethylated or low-methylated regions. Meanwhile, the majority of promoters for photoreceptor genes were found in a permissive chromatin state, but were highly-methylated. Methylome states of photoreceptor-related genes in adult RPE and embryonic retina (which mostly contain progenitors) were very similar. However, promoters of these genes were demethylated and activated during retinal development. Our data suggest that, epigenetically, adult murine RPE cells are a progenitor-like cell type. Most likely two mechanisms prevent adult RPE from reprogramming and differentiating into retinal neurons: 1) repressive chromatin in the promoter regions of non-photoreceptor retinal neuron genes; 2) highly-methylated promoters of photoreceptor-related genes.</p>',
			'date' => '2019-03-07',
			'pmid' => 'http://www.pubmed.gov/30846751',
			'doi' => '10.1038/s41598-019-40262-w',
			'modified' => '2019-05-09 17:33:09',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 124 => array(
			'id' => '3671',
			'name' => 'Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes.',
			'authors' => 'Yi G, Wierenga ATJ, Petraglia F, Narang P, Janssen-Megens EM, Mandoli A, Merkel A, Berentsen K, Kim B, Matarese F, Singh AA, Habibi E, Prange KHM, Mulder AB, Jansen JH, Clarke L, Heath S, van der Reijden BA, Flicek P, Yaspo ML, Gut I, Bock C, Schuringa JJ',
			'description' => '<p>Global investigation of histone marks in acute myeloid leukemia (AML) remains limited. Analyses of 38 AML samples through integrated transcriptional and chromatin mark analysis exposes 2 major subtypes. One subtype is dominated by patients with&nbsp;NPM1 mutations or MLL-fusion genes, shows activation of the regulatory pathways involving HOX-family genes as targets, and displays high self-renewal capacity and stemness. The second subtype is enriched for RUNX1 or spliceosome mutations, suggesting potential interplay between the 2 aberrations, and mainly depends on IRF family regulators. Cellular consequences in prognosis predict a relatively worse outcome for the first subtype. Our integrated profiling establishes a rich resource to probe AML subtypes on the basis of expression and chromatin data.</p>',
			'date' => '2019-01-22',
			'pmid' => 'http://www.pubmed.gov/30673601',
			'doi' => '10.1016/j.celrep.2018.12.098',
			'modified' => '2019-07-01 11:30:31',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 125 => array(
			'id' => '3629',
			'name' => 'Comprehensive Analysis of Chromatin States in Atypical Teratoid/Rhabdoid Tumor Identifies Diverging Roles for SWI/SNF and Polycomb in Gene Regulation.',
			'authors' => 'Erkek S, Johann PD, Finetti MA, Drosos Y, Chou HC, Zapatka M, Sturm D, Jones DTW, Korshunov A, Rhyzova M, Wolf S, Mallm JP, Beck K, Witt O, Kulozik AE, Frühwald MC, Northcott PA, Korbel JO, Lichter P, Eils R, Gajjar A, Roberts CWM, Williamson D, Hasselbla',
			'description' => '<p>Biallelic inactivation of SMARCB1, encoding a member of the SWI/SNF chromatin remodeling complex, is the hallmark genetic aberration of atypical teratoid rhabdoid tumors (ATRT). Here, we report how loss of SMARCB1 affects the epigenome in these tumors. Using chromatin immunoprecipitation sequencing (ChIP-seq) on primary tumors for a series of active and repressive histone marks, we identified the chromatin states differentially represented in ATRTs compared with other brain tumors and non-neoplastic brain. Re-expression of SMARCB1 in ATRT cell lines enabled confirmation of our genome-wide findings for the chromatin states. Additional generation of ChIP-seq data for SWI/SNF and Polycomb group proteins and the transcriptional repressor protein REST determined differential dependencies of SWI/SNF and Polycomb complexes in regulation of diverse gene sets in ATRTs.</p>',
			'date' => '2019-01-14',
			'pmid' => 'http://www.pubmed.gov/30595504',
			'doi' => '10.1016/j.ccell.2018.11.014',
			'modified' => '2019-05-08 12:27:57',
			'created' => '2019-04-25 11:11:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 126 => array(
			'id' => '3658',
			'name' => 'The Wnt-Driven Mll1 Epigenome Regulates Salivary Gland and Head and Neck Cancer.',
			'authors' => 'Zhu Q, Fang L, Heuberger J, Kranz A, Schipper J, Scheckenbach K, Vidal RO, Sunaga-Franze DY, Müller M, Wulf-Goldenberg A, Sauer S, Birchmeier W',
			'description' => '<p>We identified a regulatory system that acts downstream of Wnt/&beta;-catenin signaling in salivary gland and head and neck carcinomas. We show in a mouse tumor model of K14-Cre-induced Wnt/&beta;-catenin gain-of-function and Bmpr1a loss-of-function mutations that tumor-propagating cells exhibit increased Mll1 activity and genome-wide increased H3K4 tri-methylation at promoters. Null mutations of Mll1 in tumor mice and in xenotransplanted human head and neck tumors resulted in loss of self-renewal of tumor-propagating cells and in block of tumor formation but did not alter normal tissue homeostasis. CRISPR/Cas9 mutagenesis and pharmacological interference of Mll1 at sequences that inhibit essential protein-protein interactions or the SET enzyme active site also blocked the self-renewal of mouse and human tumor-propagating cells. Our work provides strong genetic evidence for a crucial role of Mll1 in solid tumors. Moreover, inhibitors targeting specific Mll1 interactions might offer additional directions for therapies to treat these aggressive tumors.</p>',
			'date' => '2019-01-08',
			'pmid' => 'http://www.pubmed.gov/30625324',
			'doi' => '10.1016/j.celrep.2018.12.059',
			'modified' => '2019-06-07 09:00:14',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 127 => array(
			'id' => '3686',
			'name' => 'Gamma radiation induces locus specific changes to histone modification enrichment in zebrafish and Atlantic salmon.',
			'authors' => 'Lindeman LC, Kamstra JH, Ballangby J, Hurem S, Martín LM, Brede DA, Teien HC, Oughton DH, Salbu B, Lyche JL, Aleström P',
			'description' => '<p>Ionizing radiation is a recognized genotoxic agent, however, little is known about the role of the functional form of DNA in these processes. Post translational modifications on histone proteins control the organization of chromatin and hence control transcriptional responses that ultimately affect the phenotype. The purpose of this study was to investigate effects on chromatin caused by ionizing radiation in fish. Direct exposure of zebrafish (Danio rerio) embryos to gamma radiation (10.9 mGy/h for 3h) induced hyper-enrichment of H3K4me3 at the genes hnf4a, gmnn and vegfab. A similar relative hyper-enrichment was seen at the hnf4a loci of irradiated Atlantic salmon (Salmo salar) embryos (30 mGy/h for 10 days). At the selected genes in ovaries of adult zebrafish irradiated during gametogenesis (8.7 and 53 mGy/h for 27 days), a reduced enrichment of H3K4me3 was observed, which was correlated with reduced levels of histone H3 was observed. F1 embryos of the exposed parents showed hyper-methylation of H3K4me3, H3K9me3 and H3K27me3 on the same three loci, while these differences were almost negligible in F2 embryos. Our results from three selected loci suggest that ionizing radiation can affect chromatin structure and organization, and that these changes can be detected in F1 offspring, but not in subsequent generations.</p>',
			'date' => '2019-01-01',
			'pmid' => 'http://www.pubmed.gov/30759148',
			'doi' => '10.1371/journal.pone.0212123',
			'modified' => '2019-06-28 13:57:39',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 128 => array(
			'id' => '3607',
			'name' => 'Mutant p63 Affects Epidermal Cell Identity through Rewiring the Enhancer Landscape.',
			'authors' => 'Qu J, Tanis SEJ, Smits JPH, Kouwenhoven EN, Oti M, van den Bogaard EH, Logie C, Stunnenberg HG, van Bokhoven H, Mulder KW, Zhou H',
			'description' => '<p>Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Mutations in the p63 DNA-binding domain are associated with ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome. However, the underlying molecular mechanism of these mutations remains unclear. Here, we characterized the transcriptome and epigenome of p63 mutant keratinocytes derived from EEC patients. The transcriptome of p63 mutant keratinocytes deviated from the normal epidermal cell identity. Epigenomic analyses showed an altered enhancer landscape in p63 mutant keratinocytes contributed by loss of p63-bound active enhancers and unexpected gain of enhancers. The gained enhancers were frequently bound by deregulated transcription factors such as RUNX1. Reversing RUNX1 overexpression partially rescued deregulated gene expression and the altered enhancer landscape. Our findings identify a disease mechanism whereby mutant p63 rewires the enhancer landscape and affects epidermal cell identity, consolidating the pivotal role of p63 in controlling the enhancer landscape of epidermal keratinocytes.</p>',
			'date' => '2018-12-18',
			'pmid' => 'http://www.pubmed.gov/30566872',
			'doi' => '10.1016/j.celrep.2018.11.039',
			'modified' => '2019-04-17 14:51:18',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 129 => array(
			'id' => '3509',
			'name' => 'Promoter bivalency favors an open chromatin architecture in embryonic stem cells.',
			'authors' => 'Mas G, Blanco E, Ballaré C, Sansó M, Spill YG, Hu D, Aoi Y, Le Dily F, Shilatifard A, Marti-Renom MA, Di Croce L',
			'description' => '<p>In embryonic stem cells (ESCs), developmental gene promoters are characterized by their bivalent chromatin state, with simultaneous modification by MLL2 and Polycomb complexes. Although essential for embryogenesis, bivalency is functionally not well understood. Here, we show that MLL2 plays a central role in ESC genome organization. We generate a catalog of bona fide bivalent genes in ESCs and demonstrate that loss of MLL2 leads to increased Polycomb occupancy. Consequently, promoters lose accessibility, long-range interactions are redistributed, and ESCs fail to differentiate. We pose that bivalency balances accessibility and long-range connectivity of promoters, allowing developmental gene expression to be properly modulated.</p>',
			'date' => '2018-10-17',
			'pmid' => 'http://www.pubmed.gov/30224650',
			'doi' => '10.1038/s41588-018-0218-5',
			'modified' => '2019-02-27 15:45:37',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 130 => array(
			'id' => '3552',
			'name' => 'PRC2 targeting is a therapeutic strategy for EZ score defined high-risk multiple myeloma patients and overcome resistance to IMiDs.',
			'authors' => 'Herviou L, Kassambara A, Boireau S, Robert N, Requirand G, Müller-Tidow C, Vincent L, Seckinger A, Goldschmidt H, Cartron G, Hose D, Cavalli G, Moreaux J',
			'description' => '<p>BACKGROUND: Multiple myeloma (MM) is a malignant plasma cell disease with a poor survival, characterized by the accumulation of myeloma cells (MMCs) within the bone marrow. Epigenetic modifications in MM are associated not only with cancer development and progression, but also with drug resistance. METHODS: We identified a significant upregulation of the polycomb repressive complex 2 (PRC2) core genes in MM cells in association with proliferation. We used EPZ-6438, a specific small molecule inhibitor of EZH2 methyltransferase activity, to evaluate its effects on MM cells phenotype and gene expression prolile. RESULTS: PRC2 targeting results in growth inhibition due to cell cycle arrest and apoptosis together with polycomb, DNA methylation, TP53, and RB1 target genes induction. Resistance to EZH2 inhibitor is mediated by DNA methylation of PRC2 target genes. We also demonstrate a synergistic effect of EPZ-6438 and lenalidomide, a conventional drug used for MM treatment, activating B cell transcription factors and tumor suppressor gene expression in concert with MYC repression. We establish a gene expression-based EZ score allowing to identify poor prognosis patients that could benefit from EZH2 inhibitor treatment. CONCLUSIONS: These data suggest that PRC2 targeting in association with IMiDs could have a therapeutic interest in MM patients characterized by high EZ score values, reactivating B cell transcription factors, and tumor suppressor genes.</p>',
			'date' => '2018-10-03',
			'pmid' => 'http://www.pubmed.org/30285865',
			'doi' => '10.1186/s13148-018-0554-4',
			'modified' => '2019-03-21 16:45:55',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 131 => array(
			'id' => '3396',
			'name' => 'The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity',
			'authors' => 'Domínguez-Andrés Jorge, Novakovic Boris, Li Yang, Scicluna Brendon P., Gresnigt Mark S., Arts Rob J.W., Oosting Marije, Moorlag Simone J.C.F.M., Groh Laszlo A., Zwaag Jelle, Koch Rebecca M., ter Horst Rob, Joosten Leo A.B., Wijmenga Cisca, Michelucci Ales',
			'description' => '<p>Sepsis involves simultaneous hyperactivation of the immune system and immune paralysis, leading to both organ dysfunction and increased susceptibility to secondary infections. Acute activation of myeloid cells induced itaconate synthesis, which subsequently mediated innate immune tolerance in human monocytes. In contrast, induction of trained immunity by b-glucan counteracted tolerance induced in a model of human endotoxemia by inhibiting the expression of immune-responsive gene 1 (IRG1), the enzyme that controls itaconate synthesis. b-Glucan also increased the expression of succinate dehydrogenase (SDH), contributing to the integrity of the TCA cycle and leading to an enhanced innate immune response after secondary stimulation. The role of itaconate was further validated by IRG1 and SDH polymorphisms that modulate induction of tolerance and trained immunity in human monocytes. These data demonstrate the importance of the IRG1-itaconateSDH axis in the development of immune tolerance and training and highlight the potential of b-glucaninduced trained immunity to revert immunoparalysis.</p>',
			'date' => '2018-10-01',
			'pmid' => 'http://www.pubmed.gov/30293776',
			'doi' => '10.1016/j.cmet.2018.09.003',
			'modified' => '2018-11-22 15:18:30',
			'created' => '2018-11-08 12:59:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 132 => array(
			'id' => '3566',
			'name' => 'Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes.',
			'authors' => 'Ferguson GB, Van Handel B, Bay M, Fiziev P, Org T, Lee S, Shkhyan R, Banks NW, Scheinberg M, Wu L, Saitta B, Elphingstone J, Larson AN, Riester SM, Pyle AD, Bernthal NM, Mikkola HK, Ernst J, van Wijnen AJ, Bonaguidi M, Evseenko D',
			'description' => '<p>Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application of cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differentiation. Network analysis delineated five tissue-specific gene modules; these modules and chromatin state analysis defined broad similarities in gene expression during cartilage specification and maturation in vitro and in vivo, including early expression and progressive silencing of muscle- and bone-specific genes. Finally, ontogenetic analysis of freshly isolated and pluripotent stem cell-derived articular chondrocytes identified that integrin alpha 4 defines 2 subsets of functionally and molecularly distinct chondrocytes characterized by their gene expression, osteochondral potential in vitro and proliferative signature in vivo. These analyses provide new insight into human musculoskeletal development and provide an essential comparative resource for disease modeling and regenerative medicine.</p>',
			'date' => '2018-09-07',
			'pmid' => 'http://www.pubmed.gov/30194383',
			'doi' => '10.1038/s41467-018-05573-y',
			'modified' => '2019-03-25 11:14:45',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 133 => array(
			'id' => '3596',
			'name' => 'RNA Sequencing and Pathway Analysis Identify Important Pathways Involved in Hypertrichosis and Intellectual Disability in Patients with Wiedemann-Steiner Syndrome.',
			'authors' => 'Mietton L, Lebrun N, Giurgea I, Goldenberg A, Saintpierre B, Hamroune J, Afenjar A, Billuart P, Bienvenu T',
			'description' => '<p>A growing number of histone modifiers are involved in human neurodevelopmental disorders, suggesting that proper regulation of chromatin state is essential for the development of the central nervous system. Among them, heterozygous de novo variants in KMT2A, a gene coding for histone methyltransferase, have been associated with Wiedemann-Steiner syndrome (WSS), a rare developmental disorder mainly characterized by intellectual disability (ID) and hypertrichosis. As KMT2A is known to regulate the expression of multiple target genes through methylation of lysine 4 of histone 3 (H3K4me), we sought to investigate the transcriptomic consequences of KMT2A variants involved in WSS. Using fibroblasts from four WSS patients harboring loss-of-function KMT2A variants, we performed RNA sequencing and identified a number of genes for which transcription was altered in KMT2A-mutated cells compared to the control ones. Strikingly, analysis of the pathways and biological functions significantly deregulated between patients with WSS and healthy individuals revealed a number of processes predicted to be altered that are relevant for hypertrichosis and intellectual disability, the cardinal signs of this disease.</p>',
			'date' => '2018-09-01',
			'pmid' => 'http://www.pubmed.gov/30014449',
			'doi' => '10.1007/s12017-018-8502-1',
			'modified' => '2019-04-17 15:10:22',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 134 => array(
			'id' => '3564',
			'name' => 'Atopic asthma after rhinovirus-induced wheezing is associated with DNA methylation change in the SMAD3 gene promoter.',
			'authors' => 'Lund RJ, Osmala M, Malonzo M, Lukkarinen M, Leino A, Salmi J, Vuorikoski S, Turunen R, Vuorinen T, Akdis C, Lähdesmäki H, Lahesmaa R, Jartti T',
			'description' => '<p>Children with rhinovirus-induced severe early wheezing have an increased risk of developing asthma later in life. The exact molecular mechanisms for this association are still mostly unknown. To identify potential changes in the transcriptional and epigenetic regulation in rhinovirus-associated atopic or nonatopic asthma, we analyzed a cohort of 5-year-old children (n&nbsp;=&nbsp;45) according to the virus etiology of the first severe wheezing episode at the mean age of 13&nbsp;months and to 5-year asthma outcome. The development of atopic asthma in children with early rhinovirus-induced wheezing was associated with DNA methylation changes at several genomic sites in chromosomal regions previously linked to asthma. The strongest changes in atopic asthma were detected in the promoter region of SMAD3 gene at chr 15q22.33 and introns of DDO/METTL24 genes at 6q21. These changes were validated to be present also at the average age of 8&nbsp;years.</p>',
			'date' => '2018-08-01',
			'pmid' => 'http://www.pubmed.gov/29729188',
			'doi' => '10.1111/all.13473',
			'modified' => '2019-03-25 11:19:56',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 135 => array(
			'id' => '3515',
			'name' => 'Integrative multi-omics analysis of intestinal organoid differentiation',
			'authors' => 'Rik GH Lindeboom, Lisa van Voorthuijsen1, Koen C Oost, Maria J Rodríguez-Colman, Maria V Luna-Velez, Cristina Furlan, Floriane Baraille, Pascal WTC Jansen, Agnès Ribeiro, Boudewijn MT Burgering, Hugo J Snippert, & Michiel Vermeulen',
			'description' => '<p>Intestinal organoids accurately recapitulate epithelial homeostasis in vivo, thereby representing a powerful in vitro system to investigate lineage specification and cellular differentiation. Here, we applied a multi-omics framework on stem cell-enriched and stem cell-depleted mouse intestinal organoids to obtain a holistic view of the molecular mechanisms that drive differential gene expression during adult intestinal stem cell differentiation. Our data revealed a global rewiring of the transcriptome and proteome between intestinal stem cells and enterocytes, with the majority of dynamic protein expression being transcription-driven. Integrating absolute mRNA and protein copy numbers revealed post-transcriptional regulation of gene expression. Probing the epigenetic landscape identified a large number of cell-type-specific regulatory elements, which revealed Hnf4g as a major driver of enterocyte differentiation. In summary, by applying an integrative systems biology approach, we uncovered multiple layers of gene expression regulation, which contribute to lineage specification and plasticity of the mouse small intestinal epithelium.</p>',
			'date' => '2018-06-26',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/29945941/',
			'doi' => '10.15252/msb.20188227',
			'modified' => '2022-05-18 18:45:53',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 136 => array(
			'id' => '3423',
			'name' => 'The Polycomb-Dependent Epigenome Controls β Cell Dysfunction, Dedifferentiation, and Diabetes.',
			'authors' => 'Lu TT, Heyne S, Dror E, Casas E, Leonhardt L, Boenke T, Yang CH, Sagar , Arrigoni L, Dalgaard K, Teperino R, Enders L, Selvaraj M, Ruf M, Raja SJ, Xie H, Boenisch U, Orkin SH, Lynn FC, Hoffman BG, Grün D, Vavouri T, Lempradl AM, Pospisilik JA',
			'description' => '<p>To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single-cell transcriptomics to mine for evidence of chromatin dysregulation in type 2 diabetes. We find two chromatin-state signatures that track &beta; cell dysfunction in mice and humans: ectopic activation of bivalent Polycomb-silenced domains and loss of expression at an epigenomically unique class of lineage-defining genes. &beta; cell-specific Polycomb (Eed/PRC2) loss of function in mice triggers diabetes-mimicking transcriptional signatures and highly penetrant, hyperglycemia-independent dedifferentiation, indicating that PRC2 dysregulation contributes to disease. The work provides novel resources for exploring &beta;&nbsp;cell transcriptional regulation and identifies PRC2 as necessary for long-term maintenance of &beta; cell identity. Importantly, the data suggest a two-hit (chromatin and hyperglycemia) model for loss of &beta;&nbsp;cell identity in diabetes.</p>',
			'date' => '2018-06-05',
			'pmid' => 'http://www.pubmed.gov/29754954',
			'doi' => '10.1016/j.cmet.2018.04.013',
			'modified' => '2018-12-31 11:43:24',
			'created' => '2018-12-04 09:51:07',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 137 => array(
			'id' => '3380',
			'name' => 'The reference epigenome and regulatory chromatin landscape of chronic lymphocytic leukemia',
			'authors' => 'Beekman R. et al.',
			'description' => '<p>Chronic lymphocytic leukemia (CLL) is a frequent hematological neoplasm in which underlying epigenetic alterations are only partially understood. Here, we analyze the reference epigenome of seven primary CLLs and the regulatory chromatin landscape of 107 primary cases in the context of normal B cell differentiation. We identify that the CLL chromatin landscape is largely influenced by distinct dynamics during normal B cell maturation. Beyond this, we define extensive catalogues of regulatory elements de novo reprogrammed in CLL as a whole and in its major clinico-biological subtypes classified by IGHV somatic hypermutation levels. We uncover that IGHV-unmutated CLLs harbor more active and open chromatin than IGHV-mutated cases. Furthermore, we show that de novo active regions in CLL are enriched for NFAT, FOX and TCF/LEF transcription factor family binding sites. Although most genetic alterations are not associated with consistent epigenetic profiles, CLLs with MYD88 mutations and trisomy 12 show distinct chromatin configurations. Furthermore, we observe that non-coding mutations in IGHV-mutated CLLs are enriched in H3K27ac-associated regulatory elements outside accessible chromatin. Overall, this study provides an integrative portrait of the CLL epigenome, identifies extensive networks of altered regulatory elements and sheds light on the relationship between the genetic and epigenetic architecture of the disease.</p>',
			'date' => '2018-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29785028',
			'doi' => '',
			'modified' => '2018-07-27 17:10:43',
			'created' => '2018-07-27 17:10:43',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 138 => array(
			'id' => '3469',
			'name' => 'Increased H3K9 methylation and impaired expression of Protocadherins are associated with the cognitive dysfunctions of the Kleefstra syndrome.',
			'authors' => 'Iacono G, Dubos A, Méziane H, Benevento M, Habibi E, Mandoli A, Riet F, Selloum M, Feil R, Zhou H, Kleefstra T, Kasri NN, van Bokhoven H, Herault Y, Stunnenberg HG',
			'description' => '<p>Kleefstra syndrome, a disease with intellectual disability, autism spectrum disorders and other developmental defects is caused in humans by haploinsufficiency of EHMT1. Although EHMT1 and its paralog EHMT2 were shown to be histone methyltransferases responsible for deposition of the di-methylated H3K9 (H3K9me2), the exact nature of epigenetic dysfunctions in Kleefstra syndrome remains unknown. Here, we found that the epigenome of Ehmt1+/- adult mouse brain displays a marked increase of H3K9me2/3 which correlates with impaired expression of protocadherins, master regulators of neuronal diversity. Increased H3K9me3 was present already at birth, indicating that aberrant methylation patterns are established during embryogenesis. Interestingly, we found that Ehmt2+/- mice do not present neither the marked increase of H3K9me2/3 nor the cognitive deficits found in Ehmt1+/- mice, indicating an evolutionary diversification of functions. Our finding of increased H3K9me3 in Ehmt1+/- mice is the first one supporting the notion that EHMT1 can quench the deposition of tri-methylation by other Histone methyltransferases, ultimately leading to impaired neurocognitive functioning. Our insights into the epigenetic pathophysiology of Kleefstra syndrome may offer guidance for future developments of therapeutic strategies for this disease.</p>',
			'date' => '2018-06-01',
			'pmid' => 'http://www.pubmed.gov/29554304',
			'doi' => '10.1093/nar/gky196',
			'modified' => '2019-02-15 21:04:02',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 139 => array(
			'id' => '3478',
			'name' => 'Pro-inflammatory cytokines activate hypoxia-inducible factor 3α via epigenetic changes in mesenchymal stromal/stem cells.',
			'authors' => 'Cuomo F, Coppola A, Botti C, Maione C, Forte A, Scisciola L, Liguori G, Caiafa I, Ursini MV, Galderisi U, Cipollaro M, Altucci L, Cobellis G',
			'description' => '<p>Human mesenchymal stromal/stem cells (hMSCs) emerged as a promising therapeutic tool for ischemic disorders, due to their ability to regenerate damaged tissues, promote angiogenesis and reduce inflammation, leading to encouraging, but still limited results. The outcomes in clinical trials exploring hMSC therapy are influenced by low cell retention and survival in affected tissues, partially influenced by lesion's microenvironment, where low oxygen conditions (i.e. hypoxia) and inflammation coexist. Hypoxia and inflammation are pathophysiological stresses, sharing common activators, such as hypoxia-inducible factors (HIFs) and NF-&kappa;B. HIF1&alpha; and HIF2&alpha; respond essentially to hypoxia, activating pathways involved in tissue repair. Little is known about the regulation of HIF3&alpha;. Here we investigated the role of HIF3&alpha; in vitro and in vivo. Human MSCs expressed HIF3&alpha;, differentially regulated by pro-inflammatory cytokines in an oxygen-independent manner, a novel and still uncharacterized mechanism, where NF-&kappa;B is critical for its expression. We investigated if epigenetic modifications are involved in HIF3&alpha; expression by methylation-specific PCR and histone modifications. Robust hypermethylation of histone H3 was observed across HIF3A locus driven by pro-inflammatory cytokines. Experiments in a murine model of arteriotomy highlighted the activation of Hif3&alpha; expression in infiltrated inflammatory cells, suggesting a new role for Hif3&alpha; in inflammation in vivo.</p>',
			'date' => '2018-04-11',
			'pmid' => 'http://www.pubmed.gov/29643458',
			'doi' => '10.1038/s41598-018-24221-5',
			'modified' => '2019-02-15 20:21:28',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 140 => array(
			'id' => '3463',
			'name' => 'Epigenetic modifiers promote mitochondrial biogenesis and oxidative metabolism leading to enhanced differentiation of neuroprogenitor cells.',
			'authors' => 'Martine Uittenbogaard, Christine A. Brantner, Anne Chiaramello1',
			'description' => '<p>During neural development, epigenetic modulation of chromatin acetylation is part of a dynamic, sequential and critical process to steer the fate of multipotent neural progenitors toward a specific lineage. Pan-HDAC inhibitors (HDCis) trigger neuronal differentiation by generating an "acetylation" signature and promoting the expression of neurogenic bHLH transcription factors. Our studies and others have revealed a link between neuronal differentiation and increase of mitochondrial mass. However, the neuronal regulation of mitochondrial biogenesis has remained largely unexplored. Here, we show that the HDACi, sodium butyrate (NaBt), promotes mitochondrial biogenesis via the NRF-1/Tfam axis in embryonic hippocampal progenitor cells and neuroprogenitor-like PC12-NeuroD6 cells, thereby enhancing their neuronal differentiation competency. Increased mitochondrial DNA replication by several pan-HDACis indicates a common mechanism by which they regulate mitochondrial biogenesis. NaBt also induces coordinates mitochondrial ultrastructural changes and enhanced OXPHOS metabolism, thereby increasing key mitochondrial bioenergetics parameters in neural progenitor cells. NaBt also endows the neuronal cells with increased mitochondrial spare capacity to confer resistance to oxidative stress associated with neuronal differentiation. We demonstrate that mitochondrial biogenesis is under HDAC-mediated epigenetic regulation, the timing of which is consistent with its integrative role during neuronal differentiation. Thus, our findings add a new facet to our mechanistic understanding of how pan-HDACis induce differentiation of neuronal progenitor cells. Our results reveal the concept that epigenetic modulation of the mitochondrial pool prior to neurotrophic signaling dictates the efficiency of initiation of neuronal differentiation during the transition from progenitor to differentiating neuronal cells. The histone acetyltransferase CREB-binding protein plays a key role in regulating the mitochondrial biomass. By ChIP-seq analysis, we show that NaBt confers an H3K27ac epigenetic signature in several interconnected nodes of nuclear genes vital for neuronal differentiation and mitochondrial reprogramming. Collectively, our study reports a novel developmental epigenetic layer that couples mitochondrial biogenesis to neuronal differentiation.</p>',
			'date' => '2018-03-02',
			'pmid' => 'http://www.pubmed.gov/29500414',
			'doi' => '10.1038/s41419-018-0396-1',
			'modified' => '2019-02-15 21:21:45',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 141 => array(
			'id' => '3361',
			'name' => 'Micro-ribonucleic acid-155 is a direct target of Meis1, but not a driver in acute myeloid leukemia',
			'authors' => 'Schneider E. et al.',
			'description' => '<p>Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute myeloid leukemia. The additional overexpression of miR-155 accelerated the formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells <i>in vivo</i> However, in the absence or following the removal of miR-155, leukemia onset and progression were unaffected. Although miR-155 accelerated growth and homing in addition to impairing differentiation, our data underscore the pathophysiological relevance of miR-155 as an accelerator rather than a driver of leukemogenesis. This further highlights the complexity of the oncogenic program of Meis1 to compensate for the loss of a potent oncogene such as miR-155. These findings are highly relevant to current and developing approaches for targeting miR-155 in acute myeloid leukemia.</p>',
			'date' => '2018-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29217774',
			'doi' => '',
			'modified' => '2018-04-06 15:39:36',
			'created' => '2018-04-06 15:39:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 142 => array(
			'id' => '3446',
			'name' => 'Metabolic Induction of Trained Immunity through the Mevalonate Pathway.',
			'authors' => 'Bekkering S, Arts RJW, Novakovic B, Kourtzelis I, van der Heijden CDCC, Li Y, Popa CD, Ter Horst R, van Tuijl J, Netea-Maier RT, van de Veerdonk FL, Chavakis T, Joosten LAB, van der Meer JWM, Stunnenberg H, Riksen NP, Netea MG',
			'description' => '<p>Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that activation of the cholesterol synthesis pathway, but not the synthesis of cholesterol itself, is essential for training of myeloid cells. Rather, the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways. Statins, which block mevalonate generation, prevent trained immunity induction. Furthermore, monocytes of patients with hyper immunoglobulin D syndrome (HIDS), who are mevalonate kinase deficient and accumulate mevalonate, have a constitutive trained immunity phenotype at both immunological and epigenetic levels, which could explain the attacks of sterile inflammation that these patients experience. Unraveling the role of mevalonate in trained immunity contributes to our understanding of the pathophysiology of HIDS and identifies novel therapeutic targets for clinical conditions with excessive activation of trained immunity.</p>',
			'date' => '2018-01-11',
			'pmid' => 'http://www.pubmed.gov/29328908',
			'doi' => '10.1016/j.cell.2017.11.025',
			'modified' => '2019-02-15 21:37:39',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 143 => array(
			'id' => '3408',
			'name' => 'BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity.',
			'authors' => 'Arts RJW, Moorlag SJCFM, Novakovic B, Li Y, Wang SY, Oosting M, Kumar V, Xavier RJ, Wijmenga C, Joosten LAB, Reusken CBEM, Benn CS, Aaby P, Koopmans MP, Stunnenberg HG, van Crevel R, Netea MG',
			'description' => '<p>The tuberculosis vaccine bacillus Calmette-Gu&eacute;rin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was accompanied by functional changes indicative of trained immunity. Reduction of viremia was highly correlated with the upregulation of IL-1&beta;, a heterologous cytokine associated with the induction of trained immunity, but not with&nbsp;the specific IFN&gamma; response. The importance of IL-1&beta; for the induction of trained immunity was validated through genetic, epigenetic, and immunological studies. In conclusion, BCG induces epigenetic reprogramming in human monocytes in&nbsp;vivo, followed by functional reprogramming and protection against non-related viral infections, with a key role for IL-1&beta; as a mediator of trained immunity responses.</p>',
			'date' => '2018-01-10',
			'pmid' => 'http://www.pubmed.gov/29324233',
			'doi' => '10.1016/j.chom.2017.12.010',
			'modified' => '2018-11-22 15:15:09',
			'created' => '2018-11-08 12:59:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 144 => array(
			'id' => '3440',
			'name' => 'Senescence-associated reprogramming promotes cancer stemness.',
			'authors' => 'Milanovic M, Fan DNY, Belenki D, Däbritz JHM, Zhao Z, Yu Y, Dörr JR, Dimitrova L, Lenze D, Monteiro Barbosa IA, Mendoza-Parra MA, Kanashova T, Metzner M, Pardon K, Reimann M, Trumpp A, Dörken B, Zuber J, Gronemeyer H, Hummel M, Dittmar G, Lee S, Schmitt C',
			'description' => '<p>Cellular senescence is a stress-responsive cell-cycle arrest program that terminates the further expansion of (pre-)malignant cells. Key signalling components of the senescence machinery, such as p16, p21 and p53, as well as trimethylation of lysine 9 at histone H3 (H3K9me3), also operate as critical regulators of stem-cell functions (which are collectively termed 'stemness'). In cancer cells, a gain of stemness may have profound implications for tumour aggressiveness and clinical outcome. Here we investigated whether chemotherapy-induced senescence could change stem-cell-related properties of malignant cells. Gene expression and functional analyses comparing senescent and non-senescent B-cell lymphomas from E&mu;-Myc transgenic mice revealed substantial upregulation of an adult tissue stem-cell signature, activated Wnt signalling, and distinct stem-cell markers in senescence. Using genetically switchable models of senescence targeting H3K9me3 or p53 to mimic spontaneous escape from the arrested condition, we found that cells released from senescence re-entered the cell cycle with strongly enhanced and Wnt-dependent clonogenic growth potential compared to virtually identical populations that had been equally exposed to chemotherapy but had never been senescent. In vivo, these previously senescent cells presented with a much higher tumour initiation potential. Notably, the temporary enforcement of senescence in p53-regulatable models of acute lymphoblastic leukaemia and acute myeloid leukaemia was found to reprogram non-stem bulk leukaemia cells into self-renewing, leukaemia-initiating stem cells. Our data, which are further supported by consistent results in human cancer cell lines and primary samples of human haematological malignancies, reveal that senescence-associated stemness is an unexpected, cell-autonomous feature that exerts its detrimental, highly aggressive growth potential upon escape from cell-cycle blockade, and is enriched in relapse tumours. These findings have profound implications for cancer therapy, and provide new mechanistic insights into the plasticity of cancer cells.</p>',
			'date' => '2018-01-04',
			'pmid' => 'http://www.pubmed.org/29258294',
			'doi' => '10.1038/nature25167',
			'modified' => '2019-02-15 21:39:11',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 145 => array(
			'id' => '3385',
			'name' => 'MLL2 conveys transcription-independent H3K4 trimethylation in oocytes',
			'authors' => 'Hanna C.W. et al.',
			'description' => '<p>Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyte provides an attractive system to investigate these mechanisms, because extensive H3K4me3 acquisition occurs in nondividing cells. We developed low-input chromatin immunoprecipitation to interrogate H3K4me3, H3K27ac and H3K27me3 marks throughout oogenesis. In nongrowing oocytes, H3K4me3 was restricted to active promoters, but as oogenesis progressed, H3K4me3 accumulated in a transcription-independent manner and was targeted to intergenic regions, putative enhancers and silent H3K27me3-marked promoters. Ablation of the H3K4 methyltransferase&nbsp;gene Mll2 resulted in loss of transcription-independent H3K4 trimethylation but had limited effects on transcription-coupled H3K4 trimethylation or gene expression. Deletion of Dnmt3a and Dnmt3b showed that DNA methylation protects regions from acquiring H3K4me3. Our findings reveal two independent mechanisms of targeting H3K4me3 to genomic elements, with MLL2 recruited to unmethylated CpG-rich regions independently of transcription.</p>',
			'date' => '2018-01-02',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29323282',
			'doi' => '',
			'modified' => '2018-08-07 10:26:20',
			'created' => '2018-08-07 10:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 146 => array(
			'id' => '3330',
			'name' => 'The histone code reader Spin1 controls skeletal muscle development',
			'authors' => 'Greschik H. et al.',
			'description' => '<p>While several studies correlated increased expression of the histone code reader Spin1 with tumor formation or growth, little is known about physiological functions of the protein. We generated Spin1<sup>M5</sup> mice with ablation of Spin1 in myoblast precursors using the Myf5-Cre deleter strain. Most Spin1<sup>M5</sup> mice die shortly after birth displaying severe sarcomere disorganization and necrosis. Surviving Spin1<sup>M5</sup> mice are growth-retarded and exhibit the most prominent defects in soleus, tibialis anterior, and diaphragm muscle. Transcriptome analyses of limb muscle at embryonic day (E) 15.5, E16.5, and at three weeks of age provided evidence for aberrant fetal myogenesis and identified deregulated skeletal muscle (SkM) functional networks. Determination of genome-wide chromatin occupancy in primary myoblast revealed direct Spin1 target genes and suggested that deregulated basic helix-loop-helix transcription factor networks account for developmental defects in Spin1<sup>M5</sup> fetuses. Furthermore, correlating histological and transcriptome analyses, we show that aberrant expression of titin-associated proteins, abnormal glycogen metabolism, and neuromuscular junction defects contribute to SkM pathology in Spin1<sup>M5</sup> mice. Together, we describe the first example of a histone code reader controlling SkM development in mice, which hints at Spin1 as a potential player in human SkM disease.</p>',
			'date' => '2017-11-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29168801',
			'doi' => '',
			'modified' => '2018-02-07 10:20:01',
			'created' => '2018-02-07 10:20:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 147 => array(
			'id' => '3322',
			'name' => 'In Situ Fixation Redefines Quiescence and Early Activation of Skeletal Muscle Stem Cells',
			'authors' => 'Machado L. et al.',
			'description' => '<div class="abstract">
<h2 class="sectionTitle" tabindex="0">Summary</h2>
<div class="content">
<p>State of the art techniques have been developed to isolate and analyze cells from various tissues, aiming to capture their <em>in&nbsp;vivo</em> state. However, the majority of cell isolation protocols involve lengthy mechanical and enzymatic dissociation steps followed by flow cytometry, exposing cells to stress and disrupting their physiological niche. Focusing on adult skeletal muscle stem cells, we have developed a protocol that circumvents the impact of isolation procedures and captures cells in their native quiescent state. We show that current isolation protocols induce major transcriptional changes accompanied by specific histone modifications while having negligible effects on DNA methylation. In addition to proposing a protocol to avoid isolation-induced artifacts, our study reveals previously undetected quiescence and early activation genes of potential biological interest.</p>
</div>
</div>',
			'date' => '2017-11-14',
			'pmid' => 'http://www.cell.com/cell-reports/abstract/S2211-1247(17)31543-7',
			'doi' => '',
			'modified' => '2022-05-19 16:11:43',
			'created' => '2018-02-02 16:36:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 148 => array(
			'id' => '3309',
			'name' => 'GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency',
			'authors' => 'Krendl C. et al.',
			'description' => '<p>To elucidate the molecular basis of BMP4-induced differentiation of human pluripotent stem cells (PSCs) toward progeny with trophectoderm characteristics, we produced transcriptome, epigenome H3K4me3, H3K27me3, and CpG methylation maps of trophoblast progenitors, purified using the surface marker APA. We combined them with the temporally resolved transcriptome of the preprogenitor phase and of single APA+ cells. This revealed a circuit of bivalent TFAP2A, TFAP2C, GATA2, and GATA3 transcription factors, coined collectively the "trophectoderm four" (TEtra), which are also present in human trophectoderm in vivo. At the onset of differentiation, the TEtra factors occupy multiple sites in epigenetically inactive placental genes and in <i>OCT4</i> Functional manipulation of <i>GATA3</i> and <i>TFAP2A</i> indicated that they directly couple trophoblast-specific gene induction with suppression of pluripotency. In accordance, knocking down <i>GATA3</i> in primate embryos resulted in a failure to form trophectoderm. The discovery of the TEtra circuit indicates how trophectoderm commitment is regulated in human embryogenesis.</p>',
			'date' => '2017-11-07',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29078328',
			'doi' => '',
			'modified' => '2018-01-04 10:23:33',
			'created' => '2018-01-04 10:23:33',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 149 => array(
			'id' => '3302',
			'name' => 'The mixed lineage leukemia 4 (MLL4) methyltransferase complex is involved in transforming growth factor beta (TGF-β)-activated gene transcription.',
			'authors' => 'Baas R. et al.',
			'description' => '<p>Sma and Mad related (SMAD)-mediated Transforming Growth Factor &beta; (TGF-&beta;) and Bone Morphogenetic Protein (BMP) signaling is required for various cellular processes. The activated heterotrimeric SMAD protein complexes associate with nuclear proteins such as the histone acetyltransferases p300, PCAF and the Mixed Lineage Leukemia 4 (MLL4) subunit Pax Transactivation domain-Interacting Protein (PTIP) to regulate gene transcription. We investigated the functional role of PTIP and PTIP Interacting protein 1 (PA1) in relation to TGF-&beta;-activated SMAD signaling. We immunoprecipitated PTIP and PA1 with all SMAD family members to identify the TGF-&beta; and not BMP-specific SMADs as interacting proteins. Gene silencing experiments of MLL4 and the subunits PA1 and PTIP confirm TGF-&beta;-specific genes to be regulated by the MLL4 complex, which links TGF-&beta; signaling to transcription regulation by the MLL4 methyltransferase complex.</p>',
			'date' => '2017-10-04',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28976802',
			'doi' => '',
			'modified' => '2017-12-05 10:50:08',
			'created' => '2017-12-05 10:50:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 150 => array(
			'id' => '3296',
			'name' => 'Predicting stimulation-dependent enhancer-promoter interactions from ChIP-Seq time course data',
			'authors' => 'Dzida T. et al.',
			'description' => '<p>We have developed a machine learning approach to predict stimulation-dependent enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ER&alpha;), RNA polymerase (Pol II) and histone marks H2AZ and H3K4me3 were measured over time using ChIP-Seq experiments in MCF7 cells stimulated with estrogen. A Bayesian classifier was developed which uses the correlation of temporal binding patterns at enhancers and promoters and genomic proximity as features to predict interactions. This method was trained using experimentally determined interactions from the same system and was shown to achieve much higher precision than predictions based on the genomic proximity of nearest ER&alpha;&nbsp;binding. We use the method to identify a genome-wide confident set of ER&alpha;&nbsp;target genes and their regulatory enhancers genome-wide. Validation with publicly available GRO-Seq data demonstrates that our predicted targets are much more likely to show early nascent transcription than predictions based on genomic ER&alpha;&nbsp;binding proximity alone.</p>',
			'date' => '2017-09-28',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28970965',
			'doi' => '',
			'modified' => '2017-12-04 11:06:11',
			'created' => '2017-12-04 11:06:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 151 => array(
			'id' => '3303',
			'name' => 'Genetic Predisposition to Multiple Myeloma at 5q15 Is Mediated by an ELL2 Enhancer Polymorphism',
			'authors' => 'Li N. et al.',
			'description' => '<p>Multiple myeloma (MM) is a malignancy of plasma cells. Genome-wide association studies have shown that variation at 5q15 influences MM risk. Here, we have sought to decipher the causal variant at 5q15 and the mechanism by which it influences tumorigenesis. We show that rs6877329&nbsp;G &gt; C resides in a predicted enhancer element that physically interacts with the transcription start site of ELL2. The rs6877329-C risk allele is associated with reduced enhancer activity and lowered ELL2 expression. Since ELL2 is critical to the B cell differentiation process, reduced ELL2 expression is consistent with inherited genetic variation contributing to arrest of plasma cell development, facilitating MM clonal expansion. These data provide evidence for a biological mechanism underlying a hereditary risk of MM at 5q15.</p>',
			'date' => '2017-09-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28903037',
			'doi' => '',
			'modified' => '2018-01-02 17:58:38',
			'created' => '2018-01-02 17:58:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 152 => array(
			'id' => '3298',
			'name' => 'Chromosome contacts in activated T cells identify autoimmune disease candidate genes',
			'authors' => 'Burren OS et al.',
			'description' => '<div class="abstr">
<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Autoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4<sup>+</sup> T cells. Linking such regulatory regions to gene promoters in disease-relevant cell contexts facilitates identification of candidate disease genes.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Within 4&nbsp;h, activation of CD4<sup>+</sup> T cells invokes changes in histone modifications and enhancer RNA transcription that correspond to altered expression of the interacting genes identified by promoter capture Hi-C. By integrating promoter capture Hi-C data with genetic associations for five autoimmune diseases, we prioritised 245 candidate genes with a median distance from peak signal to prioritised gene of 153&nbsp;kb. Just under half (108/245) prioritised genes related to activation-sensitive interactions. This included IL2RA, where allele-specific expression analyses were consistent with its interaction-mediated regulation, illustrating the utility of the approach.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">Our systematic experimental framework offers an alternative approach to candidate causal gene identification for variants with cell state-specific functional effects, with achievable sample sizes.</abstracttext></p>
</div>
</div>',
			'date' => '2017-09-04',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28870212',
			'doi' => '',
			'modified' => '2017-12-04 11:25:15',
			'created' => '2017-12-04 11:25:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 153 => array(
			'id' => '3262',
			'name' => 'A lncRNA fine tunes the dynamics of a cell state transition involving Lin28, let-7 and de novo DNA methylation',
			'authors' => 'Li M.A. et al.',
			'description' => '<p>Execution of pluripotency requires progression from the na&iuml;ve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) <em>linc1281,</em> hereafter <em>Ephemeron</em> (<em>Eprn</em>), that modulates the dynamics of exit from na&iuml;ve pluripotency. <em>Eprn</em> deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression. In the absence of <em>Eprn</em>, <em>Lin28a</em> expression is reduced which results in persistence of <em>let-7 microRNAs, and</em> the up-regulation of de novo methyltransferases Dnmt3a/b is delayed. <em>Dnmt3a/b</em> deletion retards ES cell transition, correlating with delayed <em>Nanog</em> promoter methylation and phenocopying loss of <em>Eprn</em> or <em>Lin28a</em>. The connection from lncRNA to miRNA and DNA methylation facilitates the acute extinction of na&iuml;ve pluripotency, a pre-requisite for rapid progression from preimplantation epiblast to gastrulation in rodents. <em>Eprn</em> illustrates how lncRNAs may introduce species-specific network modulations.</p>',
			'date' => '2017-08-18',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562443/',
			'doi' => '',
			'modified' => '2017-10-09 15:55:39',
			'created' => '2017-10-09 15:55:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 154 => array(
			'id' => '3240',
			'name' => 'Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation',
			'authors' => 'Pünzeler S. et al.',
			'description' => '<p>Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine the comprehensive interactome of H2A.Z and identify PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A is a functionally uncharacterized, vertebrate-specific protein that binds very tightly to chromatin through a concerted multivalent binding mode. Two internal protein regions mediate H2A.Z-specificity and nucleosome interaction, whereas the PWWP domain exhibits direct DNA binding. Genome-wide mapping reveals that PWWP2A binds selectively to H2A.Z-containing nucleosomes with strong preference for promoters of highly transcribed genes. In human cells, its depletion affects gene expression and impairs proliferation via a mitotic delay. While PWWP2A does not influence H2A.Z occupancy, the C-terminal tail of H2A.Z is one important mediator to recruit PWWP2A to chromatin. Knockdown of PWWP2A in <i>Xenopus</i> results in severe cranial facial defects, arising from neural crest cell differentiation and migration problems. Thus, PWWP2A is a novel H2A.Z-specific multivalent chromatin binder providing a surprising link between H2A.Z, chromosome segregation, and organ development.</p>',
			'date' => '2017-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28645917',
			'doi' => '',
			'modified' => '2017-08-29 09:45:44',
			'created' => '2017-08-29 09:45:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 155 => array(
			'id' => '3270',
			'name' => 'Mouse models of 17q21.31 microdeletion and microduplication syndromes highlight the importance of Kansl1 for cognition',
			'authors' => 'Arbogast T. et al.',
			'description' => '<p>Koolen-de Vries syndrome (KdVS) is a multi-system disorder characterized by intellectual disability, friendly behavior, and congenital malformations. The syndrome is caused either by microdeletions in the 17q21.31 chromosomal region or by variants in the KANSL1 gene. The reciprocal 17q21.31 microduplication syndrome is associated with psychomotor delay, and reduced social interaction. To investigate the pathophysiology of 17q21.31 microdeletion and microduplication syndromes, we generated three mouse models: 1) the deletion (Del/+); or 2) the reciprocal duplication (Dup/+) of the 17q21.31 syntenic region; and 3) a heterozygous Kansl1 (Kans1+/-) model. We found altered weight, general activity, social behaviors, object recognition, and fear conditioning memory associated with craniofacial and brain structural changes observed in both Del/+ and Dup/+ animals. By investigating hippocampus function, we showed synaptic transmission defects in Del/+ and Dup/+ mice. Mutant mice with a heterozygous loss-of-function mutation in Kansl1 displayed similar behavioral and anatomical phenotypes compared to Del/+ mice with the exception of sociability phenotypes. Genes controlling chromatin organization, synaptic transmission and neurogenesis were upregulated in the hippocampus of Del/+ and Kansl1+/- animals. Our results demonstrate the implication of KANSL1 in the manifestation of KdVS phenotypes and extend substantially our knowledge about biological processes affected by these mutations. Clear differences in social behavior and gene expression profiles between Del/+ and Kansl1+/- mice suggested potential roles of other genes affected by the 17q21.31 deletion. Together, these novel mouse models provide new genetic tools valuable for the development of therapeutic approaches.</p>',
			'date' => '2017-07-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28704368',
			'doi' => '',
			'modified' => '2017-10-10 17:25:37',
			'created' => '2017-10-10 17:25:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 156 => array(
			'id' => '3339',
			'name' => 'Platelet function is modified by common sequence variation in megakaryocyte super enhancers',
			'authors' => 'Petersen R. et al.',
			'description' => '<p>Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quantitative traits using cell type-matched epigenomic data and promoter long-range interactions. We identify potential regulatory functions for 423 of 565 (75%) non-coding variants associated with platelet traits and we demonstrate, through <em>ex vivo</em> and proof of principle genome editing validation, that variants in super enhancers play an important role in controlling archetypical platelet functions.</p>',
			'date' => '2017-07-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511350/#S1',
			'doi' => '',
			'modified' => '2018-02-15 10:25:39',
			'created' => '2018-02-15 10:25:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 157 => array(
			'id' => '3234',
			'name' => 'Chromatin Immunoprecipitation (ChIP) in Mouse T-cell Lines',
			'authors' => 'Giaimo B.D. et al.',
			'description' => '<p>Signaling pathways regulate gene expression programs via the modulation of the chromatin structure at different levels, such as by post-translational modifications (PTMs) of histone tails, the exchange of canonical histones with histone variants, and nucleosome eviction. Such regulation requires the binding of signal-sensitive transcription factors (TFs) that recruit chromatin-modifying enzymes at regulatory elements defined as enhancers. Understanding how signaling cascades regulate enhancer activity requires a comprehensive analysis of the binding of TFs, chromatin modifying enzymes, and the occupancy of specific histone marks and histone variants. Chromatin immunoprecipitation (ChIP) assays utilize highly specific antibodies to immunoprecipitate specific protein/DNA complexes. The subsequent analysis of the purified DNA allows for the identification the region occupied by the protein recognized by the antibody. This work describes a protocol to efficiently perform ChIP of histone proteins in a mature mouse T-cell line. The presented protocol allows for the performance of ChIP assays in a reasonable timeframe and with high reproducibility.</p>',
			'date' => '2017-06-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28654055',
			'doi' => '',
			'modified' => '2017-08-24 10:13:18',
			'created' => '2017-08-24 10:13:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 158 => array(
			'id' => '3222',
			'name' => 'DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats',
			'authors' => 'Brocks D. et al.',
			'description' => '<p>Several mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known about their genome-wide transcriptional and epigenomic consequences. By mapping global transcription start site (TSS) and chromatin dynamics, we observed the cryptic transcription of thousands of treatment-induced non-annotated TSSs (TINATs) following DNMTi and HDACi treatment. The resulting transcripts frequently splice into protein-coding exons and encode truncated or chimeric ORFs translated into products with predicted abnormal or immunogenic functions. TINAT transcription after DNMTi treatment coincided with DNA hypomethylation and gain of classical promoter histone marks, while HDACi specifically induced a subset of TINATs in association with H2AK9ac, H3K14ac, and H3K23ac. Despite this mechanistic difference, both inhibitors convergently induced transcription from identical sites, as we found TINATs to be encoded in solitary long terminal repeats of the ERV9/LTR12 family, which are epigenetically repressed in virtually all normal cells.</p>',
			'date' => '2017-06-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28604729',
			'doi' => '',
			'modified' => '2017-08-18 14:14:48',
			'created' => '2017-08-18 14:14:48',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 159 => array(
			'id' => '3241',
			'name' => 'Evolutionary re-wiring of p63 and the epigenomic regulatory landscape in keratinocytes and its potential implications on species-specific gene expression and phenotypes',
			'authors' => 'Sethi I. et al.',
			'description' => '<p>Although epidermal keratinocyte development and differentiation proceeds in similar fashion between humans and mice, evolutionary pressures have also wrought significant species-specific physiological differences. These differences between species could arise in part, by the rewiring of regulatory network due to changes in the global targets of lineage-specific transcriptional master regulators such as p63. Here we have performed a systematic and comparative analysis of the p63 target gene network within the integrated framework of the transcriptomic and epigenomic landscape of mouse and human keratinocytes. We determined that there exists a core set of &sim;1600 genomic regions distributed among enhancers and super-enhancers, which are conserved and occupied by p63 in keratinocytes from both species. Notably, these DNA segments are typified by consensus p63 binding motifs under purifying selection and are associated with genes involved in key keratinocyte and skin-centric biological processes. However, the majority of the p63-bound mouse target regions consist of either murine-specific DNA elements that are not alignable to the human genome or exhibit no p63 binding in the orthologous syntenic regions, typifying an occupancy lost subset. Our results suggest that these evolutionarily divergent regions have undergone significant turnover of p63 binding sites and are associated with an underlying inactive and inaccessible chromatin state, indicative of their selective functional activity in the transcriptional regulatory network in mouse but not human. Furthermore, we demonstrate that this selective targeting of genes by p63 correlates with subtle, but measurable transcriptional differences in mouse and human keratinocytes that converges on major metabolic processes, which often exhibit species-specific trends. Collectively our study offers possible molecular explanation for the observable phenotypic differences between the mouse and human skin and broadly informs on the prevailing principles that govern the tug-of-war between evolutionary forces of rigidity and plasticity over transcriptional regulatory programs.</p>',
			'date' => '2017-05-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28505376',
			'doi' => '',
			'modified' => '2017-08-29 12:01:20',
			'created' => '2017-08-29 12:01:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 160 => array(
			'id' => '3201',
			'name' => 'RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA(+) and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells.',
			'authors' => 'Lund R.J. et al.',
			'description' => '<p>POLR3G is expressed at high levels in human pluripotent stem cells (hPSCs) and is required for maintenance of stem cell state through mechanisms not known in detail. To explore how POLR3G regulates stem cell state, we carried out deep-sequencing analysis&nbsp;of polyA<sup>+</sup> and smallRNA transcriptomes present in hPSCs and regulated in POLR3G-dependent manner. Our data reveal that&nbsp;POLR3G regulates a specific subset of the hPSC transcriptome, including multiple transcript types, such as protein-coding genes,&nbsp;long intervening non-coding RNAs, microRNAs and small nucleolar RNAs, and affects RNA splicing. The primary function of POLR3G is in the maintenance rather than repression of transcription. The majority of POLR3G polyA<sup>+</sup> transcriptome is regulated&nbsp;during differentiation, and the key pluripotency factors bind to the promoters of at least 30% of the POLR3G-regulated transcripts. Among the direct targets of POLR3G, POLG is potentially important in sustaining stem cell status in a POLR3G-dependent manner.</p>',
			'date' => '2017-05-09',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28494942',
			'doi' => '',
			'modified' => '2017-07-03 10:04:16',
			'created' => '2017-07-03 10:04:16',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 161 => array(
			'id' => '3211',
			'name' => 'The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis.',
			'authors' => 'Aldiri I. et al.',
			'description' => '<p>In the developing retina, multipotent neural progenitors undergo unidirectional differentiation in a precise spatiotemporal order. Here we profile the epigenetic and transcriptional changes that occur during retinogenesis in mice and humans. Although some progenitor genes and cell cycle genes were epigenetically silenced during retinogenesis, the most dramatic change was derepression of cell-type-specific differentiation programs. We identified developmental-stage-specific super-enhancers and showed that most epigenetic changes are conserved in humans and mice. To determine how the epigenome changes during tumorigenesis and reprogramming, we performed integrated epigenetic analysis of murine and human retinoblastomas and induced pluripotent stem cells (iPSCs) derived from murine rod photoreceptors. The retinoblastoma epigenome mapped to the developmental stage when retinal progenitors switch from neurogenic to terminal patterns of cell division. The epigenome of retinoblastomas was more similar to that of the normal retina than that of retina-derived iPSCs, and we identified retina-specific epigenetic memory.</p>',
			'date' => '2017-05-03',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28472656',
			'doi' => '',
			'modified' => '2017-07-07 17:04:39',
			'created' => '2017-07-07 17:04:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 162 => array(
			'id' => '3187',
			'name' => 'Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions',
			'authors' => 'Frank-Bertoncelj M, Trenkmann M, Klein K, Karouzakis E, Rehrauer H, Bratus A, Kolling C, Armaka M, Filer A, Michel BA, Gay RE, Buckley CD, Kollias G, Gay S, Ospelt C',
			'description' => '<p>A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNF, creating a unique microenvironment in each joint. These findings indicate that local stroma might control positional disease patterns not only in arthritis but in any disease with a prominent stromal component.</p>',
			'date' => '2017-03-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28332497',
			'doi' => '',
			'modified' => '2017-05-24 17:07:07',
			'created' => '2017-05-24 17:07:07',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 163 => array(
			'id' => '3159',
			'name' => 'Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells',
			'authors' => 'Tumber A. et al.',
			'description' => '<p>Methylation of lysine residues on histone tail is a dynamic epigenetic modification that plays a key role in chromatin structure and gene regulation. Members of the KDM5 (also known as JARID1) sub-family are 2-oxoglutarate (2-OG) and Fe<sup>2+</sup>-dependent oxygenases acting as histone 3 lysine 4 trimethyl (H3K4me3) demethylases, regulating proliferation, stem cell self-renewal, and differentiation. Here we present the characterization of KDOAM-25, an inhibitor of KDM5 enzymes. KDOAM-25 shows biochemical half maximal inhibitory concentration values of&nbsp;&lt;100&nbsp;nM for KDM5A-D in&nbsp;vitro, high selectivity toward other 2-OG oxygenases sub-families, and no off-target activity on a panel of 55 receptors and enzymes. In human cell assay systems, KDOAM-25 has a half maximal effective concentration of &sim;50&nbsp;&mu;M and good selectivity toward other demethylases. KDM5B is overexpressed in multiple myeloma and negatively correlated with the overall survival. Multiple myeloma MM1S cells treated with KDOAM-25 show increased global H3K4 methylation at transcriptional start sites and impaired proliferation.</p>',
			'date' => '2017-03-16',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28262558',
			'doi' => '',
			'modified' => '2017-04-12 14:51:37',
			'created' => '2017-04-12 14:51:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 164 => array(
			'id' => '3172',
			'name' => 'Decoupling of DNA methylation and activity of intergenic LINE-1 promoters in colorectal cancer',
			'authors' => 'Vafadar-Isfahani N. et al.',
			'description' => '<p>Hypomethylation of LINE-1 repeats in cancer has been proposed as the main mechanism behind their activation; this assumption, however, was based on findings from early studies that were biased toward young and transpositionally active elements. Here, we investigate the relationship between methylation of 2 intergenic, transpositionally inactive LINE-1 elements and expression of the LINE-1 chimeric transcript (LCT) 13 and LCT14 driven by their antisense promoters (L1-ASP). Our data from DNA modification, expression, and 5'RACE analyses suggest that colorectal cancer methylation in the regions analyzed is not always associated with LCT repression. Consistent with this, in HCT116 colorectal cancer cells lacking DNA methyltransferases DNMT1 or DNMT3B, LCT13 expression decreases, while cells lacking both DNMTs or treated with the DNMT inhibitor 5-azacytidine (5-aza) show no change in LCT13 expression. Interestingly, levels of the H4K20me3 histone modification are inversely associated with LCT13 and LCT14 expression. Moreover, at these LINE-1s, H4K20me3 levels rather than DNA methylation seem to be good predictor of their sensitivity to 5-aza treatment. Therefore, by studying individual LINE-1 promoters we have shown that in some cases these promoters can be active without losing methylation; in addition, we provide evidence that other factors (e.g., H4K20me3 levels) play prominent roles in their regulation.</p>',
			'date' => '2017-03-16',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28300471',
			'doi' => '',
			'modified' => '2017-05-10 16:26:24',
			'created' => '2017-05-10 16:26:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 165 => array(
			'id' => '3165',
			'name' => 'Assessing histone demethylase inhibitors in cells: lessons learned',
			'authors' => 'Hatch S.B. et al.',
			'description' => '<div xmlns="http://www.w3.org/1999/xhtml" class="AbstractSection" id="ASec1">
<h3 xmlns="" class="Heading">Background</h3>
<p id="Par1" class="Para">Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The first KDM inhibitors for KDM1 have entered clinical trials, and efforts are ongoing to develop potent, selective and cell-active &lsquo;probe&rsquo; molecules for this target class. Robust cellular assays to assess the specific engagement of KDM inhibitors in cells as well as their cellular selectivity are a prerequisite for the development of high-quality inhibitors. Here we describe the use of a high-content cellular immunofluorescence assay as a method for demonstrating target engagement in cells.</p>
</div>
<div xmlns="http://www.w3.org/1999/xhtml" class="AbstractSection" id="ASec2">
<h3 xmlns="" class="Heading">Results</h3>
<p id="Par2" class="Para">A panel of assays for the Jumonji C subfamily of KDMs was developed to encompass all major branches of the JmjC phylogenetic tree. These assays compare compound activity against wild-type KDM proteins to a catalytically inactive version of the KDM, in which residues involved in the active-site iron coordination are mutated to inactivate the enzyme activity. These mutants are critical for assessing the specific effect of KDM inhibitors and for revealing indirect effects on histone methylation status. The reported assays make use of ectopically expressed demethylases, and we demonstrate their use to profile several recently identified classes of KDM inhibitors and their structurally matched inactive controls. The generated data correlate well with assay results assessing endogenous KDM inhibition and confirm the selectivity observed in biochemical assays with isolated enzymes. We find that both cellular permeability and competition with 2-oxoglutarate affect the translation of biochemical activity to cellular inhibition.</p>
</div>
<div xmlns="http://www.w3.org/1999/xhtml" class="AbstractSection" id="ASec3">
<h3 xmlns="" class="Heading">Conclusions</h3>
<p id="Par3" class="Para">High-content-based immunofluorescence assays have been established for eight KDM members of the 2-oxoglutarate-dependent oxygenases covering all major branches of the JmjC-KDM phylogenetic tree. The usage of both full-length, wild-type and catalytically inactive mutant ectopically expressed protein, as well as structure-matched inactive control compounds, allowed for detection of nonspecific effects causing changes in histone methylation as a result of compound toxicity. The developed assays offer a histone lysine demethylase family-wide tool for assessing KDM inhibitors for cell activity and on-target efficacy. In addition, the presented data may inform further studies to assess the cell-based activity of histone lysine methylation inhibitors.</p>
</div>',
			'date' => '2017-03-01',
			'pmid' => 'https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-017-0116-6',
			'doi' => '',
			'modified' => '2017-05-09 10:02:47',
			'created' => '2017-05-09 10:02:47',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 166 => array(
			'id' => '3149',
			'name' => 'RNF40 regulates gene expression in an epigenetic context-dependent manner',
			'authors' => 'Xie W. et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlates with increased gene expression. In contrast, depletion of the H2B ubiquitin ligases RNF20 or RNF40 alters the expression of only a subset of genes.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Using conditional Rnf40 knockout mouse embryo fibroblasts, we show that genes occupied by low to moderate amounts of H2Bub1 are selectively regulated in response to Rnf40 deletion, whereas genes marked by high levels of H2Bub1 are mostly unaffected by Rnf40 loss. Furthermore, we find that decreased expression of RNF40-dependent genes is highly associated with widespread narrowing of H3K4me3 peaks. H2Bub1 promotes the broadening of H3K4me3 to increase transcriptional elongation, which together lead to increased tissue-specific gene transcription. Notably, genes upregulated following Rnf40 deletion, including Foxl2, are enriched for H3K27me3, which is decreased following Rnf40 deletion due to decreased expression of the Ezh2 gene. As a consequence, increased expression of some RNF40-"suppressed" genes is associated with enhancer activation via FOXL2.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">Together these findings reveal the complexity and context-dependency whereby one histone modification can have divergent effects on gene transcription. Furthermore, we show that these effects are dependent upon the activity of other epigenetic regulatory proteins and histone modifications.</abstracttext></p>
</div>',
			'date' => '2017-02-16',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28209164',
			'doi' => '',
			'modified' => '2017-03-24 17:22:20',
			'created' => '2017-03-24 17:22:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 167 => array(
			'id' => '3140',
			'name' => 'Menin regulates Inhbb expression through an Akt/Ezh2-mediated H3K27 histone modification',
			'authors' => 'Gherardi S. et al.',
			'description' => '<p>Although Men1 is a well-known tumour suppressor gene, little is known about the functions of Menin, the protein it encodes for. Since few years, numerous publications support a major role of Menin in the control of epigenetics gene regulation. While Menin interaction with MLL complex favours transcriptional activation of target genes through H3K4me3 marks, Menin also represses gene expression via mechanisms involving the Polycomb repressing complex (PRC). Interestingly, Ezh2, the PRC-methyltransferase that catalyses H3K27me3 repressive marks and Menin have been shown to co-occupy a large number of promoters. However, lack of binding between Menin and Ezh2 suggests that another member of the PRC complex is mediating this indirect interaction. Having found that ActivinB - a TGF&beta; superfamily member encoded by the Inhbb gene - is upregulated in insulinoma tumours caused by Men1 invalidation, we hypothesize that Menin could directly participate in the epigenetic-repression of Inhbb gene expression. Using Animal model and cell lines, we report that loss of Menin is directly associated with ActivinB-induced expression both in vivo and in vitro. Our work further reveals that ActivinB expression is mediated through a direct modulation of H3K27me3 marks on the Inhbb locus in Menin-KO cell lines. More importantly, we show that Menin binds on the promoter of Inhbb gene where it favours the recruitment of Ezh2 via an indirect mechanism involving Akt-phosphorylation. Our data suggests therefore that Menin could take an important part to the Ezh2-epigenetic repressive landscape in many cells and tissues through its capacity to modulate Akt phosphorylation.</p>',
			'date' => '2017-02-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28215965',
			'doi' => '',
			'modified' => '2017-03-22 12:07:48',
			'created' => '2017-03-22 12:07:48',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 168 => array(
			'id' => '3139',
			'name' => 'A novel DLX3-PKC integrated signaling network drives keratinocyte differentiation',
			'authors' => 'Palazzo E. et al.',
			'description' => '<p>Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regulate cell cycle-related signaling and that this mechanism is functionally involved in cutaneous squamous cell carcinoma development. Here we show that DLX3 expression and its downstream signaling depend on protein kinase C &alpha; (PKC&alpha;) activity in skin. We found that following 12-O-tetradecanoyl-phorbol-13-acetate (TPA) topical treatment, DLX3 expression is significantly upregulated in the epidermis and keratinocytes from mice overexpressing PKC&alpha; by transgenic targeting (K5-PKC&alpha;), resulting in cell cycle block and terminal differentiation. Epidermis lacking DLX3 (DLX3cKO), which is linked to the development of a DLX3-dependent epidermal hyperplasia with hyperkeratosis and dermal leukocyte recruitment, displays enhanced PKC&alpha; activation, suggesting a feedback regulation of DLX3 and PKC&alpha;. Of particular significance, transcriptional activation of epidermal barrier, antimicrobial peptide and cytokine genes is significantly increased in DLX3cKO skin and further increased by TPA-dependent PKC activation. Furthermore, when inhibiting PKC activity, we show that epidermal thickness, keratinocyte proliferation and inflammatory cell infiltration are reduced and the PKC-DLX3-dependent gene expression signature is normalized. Independently of PKC, DLX3 expression specifically modulates regulatory networks such as Wnt signaling, phosphatase activity and cell adhesion. Chromatin immunoprecipitation sequencing analysis of primary suprabasal keratinocytes showed binding of DLX3 to the proximal promoter regions of genes associated with cell cycle regulation, and of structural proteins and transcription factors involved in epidermal differentiation. These results indicate that Dlx3 potentially regulates a set of crucial genes necessary during the epidermal differentiation process. Altogether, we demonstrate the existence of a robust DLX3-PKC&alpha; signaling pathway in keratinocytes that is crucial to epidermal differentiation control and cutaneous homeostasis.</p>',
			'date' => '2017-02-10',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28186503',
			'doi' => '',
			'modified' => '2017-03-22 12:00:37',
			'created' => '2017-03-22 12:00:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 169 => array(
			'id' => '3100',
			'name' => 'Muscle catabolic capacities and global hepatic epigenome are modified in juvenile rainbow trout fed different vitamin levels at first feeding',
			'authors' => 'Panserat S. et al.',
			'description' => '<p>Based on the concept of nutritional programming in mammals, we tested whether a short term hyper or hypo vitamin stimulus during first-feeding could induce long-lasting changes in nutrient metabolism in rainbow trout. Trout alevins received during the 4 first weeks of exogenous feeding a diet either without supplemental vitamins (NOSUP), a diet supplemented with a vitamin premix to satisfy the minimal requirement in all the vitamins (NRC) or a diet with a vitamin premix corresponding to an optimal vitamin nutrition (OVN). Following a common rearing period on the control diet, all three groups were then evaluated in terms of metabolic marker gene expressions at the end of the feeding period (day 119). Whereas no gene modifications for proteins involved in energy and lipid metabolism were observed in whole alevins (short-term effect), some of these genes showed a long-term molecular adaptation in the muscle of juveniles (long-term effect). Indeed, muscle of juveniles subjected at an early feeding of the OVN diet displayed up-regulated expression of markers of lipid catabolism (3-hydroxyacyl-CoA dehydrogenase &ndash; HOAD - enzyme) and mitochondrial energy metabolism (Citrate synthase - <em>cs</em>, Ubiquitinol cytochrome <em>c</em> reductase core protein 2 - QCR2, cytochrome oxidase 4 - COX4, ATP synthase form 5 - ATP5A) compared to fish fed the NOSUP diet. Moreover, some key enzymes involved in glucose catabolism (Muscle Pyruvate kinase - PKM) and amino acid catabolism (Glutamate dehydrogenase - GDH3) were also up regulated in muscle of juvenile fish fed with the OVN diet at first-feeding compared to fish fed the NOSUP diet. We researched if these permanently modified gene expressions could be related to global modifications of epigenetic marks (global DNA methylation and global histone acetylation and methylation). There was no variation of the epigenetic marks in muscle. However, we found changes in hepatic DNA methylation, global H3 acetylation and H3K4 methylation, dependent on the vitamin intake at early life. In summary, our data show, for the first time in fish, that a short-term vitamin-stimulus during early life may durably influence muscle energy and lipid metabolism as well as some hepatic epigenetic marks in rainbow trout.</p>',
			'date' => '2017-02-01',
			'pmid' => 'http://www.sciencedirect.com/science/article/pii/S0044848616309693',
			'doi' => '',
			'modified' => '2017-01-03 15:01:50',
			'created' => '2017-01-03 15:01:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 170 => array(
			'id' => '3131',
			'name' => 'DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma',
			'authors' => 'Sheffield N.C. et al.',
			'description' => '<p>Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genetically homogeneous cancers. We performed genome-scale DNA methylation sequencing for a large cohort of Ewing sarcoma tumors and analyzed epigenetic heterogeneity on three levels: between cancers, between tumors, and within tumors. We observed consistent DNA hypomethylation at enhancers regulated by the disease-defining EWS-FLI1 fusion protein, thus establishing epigenomic enhancer reprogramming as a ubiquitous and characteristic feature of Ewing sarcoma. DNA methylation differences between tumors identified a continuous disease spectrum underlying Ewing sarcoma, which reflected the strength of an EWS-FLI1 regulatory signature and a continuum between mesenchymal and stem cell signatures. There was substantial epigenetic heterogeneity within tumors, particularly in patients with metastatic disease. In summary, our study provides a comprehensive assessment of epigenetic heterogeneity in Ewing sarcoma and thereby highlights the importance of considering nongenetic aspects of tumor heterogeneity in the context of cancer biology and personalized medicine.</p>',
			'date' => '2017-01-30',
			'pmid' => 'http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4273.html',
			'doi' => '',
			'modified' => '2017-03-07 15:33:50',
			'created' => '2017-03-07 15:33:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 171 => array(
			'id' => '3144',
			'name' => 'MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct enhancer repertoire and target the RUNX1 program in 11q23 acute myeloid leukemia.',
			'authors' => 'Prange KH et al.',
			'description' => '<p>In 11q23 leukemias, the N-terminal part of the mixed lineage leukemia (MLL) gene is fused to &gt;60 different partner genes. In order to define a core set of MLL rearranged targets, we investigated the genome-wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and associated epigenetic signatures in acute myeloid leukemia (AML) cell lines THP-1 and MV4-11. We uncovered both common as well as specific MLL-AF9 and MLL-AF4 target genes, which were all marked by H3K79me2, H3K27ac and H3K4me3. Apart from promoter binding, we also identified MLL-AF9 and MLL-AF4 binding at specific subsets of non-overlapping active distal regulatory elements. Despite this differential enhancer binding, MLL-AF9 and MLL-AF4 still direct a common gene program, which represents part of the RUNX1 gene program and constitutes of CD34<sup>+</sup> and monocyte-specific genes. Comparing these data sets identified several zinc finger transcription factors (TFs) as potential MLL-AF9 co-regulators. Together, these results suggest that MLL fusions collaborate with specific subsets of TFs to deregulate the RUNX1 gene program in 11q23 AMLs.</p>',
			'date' => '2017-01-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28114278',
			'doi' => '',
			'modified' => '2017-03-23 15:13:45',
			'created' => '2017-03-23 15:13:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 172 => array(
			'id' => '3090',
			'name' => 'Arabidopsis SWI/SNF chromatin remodeling complex binds both promoters and terminators to regulate gene expression',
			'authors' => 'Archacki R. et al.',
			'description' => '<p>ATP-dependent chromatin remodeling complexes are important regulators of gene expression in Eukaryotes. In plants, SWI/SNF-type complexes have been shown critical for transcriptional control of key developmental processes, growth and stress responses. To gain insight into mechanisms underlying these roles, we performed whole genome mapping of the SWI/SNF catalytic subunit BRM in Arabidopsis thaliana, combined with transcript profiling experiments. Our data show that BRM occupies thousands of sites in Arabidopsis genome, most of which located within or close to genes. Among identified direct BRM transcriptional targets almost equal numbers were up- and downregulated upon BRM depletion, suggesting that BRM can act as both activator and repressor of gene expression. Interestingly, in addition to genes showing canonical pattern of BRM enrichment near transcription start site, many other genes showed a transcription termination site-centred BRM occupancy profile. We found that BRM-bound 3' gene regions have promoter-like features, including presence of TATA boxes and high H3K4me3 levels, and possess high antisense transcriptional activity which is subjected to both activation and repression by SWI/SNF complex. Our data suggest that binding to gene terminators and controlling transcription of non-coding RNAs is another way through which SWI/SNF complex regulates expression of its targets.</p>',
			'date' => '2016-12-19',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27994035',
			'doi' => '',
			'modified' => '2017-01-03 10:02:56',
			'created' => '2017-01-03 10:02:56',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 173 => array(
			'id' => '3096',
			'name' => 'Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals',
			'authors' => 'Schwörer S. et al.',
			'description' => '<p>The functionality of stem cells declines during ageing, and this decline contributes to ageing-associated impairments in tissue regeneration and function. Alterations in developmental pathways have been associated with declines in stem-cell function during ageing, but the nature of this process remains poorly understood. Hox genes are key regulators of stem cells and tissue patterning during embryogenesis with an unknown role in ageing. Here we show that the epigenetic stress response in muscle stem cells (also known as satellite cells) differs between aged and young mice. The alteration includes aberrant global and site-specific induction of active chromatin marks in activated satellite cells from aged mice, resulting in the specific induction of Hoxa9 but not other Hox genes. Hoxa9 in turn activates several developmental pathways and represents a decisive factor that separates satellite cell gene expression in aged mice from that in young mice. The activated pathways include most of the currently known inhibitors of satellite cell function in ageing muscle, including Wnt, TGF&beta;, JAK/STAT and senescence signalling. Inhibition of aberrant chromatin activation or deletion of Hoxa9 improves satellite cell function and muscle regeneration in aged mice, whereas overexpression of Hoxa9 mimics ageing-associated defects in satellite cells from young mice, which can be rescued by the inhibition of Hoxa9-targeted developmental pathways. Together, these data delineate an altered epigenetic stress response in activated satellite cells from aged mice, which limits satellite cell function and muscle regeneration by Hoxa9-dependent activation of developmental pathways.</p>',
			'date' => '2016-12-15',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27919074',
			'doi' => '',
			'modified' => '2017-01-03 12:28:33',
			'created' => '2017-01-03 12:28:33',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 174 => array(
			'id' => '3111',
			'name' => 'Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity',
			'authors' => 'Arts R.J. et al.',
			'description' => '<p>Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by &beta;-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases. Furthermore, fumarate itself induced an epigenetic program similar to &beta;-glucan-induced trained immunity. In line with this, inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by &beta;-glucan. Identification of the metabolic pathways leading to induction of trained immunity contributes to our understanding of innate immune memory and opens new therapeutic avenues.</p>',
			'date' => '2016-12-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27866838',
			'doi' => '',
			'modified' => '2017-01-04 11:17:08',
			'created' => '2017-01-04 11:17:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 175 => array(
			'id' => '3110',
			'name' => 'Immunometabolic Pathways in BCG-Induced Trained Immunity',
			'authors' => 'Arts R.J. et al.',
			'description' => '<p>The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity. Here, we show that BCG induction of trained immunity in monocytes is accompanied by a strong increase in glycolysis and, to a lesser extent, glutamine metabolism, both in an in-vitro model and after vaccination of mice and humans. Pharmacological and genetic modulation of rate-limiting glycolysis enzymes inhibits trained immunity, changes that are reflected by the effects on the histone marks (H3K4me3 and H3K9me3) underlying BCG-induced trained immunity. These data demonstrate that a shift of the glucose metabolism toward glycolysis is crucial for the induction of the histone modifications and functional changes underlying BCG-induced trained immunity. The identification of these pathways may be a first step toward vaccines that combine immunological and metabolic stimulation.</p>',
			'date' => '2016-12-06',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27926861',
			'doi' => '',
			'modified' => '2017-01-04 11:15:23',
			'created' => '2017-01-04 11:15:23',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 176 => array(
			'id' => '3098',
			'name' => 'TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells',
			'authors' => 'de la Rica L. et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Ten-eleven translocation (TET) enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable elements (TEs), which make up nearly half of the mouse and human genomes. Epigenetic mechanisms controlling TEs have the potential to affect their mobility and to drive the co-adoption of TEs for the benefit of the host.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">We performed a detailed investigation of the role of TET enzymes in the regulation of TEs in mouse embryonic stem cells (ESCs). We find that TET1 and TET2 bind multiple TE classes that harbour a variety of epigenetic signatures indicative of different functional roles. TETs co-bind with pluripotency factors to enhancer-like TEs that interact with highly expressed genes in ESCs whose expression is partly maintained by TET2-mediated DNA demethylation. TETs and 5-hydroxymethylcytosine (5hmC) are also strongly enriched at the 5' UTR of full-length, evolutionarily young LINE-1 elements, a pattern that is conserved in human ESCs. TETs drive LINE-1 demethylation, but surprisingly, LINE-1s are kept repressed through additional TET-dependent activities. We find that the SIN3A co-repressive complex binds to LINE-1s, ensuring their repression in a TET1-dependent manner.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">Our data implicate TET enzymes in the evolutionary dynamics of TEs, both in the context of exaptation processes and of retrotransposition control. The dual role of TET action on LINE-1s may reflect the evolutionary battle between TEs and the host.</abstracttext></p>
</div>',
			'date' => '2016-11-18',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27863519',
			'doi' => '',
			'modified' => '2017-01-03 14:23:08',
			'created' => '2017-01-03 14:23:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 177 => array(
			'id' => '3103',
			'name' => 'β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance',
			'authors' => 'Novakovic B. et al.',
			'description' => '<p>Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as lipopolysaccharide (LPS). We apply an integrated epigenomic&nbsp;approach to characterize the molecular events involved in LPS-induced tolerance in a time-dependent manner. Mechanistically, LPS-treated monocytes fail to accumulate active histone marks at promoter and enhancers of genes in the lipid metabolism and phagocytic pathways. Transcriptional inactivity in response to a second LPS exposure in tolerized macrophages is accompanied by failure to deposit active histone marks at promoters of tolerized genes. In contrast, &beta;-glucan partially reverses the LPS-induced tolerance in&nbsp;vitro. Importantly, ex&nbsp;vivo &beta;-glucan treatment of monocytes from volunteers with experimental endotoxemia re-instates their capacity for cytokine production. Tolerance is reversed at the level of distal element histone modification and transcriptional reactivation of otherwise unresponsive genes.</p>',
			'date' => '2016-11-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27863248',
			'doi' => '',
			'modified' => '2017-01-03 15:31:46',
			'created' => '2017-01-03 15:31:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 178 => array(
			'id' => '3105',
			'name' => 'EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells',
			'authors' => 'Beringer M. et al.',
			'description' => '<p>The cellular plasticity of pluripotent stem cells is thought to be sustained by genomic regions that display both active and repressive chromatin properties. These regions exhibit low levels of gene expression, yet the mechanisms controlling these levels remain unknown. Here, we describe Elongin BC as a binding factor at the promoters of bivalent sites. Biochemical and genome-wide analyses show that Elongin BC is associated with Polycomb Repressive Complex 2 (PRC2) in pluripotent stem cells. Elongin BC is recruited to chromatin by the PRC2-associated&nbsp;factor EPOP (Elongin BC and Polycomb Repressive Complex 2 Associated Protein, also termed C17orf96, esPRC2p48, E130012A19Rik), a protein expressed in the inner cell mass of the mouse blastocyst. Both EPOP and Elongin BC are required to maintain low levels of expression at PRC2 genomic targets. Our results indicate that keeping the balance between activating and repressive cues is a more general feature of chromatin in pluripotent stem cells than previously appreciated.</p>',
			'date' => '2016-11-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27863225',
			'doi' => '',
			'modified' => '2017-01-03 16:02:21',
			'created' => '2017-01-03 16:02:21',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 179 => array(
			'id' => '3087',
			'name' => 'The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs',
			'authors' => 'Mandoli A. et al.',
			'description' => '<p>The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels of histone acetylation but also at distal elements characterized by low acetylation levels and binding of the hematopoietic transcription factors LYL1 and LMO2. In contrast, ERG, FLI1, TAL1, and RUNX1 bind at all AML1-ETO-occupied regulatory regions, including those of the AML1-ETO gene itself, suggesting their involvement in regulating AML1-ETO expression levels. While expression of AML1-ETO in myeloid differentiated induced pluripotent stem cells (iPSCs) induces leukemic characteristics, overexpression increases cell death. We find that expression of wild-type transcription factors RUNX1 and ERG in AML is required to prevent this oncogene overexpression. Together our results show that the interplay of the epigenome and transcription factors prevents apoptosis in t(8;21) AML cells.</p>',
			'date' => '2016-11-15',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27851970',
			'doi' => '',
			'modified' => '2017-01-02 11:07:24',
			'created' => '2017-01-02 11:07:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 180 => array(
			'id' => '3114',
			'name' => 'Iterative Fragmentation Improves the Detection of ChIP-seq Peaks for Inactive Histone Marks',
			'authors' => 'Laczik M. et al.',
			'description' => '<p>As chromatin immunoprecipitation (ChIP) sequencing is becoming the dominant technique for studying chromatin modifications, new protocols surface to improve the method. Bioinformatics is also essential to analyze and understand the results, and precise analysis helps us to identify the effects of protocol optimizations. We applied iterative sonication - sending the fragmented DNA after ChIP through additional round(s) of shearing - to a number of samples, testing the effects on different histone marks, aiming to uncover potential benefits of inactive histone marks specifically. We developed an analysis pipeline that utilizes our unique, enrichment-type specific approach to peak calling. With the help of this pipeline, we managed to accurately describe the advantages and disadvantages of the iterative refragmentation technique, and we successfully identified possible fields for its applications, where it enhances the results greatly. In addition to the resonication protocol description, we provide guidelines for peak calling optimization and a freely implementable pipeline for data analysis.</p>',
			'date' => '2016-10-25',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27812282',
			'doi' => '',
			'modified' => '2017-01-17 16:07:44',
			'created' => '2017-01-17 16:07:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 181 => array(
			'id' => '3033',
			'name' => 'Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition',
			'authors' => 'Sciacovelli M et al.',
			'description' => '<p>Mutations of the tricarboxylic acid cycle enzyme fumarate hydratase cause hereditary leiomyomatosis and renal cell cancer<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref1" title="Tomlinson, I. P. et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat. Genet. 30, 406&ndash;410 (2002)" id="ref-link-5">1</a></sup>. Fumarate hydratase-deficient renal cancers are highly aggressive and metastasize even when small, leading to a very poor clinical outcome<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref2" title="Schmidt, L. S. &amp; Linehan, W. M. Hereditary leiomyomatosis and renal cell carcinoma. Int. J. Nephrol. Renovasc. Dis. 7, 253&ndash;260 (2014)" id="ref-link-6">2</a></sup>. Fumarate, a small molecule metabolite that accumulates in fumarate hydratase-deficient cells, plays a key role in cell transformation, making it a <i>bona fide</i> oncometabolite<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref3" title="Yang, M., Soga, T., Pollard, P. J. &amp; Adam, J. The emerging role of fumarate as an oncometabolite. Front Oncol. 2, 85 (2012)" id="ref-link-7">3</a></sup>. Fumarate has been shown to inhibit &alpha;-ketoglutarate-dependent dioxygenases that are involved in DNA and histone demethylation<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref4" title="Laukka, T. et al. Fumarate and succinate regulate expression of hypoxia-inducible genes via TET enzymes. J. Biol. Chem. 291, 4256&ndash;4265 (2016)" id="ref-link-8">4</a>, <a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref5" title="Xiao, M. et al. Inhibition of &alpha;-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev. 26, 1326&ndash;1338 (2012)" id="ref-link-9">5</a></sup>. However, the link between fumarate accumulation, epigenetic changes, and tumorigenesis is unclear. Here we show that loss of fumarate hydratase and the subsequent accumulation of fumarate in mouse and human cells elicits an epithelial-to-mesenchymal-transition (EMT), a phenotypic switch associated with cancer initiation, invasion, and metastasis<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref6" title="De Craene, B. &amp; Berx, G. Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer 13, 97&ndash;110 (2013)" id="ref-link-10">6</a></sup>. We demonstrate that fumarate inhibits Tet-mediated demethylation of a regulatory region of the antimetastatic miRNA cluster<sup><a href="http://www.nature.com.proxy.library.uu.nl/nature/journal/v537/n7621/full/nature19353.html#ref6" title="De Craene, B. &amp; Berx, G. Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer 13, 97&ndash;110 (2013)" id="ref-link-11">6</a></sup> <i>mir-200ba429</i>, leading to the expression of EMT-related transcription factors and enhanced migratory properties. These epigenetic and phenotypic changes are recapitulated by the incubation of fumarate hydratase-proficient cells with cell-permeable fumarate. Loss of fumarate hydratase is associated with suppression of miR-200 and the EMT signature in renal cancer and is associated with poor clinical outcome. These results imply that loss of fumarate hydratase and fumarate accumulation contribute to the aggressive features of fumarate hydratase-deficient tumours.</p>',
			'date' => '2016-08-31',
			'pmid' => 'http://www.nature.com/nature/journal/v537/n7621/full/nature19353.html',
			'doi' => '',
			'modified' => '2016-09-23 10:44:15',
			'created' => '2016-09-23 10:44:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 182 => array(
			'id' => '3006',
			'name' => 'reChIP-seq reveals widespread bivalency of H3K4me3 and H3K27me3 in CD4(+) memory T cells',
			'authors' => 'Kinkley S et al.',
			'description' => '<p>The combinatorial action of co-localizing chromatin modifications and regulators determines chromatin structure and function. However, identifying co-localizing chromatin features in a high-throughput manner remains a technical challenge. Here we describe a novel reChIP-seq approach and tailored bioinformatic analysis tool, normR that allows for the sequential enrichment and detection of co-localizing DNA-associated proteins in an unbiased and genome-wide manner. We illustrate the utility of the reChIP-seq method and normR by identifying H3K4me3 or H3K27me3 bivalently modified nucleosomes in primary human CD4(+) memory T cells. We unravel widespread bivalency at hypomethylated CpG-islands coinciding with inactive promoters of developmental regulators. reChIP-seq additionally uncovered heterogeneous bivalency in the population, which was undetectable by intersecting H3K4me3 and H3K27me3 ChIP-seq tracks. Finally, we provide evidence that bivalency is established and stabilized by an interplay between the genome and epigenome. Our reChIP-seq approach augments conventional ChIP-seq and is broadly applicable to unravel combinatorial modes of action.</p>',
			'date' => '2016-08-17',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27530917',
			'doi' => '',
			'modified' => '2016-08-26 11:56:46',
			'created' => '2016-08-26 11:38:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 183 => array(
			'id' => '3002',
			'name' => 'Phenotypic Plasticity through Transcriptional Regulation of the Evolutionary Hotspot Gene tan in Drosophila melanogaster',
			'authors' => 'Gibert JM et al.',
			'description' => '<p>Phenotypic plasticity is the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions. Phenotypic plasticity can be adaptive. Furthermore, it is thought to facilitate evolution. Although phenotypic plasticity is a widespread phenomenon, its molecular mechanisms are only beginning to be unravelled. Environmental conditions can affect gene expression through modification of chromatin structure, mainly via histone modifications, nucleosome remodelling or DNA methylation, suggesting that phenotypic plasticity might partly be due to chromatin plasticity. As a model of phenotypic plasticity, we study abdominal pigmentation of Drosophila melanogaster females, which is temperature sensitive. Abdominal pigmentation is indeed darker in females grown at 18&deg;C than at 29&deg;C. This phenomenon is thought to be adaptive as the dark pigmentation produced at lower temperature increases body temperature. We show here that temperature modulates the expression of tan (t), a pigmentation gene involved in melanin production. t is expressed 7 times more at 18&deg;C than at 29&deg;C in female abdominal epidermis. Genetic experiments show that modulation of t expression by temperature is essential for female abdominal pigmentation plasticity. Temperature modulates the activity of an enhancer of t without modifying compaction of its chromatin or level of the active histone mark H3K27ac. By contrast, the active mark H3K4me3 on the t promoter is strongly modulated by temperature. The H3K4 methyl-transferase involved in this process is likely Trithorax, as we show that it regulates t expression and the H3K4me3 level on the t promoter and also participates in female pigmentation and its plasticity. Interestingly, t was previously shown to be involved in inter-individual variation of female abdominal pigmentation in Drosophila melanogaster, and in abdominal pigmentation divergence between Drosophila species. Sensitivity of t expression to environmental conditions might therefore give more substrate for selection, explaining why this gene has frequently been involved in evolution of pigmentation.</p>',
			'date' => '2016-08-10',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27508387',
			'doi' => '',
			'modified' => '2016-08-25 17:23:22',
			'created' => '2016-08-25 17:23:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 184 => array(
			'id' => '3023',
			'name' => 'MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis',
			'authors' => 'Wang W et al.',
			'description' => '<p>DNA double strand break (DSB) repair is critical for generation of B-cell receptors, which are pre-requisite for B-cell progenitor survival. However, the transcription factors that promote DSB repair in B cells are not known. Here we show that MEF2C enhances the expression of DNA repair and recombination factors in B-cell progenitors, promoting DSB repair, V(D)J recombination and cell survival. Although Mef2c-deficient mice maintain relatively intact peripheral B-lymphoid cellularity during homeostasis, they exhibit poor B-lymphoid recovery after sub-lethal irradiation and 5-fluorouracil injection. MEF2C binds active regulatory regions with high-chromatin accessibility in DNA repair and V(D)J genes in both mouse B-cell progenitors and human B lymphoblasts. Loss of Mef2c in pre-B cells reduces chromatin accessibility in multiple regulatory regions of the MEF2C-activated genes. MEF2C therefore protects B lymphopoiesis during stress by ensuring proper expression of genes that encode DNA repair and B-cell factors.</p>',
			'date' => '2016-08-10',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27507714',
			'doi' => '',
			'modified' => '2016-08-31 10:42:58',
			'created' => '2016-08-31 10:42:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 185 => array(
			'id' => '3004',
			'name' => 'Toxoplasma gondii TgIST co-opts host chromatin repressors dampening STAT1-dependent gene regulation and IFN-γ-mediated host defenses',
			'authors' => 'Gay G et al.',
			'description' => '<p>An early hallmark of Toxoplasma gondii infection is the rapid control of the parasite population by a potent multifaceted innate immune response that engages resident and homing immune cells along with pro- and counter-inflammatory cytokines. In this context, IFN-&gamma; activates a variety of T. gondii-targeting activities in immune and nonimmune cells but can also contribute to host immune pathology. T. gondii has evolved mechanisms to timely counteract the host IFN-&gamma; defenses by interfering with the transcription of IFN-&gamma;-stimulated genes. We now have identified TgIST (T. gondii inhibitor of STAT1 transcriptional activity) as a critical molecular switch that is secreted by intracellular parasites and traffics to the host cell nucleus where it inhibits STAT1-dependent proinflammatory gene expression. We show that TgIST not only sequesters STAT1 on dedicated loci but also promotes shaping of a nonpermissive chromatin through its capacity to recruit the nucleosome remodeling deacetylase (NuRD) transcriptional repressor. We found that during mice acute infection, TgIST-deficient parasites are rapidly eliminated by the homing Gr1<sup>+</sup> inflammatory monocytes, thus highlighting the protective role of TgIST against IFN-&gamma;-mediated killing. By uncovering TgIST functions, this study brings novel evidence on how T. gondii has devised a molecular weapon of choice to take control over a ubiquitous immune gene expression mechanism in metazoans, as a way to promote long-term parasitism.</p>',
			'date' => '2016-08-08',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27503074',
			'doi' => '',
			'modified' => '2016-08-26 11:02:25',
			'created' => '2016-08-26 11:02:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 186 => array(
			'id' => '3003',
			'name' => 'Epigenetic dynamics of monocyte-to-macrophage differentiation',
			'authors' => 'Wallner S et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Monocyte-to-macrophage differentiation involves major biochemical and structural changes. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete transcriptome and epigenome of human monocytes that were differentiated in vitro by addition of colony-stimulating factor 1 in serum-free medium.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Numerous mRNAs and miRNAs were significantly up- or down-regulated. More than 100 discrete DNA regions, most often far away from transcription start sites, were rapidly demethylated by the ten eleven translocation enzymes, became nucleosome-free and gained histone marks indicative of active enhancers. These regions were unique for macrophages and associated with genes involved in the regulation of the actin cytoskeleton, phagocytosis and innate immune response.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">In summary, we have discovered a phagocytic gene network that is repressed by DNA methylation in monocytes and rapidly de-repressed after the onset of macrophage differentiation.</abstracttext></p>
</div>',
			'date' => '2016-07-29',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27478504',
			'doi' => '10.1186/s13072-016-0079-z',
			'modified' => '2016-08-26 11:59:54',
			'created' => '2016-08-26 10:20:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 187 => array(
			'id' => '3021',
			'name' => 'Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis',
			'authors' => 'Rinaldi L et al.',
			'description' => '<p>The genome-wide localization and function of endogenous Dnmt3a and Dnmt3b in adult stem cells are unknown. Here, we show that in human epidermal stem cells, the two proteins bind in a histone H3K36me3-dependent manner to the most active enhancers and are required to produce their associated enhancer RNAs. Both proteins prefer super-enhancers associated to genes that either define the ectodermal lineage or establish the stem cell and differentiated states. However, Dnmt3a and Dnmt3b differ in their mechanisms of enhancer regulation: Dnmt3a associates with p63 to maintain high levels of DNA hydroxymethylation at the center of enhancers in a Tet2-dependent manner, whereas Dnmt3b promotes DNA methylation along the body of the enhancer. Depletion of either protein inactivates their target enhancers and profoundly affects epidermal stem cell function. Altogether, we reveal novel functions for Dnmt3a and Dnmt3b at enhancers that could contribute to their roles in disease and tumorigenesis.</p>',
			'date' => '2016-07-26',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27476967',
			'doi' => '',
			'modified' => '2016-08-31 10:22:54',
			'created' => '2016-08-31 10:22:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 188 => array(
			'id' => '2915',
			'name' => 'PAFAH1B1 and the lncRNA NONHSAT073641 maintain an angiogenic phenotype in human endothelial cells',
			'authors' => 'Josipovic I at al.',
			'description' => '<h4>AIM:</h4>
<p><abstracttext label="AIM" nlmcategory="OBJECTIVE">Platelet-activating factor acetyl hydrolase 1B1 (PAFAH1B1, also known as Lis1) is a protein essentially involved in neurogenesis and mostly studied in the nervous system. As we observed a significant expression of PAFAH1B1 in the vascular system, we hypothesized that PAFAH1B1 is important during angiogenesis of endothelial cells as well as in human vascular diseases.</abstracttext></p>
<h4>METHOD:</h4>
<p><abstracttext label="METHOD" nlmcategory="METHODS">The functional relevance of the protein in endothelial cell angiogenic function, its downstream targets and the influence of NONHSAT073641, a long non-coding RNA (lncRNA) with 92% similarity to PAFAH1B1, were studied by knockdown and overexpression in human umbilical vein endothelial cells (HUVEC).</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Knockdown of PAFAH1B1 led to impaired tube formation of HUVEC and decreased sprouting in the spheroid assay. Accordingly, the overexpression of PAFAH1B1 increased tube number, sprout length and sprout number. LncRNA NONHSAT073641 behaved similarly. Microarray analysis after PAFAH1B1 knockdown and its overexpression indicated that the protein maintains Matrix Gla Protein (MGP) expression. Chromatin immunoprecipitation experiments revealed that PAFAH1B1 is required for active histone marks and proper binding of RNA Polymerase II to the transcriptional start site of MGP. MGP itself was required for endothelial angiogenic capacity and knockdown of both, PAFAH1B1 and MGP, reduced migration. In vascular samples of patients with chronic thromboembolic pulmonary hypertension (CTEPH), PAFAH1B1 and MGP were upregulated. The function of PAFAH1B1 required the presence of the intact protein as overexpression of NONHSAT073641, which was highly upregulated during CTEPH, did not affect PAFAH1B1 target genes.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">PAFAH1B1 and NONHSAT073641 are important for endothelial angiogenic function. This article is protected by copyright. All rights reserved.</abstracttext></p>',
			'date' => '2016-04-28',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27124368',
			'doi' => ' 10.1111/apha.12700',
			'modified' => '2016-05-12 10:42:06',
			'created' => '2016-05-12 10:42:06',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 189 => array(
			'id' => '2914',
			'name' => 'Chromatin immunoprecipitation from fixed clinical tissues reveals tumor-specific enhancer profiles.',
			'authors' => 'Cejas P et al.',
			'description' => '<p>Extensive cross-linking introduced during routine tissue fixation of clinical pathology specimens severely hampers chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) analysis from archived tissue samples. This limits the ability to study the epigenomes of valuable, clinically annotated tissue resources. Here we describe fixed-tissue chromatin immunoprecipitation sequencing (FiT-seq), a method that enables reliable extraction of soluble chromatin from formalin-fixed paraffin-embedded (FFPE) tissue samples for accurate detection of histone marks. We demonstrate that FiT-seq data from FFPE specimens are concordant with ChIP-seq data from fresh-frozen samples of the same tumors. By using multiple histone marks, we generate chromatin-state maps and identify cis-regulatory elements in clinical samples from various tumor types that can readily allow us to distinguish between cancers by the tissue of origin. Tumor-specific enhancers and superenhancers that are elucidated by FiT-seq analysis correlate with known oncogenic drivers in different tissues and can assist in the understanding of how chromatin states affect gene regulation.</p>',
			'date' => '2016-04-25',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27111282',
			'doi' => '10.1038/nm.4085',
			'modified' => '2016-05-11 17:34:25',
			'created' => '2016-05-11 17:34:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 190 => array(
			'id' => '2894',
			'name' => 'Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time',
			'authors' => 'Feichtinger J, Hernández I, Fischer C, Hanscho M, Auer N, Hackl M, Jadhav V, Baumann M, Krempl PM, Schmidl C, Farlik M, Schuster M, Merkel A, Sommer A, Heath S, Rico D, Bock C, Thallinger GG, Borth N',
			'description' => '<p>The most striking characteristic of CHO cells is their adaptability, which enables efficient production of proteins as well as growth under a variety of culture conditions, but also results in genomic and phenotypic instability. To investigate the relative contribution of genomic and epigenetic modifications towards phenotype evolution, comprehensive genome and epigenome data are presented for 6 related CHO cell lines, both in response to perturbations (different culture conditions and media as well as selection of a specific phenotype with increased transient productivity) and in steady state (prolonged time in culture under constant conditions). Clear transitions were observed in DNA-methylation patterns upon each perturbation, while few changes occurred over time under constant conditions. Only minor DNA-methylation changes were observed between exponential and stationary growth phase, however, throughout a batch culture the histone modification pattern underwent continuous adaptation. Variation in genome sequence between the 6 cell lines on the level of SNPs, InDels and structural variants is high, both upon perturbation and under constant conditions over time. The here presented comprehensive resource may open the door to improved control and manipulation of gene expression during industrial bioprocesses based on epigenetic mechanisms</p>',
			'date' => '2016-04-12',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27072894',
			'doi' => '10.1002/bit.25990',
			'modified' => '2016-04-22 12:53:44',
			'created' => '2016-04-22 12:37:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 191 => array(
			'id' => '2880',
			'name' => 'GATA-1 Inhibits PU.1 Gene via DNA and Histone H3K9 Methylation of Its Distal Enhancer in Erythroleukemia',
			'authors' => 'Burda P, Vargova J, Curik N, Salek C, Papadopoulos GL, Strouboulis J, Stopka T',
			'description' => '<p>GATA-1 and PU.1 are two important hematopoietic transcription factors that mutually inhibit each other in progenitor cells to guide entrance into the erythroid or myeloid lineage, respectively. PU.1 controls its own expression during myelopoiesis by binding to the distal URE enhancer, whose deletion leads to acute myeloid leukemia (AML). We herein present evidence that GATA-1 binds to the PU.1 gene and inhibits its expression in human AML-erythroleukemias (EL). Furthermore, GATA-1 together with DNA methyl Transferase I (DNMT1) mediate repression of the PU.1 gene through the URE. Repression of the PU.1 gene involves both DNA methylation at the URE and its histone H3 lysine-K9 methylation and deacetylation as well as the H3K27 methylation at additional DNA elements and the promoter. The GATA-1-mediated inhibition of PU.1 gene transcription in human AML-EL mediated through the URE represents important mechanism that contributes to PU.1 downregulation and leukemogenesis that is sensitive to DNA demethylation therapy.</p>',
			'date' => '2016-03-24',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27010793',
			'doi' => '10.1371/journal.pone.0152234',
			'modified' => '2016-04-06 10:26:31',
			'created' => '2016-04-06 10:26:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 192 => array(
			'id' => '2886',
			'name' => 'Role of Annexin gene and its regulation during zebrafish caudal fin regeneration',
			'authors' => 'Saxena S, Purushothaman S, Meghah V, Bhatti B, Poruri A, Meena Lakshmi MG, Sarath Babu N, Murthy CL, Mandal KK, Kumar A, Idris MM',
			'description' => '<p>The molecular mechanism of epimorphic regeneration is elusive due to its complexity and limitation in mammals. Epigenetic regulatory mechanisms play a crucial role in development and regeneration. This investigation attempted to reveal the role of epigenetic regulatory mechanisms, such as histone H3 and H4 lysine acetylation and methylation during zebrafish caudal fin regeneration. It was intriguing to observe that H3K9,14 acetylation, H4K20 trimethylation, H3K4 trimethylation and H3K9 dimethylation along with their respective regulatory genes, such as <em>GCN5, SETd8b, SETD7/9</em> and <em>SUV39h1</em>, were differentially regulated in the regenerating fin at various time points of post-amputation. Annexin genes have been associated with regeneration; this study reveals the significant upregulation of <em>ANXA2a</em> and <em>ANXA2b</em> transcripts and their protein products during the regeneration process. Chromatin Immunoprecipitation (ChIP) and PCR analysis of the regulatory regions of the <em>ANXA2a</em> and <em>ANXA2b</em> genes demonstrated the ability to repress two histone methylations, H3K27me3 and H4K20me3, in transcriptional regulation during regeneration. It is hypothesized that this novel insight into the diverse epigenetic mechanisms that play a critical role during the regeneration process may help to strategize the translational efforts, in addition to identifying the molecules involved in vertebrate regeneration.</p>',
			'date' => '2016-03-12',
			'pmid' => 'http://onlinelibrary.wiley.com/doi/10.1111/wrr.12429/abstract',
			'doi' => '10.1111/wrr.12429',
			'modified' => '2016-04-08 17:24:06',
			'created' => '2016-04-08 17:24:06',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 193 => array(
			'id' => '2856',
			'name' => 'Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis',
			'authors' => 'Weigel C. et al.',
			'description' => '<p>Radiotherapy is a fundamental part of cancer treatment but its use is limited by the onset of late adverse effects in the normal tissue, especially radiation-induced fibrosis. Since the molecular causes for fibrosis are largely unknown, we analyse if epigenetic regulation might explain inter-individual differences in fibrosis risk. DNA methylation profiling of dermal fibroblasts obtained from breast cancer patients prior to irradiation identifies differences associated with fibrosis. One region is characterized as a differentially methylated enhancer of diacylglycerol kinase alpha (<i>DGKA</i>). Decreased DNA methylation at this enhancer enables recruitment of the profibrotic transcription factor early growth response 1 (EGR1) and facilitates radiation-induced <i>DGKA</i> transcription in cells from patients later developing fibrosis. Conversely, inhibition of DGKA has pronounced effects on diacylglycerol-mediated lipid homeostasis and reduces profibrotic fibroblast activation. Collectively, DGKA is an epigenetically deregulated kinase involved in radiation response and may serve as a marker and therapeutic target for personalized radiotherapy.</p>',
			'date' => '2016-03-11',
			'pmid' => 'http://www.nature.com/ncomms/2016/160311/ncomms10893/full/ncomms10893.html',
			'doi' => '10.1038/ncomms10893',
			'modified' => '2016-03-15 11:08:21',
			'created' => '2016-03-15 11:08:21',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 194 => array(
			'id' => '2970',
			'name' => 'Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development.',
			'authors' => 'Yuan S et al.',
			'description' => '<p>Although it is believed that mammalian sperm carry small noncoding RNAs (sncRNAs) into oocytes during fertilization, it remains unknown whether these sperm-borne sncRNAs truly have any function during fertilization and preimplantation embryonic development. Germline-specific Dicer and Drosha conditional knockout (cKO) mice produce gametes (i.e. sperm and oocytes) partially deficient in miRNAs and/or endo-siRNAs, thus providing a unique opportunity for testing whether normal sperm (paternal) or oocyte (maternal) miRNA and endo-siRNA contents are required for fertilization and preimplantation development. Using the outcome of intracytoplasmic sperm injection (ICSI) as a readout, we found that sperm with altered miRNA and endo-siRNA profiles could fertilize wild-type (WT) eggs, but embryos derived from these partially sncRNA-deficient sperm displayed a significant reduction in developmental potential, which could be rescued by injecting WT sperm-derived total or small RNAs into ICSI embryos. Disrupted maternal transcript turnover and failure in early zygotic gene activation appeared to associate with the aberrant miRNA profiles in Dicer and Drosha cKO spermatozoa. Overall, our data support a crucial function of paternal miRNAs and/or endo-siRNAs in the control of the transcriptomic homeostasis in fertilized eggs, zygotes and two-cell embryos. Given that supplementation of sperm RNAs enhances both the developmental potential of preimplantation embryos and the live birth rate, it might represent a novel means to improve the success rate of assisted reproductive technologies in fertility clinics.</p>',
			'date' => '2016-02-15',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26718009',
			'doi' => '10.1242/dev.131755',
			'modified' => '2016-06-29 17:11:02',
			'created' => '2016-06-29 17:11:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 195 => array(
			'id' => '2849',
			'name' => 'MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199',
			'authors' => 'Benito JM et al.',
			'description' => '<p>Targeted therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of current research. <em>Mixed Lineage Leukemia</em> (<em>MLL</em>) mutations such as the t(4;11) translocation cause aggressive leukemias that are refractory to conventional treatment. The t(4;11) translocation produces an MLL/AF4 fusion protein that activates key target genes through both epigenetic and transcriptional elongation mechanisms. In this study, we show that t(4;11) patient cells express high levels of BCL-2 and are highly sensitive to treatment with the BCL-2-specific BH3 mimetic ABT-199. We demonstrate that MLL/AF4 specifically upregulates the <em>BCL-2</em> gene but not other BCL-2 family members via DOT1L-mediated H3K79me2/3. We use this information to show that a t(4;11) cell line is sensitive to a combination of ABT-199 and DOT1L inhibitors. In addition, ABT-199 synergizes with standard induction-type therapy in a xenotransplant model, advocating for the introduction of ABT-199 into therapeutic regimens for MLL-rearranged leukemias.</p>',
			'date' => '2015-12-29',
			'pmid' => 'http://www.cell.com/cell-reports/abstract/S2211-1247%2815%2901415-1',
			'doi' => ' http://dx.doi.org/10.1016/j.celrep.2015.12.003',
			'modified' => '2016-03-11 17:31:23',
			'created' => '2016-03-11 17:11:09',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 196 => array(
			'id' => '2810',
			'name' => 'Standardizing chromatin research: a simple and universal method for ChIP-seq',
			'authors' => 'Laura Arrigoni, Andreas S. Richter, Emily Betancourt, Kerstin Bruder, Sarah Diehl, Thomas Manke and Ulrike Bönisch',
			'description' => '<p><span>Here we&nbsp;demonstrate that harmonization of ChIP-seq workflows across cell types and conditions is possible when obtaining chromatin from properly isolated nuclei. We established an ultrasound-based nuclei extraction method (Nuclei Extraction by Sonication) that is highly effective across various organisms, cell types and cell numbers. The described method has the potential to replace complex cell-type-specific, but largely ineffective, nuclei isolation protocols. This article demonstrates protocol standardization using the Bioruptor shearing systems and the IP-Star Automation System for ChIP automation.</span></p>',
			'date' => '2015-12-23',
			'pmid' => 'http://pubmed.gov/26704968',
			'doi' => '10.1093/nar/gkv1495',
			'modified' => '2016-06-09 09:47:00',
			'created' => '2016-01-10 08:32:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 197 => array(
			'id' => '2952',
			'name' => 'Dynamic changes in histone modifications precede de novo DNA methylation in oocytes',
			'authors' => 'Stewart KR et al.',
			'description' => '<p>Erasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation establishment remain poorly understood, but a number of post-translational modifications of histones are implicated in antagonizing or recruiting the de novo DNA methylation complex. In mouse oogenesis, DNA methylation establishment occurs on a largely unmethylated genome and in nondividing cells, making it a highly informative model for examining how histone modifications can shape the DNA methylome. Using a chromatin immunoprecipitation (ChIP) and genome-wide sequencing (ChIP-seq) protocol optimized for low cell numbers and novel techniques for isolating primary and growing oocytes, profiles were generated for histone modifications implicated in promoting or inhibiting DNA methylation. CGIs destined for DNA methylation show reduced protective H3K4 dimethylation (H3K4me2) and trimethylation (H3K4me3) in both primary and growing oocytes, while permissive H3K36me3 increases specifically at these CGIs in growing oocytes. Methylome profiling of oocytes deficient in H3K4 demethylase KDM1A or KDM1B indicated that removal of H3K4 methylation is necessary for proper methylation establishment at CGIs. This work represents the first systematic study performing ChIP-seq in oocytes and shows that histone remodeling in the mammalian oocyte helps direct de novo DNA methylation events.</p>',
			'date' => '2015-12-01',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26584620',
			'doi' => '10.1101/gad.271353.115',
			'modified' => '2016-06-10 16:39:45',
			'created' => '2016-06-10 16:39:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 198 => array(
			'id' => '2963',
			'name' => 'Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma',
			'authors' => 'Aldiri I et al.',
			'description' => '<p>Retinal development requires precise temporal and spatial coordination of cell cycle exit, cell fate specification, cell migration and differentiation. When this process is disrupted, retinoblastoma, a developmental tumor of the retina, can form. Epigenetic modulators are central to precisely coordinating developmental events, and many epigenetic processes have been implicated in cancer. Studying epigenetic mechanisms in development is challenging because they often regulate multiple cellular processes; therefore, elucidating the primary molecular mechanisms involved can be difficult. Here we explore the role of Brg1 (Smarca4) in retinal development and retinoblastoma in mice using molecular and cellular approaches. Brg1 was found to regulate retinal size by controlling cell cycle length, cell cycle exit and cell survival during development. Brg1 was not required for cell fate specification but was required for photoreceptor differentiation and cell adhesion/polarity programs that contribute to proper retinal lamination during development. The combination of defective cell differentiation and lamination led to retinal degeneration in Brg1-deficient retinae. Despite the hypocellularity, premature cell cycle exit, increased cell death and extended cell cycle length, retinal progenitor cells persisted in Brg1-deficient retinae, making them more susceptible to retinoblastoma. ChIP-Seq analysis suggests that Brg1 might regulate gene expression through multiple mechanisms.</p>',
			'date' => '2015-12-01',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26628093',
			'doi' => '10.1242/dev.124800',
			'modified' => '2016-06-24 09:48:45',
			'created' => '2016-06-24 09:48:45',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 199 => array(
			'id' => '2964',
			'name' => 'Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization',
			'authors' => 'Kuznetsova T et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">The impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from remodeling of higher order chromatin architecture by activated transcription factors to recruitment of activated transcription factors to pre-established long-range interactions.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Using circular chromosome conformation capture coupled with next generation sequencing and high-resolution chromatin interaction analysis by paired-end tag sequencing of P300, we observed agonist-induced changes in long-range chromatin interactions, and uncovered interconnected enhancer-enhancer hubs spanning up to one megabase. The vast majority of activated glucocorticoid receptor and nuclear factor kappa-b appeared to join pre-existing P300 enhancer hubs without affecting the chromatin conformation. In contrast, binding of the activated transcription factors to loci with their consensus response elements led to the increased formation of an active epigenetic state of enhancers and a significant increase in long-range interactions within pre-existing enhancer networks. De novo enhancers or ligand-responsive enhancer hubs preferentially interacted with ligand-induced genes.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">We demonstrate that, at a subset of genomic loci, ligand-mediated induction leads to active enhancer formation and an increase in long-range interactions, facilitating efficient regulation of target genes. Therefore, our data suggest an active role of signal-dependent transcription factors in chromatin and long-range interaction remodeling.</abstracttext></p>
</div>',
			'date' => '2015-12-01',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26619937',
			'doi' => '10.1186/s13059-015-0832-9',
			'modified' => '2016-06-24 10:02:16',
			'created' => '2016-06-24 10:02:16',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 200 => array(
			'id' => '2909',
			'name' => 'Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells',
			'authors' => 'Rønningen T, Shah A, Reiner AH, Collas P, Moskaug JØ',
			'description' => '<p>Cellular metabolism confers wide-spread epigenetic modifications required for regulation of transcriptional networks that determine cellular states. Mesenchymal stromal cells are responsive to metabolic cues including circulating glucose levels and modulate inflammatory responses. We show here that long term exposure of undifferentiated human adipose tissue stromal cells (ASCs) to high glucose upregulates a subset of inflammation response (IR) genes and alters their promoter histone methylation patterns in a manner consistent with transcriptional de-repression. Modeling of chromatin states from combinations of histone modifications in nearly 500 IR genes unveil three overarching chromatin configurations reflecting repressive, active, and potentially active states in promoter and enhancer elements. Accordingly, we show that adipogenic differentiation in high glucose predominantly upregulates IR genes. Our results indicate that elevated extracellular glucose levels sensitize in ASCs an IR gene expression program which is exacerbated during adipocyte differentiation. We propose that high glucose exposure conveys an epigenetic 'priming' of IR genes, favoring a transcriptional inflammatory response upon adipogenic stimulation. Chromatin alterations at IR genes by high glucose exposure may play a role in the etiology of metabolic diseases.</p>',
			'date' => '2015-11-27',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26462465',
			'doi' => '10.1016/j.bbrc.2015.10.030',
			'modified' => '2016-05-09 22:54:48',
			'created' => '2016-05-09 22:54:48',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 201 => array(
			'id' => '2957',
			'name' => 'The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth',
			'authors' => 'Palazzo E et al.',
			'description' => '<p>Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epidermal hyperplasia and squamous tumorigenesis. By integrating genetic and transcriptomic approaches, we demonstrate that DLX3 operates through a p53-regulated network. DLX3 and p53 physically interact on the p21 promoter to enhance p21 expression. Elevating DLX3 in keratinocytes produces a G1-S blockade associated with p53 signature transcriptional profiles. In contrast, DLX3 loss promotes a mitogenic phenotype associated with constitutive activation of ERK. DLX3 expression is lost in human skin cancers and is extinguished during progression of experimentally induced mouse squamous cell carcinoma (SCC). Reinstatement of DLX3 function is sufficient to attenuate the migration of SCC cells, leading to decreased wound closure. Our data establish the DLX3-p53 interplay as a major regulatory axis in epidermal differentiation and suggest that DLX3 is a modulator of skin carcinogenesis.</p>',
			'date' => '2015-11-02',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26522723',
			'doi' => '10.1038/onc.2015.380',
			'modified' => '2016-06-15 16:18:44',
			'created' => '2016-06-15 16:18:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 202 => array(
			'id' => '2962',
			'name' => 'VEGF-mediated cell survival in non-small-cell lung cancer: implications for epigenetic targeting of VEGF receptors as a therapeutic approach',
			'authors' => 'Barr MP et al.',
			'description' => '<div class="">
<h4>AIMS:</h4>
<p><abstracttext label="AIMS" nlmcategory="OBJECTIVE">To evaluate the potential therapeutic utility of histone deacetylase inhibitors (HDACi) in targeting VEGF receptors in non-small-cell lung cancer.</abstracttext></p>
<h4>MATERIALS &amp; METHODS:</h4>
<p><abstracttext label="MATERIALS &amp; METHODS" nlmcategory="METHODS">Non-small-cell lung cancer cells were screened for the VEGF receptors at the mRNA and protein levels, while cellular responses to various HDACi were examined.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Significant effects on the regulation of the VEGF receptors were observed in response to HDACi. These were associated with decreased secretion of VEGF, decreased cellular proliferation and increased apoptosis which could not be rescued by addition of exogenous recombinant VEGF. Direct remodeling of the VEGFR1 and VEGFR2 promoters was observed. In contrast, HDACi treatments resulted in significant downregulation of the Neuropilin receptors.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">Epigenetic targeting of the Neuropilin receptors may offer an effective treatment for lung cancer patients in the clinical setting.</abstracttext></p>
</div>',
			'date' => '2015-10-07',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26479311',
			'doi' => '10.2217/epi.15.51',
			'modified' => '2016-06-23 15:24:41',
			'created' => '2016-06-23 15:24:41',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 203 => array(
			'id' => '2917',
			'name' => 'Chromatin assembly factor CAF-1 represses priming of plant defence response genes',
			'authors' => 'Mozgova I et al.',
			'description' => '<p><b>Plants have evolved efficient defence systems against pathogens that often rely on specific transcriptional responses. Priming is part of the defence syndrome, by establishing a hypersensitive state of defence genes such as after a first encounter with a pathogen. Because activation of defence responses has a fitness cost, priming must be tightly controlled to prevent spurious activation of defence. However, mechanisms that repress defence gene priming are poorly understood. Here, we show that the histone chaperone CAF-1 is required to establish a repressed chromatin state at defence genes. Absence of CAF-1 results in spurious activation of a salicylic acid-dependent pathogen defence response in plants grown under non-sterile conditions. Chromatin at defence response genes in CAF-1 mutants under non-inductive (sterile) conditions is marked by low nucleosome occupancy and high H3K4me3 at transcription start sites, resembling chromatin in primed wild-type plants. We conclude that CAF-1-mediated chromatin assembly prevents the establishment of a primed state that may under standard non-sterile growth conditions result in spurious activation of SA-dependent defence responses and consequential reduction of plant vigour.</b></p>',
			'date' => '2015-09-01',
			'pmid' => 'http://www.nature.com/articles/nplants2015127',
			'doi' => '10.1038/nplants.2015.127',
			'modified' => '2016-05-13 11:13:50',
			'created' => '2016-05-13 11:13:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 204 => array(
			'id' => '2817',
			'name' => 'Spatiotemporal control of estrogen-responsive transcription in ERα-positive breast cancer cells.',
			'authors' => 'P-Y Hsu, H-K Hsu, T-H Hsiao, Z Ye, E Wang, A L Profit, I Jatoi, Y Chen, N B Kirma, V X Jin, Z D Sharp and T H-M Huang',
			'description' => '<p><span>Recruitment of transcription machinery to target promoters for aberrant gene expression has been well studied, but underlying control directed by distant-acting enhancers remains unclear in cancer development. Our previous study demonstrated that distant estrogen response elements (DEREs) located on chromosome 20q13 are frequently amplified and translocated to other chromosomes in ER&alpha;-positive breast cancer cells. In this study, we used three-dimensional interphase fluorescence in situ hybridization to decipher spatiotemporal gathering of multiple DEREs in the nucleus. Upon estrogen stimulation, scattered 20q13 DEREs were mobilized to form regulatory depots for synchronized gene expression of target loci. A chromosome conformation capture assay coupled with chromatin immunoprecipitation further uncovered that ER&alpha;-bound regulatory depots are tethered to heterochromatin protein 1 (HP1) for coordinated chromatin movement and histone modifications of target loci, resulting in transcription repression. Neutralizing HP1 function dysregulated the formation of DERE-involved regulatory depots and transcription inactivation of candidate tumor-suppressor genes. Deletion of amplified DEREs using the CRISPR/Cas9 genomic-editing system profoundly altered transcriptional profiles of proliferation-associated signaling networks, resulting in reduction of cancer cell growth. These findings reveal a formerly uncharacterized feature wherein multiple copies of the amplicon congregate as transcriptional units in the nucleus for synchronous regulation of function-related loci in tumorigenesis. Disruption of their assembly can be a new strategy for treating breast cancers and other malignancies</span></p>',
			'date' => '2015-08-24',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26300005',
			'doi' => '10.1038/onc.2015.298',
			'modified' => '2016-02-10 16:20:01',
			'created' => '2016-02-10 16:20:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 205 => array(
			'id' => '2816',
			'name' => 'Non-coding recurrent mutations in chronic lymphocytic leukaemia.',
			'authors' => 'Xose S. Puente, Silvia Beà, Rafael Valdés-Mas, Neus Villamor, Jesús Gutiérrez-Abril et al.',
			'description' => '<p><span>Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3, ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding regions, including the 3' region of NOTCH1, which cause aberrant splicing events, increase NOTCH1 activity and result in a more aggressive disease. In addition, mutations in an enhancer located on chromosome 9p13 result in reduced expression of the B-cell-specific transcription factor PAX5. The accumulative number of driver alterations (0 to &ge;4) discriminated between patients with differences in clinical behaviour. This study provides an integrated portrait of the CLL genomic landscape, identifies new recurrent driver mutations of the disease, and suggests clinical interventions that may improve the management of this neoplasia.</span></p>',
			'date' => '2015-07-22',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26200345',
			'doi' => '10.1038/nature14666',
			'modified' => '2016-02-10 16:17:29',
			'created' => '2016-02-10 16:17:29',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 206 => array(
			'id' => '2893',
			'name' => 'Allele-specific binding of ZFP57 in the epigenetic regulation of imprinted and non-imprinted monoallelic expression',
			'authors' => 'Strogantsev R, Krueger F, Yamazawa K, Shi H, Gould P, Goldman-Roberts M, McEwen K, Sun B, Pedersen R, Ferguson-Smith AC',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Selective maintenance of genomic epigenetic imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary for maintaining the DNA methylation memory at multiple imprinting control regions in early mouse embryos and embryonic stem (ES) cells. Maternal-zygotic deletion of ZFP57 in mice presents a highly penetrant phenotype with no animals surviving to birth. Additionally, several cases of human transient neonatal diabetes are associated with somatic mutations in the ZFP57 coding sequence.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Here, we comprehensively map sequence-specific ZFP57 binding sites in an allele-specific manner using hybrid ES cell lines from reciprocal crosses between C57BL/6J and Cast/EiJ mice, assigning allele specificity to approximately two-thirds of all binding sites. While half of these are biallelic and include endogenous retrovirus (ERV) targets, the rest show monoallelic binding based either on parental origin or on genetic background of the allele. Parental-origin allele-specific binding is methylation-dependent and maps only to imprinting control differentially methylated regions (DMRs) established in the germline. We identify a novel imprinted gene, Fkbp6, which has a critical function in mouse male germ cell development. Genetic background-specific sequence differences also influence ZFP57 binding, as genetic variation that disrupts the consensus binding motif and its methylation is often associated with monoallelic expression of neighboring genes.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">The work described here uncovers further roles for ZFP57-mediated regulation of genomic imprinting and identifies a novel mechanism for genetically determined monoallelic gene expression.</abstracttext></p>
</div>',
			'date' => '2015-05-30',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/26025256',
			'doi' => '10.1186/s13059-015-0672-7',
			'modified' => '2016-04-14 17:20:03',
			'created' => '2016-04-14 17:20:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 207 => array(
			'id' => '2790',
			'name' => 'Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency.',
			'authors' => 'Chen H, Aksoy I, Gonnot F, Osteil P, Aubry M, Hamela C, Rognard C, Hochard A, Voisin S, Fontaine E, Mure M, Afanassieff M, Cleroux E, Guibert S, Chen J, Vallot C, Acloque H, Genthon C, Donnadieu C, De Vos J, Sanlaville D, Guérin JF, Weber M, Stanton LW, R',
			'description' => 'Leukemia inhibitory factor (LIF)/STAT3 signalling is a hallmark of naive pluripotency in rodent pluripotent stem cells (PSCs), whereas fibroblast growth factor (FGF)-2 and activin/nodal signalling is required to sustain self-renewal of human PSCs in a condition referred to as the primed state. It is unknown why LIF/STAT3 signalling alone fails to sustain pluripotency in human PSCs. Here we show that the forced expression of the hormone-dependent STAT3-ER (ER, ligand-binding domain of the human oestrogen receptor) in combination with 2i/LIF and tamoxifen allows human PSCs to escape from the primed state and enter a state characterized by the activation of STAT3 target genes and long-term self-renewal in FGF2- and feeder-free conditions. These cells acquire growth properties, a gene expression profile and an epigenetic landscape closer to those described in mouse naive PSCs. Together, these results show that temporarily increasing STAT3 activity is sufficient to reprogramme human PSCs to naive-like pluripotent cells.',
			'date' => '2015-05-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25968054',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 208 => array(
			'id' => '2611',
			'name' => 'Opposite expression of CYP51A1 and its natural antisense transcript AluCYP51A1 in adenovirus type 37 infected retinal pigmented epithelial cells.',
			'authors' => 'Pickl JM, Kamel W, Ciftci S, Punga T, Akusjärvi G',
			'description' => 'Cytochrome P450 family member CYP51A1 is a key enzyme in cholesterol biosynthesis whose deregulation is implicated in numerous diseases, including retinal degeneration. Here we describe that HAdV-37 infection leads to downregulation of CYP51A1 expression and overexpression of its antisense non-coding Alu element (AluCYP51A1) in retinal pigment epithelium (RPE) cells. This change in gene expression is associated with a reversed accumulation of a positive histone mark at the CYP51A1 and AluCYP51A1 promoters. Further, transient AluCYP51A1 RNA overexpression correlates with reduced CYP51A1 mRNA accumulation. Collectively, our data suggest that AluCYP51A1 might control CYP51A1 gene expression in HAdV-37-infected RPE cells.',
			'date' => '2015-04-20',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25907535',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 209 => array(
			'id' => '2684',
			'name' => 'A cohesin-OCT4 complex mediates Sox enhancers to prime an early embryonic lineage.',
			'authors' => 'Abboud N, Moore-Morris T, Hiriart E, Yang H, Bezerra H, Gualazzi MG, Stefanovic S, Guénantin AC, Evans SM, Pucéat M',
			'description' => 'Short- and long-scales intra- and inter-chromosomal interactions are linked to gene transcription, but the molecular events underlying these structures and how they affect cell fate decision during embryonic development are poorly understood. One of the first embryonic cell fate decisions (that is, mesendoderm determination) is driven by the POU factor OCT4, acting in concert with the high-mobility group genes Sox-2 and Sox-17. Here we report a chromatin-remodelling mechanism and enhancer function that mediate cell fate switching. OCT4 alters the higher-order chromatin structure at both Sox-2 and Sox-17 loci. OCT4 titrates out cohesin and switches the Sox-17 enhancer from a locked (within an inter-chromosomal Sox-2 enhancer/CCCTC-binding factor CTCF/cohesin loop) to an active (within an intra-chromosomal Sox-17 promoter/enhancer/cohesin loop) state. SALL4 concomitantly mobilizes the polycomb complexes at the Soxs loci. Thus, OCT4/SALL4-driven cohesin- and polycombs-mediated changes in higher-order chromatin structure mediate instruction of early cell fate in embryonic cells.',
			'date' => '2015-04-08',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25851587',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 210 => array(
			'id' => '2625',
			'name' => 'Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1.',
			'authors' => 'Tomazou EM, Sheffield NC, Schmidl C, Schuster M, Schönegger A, Datlinger P, Kubicek S, Bock C, Kovar H',
			'description' => '<p>Transcription factor fusion proteins can transform cells by inducing global changes of the transcriptome, often creating a state of oncogene addiction. Here, we investigate the role of epigenetic mechanisms in this process, focusing on Ewing sarcoma cells that are dependent on the EWS-FLI1 fusion protein. We established reference epigenome maps comprising DNA methylation, seven histone marks, open chromatin states, and RNA levels, and we analyzed the epigenome dynamics upon downregulation of the driving oncogene. Reduced EWS-FLI1 expression led to widespread epigenetic changes in&nbsp;promoters, enhancers, and super-enhancers, and we identified histone H3K27 acetylation as the most strongly affected mark. Clustering of epigenetic promoter signatures defined classes of EWS-FLI1-regulated genes that responded differently to low-dose treatment with histone deacetylase inhibitors. Furthermore, we observed strong and opposing enrichment patterns for&nbsp;E2F and AP-1 among EWS-FLI1-correlated and anticorrelated genes. Our data describe extensive genome-wide rewiring of epigenetic cell states driven by an oncogenic fusion protein.</p>',
			'date' => '2015-02-24',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25704812',
			'doi' => '',
			'modified' => '2017-02-14 12:53:04',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 211 => array(
			'id' => '2575',
			'name' => 'Embryonic stem cell differentiation requires full length Chd1.',
			'authors' => 'Piatti P, Lim CY, Nat R, Villunger A, Geley S, Shue YT, Soratroi C, Moser M, Lusser A',
			'description' => 'The modulation of chromatin dynamics by ATP-dependent chromatin remodeling factors has been recognized as an important mechanism to regulate the balancing of self-renewal and pluripotency in embryonic stem cells (ESCs). Here we have studied the effects of a partial deletion of the gene encoding the chromatin remodeling factor Chd1 that generates an N-terminally truncated version of Chd1 in mouse ESCs in vitro as well as in vivo. We found that a previously uncharacterized serine-rich region (SRR) at the N-terminus is not required for chromatin assembly activity of Chd1 but that it is subject to phosphorylation. Expression of Chd1 lacking this region in ESCs resulted in aberrant differentiation properties of these cells. The self-renewal capacity and ESC chromatin structure, however, were not affected. Notably, we found that newly established ESCs derived from Chd1(Δ2/Δ2) mutant mice exhibited similar differentiation defects as in vitro generated mutant ESCs, even though the N-terminal truncation of Chd1 was fully compatible with embryogenesis and post-natal life in the mouse. These results underscore the importance of Chd1 for the regulation of pluripotency in ESCs and provide evidence for a hitherto unrecognized critical role of the phosphorylated N-terminal SRR for full functionality of Chd1.',
			'date' => '2015-01-26',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25620209',
			'doi' => '',
			'modified' => '2015-07-24 15:39:04',
			'created' => '2015-07-24 15:39:04',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 212 => array(
			'id' => '2552',
			'name' => 'A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus.',
			'authors' => 'Lazorthes S, Vallot C, Briois S, Aguirrebengoa M, Thuret JY, Laurent GS, Rougeulle C, Kapranov P, Mann C, Trouche D, Nicolas E',
			'description' => 'Non-coding RNAs (ncRNAs) play major roles in proper chromatin organization and function. Senescence, a strong anti-proliferative process and a major anticancer barrier, is associated with dramatic chromatin reorganization in heterochromatin foci. Here we analyze strand-specific transcriptome changes during oncogene-induced human senescence. Strikingly, while differentially expressed RNAs are mostly repressed during senescence, ncRNAs belonging to the recently described vlincRNA (very long intergenic ncRNA) class are mainly activated. We show that VAD, a novel antisense vlincRNA strongly induced during senescence, is required for the maintenance of senescence features. VAD modulates chromatin structure in cis and activates gene expression in trans at the INK4 locus, which encodes cell cycle inhibitors important for senescence-associated cell proliferation arrest. Importantly, VAD inhibits the incorporation of the repressive histone variant H2A.Z at INK4 gene promoters in senescent cells. Our data underline the importance of vlincRNAs as sensors of cellular environment changes and as mediators of the correct transcriptional response.',
			'date' => '2015-01-20',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25601475',
			'doi' => '',
			'modified' => '2015-07-24 15:39:04',
			'created' => '2015-07-24 15:39:04',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 213 => array(
			'id' => '2492',
			'name' => 'Cryosectioning the intestinal crypt-villus axis: an ex vivo method to study the dynamics of epigenetic modifications from stem cells to differentiated cells',
			'authors' => 'Vincent A, Kazmierczak C, Duchêne B, Jonckheere N, Leteurtre E, Van Seuningen I',
			'description' => 'The intestinal epithelium is a particularly attractive biological adult model to study epigenetic mechanisms driving adult stem cell renewal and cell differentiation. Since epigenetic modifications are dynamic, we have developed an original ex vivo approach to study the expression and epigenetic profiles of key genes associated with either intestinal cell pluripotency or differentiation by isolating cryosections of the intestinal crypt-villus axis. Gene expression, DNA methylation and histone modifications were studied by qRT-PCR, Methylation Specific-PCR and micro-Chromatin Immunoprecipitation, respectively. Using this approach, it was possible to identify segment-specific methylation and chromatin profiles. We show that (i) expression of intestinal stem cell markers (Lgr5, Ascl2) exclusively in the crypt is associated with active histone marks, (ii) promoters of all pluripotency genes studied and transcription factors involved in intestinal cell fate (Cdx2) harbour a bivalent chromatin pattern in the crypts, (iii) expression of differentiation markers (Muc2, Sox9) along the crypt-villus axis is associated with DNA methylation. Hence, using an original model of cryosectioning along the crypt-villus axis that allows in situ detection of dynamic epigenetic modifications, we demonstrate that regulation of pluripotency and differentiation markers in healthy intestinal mucosa involves different and specific epigenetic mechanisms.',
			'date' => '2014-12-27',
			'pmid' => 'http://www.sciencedirect.com/science/article/pii/S1873506114001585',
			'doi' => '',
			'modified' => '2015-07-24 15:39:04',
			'created' => '2015-07-24 15:39:04',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 214 => array(
			'id' => '2299',
			'name' => 'Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs.',
			'authors' => 'Adoue V, Schiavi A, Light N, Almlöf JC, Lundmark P, Ge B, Kwan T, Caron M, Rönnblom L, Wang C, Chen SH, Goodall AH, Cambien F, Deloukas P, Ouwehand WH, Syvänen AC, Pastinen T',
			'description' => 'Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40-60% of these cis-rSNPs to be shared across cell types. We uncover a new class of cis-rSNPs, which disrupt footprint-derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof-of-principle for a new approach for genome-wide functional validation of transcription factor-SNP interactions. By perturbing NFκB action in lymphoblasts, we identified 489 cis-regulated transcripts with altered AE after NFκB perturbation. Altogether, we perform a comprehensive analysis of cis-variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases. ',
			'date' => '2014-10-16',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/25326100',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 215 => array(
			'id' => '2330',
			'name' => 'Obesity increases histone H3 lysine 9 and 18 acetylation at Tnfa and Ccl2 genes in mouse liver',
			'authors' => 'Mikula M, Majewska A, Ledwon JK, Dzwonek A, Ostrowski J',
			'description' => 'Obesity contributes to the development of non‑alcoholic fatty liver disease (NAFLD), which is characterized by the upregulated expression of two key inflammatory mediators: tumor necrosis factor (Tnfa) and monocyte chemotactic protein 1 (Mcp1; also known as Ccl2). However, the chromatin make-up at these genes in the liver in obese individuals has not been explored. In this study, to identify obesity-mediated epigenetic changes at Tnfa and Ccl2, we used a murine model of obesity induced by a high-fat diet (HFD) and hyperphagic (ob/ob) mice. Chromatin immunoprecipitation (ChIP) assay was used to determine the abundance of permissive histone marks, namely histone H3 lysine 9 and 18 acetylation (H3K9/K18Ac), H3 lysine 4 trimethylation (H3K4me3) and H3 lysine 36 trimethylation (H3K36me3), in conjunction with polymerase 2 RNA (Pol2) and nuclear factor (Nf)-κB recruitment in the liver. Additionally, to correlate the liver tissue‑derived ChIP measurements with a robust in vitro transcriptional response at the Tnfa and Ccl2 genes, we used lipopolysaccharide (LPS) treatment to induce an inflammatory response in Hepa1-6 cells, a cell line derived from murine hepatocytes. ChIP revealed increased H3K9/K18Ac at Tnfa and Ccl2 in the obese mice, although the differences were only statistically significant for Tnfa (p<0.05). Unexpectedly, the levels of H3K4me3 and H3K36me3 marks, as well as Pol2 and Nf-κB recruitment, did not correspond with the increased expression of these two genes in the obese mice. By contrast, the acute treatment of Hepa1-6 cells with LPS significantly increased the H3K9/K18Ac marks, as well as Pol2 and Nf-κB recruitment at both genes, while the levels of H3K4me3 and H3K36me3 marks remained unaltered. These results demonstrate that increased Tnfa and Ccl2 expression in fatty liver at the chromatin level corresponds to changes in the level of histone H3 acetylation.',
			'date' => '2014-10-03',
			'pmid' => 'http://www.spandidos-publications.com/10.3892/ijmm.2014.1958',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 216 => array(
			'id' => '2338',
			'name' => 'The specific alteration of histone methylation profiles by DZNep during early zebrafish development.',
			'authors' => 'Ostrup O, Reiner AH, Aleström P, Collas P',
			'description' => '<p>Early embryo development constitutes a unique opportunity to study acquisition of epigenetic marks, including histone methylation. This study investigates the in vivo function and specificity of 3-deazaneplanocin A (DZNep), a promising anti-cancer drug that targets polycomb complex genes. One- to two-cell stage embryos were cultured with DZNep, and subsequently evaluated at the post-mid blastula transition stage for H3K27me3, H3K4me3 and H3K9me3 occupancy and enrichment at promoters using ChIP-chip microarrays. DZNep affected promoter enrichment of H3K27me3 and H3K9me3, whereas H3K4me3 remained stable. Interestingly, DZNep induced a loss of H3K27me3 and H3K9me3 from a substantial number of promoters but did not prevent de novo acquisition of these marks on others, indicating gene-specific targeting of its action. Loss/gain of H3K27me3 on promoters did not result in changes in gene expression levels until 24h post-fertilization. In contrast, genes gaining H3K9me3 displayed strong and constant down-regulation upon DZNep treatment. H3K9me3 enrichment on these gene promoters was observed not only in the proximal area as expected, but also over the transcription start site. Altered H3K9me3 profiles were associated with severe neuronal and cranial phenotypes at day 4-5 post-fertilization. Thus, DZNep was shown to affect enrichment patterns of H3K27me3 and H3K9me3 at promoters in a gene-specific manner.</p>',
			'date' => '2014-09-28',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25260724',
			'doi' => '',
			'modified' => '2016-04-08 09:43:32',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 217 => array(
			'id' => '2228',
			'name' => 'Interrogation of allelic chromatin states in human cells by high-density ChIP-genotyping.',
			'authors' => 'Light N, Adoue V, Ge B, Chen SH, Kwan T, Pastinen T',
			'description' => 'Allele-specific (AS) assessment of chromatin has the potential to elucidate specific cis-regulatory mechanisms, which are predicted to underlie the majority of the known genetic associations to complex disease. However, development of chromatin landscapes at allelic resolution has been challenging since sites of variable signal strength require substantial read depths not commonly applied in sequencing based approaches. In this study, we addressed this by performing parallel analyses of input DNA and chromatin immunoprecipitates (ChIP) on high-density Illumina genotyping arrays. Allele-specificity for the histone modifications H3K4me1, H3K4me3, H3K27ac, H3K27me3, and H3K36me3 was assessed using ChIP samples generated from 14 lymphoblast and 6 fibroblast cell lines. AS-ChIP SNPs were combined into domains and validated using high-confidence ChIP-seq sites. We observed characteristic patterns of allelic-imbalance for each histone-modification around allele-specifically expressed transcripts. Notably, we found H3K4me1 to be significantly anti-correlated with allelic expression (AE) at transcription start sites, indicating H3K4me1 allelic imbalance as a marker of AE. We also found that allelic chromatin domains exhibit population and cell-type specificity as well as heritability within trios. Finally, we observed that a subset of allelic chromatin domains is regulated by DNase I-sensitive quantitative trait loci and that these domains are significantly enriched for genome-wide association studies hits, with autoimmune disease associated SNPs specifically enriched in lymphoblasts. This study provides the first genome-wide maps of allelic-imbalance for five histone marks. Our results provide new insights into the role of chromatin in cis-regulation and highlight the need for high-depth sequencing in ChIP-seq studies along with the need to improve allele-specificity of ChIP-enrichment.',
			'date' => '2014-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25055051',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 218 => array(
			'id' => '2298',
			'name' => 'Differences among brain tumor stem cell types and fetal neural stem cells in focal regions of histone modifications and DNA methylation, broad regions of modifications, and bivalent promoters.',
			'authors' => 'Yoo S, Bieda MC',
			'description' => 'BACKGROUND: Aberrational epigenetic marks are believed to play a major role in establishing the abnormal features of cancer cells. Rational use and development of drugs aimed at epigenetic processes requires an understanding of the range, extent, and roles of epigenetic reprogramming in cancer cells. Using ChIP-chip and MeDIP-chip approaches, we localized well-established and prevalent epigenetic marks (H3K27me3, H3K4me3, H3K9me3, DNA methylation) on a genome scale in several lines of putative glioma stem cells (brain tumor stem cells, BTSCs) and, for comparison, normal human fetal neural stem cells (fNSCs). RESULTS: We determined a substantial "core" set of promoters possessing each mark in every surveyed BTSC cell type, which largely overlapped the corresponding fNSC sets. However, there was substantial diversity among cell types in mark localization. We observed large differences among cell types in total number of H3K9me3+ positive promoters and peaks and in broad modifications (defined as >50 kb peak length) for H3K27me3 and, to a lesser extent, H3K9me3. We verified that a change in a broad modification affected gene expression of CACNG7. We detected large numbers of bivalent promoters, but most bivalent promoters did not display direct overlap of contrasting epigenetic marks, but rather occupied nearby regions of the proximal promoter. There were significant differences in the sets of promoters bearing bivalent marks in the different cell types and few consistent differences between fNSCs and BTSCs. CONCLUSIONS: Overall, our "core set" data establishes sets of potential therapeutic targets, but the diversity in sets of sites and broad modifications among cell types underscores the need to carefully consider BTSC subtype variation in epigenetic therapy. Our results point toward substantial differences among cell types in the activity of the production/maintenance systems for H3K9me3 and for broad regions of modification (H3K27me3 or H3K9me3). Finally, the unexpected diversity in bivalent promoter sets among these multipotent cells indicates that bivalent promoters may play complex roles in the overall biology of these cells. These results provide key information for forming the basis for future rational drug therapy aimed at epigenetic processes in these cells.',
			'date' => '2014-08-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25163646',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 219 => array(
			'id' => '2201',
			'name' => 'Long Noncoding RNA TARID Directs Demethylation and Activation of the Tumor Suppressor TCF21 via GADD45A.',
			'authors' => 'Arab K, Park YJ, Lindroth AM, Schäfer A, Oakes C, Weichenhan D, Lukanova A, Lundin E, Risch A, Meister M, Dienemann H, Dyckhoff G, Herold-Mende C, Grummt I, Niehrs C, Plass C',
			'description' => 'DNA methylation is a dynamic and reversible process that governs gene expression during development and disease. Several examples of active DNA demethylation have been documented, involving genome-wide and gene-specific DNA demethylation. How demethylating enzymes are targeted to specific genomic loci remains largely unknown. We show that an antisense lncRNA, termed TARID (for TCF21 antisense RNA inducing demethylation), activates TCF21 expression by inducing promoter demethylation. TARID interacts with both the TCF21 promoter and GADD45A (growth arrest and DNA-damage-inducible, alpha), a regulator of DNA demethylation. GADD45A in turn recruits thymine-DNA glycosylase for base excision repair-mediated demethylation involving oxidation of 5-methylcytosine to 5-hydroxymethylcytosine in the TCF21 promoter by ten-eleven translocation methylcytosine dioxygenase proteins. The results reveal a function of lncRNAs, serving as a genomic address label for GADD45A-mediated demethylation of specific target genes.',
			'date' => '2014-08-21',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/25087872',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 220 => array(
			'id' => '2063',
			'name' => 'Identification of a large protein network involved in epigenetic transmission in replicating DNA of embryonic stem cells.',
			'authors' => 'Aranda S, Rutishauser D, Ernfors P',
			'description' => 'Pluripotency of embryonic stem cells (ESCs) is maintained by transcriptional activities and chromatin modifying complexes highly organized within the chromatin. Although much effort has been focused on identifying genome-binding sites, little is known on their dynamic association with chromatin across cell divisions. Here, we used a modified version of the iPOND (isolation of proteins at nascent DNA) technology to identify a large protein network enriched at nascent DNA in ESCs. This comprehensive and unbiased proteomic characterization in ESCs reveals that, in addition to the core replication machinery, proteins relevant for pluripotency of ESCs are present at DNA replication sites. In particular, we show that the chromatin remodeller HDAC1-NuRD complex is enriched at nascent DNA. Interestingly, an acute block of HDAC1 in ESCs leads to increased acetylation of histone H3 lysine 9 at nascent DNA together with a concomitant loss of methylation. Consistently, in contrast to what has been described in tumour cell lines, these chromatin marks were found to be stable during cell cycle progression of ESCs. Our results are therefore compatible with a rapid deacetylation-coupled methylation mechanism during the replication of DNA in ESCs that may participate in the preservation of pluripotency of ESCs during replication.',
			'date' => '2014-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24852249',
			'doi' => '',
			'modified' => '2015-07-24 15:39:02',
			'created' => '2015-07-24 15:39:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 221 => array(
			'id' => '2107',
			'name' => 'Seminoma and embryonal carcinoma footprints identified by analysis of integrated genome-wide epigenetic and expression profiles of germ cell cancer cell lines.',
			'authors' => 'van der Zwan YG, Rijlaarsdam MA, Rossello FJ, Notini AJ, de Boer S, Watkins DN, Gillis AJ, Dorssers LC, White SJ, Looijenga LH',
			'description' => 'BACKGROUND: Originating from Primordial Germ Cells/gonocytes and developing via a precursor lesion called Carcinoma In Situ (CIS), Germ Cell Cancers (GCC) are the most common cancer in young men, subdivided in seminoma (SE) and non-seminoma (NS). During physiological germ cell formation/maturation, epigenetic processes guard homeostasis by regulating the accessibility of the DNA to facilitate transcription. Epigenetic deregulation through genetic and environmental parameters (i.e. genvironment) could disrupt embryonic germ cell development, resulting in delayed or blocked maturation. This potentially facilitates the formation of CIS and progression to invasive GCC. Therefore, determining the epigenetic and functional genomic landscape in GCC cell lines could provide insight into the pathophysiology and etiology of GCC and provide guidance for targeted functional experiments. RESULTS: This study aims at identifying epigenetic footprints in SE and EC cell lines in genome-wide profiles by studying the interaction between gene expression, DNA CpG methylation and histone modifications, and their function in the pathophysiology and etiology of GCC. Two well characterized GCC-derived cell lines were compared, one representative for SE (TCam-2) and the other for EC (NCCIT). Data were acquired using the Illumina HumanHT-12-v4 (gene expression) and HumanMethylation450 BeadChip (methylation) microarrays as well as ChIP-sequencing (activating histone modifications (H3K4me3, H3K27ac)). Results indicate known germ cell markers not only to be differentiating between SE and NS at the expression level, but also in the epigenetic landscape. CONCLUSION: The overall similarity between TCam-2/NCCIT support an erased embryonic germ cell arrested in early gonadal development as common cell of origin although the exact developmental stage from which the tumor cells are derived might differ. Indeed, subtle difference in the (integrated) epigenetic and expression profiles indicate TCam-2 to exhibit a more germ cell-like profile, whereas NCCIT shows a more pluripotent phenotype. The results provide insight into the functional genome in GCC cell lines.',
			'date' => '2014-06-02',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24887064',
			'doi' => '',
			'modified' => '2015-07-24 15:39:03',
			'created' => '2015-07-24 15:39:03',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 222 => array(
			'id' => '2054',
			'name' => 'Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer',
			'authors' => 'Zecchini V, Madhu B, Russell R, Pértega-Gomes N, Warren A, Gaude E, Borlido J, Stark R, Ireland-Zecchini H, Rao R, Scott H, Boren J, Massie C, Asim M, Brindle K, Griffiths J, Frezza C, Neal DE, Mills IG',
			'description' => 'Tumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. Hypoxia-inducible factor 1A (HIF1A) is a major regulator of this process, but its activation under normoxic conditions, termed pseudohypoxia, is not well documented. Here, using an integrative approach combining the first genome-wide mapping of chromatin binding for an endocytic adaptor, ARRB1, both in vitro and in vivo with gene expression profiling, we demonstrate that nuclear ARRB1 contributes to this metabolic shift in prostate cancer cells via regulation of HIF1A transcriptional activity under normoxic conditions through regulation of succinate dehydrogenase A (SDHA) and fumarate hydratase (FH) expression. ARRB1-induced pseudohypoxia may facilitate adaptation of cancer cells to growth in the harsh conditions that are frequently encountered within solid tumours. Our study is the first example of an endocytic adaptor protein regulating metabolic pathways. It implicates ARRB1 as a potential tumour promoter in prostate cancer and highlights the importance of metabolic alterations in prostate cancer.',
			'date' => '2014-05-16',
			'pmid' => 'http://onlinelibrary.wiley.com/doi/10.15252/embj.201386874/full',
			'doi' => '',
			'modified' => '2015-07-24 15:39:02',
			'created' => '2015-07-24 15:39:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 223 => array(
			'id' => '1891',
			'name' => 'Stage-specific control of early B cell development by the transcription factor Ikaros.',
			'authors' => 'Schwickert TA, Tagoh H, Gültekin S, Dakic A, Axelsson E, Minnich M, Ebert A, Werner B, Roth M, Cimmino L, Dickins RA, Zuber J, Jaritz M, Busslinger M',
			'description' => 'The transcription factor Ikaros is an essential regulator of lymphopoiesis. Here we studied its B cell-specific function by conditional inactivation of the gene encoding Ikaros (Ikzf1) in pro-B cells. B cell development was arrested at an aberrant 'pro-B cell' stage characterized by increased cell adhesion and loss of signaling via the pre-B cell signaling complex (pre-BCR). Ikaros activated genes encoding signal transducers of the pre-BCR and repressed genes involved in the downregulation of pre-BCR signaling and upregulation of the integrin signaling pathway. Unexpectedly, derepression of expression of the transcription factor Aiolos did not compensate for the loss of Ikaros in pro-B cells. Ikaros induced or suppressed active chromatin at regulatory elements of activated or repressed target genes. Notably, binding of Ikaros and expression of its target genes were dynamically regulated at distinct stages of early B lymphopoiesis.',
			'date' => '2014-03-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24509509',
			'doi' => '',
			'modified' => '2015-07-24 15:39:02',
			'created' => '2015-07-24 15:39:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 224 => array(
			'id' => '1793',
			'name' => 'A novel microscopy-based high-throughput screening method to identify proteins that regulate global histone modification levels.',
			'authors' => 'Baas R, Lelieveld D, van Teeffelen H, Lijnzaad P, Castelijns B, van Schaik FM, Vermeulen M, Egan DA, Timmers HT, de Graaf P',
			'description' => '<p>Posttranslational modifications of histones play an important role in the regulation of gene expression and chromatin structure in eukaryotes. The balance between chromatin factors depositing (writers) and removing (erasers) histone marks regulates the steady-state levels of chromatin modifications. Here we describe a novel microscopy-based screening method to identify proteins that regulate histone modification levels in a high-throughput fashion. We named our method CROSS, for Chromatin Regulation Ontology SiRNA Screening. CROSS is based on an siRNA library targeting the expression of 529 proteins involved in chromatin regulation. As a proof of principle, we used CROSS to identify chromatin factors involved in histone H3 methylation on either lysine-4 or lysine-27. Furthermore, we show that CROSS can be used to identify chromatin factors that affect growth in cancer cell lines. Taken together, CROSS is a powerful method to identify the writers and erasers of novel and known chromatin marks and facilitates the identification of drugs targeting epigenetic modifications.</p>',
			'date' => '2014-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24334265',
			'doi' => '',
			'modified' => '2016-04-12 09:46:40',
			'created' => '2015-07-24 15:39:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 225 => array(
			'id' => '1783',
			'name' => 'Pan-histone demethylase inhibitors simultaneously targeting Jumonji C and lysine-specific demethylases display high anticancer activities.',
			'authors' => 'Rotili D, Tomassi S, Conte M, Benedetti R, Tortorici M, Ciossani G, Valente S, Marrocco B, Labella D, Novellino E, Mattevi A, Altucci L, Tumber A, Yapp C, King ON, Hopkinson RJ, Kawamura A, Schofield CJ, Mai A',
			'description' => 'In prostate cancer, two different types of histone lysine demethylases (KDM), LSD1/KDM1 and JMJD2/KDM4, are coexpressed and colocalize with the androgen receptor. We designed and synthesized hybrid LSD1/JmjC or "pan-KDM" inhibitors 1-6 by coupling the skeleton of tranylcypromine 7, a known LSD1 inhibitor, with 4-carboxy-4'-carbomethoxy-2,2'-bipyridine 8 or 5-carboxy-8-hydroxyquinoline 9, two 2-oxoglutarate competitive templates developed for JmjC inhibition. Hybrid compounds 1-6 are able to simultaneously target both KDM families and have been validated as potential antitumor agents in cells. Among them, 2 and 3 increase H3K4 and H3K9 methylation levels in cells and cause growth arrest and substantial apoptosis in LNCaP prostate and HCT116 colon cancer cells. When tested in noncancer mesenchymal progenitor (MePR) cells, 2 and 3 induced little and no apoptosis, respectively, thus showing cancer-selective inhibiting action.',
			'date' => '2014-01-09',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24325601',
			'doi' => '',
			'modified' => '2015-07-24 15:39:01',
			'created' => '2015-07-24 15:39:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 226 => array(
			'id' => '1727',
			'name' => 'Interplay between active chromatin marks and RNA-directed DNA methylation in Arabidopsis thaliana.',
			'authors' => 'Greenberg MV, Deleris A, Hale CJ, Liu A, Feng S, Jacobsen SE',
			'description' => 'DNA methylation is an epigenetic mark that is associated with transcriptional repression of transposable elements and protein-coding genes. Conversely, transcriptionally active regulatory regions are strongly correlated with histone 3 lysine 4 di- and trimethylation (H3K4m2/m3). We previously showed that Arabidopsis thaliana plants with mutations in the H3K4m2/m3 demethylase JUMONJI 14 (JMJ14) exhibit a mild reduction in RNA-directed DNA methylation (RdDM) that is associated with an increase in H3K4m2/m3 levels. To determine whether this incomplete RdDM reduction was the result of redundancy with other demethylases, we examined the genetic interaction of JMJ14 with another class of H3K4 demethylases: lysine-specific demethylase 1-like 1 and lysine-specific demethylase 1-like 2 (LDL1 and LDL2). Genome-wide DNA methylation analyses reveal that both families cooperate to maintain RdDM patterns. ChIP-seq experiments show that regions that exhibit an observable DNA methylation decrease are co-incidental with increases in H3K4m2/m3. Interestingly, the impact on DNA methylation was stronger at DNA-methylated regions adjacent to H3K4m2/m3-marked protein-coding genes, suggesting that the activity of H3K4 demethylases may be particularly crucial to prevent spreading of active epigenetic marks. Finally, RNA sequencing analyses indicate that at RdDM targets, the increase of H3K4m2/m3 is not generally associated with transcriptional de-repression. This suggests that the histone mark itself--not transcription--impacts the extent of RdDM.',
			'date' => '2013-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/24244201',
			'doi' => '',
			'modified' => '2015-07-24 15:39:01',
			'created' => '2015-07-24 15:39:01',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 227 => array(
			'id' => '1581',
			'name' => 'A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis.',
			'authors' => 'Kollmann K, Heller G, Schneckenleithner C, Warsch W, Scheicher R, Ott RG, Schäfer M, Fajmann S, Schlederer M, Schiefer AI, Reichart U, Mayerhofer M, Hoeller C, Zöchbauer-Müller S, Kerjaschki D, Bock C, Kenner L, Hoefler G, Freissmuth M, Green AR, Moriggl ',
			'description' => 'In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185(BCR-ABL+) B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16(INK4a) and the pro-angiogenic factor VEGF-A. This function is independent of CDK6's kinase activity. High CDK6 expression thus suppresses proliferation by upregulating p16(INK4a), providing an internal safeguard. However, in the absence of p16(INK4a), CDK6 can exert its full tumor-promoting function by enhancing proliferation and stimulating angiogenesis. The finding that CDK6 connects cell-cycle progression to angiogenesis confirms CDK6's central role in hematopoietic malignancies and could underlie the selection pressure to upregulate CDK6 and silence p16(INK4a).',
			'date' => '2013-08-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23948297',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 228 => array(
			'id' => '1512',
			'name' => 'Disease-Related Growth Factor and Embryonic Signaling Pathways Modulate an Enhancer of TCF21 Expression at the 6q23.2 Coronary Heart Disease Locus.',
			'authors' => 'Miller CL, Anderson DR, Kundu RK, Raiesdana A, Nürnberg ST, Diaz R, Cheng K, Leeper NJ, Chen CH, Chang IS, Schadt EE, Hsiung CA, Assimes TL, Quertermous T',
			'description' => 'Coronary heart disease (CHD) is the leading cause of mortality in both developed and developing countries worldwide. Genome-wide association studies (GWAS) have now identified 46 independent susceptibility loci for CHD, however, the biological and disease-relevant mechanisms for these associations remain elusive. The large-scale meta-analysis of GWAS recently identified in Caucasians a CHD-associated locus at chromosome 6q23.2, a region containing the transcription factor TCF21 gene. TCF21 (Capsulin/Pod1/Epicardin) is a member of the basic-helix-loop-helix (bHLH) transcription factor family, and regulates cell fate decisions and differentiation in the developing coronary vasculature. Herein, we characterize a cis-regulatory mechanism by which the lead polymorphism rs12190287 disrupts an atypical activator protein 1 (AP-1) element, as demonstrated by allele-specific transcriptional regulation, transcription factor binding, and chromatin organization, leading to altered TCF21 expression. Further, this element is shown to mediate signaling through platelet-derived growth factor receptor beta (PDGFR-β) and Wilms tumor 1 (WT1) pathways. A second disease allele identified in East Asians also appears to disrupt an AP-1-like element. Thus, both disease-related growth factor and embryonic signaling pathways may regulate CHD risk through two independent alleles at TCF21.',
			'date' => '2013-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23874238',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 229 => array(
			'id' => '1465',
			'name' => 'Bivalent chromatin marks developmental regulatory genes in the mouse embryonic germline in vivo.',
			'authors' => 'Sachs M, Onodera C, Blaschke K, Ebata KT, Song JS, Ramalho-Santos M',
			'description' => 'Developmental regulatory genes have both activating (H3K4me3) and repressive (H3K27me3) histone modifications in embryonic stem cells (ESCs). This bivalent configuration is thought to maintain lineage commitment programs in a poised state. However, establishing physiological relevance has been complicated by the high number of cells required for chromatin immunoprecipitation (ChIP). We developed a low-cell-number chromatin immunoprecipitation (low-cell ChIP) protocol to investigate the chromatin of mouse primordial germ cells (PGCs). Genome-wide analysis of embryonic day 11.5 (E11.5) PGCs revealed H3K4me3/H3K27me3 bivalent domains highly enriched at developmental regulatory genes in a manner remarkably similar to ESCs. Developmental regulators remain bivalent and transcriptionally silent through the initiation of sexual differentiation at E13.5. We also identified >2,500 "orphan" bivalent domains that are distal to known genes and expressed in a tissue-specific manner but silent in PGCs. Our results demonstrate the existence of bivalent domains in the germline and raise the possibility that the somatic program is continuously maintained as bivalent, potentially imparting transgenerational epigenetic inheritance.',
			'date' => '2013-06-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23727241',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 230 => array(
			'id' => '1458',
			'name' => 'Integrative analysis of deep sequencing data identifies estrogen receptor early response genes and links ATAD3B to poor survival in breast cancer.',
			'authors' => 'Ovaska K, Matarese F, Grote K, Charapitsa I, Cervera A, Liu C, Reid G, Seifert M, Stunnenberg HG, Hautaniemi S',
			'description' => 'Identification of responsive genes to an extra-cellular cue enables characterization of pathophysiologically crucial biological processes. Deep sequencing technologies provide a powerful means to identify responsive genes, which creates a need for computational methods able to analyze dynamic and multi-level deep sequencing data. To answer this need we introduce here a data-driven algorithm, SPINLONG, which is designed to search for genes that match the user-defined hypotheses or models. SPINLONG is applicable to various experimental setups measuring several molecular markers in parallel. To demonstrate the SPINLONG approach, we analyzed ChIP-seq data reporting PolII, estrogen receptor α (ERα), H3K4me3 and H2A.Z occupancy at five time points in the MCF-7 breast cancer cell line after estradiol stimulus. We obtained 777 ERa early responsive genes and compared the biological functions of the genes having ERα binding within 20 kb of the transcription start site (TSS) to genes without such binding site. Our results show that the non-genomic action of ERα via the MAPK pathway, instead of direct ERa binding, may be responsible for early cell responses to ERα activation. Our results also indicate that the ERα responsive genes triggered by the genomic pathway are transcribed faster than those without ERα binding sites. The survival analysis of the 777 ERα responsive genes with 150 primary breast cancer tumors and in two independent validation cohorts indicated the ATAD3B gene, which does not have ERα binding site within 20 kb of its TSS, to be significantly associated with poor patient survival.',
			'date' => '2013-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23818839',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 231 => array(
			'id' => '1425',
			'name' => 'Expression of a large LINE-1-driven antisense RNA is linked to epigenetic silencing of the metastasis suppressor gene TFPI-2 in cancer.',
			'authors' => 'Cruickshanks HA, Vafadar-Isfahani N, Dunican DS, Lee A, Sproul D, Lund JN, Meehan RR, Tufarelli C',
			'description' => 'LINE-1 retrotransposons are abundant repetitive elements of viral origin, which in normal cells are kept quiescent through epigenetic mechanisms. Activation of LINE-1 occurs frequently in cancer and can enable LINE-1 mobilization but also has retrotransposition-independent consequences. We previously reported that in cancer, aberrantly active LINE-1 promoters can drive transcription of flanking unique sequences giving rise to LINE-1 chimeric transcripts (LCTs). Here, we show that one such LCT, LCT13, is a large transcript (>300 kb) running antisense to the metastasis-suppressor gene TFPI-2. We have modelled antisense RNA expression at TFPI-2 in transgenic mouse embryonic stem (ES) cells and demonstrate that antisense RNA induces silencing and deposition of repressive histone modifications implying a causal link. Consistent with this, LCT13 expression in breast and colon cancer cell lines is associated with silencing and repressive chromatin at TFPI-2. Furthermore, we detected LCT13 transcripts in 56% of colorectal tumours exhibiting reduced TFPI-2 expression. Our findings implicate activation of LINE-1 elements in subsequent epigenetic remodelling of surrounding genes, thus hinting a novel retrotransposition-independent role for LINE-1 elements in malignancy.',
			'date' => '2013-05-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23703216',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 232 => array(
			'id' => '1389',
			'name' => 'The developmental epigenomics toolbox: ChIP-seq and MethylCap-seq profiling of early zebrafish embryos.',
			'authors' => 'Bogdanović O, Fernández-Miñán A, Tena JJ, de la Calle-Mustienes E, Gómez-Skarmeta JL',
			'description' => 'Genome-wide profiling of DNA methylation and histone modifications answered many questions as to how the genes are regulated on a global scale and what their epigenetic makeup is. Yet, little is known about the function of these marks during early vertebrate embryogenesis. Here we provide detailed protocols for ChIP-seq and MethylCap-seq procedures applied to zebrafish (Danio rerio) embryonic material at four developmental stages. As a proof of principle, we have profiled on a global scale a number of post-translational histone modifications including H3K4me1, H3K4me3 and H3K27ac. We demonstrate that these marks are dynamic during early development and that such developmental transitions can be detected by ChIP-seq. In addition, we applied MethylCap-seq to show that developmentally-regulated DNA methylation remodeling can be detected by such a procedure. Our MethylCap-seq data concur with previous DNA methylation studies of early zebrafish development rendering this method highly suitable for the global assessment of DNA methylation in early vertebrate embryos.',
			'date' => '2013-04-23',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23624103',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 233 => array(
			'id' => '1285',
			'name' => 'Genome-wide analysis of LXRα activation reveals new transcriptional networks in human atherosclerotic foam cells.',
			'authors' => 'Feldmann R, Fischer C, Kodelja V, Behrens S, Haas S, Vingron M, Timmermann B, Geikowski A, Sauer S',
			'description' => 'Increased physiological levels of oxysterols are major risk factors for developing atherosclerosis and cardiovascular disease. Lipid-loaded macrophages, termed foam cells, are important during the early development of atherosclerotic plaques. To pursue the hypothesis that ligand-based modulation of the nuclear receptor LXRα is crucial for cell homeostasis during atherosclerotic processes, we analysed genome-wide the action of LXRα in foam cells and macrophages. By integrating chromatin immunoprecipitation-sequencing (ChIP-seq) and gene expression profile analyses, we generated a highly stringent set of 186 LXRα target genes. Treatment with the nanomolar-binding ligand T0901317 and subsequent auto-regulatory LXRα activation resulted in sequence-dependent sharpening of the genome-binding patterns of LXRα. LXRα-binding loci that correlated with differential gene expression revealed 32 novel target genes with potential beneficial effects, which in part explained the implications of disease-associated genetic variation data. These observations identified highly integrated LXRα ligand-dependent transcriptional networks, including the APOE/C1/C4/C2-gene cluster, which contribute to the reversal of cholesterol efflux and the dampening of inflammation processes in foam cells to prevent atherogenesis.',
			'date' => '2013-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23393188',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 234 => array(
			'id' => '1304',
			'name' => 'Regulation of transcription through acetylation of H3K122 on the lateral surface of the histone octamer.',
			'authors' => 'Tropberger P, Pott S, Keller C, Kamieniarz-Gdula K, Caron M, Richter F, Li G, Mittler G, Liu ET, Bühler M, Margueron R, Schneider R',
			'description' => 'Histone modifications are key regulators of chromatin function. However, little is known to what extent histone modifications can directly impact on chromatin. Here, we address how a modification within the globular domain of histones regulates chromatin function. We demonstrate that H3K122ac can be sufficient to stimulate transcription and that mutation of H3K122 impairs transcriptional activation, which we attribute to a direct effect of H3K122ac on histone-DNA binding. In line with this, we find that H3K122ac defines genome-wide genetic elements and chromatin features associated with active transcription. Furthermore, H3K122ac is catalyzed by the coactivators p300/CBP and can be induced by nuclear hormone receptor signaling. Collectively, this suggests that transcriptional regulators elicit their effects not only via signaling to histone tails but also via direct structural perturbation of nucleosomes by directing acetylation to their lateral surface.',
			'date' => '2013-02-14',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23415232',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 235 => array(
			'id' => '1497',
			'name' => 'Histone lysine trimethylation or acetylation can be modulated by phytoestrogen, estrogen or anti-HDAC in breast cancer cell lines.',
			'authors' => 'Dagdemir A, Durif J, Ngollo M, Bignon YJ, Bernard-Gallon D',
			'description' => '<p>AIM: The isoflavones genistein, daidzein and equol (daidzein metabolite) have been reported to interact with epigenetic modifications, specifically hypermethylation of tumor suppressor genes. The objective of this study was to analyze and understand the mechanisms by which phytoestrogens act on chromatin in breast cancer cell lines. MATERIALS &amp; METHODS: Two breast cancer cell lines, MCF-7 and MDA-MB 231, were treated with genistein (18.5 &micro;M), daidzein (78.5 &micro;M), equol (12.8 &micro;M), 17&beta;-estradiol (10 nM) and suberoylanilide hydroxamic acid (1 &micro;M) for 48 h. A control with untreated cells was performed. 17&beta;-estradiol and an anti-HDAC were used to compare their actions with phytoestrogens. The chromatin immunoprecipitation coupled with quantitative PCR was used to follow soy phytoestrogen effects on H3 and H4 histones on H3K27me3, H3K9me3, H3K4me3, H4K8ac and H3K4ac marks, and we selected six genes (EZH2, BRCA1, ER&alpha;, ER&beta;, SRC3 and P300) for analysis. RESULTS: Soy phytoestrogens induced a decrease in trimethylated marks and an increase in acetylating marks studied at six selected genes. CONCLUSION: We demonstrated that soy phytoestrogens tend to modify transcription through the demethylation and acetylation of histones in breast cancer cell lines.</p>',
			'date' => '2013-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23414320',
			'doi' => '',
			'modified' => '2016-05-03 12:17:35',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 236 => array(
			'id' => '1267',
			'name' => 'Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA.',
			'authors' => 'Fadloun A, Le Gras S, Jost B, Ziegler-Birling C, Takahashi H, Gorab E, Carninci P, Torres-Padilla ME',
			'description' => 'How a more plastic chromatin state is maintained and reversed during development is unknown. Heterochromatin-mediated silencing of repetitive elements occurs in differentiated cells. Here, we used repetitive elements, including retrotransposons, as model loci to address how and when heterochromatin forms during development. RNA sequencing throughout early mouse embryogenesis revealed that repetitive-element expression is dynamic and stage specific, with most repetitive elements becoming repressed before implantation. We show that LINE-1 and IAP retrotransposons become reactivated from both parental genomes after fertilization. Chromatin immunoprecipitation for H3K4me3 and H3K9me3 in 2- and 8-cell embryos indicates that their developmental silencing follows loss of activating marks rather than acquisition of conventional heterochromatic marks. Furthermore, short LINE-1 RNAs regulate LINE-1 transcription in vivo. Our data indicate that reprogramming after mammalian fertilization comprises a robust transcriptional activation of retrotransposons and that repetitive elements are initially regulated through RNA.',
			'date' => '2013-01-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23353788',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 237 => array(
			'id' => '1195',
			'name' => 'Ezh2 maintains a key phase of muscle satellite cell expansion but does not regulate terminal differentiation.',
			'authors' => 'Woodhouse S, Pugazhendhi D, Brien P, Pell JM.',
			'description' => 'Tissue generation and repair requires a stepwise process of cell fate restriction to ensure adult stem cells differentiate in a timely and appropriate manner. A crucial role has been implicated for Polycomb-group (PcG) proteins and the H3K27me3 repressive histone mark, in coordinating the transcriptional programmes necessary for this process, but the targets and developmental timing for this repression remain unclear. To address these questions, we generated novel genome-wide maps of H3K27me3 and H3K4me3 in freshly isolated muscle stem cells. These data, together with the analysis of two conditional Ezh2-null mouse strains, identified a critical proliferation phase in which Ezh2 activity is essential. Mice lacking Ezh2 in satellite cells exhibited decreased muscle growth, severely impaired regeneration and reduced stem cell number, due to a profound failure of the proliferative progenitor population to expand. Surprisingly, deletion of Ezh2 after the onset of terminal differentiation did not impede muscle repair or homeostasis. Using these knockout models, RNA-Seq and the ChIP-Seq datasets we show that Ezh2 does not regulate the muscle differentiation process in vivo. These results emphasise the lineage and cell type specific functions for Ezh2 and the Polycomb repressive complex 2.',
			'date' => '2012-11-30',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/23203812',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 238 => array(
			'id' => '1162',
			'name' => 'Limitations and possibilities of low cell number ChIP-seq.',
			'authors' => 'Gilfillan GD, Hughes T, Sheng Y, Hjorthaug HS, Straub T, Gervin K, Harris JR, Undlien DE, Lyle R',
			'description' => 'ABSTRACT: BACKGROUND: Chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq) offers high resolution, genome-wide analysis of DNA-protein interactions. However, current standard methods require abundant starting material in the range of 1--20 million cells per immunoprecipitation, and remain a bottleneck to the acquisition of biologically relevant epigenetic data. Using a ChIP-seq protocol optimised for low cell numbers (down to 100,000 cells / IP), we examined the performance of the ChIP-seq technique on a series of decreasing cell numbers. RESULTS: We present an enhanced native ChIP-seq method tailored to low cell numbers that represents a 200-fold reduction in input requirements over existing protocols. The protocol was tested over a range of starting cell numbers covering three orders of magnitude, enabling determination of the lower limit of the technique. At low input cell numbers, increased levels of unmapped and duplicate reads reduce the number of unique reads generated, and can drive up sequencing costs and affect sensitivity if ChIP is attempted from too few cells. CONCLUSIONS: The optimised method presented here considerably reduces the input requirements for performing native ChIP-seq. It extends the applicability of the technique to isolated primary cells and rare cell populations (e.g. biobank samples, stem cells), and in many cases will alleviate the need for cell culture and any associated alteration of epigenetic marks. However, this study highlights a challenge inherent to ChIP-seq from low cell numbers: as cell input numbers fall, levels of unmapped sequence reads and PCR-generated duplicate reads rise. We discuss a number of solutions to overcome the effects of reducing cell number that may aid further improvements to ChIP performance.',
			'date' => '2012-11-21',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23171294',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 239 => array(
			'id' => '1143',
			'name' => 'Protein Group Modification and Synergy in the SUMO Pathway as Exemplified in DNA Repair.',
			'authors' => 'Psakhye I, Jentsch S',
			'description' => 'Protein modification by SUMO affects a wide range of protein substrates. Surprisingly, although SUMO pathway mutants display strong phenotypes, the function of individual SUMO modifications is often enigmatic, and SUMOylation-defective mutants commonly lack notable phenotypes. Here, we use DNA double-strand break repair as an example and show that DNA damage triggers a SUMOylation wave, leading to simultaneous multisite modifications of several repair proteins of the same pathway. Catalyzed by a DNA-bound SUMO ligase and triggered by single-stranded DNA, SUMOylation stabilizes physical interactions between the proteins. Notably, only wholesale elimination of SUMOylation of several repair proteins significantly affects the homologous recombination pathway by considerably slowing down DNA repair. Thus, SUMO acts synergistically on several proteins, and individual modifications only add up to efficient repair. We propose that SUMOylation may thus often target a protein group rather than individual proteins, whereas localized modification enzymes and highly specific triggers ensure specificity.',
			'date' => '2012-11-09',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23122649',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 240 => array(
			'id' => '1137',
			'name' => 'IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer.',
			'authors' => 'Baird AM, Leonard J, Naicker KM, Kilmartin L, O'Byrne KJ, Gray SG',
			'description' => 'BACKGROUND: IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC). METHODS: RT-PCR and chromatin immunopreciptiation (ChIP) were used to examine the levels, epigenetic regulation and effects of various drugs (DNA methyltransferase inhibitors, Histone Deacetylase inhibitors and Gemcitabine) on IL-23 expression in NSCLC cells and macrophages. The effects of recombinant IL-23 protein on cellular proliferation were examined by MTT assay. Statistical analysis consisted of Student's t-test or one way analysis of variance (ANOVA) where groups in the experiment were three or more. RESULTS: In a cohort of primary non-small cell lung cancer (NSCLC) tumours, IL-23A expression was significantly elevated in patient tumour samples (p<0.05). IL-23A expression is epigenetically regulated through histone post-translational modifications and DNA CpG methylation. Gemcitabine, a chemotherapy drug indicated for first-line treatment of NSCLC also induced IL-23A expression. Recombinant IL-23 significantly increased cellular proliferation in NSCLC cell lines. CONCLUSIONS: These results may therefore have important implications for treating NSCLC patients with either epigenetic targeted therapies or Gemcitabine.',
			'date' => '2012-10-29',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23116756',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 241 => array(
			'id' => '1078',
			'name' => 'New partners in regulation of gene expression: the enhancer of trithorax and polycomb corto interacts with methylated ribosomal protein l12 via its chromodomain.',
			'authors' => 'Coléno-Costes A, Jang SM, de Vanssay A, Rougeot J, Bouceba T, Randsholt NB, Gibert JM, Le Crom S, Mouchel-Vielh E, Bloyer S, Peronnet F',
			'description' => 'Chromodomains are found in many regulators of chromatin structure, and most of them recognize methylated lysines on histones. Here, we investigate the role of the Drosophila melanogaster protein Corto's chromodomain. The Enhancer of Trithorax and Polycomb Corto is involved in both silencing and activation of gene expression. Over-expression of the Corto chromodomain (CortoCD) in transgenic flies shows that it is a chromatin-targeting module, critical for Corto function. Unexpectedly, mass spectrometry analysis reveals that polypeptides pulled down by CortoCD from nuclear extracts correspond to ribosomal proteins. Furthermore, real-time interaction analyses demonstrate that CortoCD binds with high affinity RPL12 tri-methylated on lysine 3. Corto and RPL12 co-localize with active epigenetic marks on polytene chromosomes, suggesting that both are involved in fine-tuning transcription of genes in open chromatin. RNA-seq based transcriptomes of wing imaginal discs over-expressing either CortoCD or RPL12 reveal that both factors deregulate large sets of common genes, which are enriched in heat-response and ribosomal protein genes, suggesting that they could be implicated in dynamic coordination of ribosome biogenesis. Chromatin immunoprecipitation experiments show that Corto and RPL12 bind hsp70 and are similarly recruited on gene body after heat shock. Hence, Corto and RPL12 could be involved together in regulation of gene transcription. We discuss whether pseudo-ribosomal complexes composed of various ribosomal proteins might participate in regulation of gene expression in connection with chromatin regulators.',
			'date' => '2012-10-11',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/23071455',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 242 => array(
			'id' => '831',
			'name' => 'Extensive promoter hypermethylation and hypomethylation is associated with aberrant microRNA expression in chronic lymphocytic leukemia.',
			'authors' => 'Baer C, Claus R, Frenzel LP, Zucknick M, Park YJ, Gu L, Weichenhan D, Fischer M, Pallasch CP, Herpel E, Rehli M, Byrd JC, Wendtner CM, Plass C',
			'description' => '<p>Dysregulated microRNA (miRNA) expression contributes to the pathogenesis of hematopoietic malignancies, including chronic lymphocytic leukemia (CLL). However, an understanding of the mechanisms that cause aberrant miRNA transcriptional control is lacking. In this study, we comprehensively investigated the role and extent of miRNA epigenetic regulation in CLL. Genome-wide profiling performed on 24 CLL and 10 healthy B cell samples revealed global DNA methylation patterns upstream of miRNA sequences that distinguished malignant from healthy cells and identified putative miRNA promoters. Integration of DNA methylation and miRNA promoter data led to the identification of 128 recurrent miRNA targets for aberrant promoter DNA methylation. DNA hypomethylation accounted for over 60% of all aberrant promoter-associated DNA methylation in CLL, and promoter DNA hypomethylation was restricted to well-defined regions. Individual hyper- and hypomethylated promoters allowed discrimination of CLL samples from healthy controls. Promoter DNA methylation patterns were confirmed in an independent patient cohort, with eleven miRNAs consistently demonstrating an inverse correlation between DNA methylation status and expression level. Together, our findings characterize the role of epigenetic changes in the regulation of miRNA transcription and create a repository of disease-specific promoter regions that may provide additional insights into the pathogenesis of CLL.</p>',
			'date' => '2012-06-18',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22710432',
			'doi' => '',
			'modified' => '2016-05-03 12:14:21',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 243 => array(
			'id' => '1204',
			'name' => 'The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells.',
			'authors' => 'Karpiuk O, Najafova Z, Kramer F, Hennion M, Galonska C, König A, Snaidero N, Vogel T, Shchebet A, Begus-Nahrmann Y, Kassem M, Simons M, Shcherbata H, Beissbarth T, Johnsen SA',
			'description' => 'Extensive changes in posttranslational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly understood. We show that histone H2B monoubiquitination (H2Bub1) significantly increases during differentiation of human mesenchymal stem cells (hMSCs) and various lineage-committed precursor cells and in diverse organisms. Furthermore, the H2B ubiquitin ligase RNF40 is required for the induction of differentiation markers and transcriptional reprogramming of hMSCs. This function is dependent upon CDK9 and the WAC adaptor protein, which are required for H2B monoubiquitination. Finally, we show that RNF40 is required for the resolution of the H3K4me3/H3K27me3 bivalent poised state on lineage-specific genes during the transition from an inactive to an active chromatin conformation. Thus, these data indicate that H2Bub1 is required for maintaining multipotency of hMSCs and plays a central role in controlling stem cell differentiation.',
			'date' => '2012-06-08',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22681891',
			'doi' => '',
			'modified' => '2015-07-24 15:38:59',
			'created' => '2015-07-24 15:38:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 244 => array(
			'id' => '792',
			'name' => 'Intronic RNAs mediate EZH2 regulation of epigenetic targets.',
			'authors' => 'Guil S, Soler M, Portela A, Carrère J, Fonalleras E, Gómez A, Villanueva A, Esteller M',
			'description' => 'Epigenetic deregulation at a number of genomic loci is one of the hallmarks of cancer. A role for some RNA molecules in guiding repressive polycomb complex PRC2 to specific chromatin regions has been proposed. Here we use an in vivo cross-linking method to detect and identify direct PRC2-RNA interactions in human cancer cells, revealing a number of intronic RNA sequences capable of binding to the core component EZH2 and regulating the transcriptional output of its genomic counterpart. Overexpression of EZH2-bound intronic RNA for the H3K4 methyltransferase gene SMYD3 is concomitant with an increase in EZH2 occupancy throughout the corresponding genomic fragment and is sufficient to reduce levels of the endogenous transcript and protein, resulting in reduced growth capability in cell culture and animal models. These findings reveal the role of intronic RNAs in fine-tuning gene expression regulation at the level of transcriptional control.',
			'date' => '2012-06-03',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22659877',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 245 => array(
			'id' => '732',
			'name' => 'The transcriptional and epigenomic foundations of ground state pluripotency.',
			'authors' => 'Marks H, Kalkan T, Menafra R, Denissov S, Jones K, Hofemeister H, Nichols J, Kranz A, Francis Stewart A, Smith A, Stunnenberg HG',
			'description' => 'Mouse embryonic stem (ES) cells grown in serum exhibit greater heterogeneity in morphology and expression of pluripotency factors than ES cells cultured in defined medium with inhibitors of two kinases (Mek and GSK3), a condition known as "2i" postulated to establish a naive ground state. We show that the transcriptome and epigenome profiles of serum- and 2i-grown ES cells are distinct. 2i-treated cells exhibit lower expression of lineage-affiliated genes, reduced prevalence at promoters of the repressive histone modification H3K27me3, and fewer bivalent domains, which are thought to mark genes poised for either up- or downregulation. Nonetheless, serum- and 2i-grown ES cells have similar differentiation potential. Precocious transcription of developmental genes in 2i is restrained by RNA polymerase II promoter-proximal pausing. These findings suggest that transcriptional potentiation and a permissive chromatin context characterize the ground state and that exit from it may not require a metastable intermediate or multilineage priming.',
			'date' => '2012-04-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22541430',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 246 => array(
			'id' => '456',
			'name' => 'Control of ground-state pluripotency by allelic regulation of Nanog.',
			'authors' => 'Miyanari Y, Torres-Padilla ME',
			'description' => 'Pluripotency is established through genome-wide reprogramming during mammalian pre-implantation development, resulting in the formation of the naive epiblast. Reprogramming involves both the resetting of epigenetic marks and the activation of pluripotent-cell-specific genes such as Nanog and Oct4 (also known as Pou5f1). The tight regulation of these genes is crucial for reprogramming, but the mechanisms that regulate their expression in vivo have not been uncovered. Here we show that Nanog-but not Oct4-is monoallelically expressed in early pre-implantation embryos. Nanog then undergoes a progressive switch to biallelic expression during the transition towards ground-state pluripotency in the naive epiblast of the late blastocyst. Embryonic stem (ES) cells grown in leukaemia inhibitory factor (LIF) and serum express Nanog mainly monoallelically and show asynchronous replication of the Nanog locus, a feature of monoallelically expressed genes, but ES cells activate both alleles when cultured under 2i conditions, which mimic the pluripotent ground state in vitro. Live-cell imaging with reporter ES cells confirmed the allelic expression of Nanog and revealed allelic switching. The allelic expression of Nanog is regulated through the fibroblast growth factor-extracellular signal-regulated kinase signalling pathway, and it is accompanied by chromatin changes at the proximal promoter but occurs independently of DNA methylation. Nanog-heterozygous blastocysts have fewer inner-cell-mass derivatives and delayed primitive endoderm formation, indicating a role for the biallelic expression of Nanog in the timely maturation of the inner cell mass into a fully reprogrammed pluripotent epiblast. We suggest that the tight regulation of Nanog dose at the chromosome level is necessary for the acquisition of ground-state pluripotency during development. Our data highlight an unexpected role for allelic expression in controlling the dose of pluripotency factors in vivo, adding an extra level to the regulation of reprogramming.',
			'date' => '2012-02-12',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22327294',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 247 => array(
			'id' => '919',
			'name' => 'Prepatterning of developmental gene expression by modified histones before zygotic genome activation.',
			'authors' => 'Lindeman LC, Andersen IS, Reiner AH, Li N, Aanes H, Østrup O, Winata C, Mathavan S, Müller F, Aleström P, Collas P',
			'description' => 'A hallmark of anamniote vertebrate development is a window of embryonic transcription-independent cell divisions before onset of zygotic genome activation (ZGA). Chromatin determinants of ZGA are unexplored; however, marking of developmental genes by modified histones in sperm suggests a predictive role of histone marks for ZGA. In zebrafish, pre-ZGA development for ten cell cycles provides an opportunity to examine whether genomic enrichment in modified histones is present before initiation of transcription. By profiling histone H3 trimethylation on all zebrafish promoters before and after ZGA, we demonstrate here an epigenetic prepatterning of developmental gene expression. This involves pre-ZGA marking of transcriptionally inactive genes involved in homeostatic and developmental regulation by permissive H3K4me3 with or without repressive H3K9me3 or H3K27me3. Our data suggest that histone modifications are instructive for the developmental gene expression program.',
			'date' => '2011-12-13',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/22137762',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 248 => array(
			'id' => '913',
			'name' => 'IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF.',
			'authors' => 'Baird AM, Gray SG, O'Byrne KJ',
			'description' => 'BACKGROUND: IL-20 is a pleiotrophic member of the IL-10 family and plays a role in skin biology and the development of haematopoietic cells. Recently, IL-20 has been demonstrated to have potential anti-angiogenic effects in non-small cell lung cancer (NSCLC) by down regulating COX-2. METHODS: The expression of IL-20 and its cognate receptors (IL-20RA/B and IL-22R1) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of this family was examined in normal bronchial epithelial and NSCLC cell lines. Furthermore, the effect of IL-20 on VEGF family members was examined. RESULTS: The expression of IL-20 and its receptors are frequently dysregulated in NSCLC. IL-20RB mRNA was significantly elevated in NSCLC tumours (p<0.01). Protein levels of the receptors, IL-20RB and IL-22R1, were significantly increased (p<0.01) in the tumours of NSCLC patients. IL-20 and its receptors were found to be epigenetically regulated through histone post-translational modifications and DNA CpG residue methylation. In addition, treatment with recombinant IL-20 resulted in decreased expression of the VEGF family members at the mRNA level. CONCLUSIONS: This family of genes are dysregulated in NSCLC and are subject to epigenetic regulation. Whilst the anti-angiogenic properties of IL-20 require further clarification, targeting this family via epigenetic means may be a viable therapeutic option in lung cancer treatment.',
			'date' => '2011-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21565488',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 249 => array(
			'id' => '637',
			'name' => 'H3.5 is a novel hominid-specific histone H3 variant that is specifically expressed in the seminiferous tubules of human testes.',
			'authors' => 'Schenk R, Jenke A, Zilbauer M, Wirth S, Postberg J',
			'description' => 'The incorporation of histone variants into chromatin plays an important role for the establishment of particular chromatin states. Six human histone H3 variants are known to date, not counting CenH3 variants: H3.1, H3.2, H3.3 and the testis-specific H3.1t as well as the recently described variants H3.X and H3.Y. We report the discovery of H3.5, a novel non-CenH3 histone H3 variant. H3.5 is encoded on human chromosome 12p11.21 and probably evolved in a common ancestor of all recent great apes (Hominidae) as a consequence of H3F3B gene duplication by retrotransposition. H3.5 mRNA is specifically expressed in seminiferous tubules of human testis. Interestingly, H3.5 has two exact copies of ARKST motifs adjacent to lysine-9 or lysine-27, and lysine-79 is replaced by asparagine. In the Hek293 cell line, ectopically expressed H3.5 is assembled into chromatin and targeted by PTM. H3.5 preferentially colocalizes with euchromatin, and it is associated with actively transcribed genes and can replace an essential function of RNAi-depleted H3.3 in cell growth.',
			'date' => '2011-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21274551',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 250 => array(
			'id' => '256',
			'name' => 'Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer',
			'authors' => 'O'Byrne KJ, Baird AM, Kilmartin L, Leonard J, Sacevich C, Gray SG.',
			'description' => 'Due to their inherently hypoxic environment, cancer cells often resort to glycolysis, or the anaerobic breakdown of glucose to form ATP to provide for their energy needs, known as the Warburg effect. At the same time, overexpression of the insulin receptor in non-small cell lung cancer (NSCLC) is associated with an increased risk of metastasis and decreased survival. The uptake of glucose into cells is carried out via glucose transporters or GLUTs. Of these, GLUT-4 is essential for insulin-stimulated glucose uptake. Following treatment with the epigenetic targeting agents histone deacetylase inhibitors (HDACi), GLUT-3 and GLUT-4 expression were found to be induced in NSCLC cell lines, with minimal responses in transformed normal human bronchial epithelial cells (HBECs). Similar results for GLUT-4 were observed in cells derived from liver, muscle, kidney and pre-adipocytes. Bioinformatic analysis of the promoter for GLUT-4 indicates that it may also be regulated by several chromatin binding factors or complexes including CTCF, SP1 and SMYD3. Chromatin immunoprecipitation studies demonstrate that the promoter for GLUT-4 is dynamically remodeled in response to HDACi. Overall, these results may have value within the clinical setting as (a) it may be possible to use this to enhance fluorodeoxyglucose (18F) positron emission tomography (FDG-PET) imaging sensitivity; (b) it may be possible to target NSCLC through the use of HDACi and insulin mediated uptake of the metabolic targeting drugs such as 2-deoxyglucose (2-DG); or (c) enhance or sensitize NSCLC to chemotherapy. ',
			'date' => '2011-03-25',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/24212773',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 251 => array(
			'id' => '265',
			'name' => 'Characterisation of genome-wide PLZF/RARA target genes.',
			'authors' => 'Spicuglia S, Vincent-Fabert C, Benoukraf T, Tibéri G, Saurin AJ, Zacarias-Cabeza J, Grimwade D, Mills K, Calmels B, Bertucci F, Sieweke M, Ferrier P, Duprez E',
			'description' => 'The PLZF/RARA fusion protein generated by the t(11;17)(q23;q21) translocation in acute promyelocytic leukaemia (APL) is believed to act as an oncogenic transcriptional regulator recruiting epigenetic factors to genes important for its transforming potential. However, molecular mechanisms associated with PLZF/RARA-dependent leukaemogenesis still remain unclear.We searched for specific PLZF/RARA target genes by ChIP-on-chip in the haematopoietic cell line U937 conditionally expressing PLZF/RARA. By comparing bound regions found in U937 cells expressing endogenous PLZF with PLZF/RARA-induced U937 cells, we isolated specific PLZF/RARA target gene promoters. We next analysed gene expression profiles of our identified target genes in PLZF/RARA APL patients and analysed DNA sequences and epigenetic modification at PLZF/RARA binding sites. We identify 413 specific PLZF/RARA target genes including a number encoding transcription factors involved in the regulation of haematopoiesis. Among these genes, 22 were significantly down regulated in primary PLZF/RARA APL cells. In addition, repressed PLZF/RARA target genes were associated with increased levels of H3K27me3 and decreased levels of H3K9K14ac. Finally, sequence analysis of PLZF/RARA bound sequences reveals the presence of both consensus and degenerated RAREs as well as enrichment for tissue-specific transcription factor motifs, highlighting the complexity of targeting fusion protein to chromatin. Our study suggests that PLZF/RARA directly targets genes important for haematopoietic development and supports the notion that PLZF/RARA acts mainly as an epigenetic regulator of its direct target genes.',
			'date' => '2011-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21949697',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 252 => array(
			'id' => '585',
			'name' => 'Tiling histone H3 lysine 4 and 27 methylation in zebrafish using high-density microarrays.',
			'authors' => 'Lindeman LC, Reiner AH, Mathavan S, Aleström P, Collas P',
			'description' => 'BACKGROUND: Uncovering epigenetic states by chromatin immunoprecipitation and microarray hybridization (ChIP-chip) has significantly contributed to the understanding of gene regulation at the genome-scale level. Many studies have been carried out in mice and humans; however limited high-resolution information exists to date for non-mammalian vertebrate species. PRINCIPAL FINDINGS: We report a 2.1-million feature high-resolution Nimblegen tiling microarray for ChIP-chip interrogations of epigenetic states in zebrafish (Danio rerio). The array covers 251 megabases of the genome at 92 base-pair resolution. It includes ∼15 kb of upstream regulatory sequences encompassing all RefSeq promoters, and over 5 kb in the 5' end of coding regions. We identify with high reproducibility, in a fibroblast cell line, promoters enriched in H3K4me3, H3K27me3 or co-enriched in both modifications. ChIP-qPCR and sequential ChIP experiments validate the ChIP-chip data and support the co-enrichment of trimethylated H3K4 and H3K27 on a subset of genes. H3K4me3- and/or H3K27me3-enriched genes are associated with distinct transcriptional status and are linked to distinct functional categories. CONCLUSIONS: We have designed and validated for the scientific community a comprehensive high-resolution tiling microarray for investigations of epigenetic states in zebrafish, a widely used developmental and disease model organism.',
			'date' => '2010-12-20',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/21187971',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 253 => array(
			'id' => '413',
			'name' => 'Autonomous silencing of the imprinted Cdkn1c gene in stem cells',
			'authors' => 'Wood MD, Hiura H, Tunster S, Arima T, Shin J-H, Higgins M, John1 RM',
			'description' => 'Parent-of-origin specific expression of imprinted genes relies on the differential DNA methylation of specific genomic regions. Differentially methylated regions (DMRs) acquire DNA methylation either during gametogenesis (primary DMR) or after fertilization when allele-specific expression is established (secondary DMR). Little is known about the function of these secondary DMRs. We investigated the DMR spanning Cdkn1c in mouse embryonic stem cells, androgenetic stem cells and embryonic germ stem cells. In all cases, expression of Cdkn1c was appropriately repressed in in vitro differentiated cells. However, stem cells failed to de novo methylate the silenced gene even after sustained differentiation. In the absence of maintained DNA methylation (Dnmt1-/-), Cdkn1c escapes silencing demonstrating the requirement for DNA methylation in long term silencing in vivo. We propose that post-fertilization differential methylation reflects the importance of retaining single gene dosage of a subset of imprinted loci in the adult.',
			'date' => '2010-04-01',
			'pmid' => 'http://www.pubmed/20372090',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 254 => array(
			'id' => '69',
			'name' => 'The histone variant macroH2A is an epigenetic regulator of key developmental genes.',
			'authors' => 'Buschbeck M, Uribesalgo I, Wibowo I, Rué P, Martin D, Gutierrez A, Morey L, Guigó R, López-Schier H, Di Croce L',
			'description' => 'The histone variants macroH2A1 and macroH2A2 are associated with X chromosome inactivation in female mammals. However, the physiological function of macroH2A proteins on autosomes is poorly understood. Microarray-based analysis in human male pluripotent cells uncovered occupancy of both macroH2A variants at many genes encoding key regulators of development and cell fate decisions. On these genes, the presence of macroH2A1+2 is a repressive mark that overlaps locally and functionally with Polycomb repressive complex 2. We demonstrate that macroH2A1+2 contribute to the fine-tuning of temporal activation of HOXA cluster genes during neuronal differentiation. Furthermore, elimination of macroH2A2 function in zebrafish embryos produced severe but specific phenotypes. Taken together, our data demonstrate that macroH2A variants constitute an important epigenetic mark involved in the concerted regulation of gene expression programs during cellular differentiation and vertebrate development.',
			'date' => '2009-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/19734898',
			'doi' => '',
			'modified' => '2015-07-24 15:38:56',
			'created' => '2015-07-24 15:38:56',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 255 => array(
			'id' => '117',
			'name' => 'High-resolution analysis of epigenetic changes associated with X inactivation.',
			'authors' => 'Marks H, Chow JC, Denissov S, Françoijs KJ, Brockdorff N, Heard E, Stunnenberg HG',
			'description' => 'Differentiation of female murine ES cells triggers silencing of one X chromosome through X-chromosome inactivation (XCI). Immunofluorescence studies showed that soon after Xist RNA coating the inactive X (Xi) undergoes many heterochromatic changes, including the acquisition of H3K27me3. However, the mechanisms that lead to the establishment of heterochromatin remain unclear. We first analyze chromatin changes by ChIP-chip, as well as RNA expression, around the X-inactivation center (Xic) in female and male ES cells, and their day 4 and 10 differentiated derivatives. A dynamic epigenetic landscape is observed within the Xic locus. Tsix repression is accompanied by deposition of H3K27me3 at its promoter during differentiation of both female and male cells. However, only in female cells does an active epigenetic landscape emerge at the Xist locus, concomitant with high Xist expression. Several regions within and around the Xic show unsuspected chromatin changes, and we define a series of unusual loci containing highly enriched H3K27me3. Genome-wide ChIP-seq analyses show a female-specific quantitative increase of H3K27me3 across the X chromosome as XCI proceeds in differentiating female ES cells. Using female ES cells with nonrandom XCI and polymorphic X chromosomes, we demonstrate that this increase is specific to the Xi by allele-specific SNP mapping of the ChIP-seq tags. H3K27me3 becomes evenly associated with the Xi in a chromosome-wide fashion. A selective and robust increase of H3K27me3 and concomitant decrease in H3K4me3 is observed over active genes. This indicates that deposition of H3K27me3 during XCI is tightly associated with the act of silencing of individual genes across the Xi.',
			'date' => '2009-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/19581487',
			'doi' => '',
			'modified' => '2015-07-24 15:38:57',
			'created' => '2015-07-24 15:38:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 256 => array(
			'id' => '1435',
			'name' => 'H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming.',
			'authors' => 'Daujat S, Weiss T, Mohn F, Lange UC, Ziegler-Birling C, Zeissler U, Lappe M, Schübeler D, Torres-Padilla ME, Schneider R',
			'description' => 'Histone modifications are central to the regulation of all DNA-dependent processes. Lys64 of histone H3 (H3K64) lies within the globular domain at a structurally important position. We identify trimethylation of H3K64 (H3K64me3) as a modification that is enriched at pericentric heterochromatin and associated with repeat sequences and transcriptionally inactive genomic regions. We show that this new mark is dynamic during the two main epigenetic reprogramming events in mammals. In primordial germ cells, H3K64me3 is present at the time of specification, but it disappears transiently during reprogramming. In early mouse embryos, it is inherited exclusively maternally; subsequently, the modification is rapidly removed, suggesting an important role for H3K64me3 turnover in development. Taken together, our findings establish H3K64me3 as a previously uncharacterized histone modification that is preferentially localized to repressive chromatin. We hypothesize that H3K64me3 helps to 'secure' nucleosomes, and perhaps the surrounding chromatin, in an appropriately repressed state during development.',
			'date' => '2009-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/19561610',
			'doi' => '',
			'modified' => '2015-07-24 15:39:00',
			'created' => '2015-07-24 15:39:00',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 257 => array(
			'id' => '2600',
			'name' => 'Epigenetic-Mediated Downregulation of μ-Protocadherin in Colorectal Tumours',
			'authors' => 'Bujko M, Kober P, Statkiewicz M, Mikula M, Ligaj M, Zwierzchowski L, Ostrowski J, Siedlecki JA',
			'description' => 'Carcinogenesis involves altered cellular interaction and tissue morphology that partly arise from aberrant expression of cadherins. Mucin-like protocadherin is implicated in intercellular adhesion and its expression was found decreased in colorectal cancer (CRC). This study has compared MUPCDH (CDHR5) expression in three key types of colorectal tissue samples, for normal mucosa, adenoma, and carcinoma. A gradual decrease of mRNA levels and protein expression was observed in progressive stages of colorectal carcinogenesis which are consistent with reports of increasing MUPCDH 5′ promoter region DNA methylation. High MUPCDH methylation was also observed in HCT116 and SW480 CRC cell lines that revealed low gene expression levels compared to COLO205 and HT29 cell lines which lack DNA methylation at the MUPCDH locus. Furthermore, HCT116 and SW480 showed lower levels of RNA polymerase II and histone H3 lysine 4 trimethylation (H3K4me3) as well as higher levels of H3K27 trimethylation at the MUPCDH promoter. MUPCDH expression was however restored in HCT116 and SW480 cells in the presence of 5-Aza-2′-deoxycytidine (DNA methyltransferase inhibitor). Results indicate that μ-protocadherin downregulation occurs during early stages of tumourigenesis and progression into the adenoma-carcinoma sequence. Epigenetic mechanisms are involved in this silencing.',
			'date' => '0000-00-00',
			'pmid' => 'http://www.hindawi.com/journals/grp/2015/317093/',
			'doi' => '',
			'modified' => '2015-07-24 15:39:05',
			'created' => '2015-07-24 15:39:05',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 258 => array(
			'id' => '783',
			'name' => 'Analysis of active chromatin modifications in early mammalian embryos reveals uncoupling of H2A.Z acetylation and H3K36 trimethylation from embryonic genome activation',
			'authors' => 'Bošković A, Bender A, Gall L, Ziegler-Birling C, Beaujean N, Torres-Padilla ME',
			'description' => 'Early embryonic development is characterized by dramatic changes in cell potency and chromatin organization. The role of histone variants in the context of chromatin remodeling during embryogenesis remains under investigated. In particular, the nuclear distribution of the histone variant H2A.Z and its modifications have not been examined. Here we investigated the dynamics of acetylation of H2A.Z and two other active chromatin marks, H3K9ac and H3K36me3, throughout murine and bovine pre-implantation development. We show that H2A.Z distribution is dynamic during the earliest stages of mouse development, with protein levels significantly varying across stages and lowest at the 2-cell stage. When present, H2A.Z localizes preferentially to euchromatin at all stages analyzed. H2A.Z is acetylated in preimplantation blastomeres and is preferentially localized to euchromatin, in line with the known role of H2A.Zac in transcriptional activation. Interestingly, however, H2A.Zac is undetectable in mouse embryos at the 2-cell stage, the time of major embryonic genome activation (EGA). Similarly, H3K36me3 is present exclusively in the maternal chromatin immediately after fertilization but becomes undetectable in interphase nuclei at the 2-cell stage, suggesting uncoupling of these active marks with global embryonic transcription activation. In bovine embryos, which undergo EGA at the 8-cell stage, H2A.Zac can be detected in zygotes, 4-, 8- and 16-cell stage embryos as well as in blastocysts, indicating that the dynamics of H2A.Zac is not conserved in mammals. In contrast, H3K36me3 displays mostly undetectable and heterogeneous localization pattern throughout bovine pre-implantation development. Thus, our results suggest that ‘canonical’ active chromatin marks exhibit a dynamic behavior in embryonic nuclei, which is both stage- and speciesspecific. We hypothesize that chromatin of early embryonic nuclei is subject to fine-tuning through differential acquisition of histone marks, allowing for proper chromatin remodeling and developmental progression in a species-specific fashion.',
			'date' => '0000-00-00',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/22647320',
			'doi' => '',
			'modified' => '2015-07-24 15:38:58',
			'created' => '2015-07-24 15:38:58',
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		(int) 0 => array(
			'id' => '74',
			'name' => 'H3K4me3 polyclonal antibody Premium, 50 μl size',
			'description' => '<p>I have used Diagenode's antibodies for my ChIP&ndash;qPCR experiments in HK-2 cells. The antibodies performed very well in our experiments with specific signal, and good signal to noise ratio in the promoter of the gapdh gene.</p>
<center><img src="../../img/categories/antibodies/H3K4me3-hk2.png" /></center>
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong> ChIP assays were performed using human HK-2 cells, the Diagenode antibody against H3K4me3 (Cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with standard fixation and sonication protocol, using sheared chromatin from 4 million cells. A total amount of 4 ug of antibody were used per ChIP experiment, normal mouse IgG (4 &mu;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). These results are in accordance with the observation that trimethylation of K4 at histone H3 is associated with the promoters of active genes.</small></p>',
			'author' => 'Claudio Cappelli PhD. Post-Doc. Investigator, Laboratory of Molecular Pathology, Institute of Biochemestry and Microbiology, University Austral of Chile, about H3K4me3 polyclonal antibody Premium, 50 μl size.',
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			'id' => '53',
			'name' => 'antibodies-florian-heidelberg',
			'description' => '<p>In life sciences, epigenetics is nowadays the most rapid developing field with new astonishing discoveries made every day. To keep pace with this field, we are in need of reliable tools to foster our research - tools Diagenode provides us with. From <strong>antibodies</strong> to <strong>automated solutions</strong> - all from one source and with robust support. Antibodies used in our lab: H3K27me3 polyclonal antibody &ndash; Premium, H3K4me3 polyclonal antibody &ndash; Premium, H3K9me3 polyclonal antibody &ndash; Premium, H3K4me1 polyclonal antibody &ndash; Premium, CTCF polyclonal antibody &ndash; Classic, Rabbit IgG.</p>',
			'author' => 'Dr. Florian Uhle, Dept. of Anesthesiology, Heidelberg University Hospital, Germany',
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			'slug' => 'antibodies-florian-heidelberg',
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			'modified' => '2016-03-11 10:43:28',
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			'id' => '50',
			'name' => 'Dimitrova-testimonial',
			'description' => '<p>We use the <strong>Bioruptor</strong> sonication device and the antibody against the histone modification H3K4me3 in our lab. The Bioruptor device is used for the shearing of chromatin in ChIP-Seq experiments and for generation of protein lysates (whole cell extracts). Thanks to the Bioruptor device we achieve excellent and reproducible results in both applications. The <strong>H3K4me3 antibody</strong> is used in our ChIP-Seq experiments as well as Western Blotting. With this antibody we are able to generate highly enriched ChIP-Seq samples with extremely low background. In Western Blot we can detect one specific, strong band with the H3K4me3 antibody.</p>
<p>Diagenode provides not only very good products for research but also an excellent customer support.</p>',
			'author' => 'Dr Lora Dimitrova, Charité-Universitätsmedizin Berlin, Germany',
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		(int) 3 => array(
			'id' => '48',
			'name' => 'Thanks Diagenode for saving my PhD!',
			'description' => '<p><span>I work with Diagenode&rsquo;s <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> and shear the DNA on the <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a> for the last year and I have to say that these two products saved my PhD project! Some time ago, our well-established ChIP protocol suddenly stopped to work and after long time of figuring out the reason, we invested into <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a>. </span><span>I am very satisfied from the way it works, plus it&rsquo;s super quiet! Combining the sonicator with the <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> we finally got things working.&nbsp;</span><span>I have also decided to try the <a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns">Microplex Library Prep kit</a>, which is amazing. I have been working with other kits and I find this one efficient and very easy to use. </span><span>Recently, I have tested one of the epigenetics antibody (<a href="../products/search?keyword=H3K4me3">H3K4me3</a>) and it works very well on the plant tissue, together with the ChIP-seq kit and Bioruptor. </span></p>
<p>Thanks Diagenode for saving my PhD!</p>',
			'author' => 'Kamila Kwasniewska, Plant Developmental Genetics, Smurfit Institute, Trinity College, Dublin',
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			'created' => '2016-02-01 09:56:38',
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			'id' => '43',
			'name' => 'Microchip Andrea',
			'description' => '<p>I am working with the <a href="../p/true-microchip-kit-x16-16-rxns">True MicroChIP</a> &amp; <a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns">Microplex Library Preparation</a> Kits and several histone modification antibodies like H3K27ac, H3K4me3, H3K36me3, and H3K27me3.&nbsp;I got always very good and reproducible results for my ChIP-seq experiments.</p>',
			'author' => 'Andrea Thiesen, ZMB, Developmental Biology, Prof. Dr. Andrea Vortkamp´s lab, University Duisburg-Essen, Germany',
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			'slug' => 'microchip-andrea',
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			'modified' => '2016-03-09 16:00:08',
			'created' => '2015-12-07 13:04:58',
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		'name' => 'H3K4me3 Antibody',
		'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
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<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
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<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
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<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
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<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
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<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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$testimonials = '<blockquote><p>I have used Diagenode's antibodies for my ChIP&ndash;qPCR experiments in HK-2 cells. The antibodies performed very well in our experiments with specific signal, and good signal to noise ratio in the promoter of the gapdh gene.</p>
<center><img src="../../img/categories/antibodies/H3K4me3-hk2.png" /></center>
<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong> ChIP assays were performed using human HK-2 cells, the Diagenode antibody against H3K4me3 (Cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with standard fixation and sonication protocol, using sheared chromatin from 4 million cells. A total amount of 4 ug of antibody were used per ChIP experiment, normal mouse IgG (4 &mu;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). These results are in accordance with the observation that trimethylation of K4 at histone H3 is associated with the promoters of active genes.</small></p><cite>Claudio Cappelli PhD. Post-Doc. Investigator, Laboratory of Molecular Pathology, Institute of Biochemestry and Microbiology, University Austral of Chile, about H3K4me3 polyclonal antibody Premium, 50 μl size.</cite></blockquote>
<blockquote><p>In life sciences, epigenetics is nowadays the most rapid developing field with new astonishing discoveries made every day. To keep pace with this field, we are in need of reliable tools to foster our research - tools Diagenode provides us with. From <strong>antibodies</strong> to <strong>automated solutions</strong> - all from one source and with robust support. Antibodies used in our lab: H3K27me3 polyclonal antibody &ndash; Premium, H3K4me3 polyclonal antibody &ndash; Premium, H3K9me3 polyclonal antibody &ndash; Premium, H3K4me1 polyclonal antibody &ndash; Premium, CTCF polyclonal antibody &ndash; Classic, Rabbit IgG.</p><cite>Dr. Florian Uhle, Dept. of Anesthesiology, Heidelberg University Hospital, Germany</cite></blockquote>
<blockquote><p>We use the <strong>Bioruptor</strong> sonication device and the antibody against the histone modification H3K4me3 in our lab. The Bioruptor device is used for the shearing of chromatin in ChIP-Seq experiments and for generation of protein lysates (whole cell extracts). Thanks to the Bioruptor device we achieve excellent and reproducible results in both applications. The <strong>H3K4me3 antibody</strong> is used in our ChIP-Seq experiments as well as Western Blotting. With this antibody we are able to generate highly enriched ChIP-Seq samples with extremely low background. In Western Blot we can detect one specific, strong band with the H3K4me3 antibody.</p>
<p>Diagenode provides not only very good products for research but also an excellent customer support.</p><cite>Dr Lora Dimitrova, Charité-Universitätsmedizin Berlin, Germany</cite></blockquote>
<blockquote><p><span>I work with Diagenode&rsquo;s <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> and shear the DNA on the <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a> for the last year and I have to say that these two products saved my PhD project! Some time ago, our well-established ChIP protocol suddenly stopped to work and after long time of figuring out the reason, we invested into <a href="../p/bioruptor-pico-sonication-device">Bioruptor Pico</a>. </span><span>I am very satisfied from the way it works, plus it&rsquo;s super quiet! Combining the sonicator with the <a href="../p/plant-chip-seq-kit-x24-24-rxns">Plant ChIP-seq kit</a> we finally got things working.&nbsp;</span><span>I have also decided to try the <a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns">Microplex Library Prep kit</a>, which is amazing. I have been working with other kits and I find this one efficient and very easy to use. </span><span>Recently, I have tested one of the epigenetics antibody (<a href="../products/search?keyword=H3K4me3">H3K4me3</a>) and it works very well on the plant tissue, together with the ChIP-seq kit and Bioruptor. </span></p>
<p>Thanks Diagenode for saving my PhD!</p><cite>Kamila Kwasniewska, Plant Developmental Genetics, Smurfit Institute, Trinity College, Dublin</cite></blockquote>
<blockquote><p>I am working with the <a href="../p/true-microchip-kit-x16-16-rxns">True MicroChIP</a> &amp; <a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns">Microplex Library Preparation</a> Kits and several histone modification antibodies like H3K27ac, H3K4me3, H3K36me3, and H3K27me3.&nbsp;I got always very good and reproducible results for my ChIP-seq experiments.</p><cite>Andrea Thiesen, ZMB, Developmental Biology, Prof. Dr. Andrea Vortkamp´s lab, University Duisburg-Essen, Germany</cite></blockquote>
'
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	'author' => 'Andrea Thiesen, ZMB, Developmental Biology, Prof. Dr. Andrea Vortkamp´s lab, University Duisburg-Essen, Germany',
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	'modified' => '2016-03-09 16:00:08',
	'created' => '2015-12-07 13:04:58',
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<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<div class="row">
<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-a.png" width="800" /></center></div>
<div class="small-12 columns"><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-cuttag-b.png" width="800" /></center></div>
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<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<div class="row">
<div class="small-6 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig3-ELISA.jpg" width="350" /></center><center></center><center></center><center></center><center></center></div>
<div class="small-6 columns">
<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="row">
<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
<div class="small-6 columns">
<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="small-4 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig5-WB.jpg" /></div>
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<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig6-if.jpg" /></center></div>
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<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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	'description' => '<p><span>Polyclonal antibody raised in rabbit against the region of histone <strong>H3 containing the trimethylated lysine 4</strong> (<strong>H3K4me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
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<p><small><strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K4me3 (cat. No. C15410003) and optimized PCR primer pairs for qPCR. ChIP was performed with the iDeal ChIP-seq kit (cat. No. C01010051), using sheared chromatin from 500,000 cells. A titration consisting of 0.5, 1, 2 and 5 &micro;g of antibody per ChIP experiment was analyzed. IgG (1 &micro;g/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as positive controls, and for the inactive MYOD1 gene and the Sat2 satellite repeat, used as negative controls. Figure 1 shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis). </small></p>
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<div class="small-12 columns"><center>A.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2a-ChIP-seq.jpg" width="800" /></center><center>B.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2b-ChIP-seq.jpg" width="800" /></center><center>C.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2c-ChIP-seq.jpg" width="800" /></center><center>D.<img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig2d-ChIP-seq.jpg" width="800" /></center></div>
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<p><small><strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K4me3</strong><br />ChIP was performed on sheared chromatin from 1 million HeLaS3 cells using 1 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2 shows the peak distribution along the complete sequence and a 600 kb region of the X-chromosome (figure 2A and B) and in two regions surrounding the GAPDH and EIF4A2 positive control genes, respectively (figure 2C and D). These results clearly show an enrichment of the H3K4 trimethylation at the promoters of active genes.</small></p>
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<p><small><strong>Figure 3. Cut&amp;Tag results obtained with the Diagenode antibody directed against H3K4me3</strong><br />CUT&amp;TAG (Kaya-Okur, H.S., Nat Commun 10, 1930, 2019) was performed on 50,000 K562 cells using 0.5 &micro;g of the Diagenode antibody against H3K4me3 (cat. No. C15410003) and the Diagenode pA-Tn5 transposase (C01070001). The libraries were subsequently analysed on an Illumina NextSeq 500 sequencer (2x75 paired-end reads) according to the manufacturer's instructions. The tags were aligned to the human genome (hg19) using the BWA algorithm. Figure 3 shows the peak distribution in 2 genomic regions surrounding the FOS gene on chromosome 14 and the ACTB gene on chromosome 7 (figure 3A and B, respectively).</small></p>
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<p><small><strong>Figure 4. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 4), the titer of the antibody was estimated to be 1:11,000.</small></p>
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<div class="small-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig4-DB.jpg" /></div>
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<p><small><strong>Figure 5. Cross reactivity tests using the Diagenode antibody directed against H3K4me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K4me3 (cat. No. C15410003), a Dot Blot analysis was performed with peptides containing other histone modifications and the unmodified H3K4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:2,000. Figure 5A shows a high specificity of the antibody for the modification of interest.</small></p>
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<p><small><strong>Figure 6. Western blot analysis using the Diagenode antibody directed against H3K4me3</strong><br />Western blot was performed on whole cell extracts (40 &micro;g, lane 1) from HeLa cells, and on 1 &micro;g of recombinant histone H3 (lane 2) using the Diagenode antibody against H3K4me3 (cat. No. C15410003). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is indicated on the right; the marker (in kDa) is shown on the left.</small></p>
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<p><small><strong>Figure 7. Immunofluorescence using the Diagenode antibody directed against H3K4me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K4me3 (cat. No. C15410003) and with DAPI. Cells were fixed with 4% formaldehyde for 20&rsquo; and blocked with PBS/TX-100 containing 5% normal goat serum. The cells were immunofluorescently labelled with the H3K4me3 antibody (left) diluted 1:200 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa568 or with DAPI (middle), which specifically labels DNA. The right picture shows a merge of both stainings.</small></p>
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<p><a href="https://www.diagenode.com/en/pages/cut-and-tag">Performance of Diagenode's antibodies in CUT&amp;Tag</a></p>
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	'id' => '783',
	'name' => 'Analysis of active chromatin modifications in early mammalian embryos reveals uncoupling of H2A.Z acetylation and H3K36 trimethylation from embryonic genome activation',
	'authors' => 'Bošković A, Bender A, Gall L, Ziegler-Birling C, Beaujean N, Torres-Padilla ME',
	'description' => 'Early embryonic development is characterized by dramatic changes in cell potency and chromatin organization. The role of histone variants in the context of chromatin remodeling during embryogenesis remains under investigated. In particular, the nuclear distribution of the histone variant H2A.Z and its modifications have not been examined. Here we investigated the dynamics of acetylation of H2A.Z and two other active chromatin marks, H3K9ac and H3K36me3, throughout murine and bovine pre-implantation development. We show that H2A.Z distribution is dynamic during the earliest stages of mouse development, with protein levels significantly varying across stages and lowest at the 2-cell stage. When present, H2A.Z localizes preferentially to euchromatin at all stages analyzed. H2A.Z is acetylated in preimplantation blastomeres and is preferentially localized to euchromatin, in line with the known role of H2A.Zac in transcriptional activation. Interestingly, however, H2A.Zac is undetectable in mouse embryos at the 2-cell stage, the time of major embryonic genome activation (EGA). Similarly, H3K36me3 is present exclusively in the maternal chromatin immediately after fertilization but becomes undetectable in interphase nuclei at the 2-cell stage, suggesting uncoupling of these active marks with global embryonic transcription activation. In bovine embryos, which undergo EGA at the 8-cell stage, H2A.Zac can be detected in zygotes, 4-, 8- and 16-cell stage embryos as well as in blastocysts, indicating that the dynamics of H2A.Zac is not conserved in mammals. In contrast, H3K36me3 displays mostly undetectable and heterogeneous localization pattern throughout bovine pre-implantation development. Thus, our results suggest that ‘canonical’ active chromatin marks exhibit a dynamic behavior in embryonic nuclei, which is both stage- and speciesspecific. We hypothesize that chromatin of early embryonic nuclei is subject to fine-tuning through differential acquisition of histone marks, allowing for proper chromatin remodeling and developmental progression in a species-specific fashion.',
	'date' => '0000-00-00',
	'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/22647320',
	'doi' => '',
	'modified' => '2015-07-24 15:38:58',
	'created' => '2015-07-24 15:38:58',
	'ProductsPublication' => array(
		'id' => '953',
		'product_id' => '2172',
		'publication_id' => '783'
	)
)
$externalLink = ' <a href="http://www.ncbi.nlm.nih.gov/pubmed/22647320" target="_blank"><i class="fa fa-external-link"></i></a>'
include - APP/View/Products/view.ctp, line 755
View::_evaluate() - CORE/Cake/View/View.php, line 971
View::_render() - CORE/Cake/View/View.php, line 933
View::render() - CORE/Cake/View/View.php, line 473
Controller::render() - CORE/Cake/Controller/Controller.php, line 963
ProductsController::slug() - APP/Controller/ProductsController.php, line 1052
ReflectionMethod::invokeArgs() - [internal], line ??
Controller::invokeAction() - CORE/Cake/Controller/Controller.php, line 491
Dispatcher::_invoke() - CORE/Cake/Routing/Dispatcher.php, line 193
Dispatcher::dispatch() - CORE/Cake/Routing/Dispatcher.php, line 167
[main] - APP/webroot/index.php, line 118

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