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MicroPlex Library Preparation Kit v2 (12 indices)

Catalog Number

Format

Price

C05010012
(C05010010)

12 rxns

$1,215.00

ChIP-seq専用に最適化

MicroPlex Library Preparation™kit は、ChIP-seq専用に検証されていて、ピコグラム単位の入力だけで索引付きライブラリー調製できる唯一のキットです。 True MicroChIP kitと組み合わせることで、わずか10,000細胞でChIP-seqを行えます。細胞入力数、手順数、用品数が減少するだけでなく、結果までの時間も短縮できます！

TESTIMONIAL
We used the MicroPlex version 2 kit to generate libraries using ChIP DNA for several transcription factors and compared the results to a standard library generation protocol starting from 5ng of ChIP DNA. Even when we reduced the starting amount of DNA by 10-fold, the MicroPlex Kit produced the same high yields and quality of the libraries. As expected, the number of duplicate reads increased but 15 to 20 million unique reads were sufficient to achieve excellent enrichment data. We found that no information was lost, and the MicroPlex Kit helped produce data that was consistent with the standard protocol despite the lower input. On top of this, the MicroPlex Kit was extremely user-friendly and saved us time. The MicroPlex version 2 kit will make challenging ChIP-seq experiments that rely on very limited amount of starting material much easier with robust results.
Katia Basso, PhD, Assistant Professor, Columbia University, New York

特徴
- 1 tube, 2 hours, 3 steps protocol
- Input: 50 pg – 50 ng
- Reduce potential bias - few PCR amplification cycles needed
- High sensitivity ChIP-seq - low PCR duplication rate
- Great multiplexing flexibility with 12 barcodes (8 nt) included
- Validated with the IP-Star^® Automated Platform
How it works

Microplex workflow - protocol with single indexes
An input of 50 pg to 50 ng of fragmented dsDNA is converted into sequencing-ready libraries for Illumina® NGS platforms using a fast and simple 3-step protocol
- Read more about MicroPlex workflow
  
  Step 1. Template Preparation provides efficient repair of the fragmented double-stranded DNA input.
  
  In this step, the DNA is repaired and yields molecules with blunt ends.
  
  Step 2. Library Synthesis. enables ligation of MicroPlex patented stem- loop adapters.
  
  In the next step, stem-loop adaptors with blocked 5’ ends are ligated with high efficiency to the 5’ end of the genomic DNA, leaving a nick at the 3’ 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.
  
  Step 3. Library Amplification 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.
  
  In the final step, the 3’ 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.
  
  Obtained libraries are purified, quantified and sized. The libraries pooling can be performed as well before sequencing.
Reliable detection of enrichments in ChIP-seq

Figure A. 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^® Genome Analyzer. Cluster generation and sequencing were performed according to the manufacturer's instructions.

Figure B. 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.
お客様の声
We sheared the DNA on the Diagenode One and used the MicroPlex Library Preparation v2 Kit to create DNA libraries for whole genome sequencing of four plant species for which there is no reference genome available. Previous attempts with a commercial Tn5-transposase based method gave unsatisfactory results. However, the Diagenode MicroPlex kit was quicker, easier, and gave the expected profile of fragment sizes. In just 30 seconds of sonication, we obtained a fragment distribution centered at 270 bp. The library construction took only 2 hours with this kit. The library was sequenced in a NexSeq 550 in High-Output mode, giving 85% based with>Q30.
PhD. Ricardo Verdugo, Assistant Professor, University of Chile

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

There are so many ChIP-related products on the market, but I feel so lucky that I have been using the ones from Diagenode since I started my CHIP-seq project. I have used their iDeal CHIP-seq Kit for Transcription Factors and MicroPlex Library Prep Kit v2. Both of them are fantastic and very reproducible. With the very-well written protocols, you will just be home and dry. Particularly, I want to thank the technical support, who is very patient, knowledgeable and extremely helpful. I would definitely recommend my colleagues to use the CHIP products from Diagenode.
Dr Kaiyu Lei, Faculty of Medicine, Department of Surgery & Cancer, Imperial College London

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

The Diagenode MicroPlex kit is the quickest and most efficient way to make sequencing libraries, especially from samples with very low inputs. We regularly start with picogram amounts of ChIP material and produce excellent quality libraries that would be impossible to make using normal methods. Sequencing libraries made from the MicroPlex kit give us excellent results even in large genomes. The kit performs very well, and we will use the kit in the future for studies with low cell numbers or starting material.
Dr. Morgan Sammons, Lab of Dr. Shelley Berger, University of Pennsylvania

出版物

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Differentiation block in acute myeloid leukemia regulated by intronicsequences of FTO
Camera F. et al.
Iroquois transcription factor gene IRX3 is highly expressed in 20â€“30\% of acute myeloid leukemia (AML) and contributes to the pathognomonic differentiation block. Intron 8 FTO sequences âˆ¼220kB downstream of IRX3 exhibit histone acetylation, DNA methylation, and contacts with th...

Supraphysiological Androgens Promote the Tumor Suppressive Activity of the Androgen Receptor Through cMYC Repression and Recruitment of the DREAM Complex
Nyquist M. et al.
The androgen receptor (AR) pathway regulates key cell survival programs in prostate epithelium. The AR represents a near-universal driver and therapeutic vulnerability in metastatic prostate cancer, and targeting AR has a remarkable therapeutic index. Though most approaches directed toward AR focus on inhibiting AR ...

In skeletal muscle and neural crest cells, SMCHD1 regulates biologicalpathways relevant for Bosma syndrome and facioscapulohumeral dystrophyphenotype.
Laberthonnière C. et al.
Many genetic syndromes are linked to mutations in genes encoding factors that guide chromatin organization. Among them, several distinct rare genetic diseases are linked to mutations in SMCHD1 that encodes the structural maintenance of chromosomes flexible hinge domain containing 1 chromatin-associated factor. In hu...

Hypomethylation and overexpression of Th17-associated genes is ahallmark of intestinal CD4+ lymphocytes in Crohn's disease.
Sun Z. et al.
BACKGROUND: The development of Crohn's disease (CD) involves immune cell signaling pathways regulated by epigenetic modifications. Aberrant DNA methylation has been identified in peripheral blood and bulk intestinal tissue from CD patients. However, the DNA methylome of disease-associated intestinal CD4 + lymphocyte...

Mutant FUS induces chromatin reorganization in the hippocampus andalters memory processes.
Tzeplaeff L. et al.
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 mislocalizati...

Transient suppression of SUMOylation in embryonic stem cells generatesembryo-like structures.
Cossec J-C. et al.
Recent advances in synthetic embryology have opened new avenues for understanding the complex events controlling mammalian peri-implantation development. Here, we show that mouse embryonic stem cells (ESCs) solely exposed to chemical inhibition of SUMOylation generate embryo-like structures comprising anterior neura...

ZEB1 controls a lineage-specific transcriptional program essential formelanoma cell state transitions
Tang Y. et al.
Cell plasticity sustains intra-tumor heterogeneity and treatment resistance in melanoma. Deciphering the transcriptional mechanisms governing reversible phenotypic transitions between proliferative/differentiated and invasive/stem-like states is required in order to design novel therapeutic strategies. EMT-inducing ...

Gene Regulatory Interactions at Lamina-Associated Domains
Madsen-Østerbye J. et al.
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 regu...

Mechanisms and function of de novo DNA methylation in placentaldevelopment reveals an essential role for DNMT3B.
Andrews S. et al.
DNA methylation is a repressive epigenetic modification that is essential for development, exemplified by the embryonic and perinatal lethality observed in mice lacking de novo DNA methyltransferases (DNMTs). Here we characterise the role for DNMT3A, 3B and 3L in gene regulation and development of the mouse placenta...

TCDD induces multigenerational alterations in the expression ofmicroRNA in the thymus through epigenetic modifications
Singh Narendra P et al.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, is an environmental contaminant that is known for mediating toxicity across generations. However, whether TCDD can induce multigenerational changes in the expression of miRNAs (miRs) has not been previously studied. In the current study, we investigate...

The histone acetyltransferase KAT6A is recruited to unmethylatedCpG islands via a DNA binding winged helix domain.
Weber L.M. et al.
The lysine acetyltransferase KAT6A (MOZ, MYST3) belongs to the MYST family of chromatin regulators, facilitating histone acetylation. Dysregulation of KAT6A has been implicated in developmental syndromes and the onset of acute myeloid leukemia (AML). Previous work suggests that KAT6A is recruited to its genomic targ...

Polyglutamine-expanded ATXN7 alters a specific epigenetic signatureunderlying photoreceptor identity gene expression in SCA7 mouseretinopathy.
Niewiadomska-Cimicka A.et al.
BACKGROUND: Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder that primarily affects the cerebellum and retina. SCA7 is caused by a polyglutamine expansion in the ATXN7 protein, a subunit of the transcriptional coactivator SAGA that acetylates histone H3 to deposit narrow H3K9ac mark at DNA regula...

Intranasal administration of Acinetobacter lwoffii in a murine model ofasthma induces IL-6-mediated protection associated with cecal microbiotachanges.
Alashkar A. B. et al.
BACKGROUND: Early-life exposure to certain environmental bacteria including Acinetobacter lwoffii (AL) has been implicated in protection from chronic inflammatory diseases including asthma later in life. However, the underlying mechanisms at the immune-microbe interface remain largely unknown. METHODS: The effects o...

Identification of genomic binding sites and direct target genes for thetranscription factor DDIT3/CHOP.
Osman A. et al.
DDIT3 is a tightly regulated basic leucine zipper (bZIP) transcription factor and key regulator in cellular stress responses. It is involved in a variety of pathological conditions and may cause cell cycle block and apoptosis. It is also implicated in differentiation of some specialized cell types and as an oncogene...

Cryptococcal Hsf3 controls intramitochondrial ROS homeostasis byregulating the respiratory process.
Gao X.et al.
Mitochondrial quality control prevents accumulation of intramitochondrial-derived reactive oxygen species (mtROS), thereby protecting cells against DNA damage, genome instability, and programmed cell death. However, underlying mechanisms are incompletely understood, particularly in fungal species. Here, we show that...

Dominant role of DNA methylation over H3K9me3 for IAP silencingin endoderm.
Wang Z. et al.
Silencing of endogenous retroviruses (ERVs) is largely mediated by repressive chromatin modifications H3K9me3 and DNA methylation. On ERVs, these modifications are mainly deposited by the histone methyltransferase Setdb1 and by the maintenance DNA methyltransferase Dnmt1. Knock-out of either Setdb1 or Dnmt1 leads to...

HDAC1 and PRC2 mediate combinatorial control in SPI1/PU.1-dependentgene repression in murine erythroleukaemia.
Gregoricchio S. et al.
Although originally described as transcriptional activator, SPI1/PU.1, a major player in haematopoiesis whose alterations are associated with haematological malignancies, has the ability to repress transcription. Here, we investigated the mechanisms underlying gene repression in the erythroid lineage, in which SPI1 ...

Dual role of histone variant H3.3B in spermatogenesis: positiveregulation of piRNA transcription and implication in X-chromosomeinactivation.
Fontaine E. et al.
The histone variant H3.3 is encoded by two distinct genes, H3f3a and H3f3b, exhibiting identical amino-acid sequence. H3.3 is required for spermatogenesis, but the molecular mechanism of its spermatogenic function remains obscure. Here, we have studied the role of each one of H3.3A and H3.3B proteins in spermatogene...

TBX2 acts as a potent transcriptional silencer of tumour suppressor genesthrough interaction with the CoREST complex to sustain theproliferation of breast cancers.
McIntyre A.J. et al.
Chromosome 17q23 amplification occurs in 20\% of primary breast tumours and is associated with poor outcome. The TBX2 gene is located on 17q23 and is often over-expressed in this breast tumour subset. TBX2 is an anti-senescence gene, promoting cell growth and survival through repression of Tumour Suppressor Genes (T...

Caffeine intake exerts dual genome-wide effects on hippocampal metabolismand learning-dependent transcription.
Paiva I. et al.
Caffeine is the most widely consumed psychoactive substance in the world. Strikingly, the molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal omics techniq...

Epigenetic Mechanisms Mediating Cell State Transitions in Chondrocytes
Wuelling M. et al.
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 chon...

The CpG Island-Binding Protein SAMD1 Contributes to anUnfavorable Gene Signature in HepG2 Hepatocellular CarcinomaCells.
Simon C. et al.
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-...

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...

CREBBP/EP300 acetyltransferase inhibition disrupts FOXA1-bound enhancers to inhibit the proliferation of ER+ breast cancer cells.
Bommi-Reddy A. et al.
Therapeutic targeting of the estrogen receptor (ER) is a clinically validated approach for estrogen receptor positive breast cancer (ER+ BC), but sustained response is limited by acquired resistance. Targeting the transcriptional coactivators required for estrogen receptor activity represents an alternative approach...

NuA4 and H2A.Z control environmental responses and autotrophicgrowth in Arabidopsis
Bieluszewski T. et al.
Nucleosomal acetyltransferase of H4 (NuA4) is an essential transcriptional coactivator in eukaryotes, but remains poorly characterized in plants. Here, we describe Arabidopsis homologs of the NuA4 scaffold proteins Enhancer of Polycomb-Like 1 (AtEPL1) and Esa1-Associated Factor 1 (AtEAF1). Loss of AtEAF1 results in ...

Three classes of epigenomic regulators converge to hyperactivate theessential maternal gene deadhead within a heterochromatin mini-domain.
Torres-Campana D. et al.
The formation of a diploid zygote is a highly complex cellular process that is entirely controlled by maternal gene products stored in the egg cytoplasm. This highly specialized transcriptional program is tightly controlled at the chromatin level in the female germline. As an extreme case in point, the massive and s...

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...

Decreased PRC2 activity supports the survival of basal-like breastcancer cells to cytotoxic treatments
Mieczkowska IK et al.
Breast cancer (BC) is the most common cancer occurring in women but also rarely develops in men. Recent advances in early diagnosis and development of targeted therapies have greatly improved the survival rate of BC patients. However, the basal-like BC subtype (BLBC), largely overlapping with the triple-negative BC ...

Ago1 controls myogenic differentiation by regulating eRNA-mediatedCBP-guided epigenome reprogramming.
Fallatah Bodor et al.
The role of chromatin-associated RNAi components in the nucleus of mammalian cells and in particular in the context of developmental programs remains to be elucidated. Here, we investigate the function of nuclear Argonaute 1 (Ago1) in gene expression regulation during skeletal muscle differentiation. We show that Ag...

Extensive NEUROG3 occupancy in the human pancreatic endocrine generegulatory network.
Schreiber V. et al.
OBJECTIVE: Mice lacking the bHLH transcription factor (TF) Neurog3 do not form pancreatic islet cells, including insulin-secreting beta cells, the absence of which leads to diabetes. In humans, homozygous mutations of NEUROG3 manifest with neonatal or childhood diabetes. Despite this critical role in islet cell deve...

Alveolar macrophages from persons living with HIV show impairedepigenetic response to Mycobacterium tuberculosis.
Correa-Macedo Wilian et al.
Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV a...

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...

The related coactivator complexes SAGA and ATAC control embryonicstem cell self-renewal through acetyltransferase-independent mechanisms
Fischer Veronique et al.
SUMMARY SAGA (Spt-Ada-Gcn5 acetyltransferase) and ATAC (Ada-two-A-containing) are two related coactivator complexes, sharing the same histone acetyltransferase (HAT) subunit. The HAT activities of SAGA and ATAC are required for metazoan development, but the role of these complexes in RNA polymerase II transcription ...

Altered Chromatin States Drive Cryptic Transcription in AgingMammalian Stem Cells.
McCauley Brenna S et al.
A repressive chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation suppresses cryptic transcription in embryonic stem cells. Cryptic transcription is elevated with age in yeast and nematodes, and reducing it extends yeast lifespan, though whether this occurs in mammals is unk...

Metabolically controlled histone H4K5 acylation/acetylation ratiodrives BRD4 genomic distribution.
Gao M. et al.
In addition to acetylation, histones are modified by a series of competing longer-chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions hinder our understanding of histone acylations' specific roles. Here, by...

Heterogeneity of neurons reprogrammed from spinal cord astrocytes by theproneural factors Ascl1 and Neurogenin2
Kempf J. et al.
Summary Astrocytes are a viable source for generating new neurons via direct conversion. However, little is known about the neurogenic cascades triggered in astrocytes from different regions of the CNS. Here, we examine the transcriptome induced by the proneural factors Ascl1 and Neurog2 in spinal cord-derived astro...

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...

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...

Waves of sumoylation support transcription dynamics during adipocytedifferentiation
Zhao, X. et al.
Tight control of gene expression networks required for adipose tissue formation and plasticity is essential for adaptation to energy needs and environmental cues. However, little is known about the mechanisms that orchestrate the dramatic transcriptional changes leading to adipocyte differentiation. We investigated ...

Polycomb Repressive Complex 2 and KRYPTONITE regulate pathogen-inducedprogrammed cell death in Arabidopsis.
Dvořák Tomaštíková E. et al.
The Polycomb Repressive Complex 2 (PRC2) is well-known for its role in controlling developmental transitions by suppressing the premature expression of key developmental regulators. Previous work revealed that PRC2 also controls the onset of senescence, a form of developmental programmed cell death (PCD) in plants. ...

An integrated multi-omics analysis identifies prognostic molecularsubtypes of non-muscle-invasive bladder cancer
Lindskrog Sia Viborg et al.
The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, ...

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...

VPRBP functions downstream of the androgen receptor and OGT to restrict p53 activation in prostate cancer
Poulose N. et al.
Androgen receptor (AR) is a major driver of prostate cancer (PCa) initiation and progression. O-GlcNAc transferase (OGT), the enzyme that catalyses the covalent addition of UDP-N-acetylglucosamine (UDP-GlcNAc) to serine and threonine residues of proteins, is often up-regulated in PCa with its expression correlated w...

JAZF1, A Novel p400/TIP60/NuA4 Complex Member, Regulates H2A.ZAcetylation at Regulatory Regions.
Procida, Tara and Friedrich, Tobias and Jack, Antonia P M and Peritore,Martina and Bönisch, Clemens and Eberl, H Christian and Daus, Nadine andKletenkov, Konstantin and Nist, Andrea and Stiewe, Thorsten and Borggrefe,Tilman and Mann, Matthias and Bartk
Histone variants differ in amino acid sequence, expression timing and genomic localization sites from canonical histones and convey unique functions to eukaryotic cells. Their tightly controlled spatial and temporal deposition into specific chromatin regions is accomplished by dedicated chaperone and/or remodeling c...

Epigenetic impairment and blunted transcriptional response to Mycobacteriumtuberculosis of alveolar macrophages from persons living with HIV
Correa-Macedo, W. et al.
Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV a...

Histone demethylase JMJD2B/KDM4B regulates transcriptional program viadistinctive epigenetic targets and protein interactors for the maintenanceof trophoblast stem cells.
Mak, Kylie Hin-Man et al.
Trophoblast stem cell (TSC) is crucial to the formation of placenta in mammals. Histone demethylase JMJD2 (also known as KDM4) family proteins have been previously shown to support self-renewal and differentiation of stem cells. However, their roles in the context of the trophoblast lineage remain unclear. Here, we ...

Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture.
Yusufova, Nevin and Kloetgen, Andreas and Teater, Matt and Osunsade,Adewola and Camarillo, Jeannie M and Chin, Christopher R and Doane, AshleyS and Venters, Bryan J and Portillo-Ledesma, Stephanie and Conway, Josephand Phillip, Jude M and Elemento, Oli
Linker histone H1 proteins bind to nucleosomes and facilitate chromatin compaction, although their biological functions are poorly understood. Mutations in the genes that encode H1 isoforms B-E (H1B, H1C, H1D and H1E; also known as H1-5, H1-2, H1-3 and H1-4, respectively) are highly recurrent in B cell lymphoma...

Multi-omic comparison of Alzheimer's variants in human ESC-derivedmicroglia reveals convergence at APOE.
Liu, Tongfei and Zhu, Bing and Liu, Yan and Zhang, Xiaoming and Yin, Junand Li, Xiaoguang and Jiang, LuLin and Hodges, Andrew P and Rosenthal, SaraBrin and Zhou, Lisa and Yancey, Joel and McQuade, Amanda and Blurton-Jones,Mathew and Tanzi, Rudolph E an
Variations in many genes linked to sporadic Alzheimer's disease (AD) show abundant expression in microglia, but relationships among these genes remain largely elusive. Here, we establish isogenic human ESC-derived microglia-like cell lines (hMGLs) harboring AD variants in CD33, INPP5D, SORL1, and TREM2 loci and cura...

A genetic variant controls interferon-β gene expression in human myeloidcells by preventing C/EBP-β binding on a conserved enhancer.
Assouvie, Anaïs and Rotival, Maxime and Hamroune, Juliette and Busso,Didier and Romeo, Paul-Henri and Quintana-Murci, Lluis and Rousselet,Germain
Interferon β (IFN-β) is a cytokine that induces a global antiviral proteome, and regulates the adaptive immune response to infections and tumors. Its effects strongly depend on its level and timing of expression. Therefore, the transcription of its coding gene IFNB1 is strictly controlled. We have previous...

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...

Trans- and cis-acting effects of Firre on epigenetic features of theinactive X chromosome.
Fang, He and Bonora, Giancarlo and Lewandowski, Jordan P and Thakur,Jitendra and Filippova, Galina N and Henikoff, Steven and Shendure, Jay andDuan, Zhijun and Rinn, John L and Deng, Xinxian and Noble, William S andDisteche, Christine M
Firre encodes a lncRNA involved in nuclear organization. Here, we show that Firre RNA expressed from the active X chromosome maintains histone H3K27me3 enrichment on the inactive X chromosome (Xi) in somatic cells. This trans-acting effect involves SUZ12, reflecting interactions between Firre RNA and components of t...

The histone H2B ubiquitin ligase RNF40 is required for HER2-drivenmammary tumorigenesis.
Wegwitz, Florian and Prokakis, Evangelos and Pejkovska, Anastasija andKosinsky, Robyn Laura and Glatzel, Markus and Pantel, Klaus and Wikman,Harriet and Johnsen, Steven A
The HER2-positive breast cancer subtype (HER2-BC) displays a particularly aggressive behavior. Anti-HER2 therapies have significantly improved the survival of patients with HER2-BC. However, a large number of patients become refractory to current targeted therapies, necessitating the development of new treatment str...

Polycomb Repressive Complex 2-mediated histone modification H3K27me3 isassociated with embryogenic potential in Norway spruce.
Nakamura, Miyuki and Batista, Rita A and Köhler, Claudia and Hennig, Lars
Epigenetic reprogramming during germ cell formation is essential to gain pluripotency and thus embryogenic potential. The histone modification H3K27me3, which is catalysed by the Polycomb repressive complex 2 (PRC2), regulates important developmental processes in both plants and animals, and defects in PRC2 componen...

Age-associated cryptic transcription in mammalian stem cells is linked topermissive chromatin at cryptic promoters
McCauley B. S. et al.
Suppressing spurious cryptic transcription by a repressive intragenic chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation is critical for maintaining self-renewal capacity in mouse embryonic stem cells. In yeast and nematodes, such cryptic transcription is elevated with age...

RNF40 exerts stage-dependent functions in differentiating osteoblasts andis essential for bone cell crosstalk.
Najafova, Zeynab and Liu, Peng and Wegwitz, Florian and Ahmad, Mubashir andTamon, Liezel and Kosinsky, Robyn Laura and Xie, Wanhua and Johnsen, StevenA and Tuckermann, Jan
The role of histone ubiquitination in directing cell lineage specification is only poorly understood. Our previous work indicated a role of the histone 2B ubiquitin ligase RNF40 in controlling osteoblast differentiation in vitro. Here, we demonstrate that RNF40 has a stage-dependent function in controlling osteoblas...

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...

Combined treatment with CBP and BET inhibitors reverses inadvertentactivation of detrimental super enhancer programs in DIPG cells.
Wiese, M and Hamdan, FH and Kubiak, K and Diederichs, C and Gielen, GHand Nussbaumer, G and Carcaboso, AM and Hulleman, E and Johnsen, SA andKramm, CM
Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation. Hyperacetyla...

Exploring the virulence gene interactome with CRISPR/dCas9 in the humanmalaria parasite.
Bryant, JM and Baumgarten, S and Dingli, F and Loew, D and Sinha, A andClaës, A and Preiser, PR and Dedon, PC and Scherf, A
Mutually exclusive expression of the var multigene family is key to immune evasion and pathogenesis in Plasmodium falciparum, but few factors have been shown to play a direct role. We adapted a CRISPR-based proteomics approach to identify novel factors associated with var genes in their natural chromatin context. Ca...

Tissue-Specific In Vivo Biotin Chromatin Immunoprecipitation withSequencing in Zebrafish and Chicken
Lukoseviciute, Martyna and Ling, Irving T.C. and Senanayake, Upeka andCandido-Ferreira, Ivan and Taylor, Gunes and Williams, Ruth M. andSauka-Spengler, Tatjana
Chromatin immunoprecipitation with sequencing (ChIP-seq) has been instrumental in understanding transcription factor (TF) binding during gene regulation. ChIP-seq requires specific antibodies against desired TFs, which are not available for numerous species. Here, we describe a tissue-specific biotin ChIP-seq protoc...

The gut microbiome switches mutant p53 from tumour-suppressive tooncogenic.
Kadosh, E and Snir-Alkalay, I and Venkatachalam, A and May, S and Lasry, Aand Elyada, E and Zinger, A and Shaham, M and Vaalani, G and Mernberger, Mand Stiewe, T and Pikarsky, E and Oren, M and Ben-Neriah, Y
Somatic mutations in p53, which inactivate the tumour-suppressor function of p53 and often confer oncogenic gain-of-function properties, are very common in cancer. Here we studied the effects of hotspot gain-of-function mutations in Trp53 (the gene that encodes p53 in mice) in mouse models of WNT-driven intestinal c...

Egr2-guided histone H2B monoubiquitination is required for peripheral nervous system myelination.
Wüst HM, Wegener A, Fröb F, Hartwig AC, Wegwitz F, Kari V, Schimmel M, Tamm ER, Johnsen SA, Wegner M, Sock E
Schwann cells are the nerve ensheathing cells of the peripheral nervous system. Absence, loss and malfunction of Schwann cells or their myelin sheaths lead to peripheral neuropathies such as Charcot-Marie-Tooth disease in humans. During Schwann cell development and myelination chromatin is dramatically modified. How...

Battle of the sex chromosomes: competition between X- and Y-chromosomeencoded proteins for partner interaction and chromatin occupancy drivesmulti-copy gene expression and evolution in muroid rodents.
Moretti, C and Blanco, M and Ialy-Radio, C and Serrentino, ME and Gobé,C and Friedman, R and Battail, C and Leduc, M and Ward, MA and Vaiman, Dand Tores, F and Cocquet, J
Transmission distorters (TDs) are genetic elements that favor their own transmission to the detriments of others. Slx/Slxl1 (Sycp3-like-X-linked and Slx-like1) and Sly (Sycp3-like-Y-linked) are TDs which have been co-amplified on the X and Y chromosomes of Mus species. They are involved in an intragenomic conflict i...

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters hepatic polyunsaturated fatty acid metabolism and eicosanoid biosynthesis in female Sprague-Dawley rats.
Doskey CM, Fader KA, Nault R, Lydic T, Matthews J, Potter D, Sharratt B, Williams K, Zacharewski T
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent aryl hydrocarbon receptor (AhR) agonist that elicits a broad spectrum of dose-dependent hepatic effects including lipid accumulation, inflammation, and fibrosis. To determine the role of inflammatory lipid mediators in TCDD-mediated hepatotoxicity, eicosanoid me...

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...

Vulnerability of drug-resistant EML4-ALK rearranged lung cancer to transcriptional inhibition.
Paliouras AR, Buzzetti M, Shi L, Donaldson IJ, Magee P, Sahoo S, Leong HS, Fassan M, Carter M, Di Leva G, Krebs MG, Blackhall F, Lovly CM, Garofalo M
A subset of lung adenocarcinomas is driven by the EML4-ALK translocation. Even though ALK inhibitors in the clinic lead to excellent initial responses, acquired resistance to these inhibitors due to on-target mutations or parallel pathway alterations is a major clinical challenge. Exploring these mechanisms of resis...

Removal of H2Aub1 by ubiquitin-specific proteases 12 and 13 is required for stable Polycomb-mediated gene repression in Arabidopsis.
Kralemann LEM, Liu S, Trejo-Arellano MS, Muñoz-Viana R, Köhler C, Hennig L
BACKGROUND: Stable gene repression is essential for normal growth and development. Polycomb repressive complexes 1 and 2 (PRC1&2) are involved in this process by establishing monoubiquitination of histone 2A (H2Aub1) and subsequent trimethylation of lysine 27 of histone 3 (H3K27me3). Previous work proposed that ...

Delineating the early transcriptional specification of the mammalian trachea and esophagus.
Kuwahara A, Lewis AE, Coombes C, Leung FS, Percharde M, Bush JO
The genome-scale transcriptional programs that specify the mammalian trachea and esophagus are unknown. Though NKX2-1 and SOX2 are hypothesized to be co-repressive master regulators of tracheoesophageal fates, this is untested at a whole transcriptomic scale and their downstream networks remain unidentified. By comb...

Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response.
Béguelin W, Teater M, Meydan C, Hoehn KB, Phillip JM, Soshnev AA, Venturutti L, Rivas MA, Calvo-Fernández MT, Gutierrez J, Camarillo JM, Takata K, Tarte K, Kelleher NL, Steidl C, Mason CE, Elemento O, Allis CD, Kleinstein SH, Melnick AM
Follicular lymphomas (FLs) are slow-growing, indolent tumors containing extensive follicular dendritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations. Paradoxically, FLs originate from highly proliferative germinal center (GC) B cells with proliferation strictly dependent on interactions with T fo...

H2A.Z is dispensable for both basal and activated transcription inpost-mitotic mouse muscles.
Belotti E. et al.
While the histone variant H2A.Z is known to be required for mitosis, it is also enriched in nucleosomes surrounding the transcription start site of active promoters, implicating H2A.Z in transcription. However, evidence obtained so far mainly rely on correlational data generated in actively dividing cells. We have e...

Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes.
Crespo M, Damont A, Blanco M, Lastrucci E, Kennani SE, Ialy-Radio C, Khattabi LE, Terrier S, Louwagie M, Kieffer-Jaquinod S, Hesse AM, Bruley C, Chantalat S, Govin J, Fenaille F, Battail C, Cocquet J, Pflieger D
Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and ...

Anti-adipogenic signals at the onset of obesity-related inflammation in white adipose tissue.
Caputo T, Tran VDT, Bararpour N, Winkler C, Aguileta G, Trang KB, Giordano Attianese GMP, Wilson A, Thomas A, Pagni M, Guex N, Desvergne B, Gilardi F
Chronic inflammation that affects primarily metabolic organs, such as white adipose tissue (WAT), is considered as a major cause of human obesity-associated co-morbidities. However, the molecular mechanisms initiating this inflammation in WAT are poorly understood. By combining transcriptomics, ChIP-seq and modeling...

HDAC3 functions as a positive regulator in Notch signal transduction.
Ferrante F, Giaimo BD, Bartkuhn M, Zimmermann T, Close V, Mertens D, Nist A, Stiewe T, Meier-Soelch J, Kracht M, Just S, Klöble P, Oswald F, Borggrefe T
Aberrant Notch signaling plays a pivotal role in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL). Amplitude and duration of the Notch response is controlled by ubiquitin-dependent proteasomal degradation of the Notch1 intracellular domain (NICD1), a hallmark of the leukemogenic pro...

Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon.
Zambusi A, Pelin Burhan Ö, Di Giaimo R, Schmid B, Ninkovic J
Granulins (GRN) are secreted factors that promote neuronal survival and regulate inflammation in various pathological conditions. However, their roles in physiological conditions in the brain remain poorly understood. To address this knowledge gap, we analysed the telencephalon in Grn-deficient zebrafish and identif...

An inferred fitness consequence map of the rice genome.
Joly-Lopez Z, Platts AE, Gulko B, Choi JY, Groen SC, Zhong X, Siepel A, Purugganan MD
The extent to which sequence variation impacts plant fitness is poorly understood. High-resolution maps detailing the constraint acting on the genome, especially in regulatory sites, would be beneficial as functional annotation of noncoding sequences remains sparse. Here, we present a fitness consequence (fitCons) m...

Dual-initiation promoters with intertwined canonical and TCT/TOP transcription start sites diversify transcript processing.
Nepal C, Hadzhiev Y, Balwierz P, Tarifeño-Saldivia E, Cardenas R, Wragg JW, Suzuki AM, Carninci P, Peers B, Lenhard B, Andersen JB, Müller F
Variations in transcription start site (TSS) selection reflect diversity of preinitiation complexes and can impact on post-transcriptional RNA fates. Most metazoan polymerase II-transcribed genes carry canonical initiation with pyrimidine/purine (YR) dinucleotide, while translation machinery-associated genes carry p...

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...

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...

Combinatorial action of NF-Y and TALE at embryonic enhancers defines distinct gene expression programs during zygotic genome activation in zebrafish.
Stanney W, Ladam F, Donaldson IJ, Parsons TJ, Maehr R, Bobola N, Sagerström CG
Animal embryogenesis is initiated by maternal factors, but zygotic genome activation (ZGA) shifts regulatory control to the embryo during blastula stages. ZGA is thought to be mediated by maternally provided transcription factors (TFs), but few such TFs have been identified in vertebrates. Here we report that NF-Y a...

Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites.
Hammam E, Ananda G, Sinha A, Scheidig-Benatar C, Bohec M, Preiser PR, Dedon PC, Scherf A, Vembar SS
DNA cytosine modifications are key epigenetic regulators of cellular processes in mammalian cells, with their misregulation leading to varied disease states. In the human malaria parasite Plasmodium falciparum, a unicellular eukaryotic pathogen, little is known about the predominant cytosine modifications, cytosine ...

A stress-responsive enhancer induces dynamic drug resistance in acute myeloid leukemia.
Williams MS, Amaral FM, Simeoni F, Somervaille TC
The drug efflux pump ABCB1 is a key driver of chemoresistance, and high expression predicts for treatment failure in acute myeloid leukemia (AML). In this study, we identified and functionally validated the network of enhancers that controls expression of ABCB1. We show that exposure of leukemia cells to daunorubici...

Distinct CoREST complexes act in a cell-type-specific manner.
Mačinković I, Theofel I, Hundertmark T, Kovač K, Awe S, Lenz J, Forné I, Lamp B, Nist A, Imhof A, Stiewe T, Renkawitz-Pohl R, Rathke C, Brehm A
CoREST has been identified as a subunit of several protein complexes that generate transcriptionally repressive chromatin structures during development. However, a comprehensive analysis of the CoREST interactome has not been carried out. We use proteomic approaches to define the interactomes of two dCoREST isoforms...

Residual apoptotic activity of a tumorigenic p53 mutant improves cancer therapy responses.
Timofeev O, Klimovich B, Schneikert J, Wanzel M, Pavlakis E, Noll J, Mutlu S, Elmshäuser S, Nist A, Mernberger M, Lamp B, Wenig U, Brobeil A, Gattenlöhner S, Köhler K, Stiewe T
Engineered p53 mutant mice are valuable tools for delineating p53 functions in tumor suppression and cancer therapy. Here, we have introduced the R178E mutation into the Trp53 gene of mice to specifically ablate the cooperative nature of p53 DNA binding. Trp53 mice show no detectable target gene regulation and, at f...

EOMES interacts with RUNX3 and BRG1 to promote innate memory cell formation through epigenetic reprogramming.
Istaces N, Splittgerber M, Lima Silva V, Nguyen M, Thomas S, Le A, Achouri Y, Calonne E, Defrance M, Fuks F, Goriely S, Azouz A
Memory CD8 T cells have the ability to provide lifelong immunity against pathogens. Although memory features generally arise after challenge with a foreign antigen, naïve CD8 single positive (SP) thymocytes may acquire phenotypic and functional characteristics of memory cells in response to cytokines such as in...

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...

ARID1A facilitates KRAS signaling-regulated enhancer activity in an AP1-dependent manner in colorectal cancer cells.
Sen M, Wang X, Hamdan FH, Rapp J, Eggert J, Kosinsky RL, Wegwitz F, Kutschat AP, Younesi FS, Gaedcke J, Grade M, Hessmann E, Papantonis A, Strӧbel P, Johnsen SA
BACKGROUND: ARID1A (AT-rich interactive domain-containing protein 1A) is a subunit of the BAF chromatin remodeling complex and plays roles in transcriptional regulation and DNA damage response. Mutations in ARID1A that lead to inactivation or loss of expression are frequent and widespread across many cancer typ...

Guidelines for optimized gene knockout using CRISPR/Cas9
Campenhout CV et al.
CRISPR/Cas9 technology has evolved as the most powerful approach to generate genetic models both for fundamental and preclinical research. Despite its apparent simplicity, the outcome of a genome-editing experiment can be substantially impacted by technical parameters and biological considerations. Here, we present ...

BRCA1 mutations attenuate super-enhancer function and chromatin looping in haploinsufficient human breast epithelial cells.
Zhang X, Wang Y, Chiang HC, Hsieh YP, Lu C, Park BH, Jatoi I, Jin VX, Hu Y, Li R
BACKGROUND: BRCA1-associated breast cancer originates from luminal progenitor cells. BRCA1 functions in multiple biological processes, including double-strand break repair, replication stress suppression, transcriptional regulation, and chromatin reorganization. While non-malignant cells carrying cancer-predisposing...

Point mutations in the PDX1 transactivation domain impair human β-cell development and function.
Wang X, Sterr M, Ansarullah , Burtscher I, Böttcher A, Beckenbauer J, Siehler J, Meitinger T, Häring HU, Staiger H, Cernilogar FM, Schotta G, Irmler M, Beckers J, Wright CVE, Bakhti M, Lickert H
OBJECTIVE: Hundreds of missense mutations in the coding region of PDX1 exist; however, if these mutations predispose to diabetes mellitus is unknown. METHODS: In this study, we screened a large cohort of subjects with increased risk for diabetes and identified two subjects with impaired glucose tolerance carrying co...

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...

Transcriptome-wide dynamics of extensive m6A mRNA methylation during Plasmodium falciparum blood-stage development
Sebastian Baumgarten, Jessica M. Bryant, Ameya Sinha, Thibaud Reyser, Peter R. Preiser, Peter C. Dedon, Artur Scherf
Malaria pathogenesis results from the asexual replication of Plasmodium falciparum within human red blood cells, which relies on a precisely timed cascade of gene expression over a 48-hour life cycle. Although substantial post-transcriptional regulation of this hardwired program has been observed, it remains unclear...

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...

NF-κB p65 dimerization and DNA-binding is important for inflammatory gene expression.
Riedlinger T, Liefke R, Meier-Soelch J, Jurida L, Nist A, Stiewe T, Kracht M, Schmitz ML
Increasing evidence shows that many transcription factors execute important biologic functions independent from their DNA-binding capacity. The NF-κB p65 (RELA) subunit is a central regulator of innate immunity. Here, we investigated the relative functional contribution of p65 DNA-binding and dimerization in p...

Differential regulation of RNA polymerase III genes during liver regeneration.
Yeganeh M, Praz V, Carmeli C, Villeneuve D, Rib L, Guex N, Herr W, Delorenzi M, Hernandez N,
Mouse liver regeneration after partial hepatectomy involves cells in the remaining tissue synchronously entering the cell division cycle. We have used this system and H3K4me3, Pol II and Pol III profiling to characterize adaptations in Pol III transcription. Our results broadly define a class of genes close to H3K4m...

CBX7 Induces Self-Renewal of Human Normal and Malignant Hematopoietic Stem and Progenitor Cells by Canonical and Non-canonical Interactions.
Jung J, Buisman SC, Weersing E, Dethmers-Ausema A, Zwart E, Schepers H, Dekker MR, Lazare SS, Hammerl F, Skokova Y, Kooistra SM, Klauke K, Poot RA, Bystrykh LV, de Haan G
In this study, we demonstrate that, among all five CBX Polycomb proteins, only CBX7 possesses the ability to control self-renewal of human hematopoietic stem and progenitor cells (HSPCs). Xenotransplantation of CBX7-overexpressing HSPCs resulted in increased multi-lineage long-term engraftment and myelopoiesis. ...

Fluorescence-Activated Cell Sorting-Based Isolation and Characterization of Neural Stem Cells from the Adult Zebrafish Telencephalon.
Di Giaimo R, Aschenbroich S, Ninkovic J
Adult mammalian brain, including humans, has rather limited addition of new neurons and poor regenerative capacity. In contrast, neural stem cells (NSC) with glial identity and neurogenesis are highly abundant throughout the adult zebrafish brain. Importantly, the activation of NSC and production of new neurons in r...

DeltaNp63-dependent super enhancers define molecular identity in pancreatic cancer by an interconnected transcription factor network.
Hamdan FH, Johnsen SA
Molecular subtyping of cancer offers tremendous promise for the optimization of a precision oncology approach to anticancer therapy. Recent advances in pancreatic cancer research uncovered various molecular subtypes with tumors expressing a squamous/basal-like gene expression signature displaying a worse prognosis. ...

The Aryl Hydrocarbon Receptor Pathway Defines the Time Frame for Restorative Neurogenesis.
Di Giaimo R, Durovic T, Barquin P, Kociaj A, Lepko T, Aschenbroich S, Breunig CT, Irmler M, Cernilogar FM, Schotta G, Barbosa JS, Trümbach D, Baumgart EV, Neuner AM, Beckers J, Wurst W, Stricker SH, Ninkovic J
Zebrafish have a high capacity to replace lost neurons after brain injury. New neurons involved in repair are generated by a specific set of glial cells, known as ependymoglial cells. We analyze changes in the transcriptome of ependymoglial cells and their progeny after injury to infer the molecular pathways governi...

Genome-wide identification of RETINOBLASTOMA RELATED 1 binding sites in Arabidopsis reveals novel DNA damage regulators.
Bouyer D, Heese M, Chen P, Harashima H, Roudier F, Grüttner C, Schnittger A
Retinoblastoma (pRb) is a multifunctional regulator, which was likely present in the last common ancestor of all eukaryotes. The Arabidopsis pRb homolog RETINOBLASTOMA RELATED 1 (RBR1), similar to its animal counterparts, controls not only cell proliferation but is also implicated in developmental decisions, stress ...

SUMO Safeguards Somatic and Pluripotent Cell Identities by Enforcing Distinct Chromatin States
Cossec Jack-Christophe, Theurillat Ilan, Chica Claudia, Búa Aguín Sabela, Gaume Xavier, Andrieux Alexandra, Iturbide Ane, Jouvion Gregory, Li Han, Bossis Guillaume, Seeler Jacob-Sebastian, Torres-Padilla Maria-Elena, Dejean Anne
Understanding general principles that safeguard cellular identity should reveal critical insights into common mechanisms underlying specification of varied cell types. Here, we show that SUMO modification acts to stabilize cell fate in a variety of contexts. Hyposumoylation enhances pluripotency reprogramming in vit...

Caenorhabditis elegans sperm carry a histone-based epigenetic memory of both spermatogenesis and oogenesis.
Tabuchi TM, Rechtsteiner A, Jeffers TE, Egelhofer TA, Murphy CT, Strome S
Paternal contributions to epigenetic inheritance are not well understood. Paternal contributions via marked nucleosomes are particularly understudied, in part because sperm in some organisms replace the majority of nucleosome packaging with protamine packaging. Here we report that in Caenorhabditis elegans sperm, th...

PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex.
Link S, Spitzer RMM, Sana M, Torrado M, Völker-Albert MC, Keilhauer EC, Burgold T, Pünzeler S, Low JKK, Lindström I, Nist A, Regnard C, Stiewe T, Hendrich B, Imhof A, Mann M, Mackay JP, Bartkuhn M, Hake SB
Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and cranial-facial development. Here, using in vitro assays, we show that...

Convergent evolution of complex genomic rearrangements in two fungal meiotic drive elements.
Svedberg J, Hosseini S, Chen J, Vogan AA, Mozgova I, Hennig L, Manitchotpisit P, Abusharekh A, Hammond TM, Lascoux M, Johannesson H
Meiotic drive is widespread in nature. The conflict it generates is expected to be an important motor for evolutionary change and innovation. In this study, we investigated the genomic consequences of two large multi-gene meiotic drive elements, Sk-2 and Sk-3, found in the filamentous ascomycete Neurospora intermedi...

Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclones.
de Boer B, Prick J, Pruis MG, Keane P, Imperato MR, Jaques J, Brouwers-Vos AZ, Hogeling SM, Woolthuis CM, Nijk MT, Diepstra A, Wandinger S, Versele M, Attar RM, Cockerill PN, Huls G, Vellenga E, Mulder AB, Bonifer C, Schuringa JJ
Intra-tumor heterogeneity caused by clonal evolution is a major problem in cancer treatment. To address this problem, we performed label-free quantitative proteomics on primary acute myeloid leukemia (AML) samples. We identified 50 leukemia-enriched plasma membrane proteins enabling the prospective isolation of gene...

Genomic Location of PRMT6-Dependent H3R2 Methylation Is Linked to the Transcriptional Outcome of Associated Genes.
Bouchard C, Sahu P, Meixner M, Nötzold RR, Rust MB, Kremmer E, Feederle R, Hart-Smith G, Finkernagel F, Bartkuhn M, Savai Pullamsetti S, Nist A, Stiewe T, Philipsen S, Bauer UM
Protein arginine methyltransferase 6 (PRMT6) catalyzes asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a). This mark has been reported to associate with silent genes. Here, we use a cell model of neural differentiation, which upon PRMT6 knockout exhibits proliferation and differentiation defects. S...

Enhancer-driven transcriptional regulation is a potential key determinant for human visceral and subcutaneous adipocytes.
Liefke R, Bokelmann K, Ghadimi BM, Dango S
Obesity is characterized by the excess of body fat leading to impaired health. Abdominal fat is particularly harmful and is associated with cardiovascular and metabolic diseases and cancer. In contrast, subcutaneous fat is generally considered less detrimental. The mechanisms that establish the cellular characterist...

Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx.
Hensel KO, Cantner F, Bangert F, Wirth S, Postberg J
BACKGROUND: In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of cccDNA and HBx remains unexplored. RESULTS: To identify virus-host genome...

Genome-wide rules of nucleosome phasing
Sandro Baldi, Dhawal S. Jain1, Lisa Harpprecht1, Angelika Zabel1, Marion Scheibe, Falk Butter, Tobias Straub and Peter B. Becker
Regular successions of positioned nucleosomes – phased nucleosome arrays (PNAs) – are predominantly known from transcriptional start sites (TSS). It is unclear whether PNAs occur elsewhere in the genome. To generate a comprehensive inventory of PNAs for Drosophila, we applied spectral analysis to nucleos...

Insulin promoter in human pancreatic β cells contacts diabetes susceptibility loci and regulates genes affecting insulin metabolism.
Jian X, Felsenfeld G
Both type 1 and type 2 diabetes involve a complex interplay between genetic, epigenetic, and environmental factors. Our laboratory has been interested in the physical interactions, in nuclei of human pancreatic β cells, between the insulin ( gene and other genes that are involved in insulin metabolism. We have ...

Modulation of gene transcription and epigenetics of colon carcinoma cells by bacterial membrane vesicles.
Vdovikova S, Gilfillan S, Wang S, Dongre M, Wai SN, Hurtado A
Interactions between bacteria and colon cancer cells influence the transcription of the host cell. Yet is it undetermined whether the bacteria itself or the communication between the host and bacteria is responsible for the genomic changes in the eukaryotic cell. Now, we have investigated the genomic and epigenetic ...

Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI as a co-repressor for RUNX1.
Feld C, Sahu P, Frech M, Finkernagel F, Nist A, Stiewe T, Bauer UM, Neubauer A
SKI is a transcriptional co-regulator and overexpressed in various human tumors, for example in acute myeloid leukemia (AML). SKI contributes to the origin and maintenance of the leukemic phenotype. Here, we use ChIP-seq and RNA-seq analysis to identify the epigenetic alterations induced by SKI overexpression in AML...

A long range distal enhancer controls temporal fine-tuning of PAX6 expression in neuronal precursors.
Lacomme M, Medevielle F, Bourbon HM, Thierion E, Kleinjan DJ, Roussat M, Pituello F, Bel-Vialar S
Proper embryonic development relies on a tight control of spatial and temporal gene expression profiles in a highly regulated manner. One good example is the ON/OFF switching of the transcription factor PAX6 that governs important steps of neurogenesis. In the neural tube PAX6 expression is initiated in neural proge...

HDAC1 and HDAC2 Modulate TGF-β Signaling during Endothelial-to-Hematopoietic Transition.
Thambyrajah R, Fadlullah MZH, Proffitt M, Patel R, Cowley SM, Kouskoff V, Lacaud G
The first hematopoietic stem and progenitor cells are generated during development from hemogenic endothelium (HE) through trans-differentiation. The molecular mechanisms underlying this endothelial-to-hematopoietic transition (EHT) remain poorly understood. Here, we explored the role of the epigenetic regulators HD...

EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma.
Gorthi A, Romero JC, Loranc E, Cao L, Lawrence LA, Goodale E, Iniguez AB, Bernard X, Masamsetti VP, Roston S, Lawlor ER, Toretsky JA, Stegmaier K, Lessnick SL, Chen Y, Bishop AJR
Ewing sarcoma is an aggressive paediatric cancer of the bone and soft tissue. It results from a chromosomal translocation, predominantly t(11;22)(q24:q12), that fuses the N-terminal transactivation domain of the constitutively expressed EWSR1 protein with the C-terminal DNA binding domain of the rarely expressed FLI...

A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.
Zanghì G, Vembar SS, Baumgarten S, Ding S, Guizetti J, Bryant JM, Mattei D, Jensen ATR, Rénia L, Goh YS, Sauerwein R, Hermsen CC, Franetich JF, Bordessoulles M, Silvie O, Soulard V, Scatton O, Chen P, Mecheri S, Mazier D, Scherf A
Heterochromatin plays a central role in the process of immune evasion, pathogenesis, and transmission of the malaria parasite Plasmodium falciparum during blood stage infection. Here, we use ChIP sequencing to demonstrate that sporozoites from mosquito salivary glands expand heterochromatin at subtelomeric regions t...

Genome-wide analysis of PDX1 target genes in human pancreatic progenitors.
Wang X, Sterr M, Burtscher I, Chen S, Hieronimus A, Machicao F, Staiger H, Häring HU, Lederer G, Meitinger T, Cernilogar FM, Schotta G, Irmler M, Beckers J, Hrabě de Angelis M, Ray M, Wright CVE, Bakhti M, Lickert H
OBJECTIVE: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the function of Pdx1 is well studied in pre-clinical models during insuli...

A multi-omics study of the grapevine-downy mildew (Plasmopara viticola) pathosystem unveils a complex protein coding- and noncoding-based arms race during infection.
Brilli M, Asquini E, Moser M, Bianchedi PL, Perazzolli M, Si-Ammour A
Fungicides are applied intensively to prevent downy mildew infections of grapevines (Vitis vinifera) with high impact on the environment. In order to develop alternative strategies we sequenced the genome of the oomycete pathogen Plasmopara viticola causing this disease. We show that it derives from a Phytophthora-l...

BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis.
Kaufmann E, Sanz J, Dunn JL, Khan N, Mendonça LE, Pacis A, Tzelepis F, Pernet E, Dumaine A, Grenier JC, Mailhot-Léonard F, Ahmed E, Belle J, Besla R, Mazer B, King IL, Nijnik A, Robbins CS, Barreiro LB, Divangahi M
The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and location for generating such innate memory responses in vivo rem...

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...

Functional dissection of Drosophila melanogaster SUUR protein influence on H3K27me3 profile
Posukh O. V. et al.
Background In eukaryotes, heterochromatin replicates late in S phase of the cell cycle and contains specific covalent modifications of histones. SuUR mutation found in Drosophila makes heterochromatin replicate earlier than in wild type and reduces the level of repressive histone modifications. SUUR protein was s...

An endosiRNA-Based Repression Mechanism Counteracts Transposon Activation during Global DNA Demethylation in Embryonic Stem Cells
Berrens R.V. et al.
Erasure of DNA methylation and repressive chromatin marks in the mammalian germline leads to risk of transcriptional activation of transposable elements (TEs). Here, we used mouse embryonic stem cells (ESCs) to identify an endosiRNA-based mechanism involved in suppression of TE transcription. In ESCs with DNA demeth...

Epigenome profiling and editing of neocortical progenitor cells during development
Albert M. et al.
The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resoluti...

Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles
Marincevic-Zuniga Y. et al.
BACKGROUND: Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL). In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts. METHODS: We combined fusion gene detec...

Dynamics of RNA Polymerase II Pausing and Bivalent Histone H3 Methylation during Neuronal Differentiation in Brain Development
Liu J. et al.
During cellular differentiation, genes important for differentiation are expected to be silent in stem/progenitor cells yet can be readily activated. RNA polymerase II (Pol II) pausing and bivalent chromatin marks are two paradigms suited for establishing such a poised state of gene expression; however, their specif...

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...

Krox20 hindbrain regulation incorporates multiple modes of cooperation between cis-acting elements
Thierion E. et al.
Developmental genes can harbour multiple transcriptional enhancers that act simultaneously or in succession to achieve robust and precise spatiotemporal expression. However, the mechanisms underlying cooperation between cis-acting elements are poorly documented, notably in vertebrates. The mouse gene Krox20 encodes ...

Ectopic application of the repressive histone modification H3K9me2 establishes post-zygotic reproductive isolation in Arabidopsis thaliana
Jiang H. et al.
Hybrid seed lethality as a consequence of interspecies or interploidy hybridizations is a major mechanism of reproductive isolation in plants. This mechanism is manifested in the endosperm, a dosage-sensitive tissue supporting embryo growth. Deregulated expression of imprinted genes such as ADMETOS (ADM) underpin th...

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: Alterations in biosynthesis, enterohepatic circulation, and microbial metabolism.
Fader K. et al.
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant which elicits hepatotoxicity through activation of the aryl hydrocarbon receptor (AhR). Male C57BL/6 mice orally gavaged with TCDD (0.01-30 µg/kg) every 4 days for 28 days exhibited bile duct proliferation and perichola...

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...

CRISPR/Cas9 Genome Editing Reveals That the Intron Is Not Essential for var2csa Gene Activation or Silencing in Plasmodium falciparum
Bryant J.M. et al.
Plasmodium falciparum relies on monoallelic expression of 1 of 60 var virulence genes for antigenic variation and host immune evasion. Each var gene contains a conserved intron which has been implicated in previous studies in both activation and repression of transcription via several epigenetic mechanisms, includin...

Genome-wide mapping and analysis of aryl hydrocarbon receptor (AHR)- and aryl hydrocarbon receptor repressor (AHRR)-binding sites in human breast cancer cells
Sunny Y. Yang, Shaimaa Ahmed, Somisetty V. Satheesh, Jason Matthews
The aryl hydrocarbon receptor (AHR) mediates the toxic actions of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), and also plays roles in vascular development, the immune response, and cell cycle regulation. The AHR repressor (AHRR) is an AHR-regulated gene and a negative regulato...

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...

Characterization of the Polycomb-Group Mark H3K27me3 in Unicellular Algae
Mikulski P. et al.
Polycomb Group (PcG) proteins mediate chromatin repression in plants and animals by catalyzing H3K27 methylation and H2AK118/119 mono-ubiquitination through the activity of the Polycomb repressive complex 2 (PRC2) and PRC1, respectively. PcG proteins were extensively studied in higher plants, but their function and ...

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...

First landscape of binding to chromosomes for a domesticated mariner transposase in the human genome: diversity of genomic targets of SETMAR isoforms in two colorectal cell lines
Antoine-Lorquin A. et al.
Setmar is a 3-exons gene coding a SET domain fused to a Hsmar1 transposase. Its different transcripts theoretically encode 8 isoforms with SET moieties differently spliced. In vitro, the largest isoform binds specifically to Hsmar1 DNA ends and with no specificity to DNA when it is associated with hPso4. In colon ce...

Crebbp loss cooperates with Bcl2 over-expression to promote lymphoma in mice
Idoia García-Ramírez, Saber Tadros, Inés González-Herrero, Alberto Martín-Lorenzo, Guillermo Rodríguez-Hernández, Dalia Moore, Lucía Ruiz-Roca, Oscar Blanco, Diego Alonso-López, Javier De Las Rivas, Keenan Hartert, Romain Duval, David Klinkebiel, Martin B
CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits in B-cell development and can cooperate with Bcl2 over-expression to promote B-cell lymphoma. Through tra...

Aorta macrophage inflammatory and epigenetic changes in a murine model of obstructive sleep apnea: Potential role of CD36.
Cortese R. et al.
Obstructive sleep apnea (OSA) affects 8-10% of the population, is characterized by chronic intermittent hypoxia (CIH), and causally associates with cardiovascular morbidities. In CIH-exposed mice, closely mimicking the chronicity of human OSA, increased accumulation and proliferation of pro-inflammatory metabolic M1...

Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia
Chen S. et al.
Severe neonatal hyperbilirubinemia (SNH) and the onset of bilirubin encephalopathy and kernicterus result in part from delayed expression of UDP-glucuronosyltransferase 1A1 (UGT1A1) and the inability to metabolize bilirubin. Although there is a good understanding of the early events after birth that lead to the rapi...

The Drosophila speciation factor HMR localizes to genomic insulator sites
Gerland T.A. et al.
Hybrid incompatibility between Drosophila melanogaster and D. simulans is caused by a lethal interaction of the proteins encoded by the Hmr and Lhr genes. In D. melanogaster the loss of HMR results in mitotic defects, an increase in transcription of transposable elements and a deregulation of heterochromatic genes. ...

Applying the INTACT method to purify endosperm nuclei and to generate parental-specific epigenome profiles.
Moreno-Romero J. et al.
The early endosperm tissue of dicot species is very difficult to isolate by manual dissection. This protocol details how to apply the INTACT (isolation of nuclei tagged in specific cell types) system for isolating early endosperm nuclei of Arabidopsis at high purity and how to generate parental-specific epigenome pr...

BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire
Najafova Z. et al.
Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in pr...

CTCF modulates Estrogen Receptor function through specific chromatin and nuclear matrix interactions
Fiorito E. et al.
Enhancer regions and transcription start sites of estrogen-target regulated genes are connected by means of Estrogen Receptor long-range chromatin interactions. Yet, the complete molecular mechanisms controlling the transcriptional output of engaged enhancers and subsequent activation of coding genes remain elusive....

PionX sites mark the X chromosome for dosage compensation
Villa R et al.
The rules defining which small fraction of related DNA sequences can be selectively bound by a transcription factor are poorly understood. One of the most challenging tasks in DNA recognition is posed by dosage compensation systems that require the distinction between sex chromosomes and autosomes. In Drosophila mel...

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...

Deletion of Polycomb Repressive Complex 2 From Mouse Intestine Causes Loss of Stem Cells
Koppens MA et al.
BACKGROUND & AIMS: The polycomb repressive complex 2 (PRC2) regulates differentiation by contributing to repression of gene expression and thereby stabilizing the fate of stem cells and their progeny. PRC2 helps to maintain adult stem cell populations, but little is known about its functions in intestinal stem ...

Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells
von Meyenn F et al.
Global demethylation is part of a conserved program of epigenetic reprogramming to naive pluripotency. The transition from primed hypermethylated embryonic stem cells (ESCs) to naive hypomethylated ones (serum-to-2i) is a valuable model system for epigenetic reprogramming. We present a mathematical model, which accu...

Parental epigenetic asymmetry of PRC2-mediated histone modifications in the Arabidopsis endosperm
Moreno-Romero J et al.
Parental genomes in the endosperm are marked by differential DNA methylation and are therefore epigenetically distinct. This epigenetic asymmetry is established in the gametes and maintained after fertilization by unknown mechanisms. In this manuscript, we have addressed the key question whether parentally inherited...

関連商品
- C01010132
  
  True MicroChIP kit
- C01010055
  
  iDeal ChIP-seq kit for Transcription Factors

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			'name' => 'MicroPlex Library Preparation Kit v2 (12 indices)',
			'description' => '<p><strong>ChIP-seq</strong><strong>専用に最適化</strong></p>
<p>MicroPlex Library Preparation&trade;kit は、ChIP-seq専用に検証されていて、ピコグラム単位の入力だけで索引付きライブラリー調製できる唯一のキットです。 <span><a href="http://www.diagenode.com/en/catalog/chromatin-function-74/chromatin-immunoprecipitation-75/manual-chip-kits-77/product/true-microchip-kit-x16-2532">True MicroChIP kit</a></span>と組み合わせることで、わずか10,000細胞でChIP-seqを行えます。細胞入力数、手順数、用品数が減少するだけでなく、結果までの時間も短縮できます！</p>',
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<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>
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<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>',
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<p>MicroPlex Library Preparation&trade;kit は、ChIP-seq専用に検証されていて、ピコグラム単位の入力だけで索引付きライブラリー調製できる唯一のキットです。 <span><a href="http://www.diagenode.com/en/catalog/chromatin-function-74/chromatin-immunoprecipitation-75/manual-chip-kits-77/product/true-microchip-kit-x16-2532">True MicroChIP kit</a></span>と組み合わせることで、わずか10,000細胞でChIP-seqを行えます。細胞入力数、手順数、用品数が減少するだけでなく、結果までの時間も短縮できます！</p>',
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<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>
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<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>
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<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>',
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<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>',
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<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>',
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<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>
<p>
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</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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			'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',
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			'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',
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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]
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			'Image' => array(
				[maximum depth reached]
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		)
	),
	'Application' => array(
		(int) 0 => array(
			'id' => '14',
			'position' => '10',
			'parent_id' => '3',
			'name' => 'DNA/RNA library preparation',
			'description' => '<div class="row">
<div class="small-12 medium-12 large-12 columns">
<p><span style="font-weight: 400;">Most of the major next-generation sequencing platforms require ligation of specific adaptor oligos to </span><a href="../applications/dna-rna-shearing"><span style="font-weight: 400;">fragmented DNA or RNA</span></a><span style="font-weight: 400;"> prior to sequencing</span></p>
<p><span style="font-weight: 400;">After input DNA has been fragmented, it is end-repaired and blunt-ended</span><span style="font-weight: 400;">. The next step is a A-tailing in which dAMP is added to the 3&acute; end of the blunt phosphorylated DNA fragments to prevent concatemerization and to allow the ligation of adaptors with complementary dT overhangs. In addition, barcoded adapters can be incorporated to facilitate multiplexing prior to or during amplification.</span></p>
<center><img src="https://www.diagenode.com/img/categories/library-prep/flux.png" /></center>
<p><span style="font-weight: 400;">Diagenode offers a comprehensive product portfolio for library preparation:<br /></span></p>
<strong><a href="https://www.diagenode.com/en/categories/Library-preparation-for-RNA-seq">D-Plex&nbsp;RNA-seq Library Preparation Kits</a></strong><br />
<p><span style="font-weight: 400;">Diagenode&rsquo;s new RNA-sequencing solutions utilize the innovative c</span><span style="font-weight: 400;">apture and a</span><span style="font-weight: 400;">mplification by t</span><span style="font-weight: 400;">ailing and s</span><span style="font-weight: 400;">witching&rdquo;</span><span style="font-weight: 400;">, a ligation-free method to produce DNA libraries for next generation sequencing from low input amounts of RNA. </span><span style="font-weight: 400;"></span><a href="../categories/Library-preparation-for-RNA-seq">Learn more</a></p>
<strong><a href="../categories/library-preparation-for-ChIP-seq">ChIP-seq and DNA sequencing library preparation solutions</a></strong><br />
<p><span style="font-weight: 400;">Our kits have been optimized for DNA library preparation used for next generation sequencing for a wide range of inputs. Using a simple three-step protocols, our</span><a href="http://www.diagenode.com/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns"><span style="font-weight: 400;"> </span></a><span style="font-weight: 400;">kits are an optimal choice for library preparation from DNA inputs down to 50 pg.&nbsp;</span><a href="../categories/library-preparation-for-ChIP-seq">Learn more</a></p>
<a href="../p/bioruptor-pico-sonication-device"><span style="font-weight: 400;"></span><strong>Bioruptor Pico - short fragments</strong></a><a href="../categories/library-preparation-for-ChIP-seq-and-DNA-sequencing"><span style="font-weight: 400;"></span></a><br />
<p><span style="font-weight: 400;"></span><span style="font-weight: 400;">Our well-cited Bioruptor Pico is the shearing device of choice for chromatin and DNA fragmentation. Obtain uniform and tight fragment distributions &nbsp;between 150bp -2kb. </span><a href="../p/bioruptor-pico-sonication-device">Learn more</a></p>
<strong><a href="../p/megaruptor2-1-unit"><span href="../p/bioruptor-pico-sonication-device">Megaruptor</span>&reg; - long fragments</a></strong><a href="../p/bioruptor-pico-sonication-device"><span style="font-weight: 400;"></span></a><a href="../categories/library-preparation-for-ChIP-seq-and-DNA-sequencing"><span style="font-weight: 400;"></span></a><br />
<p><span style="font-weight: 400;"></span><span style="font-weight: 400;">The Megaruptor is designed to shear DNA from 3kb-75kb for long-read sequencing.&nbsp; <a href="../p/megaruptor2-1-unit">Learn more</a></span></p>
<span href="../p/bioruptor-pico-sonication-device"></span><span style="font-weight: 400;"></span></div>
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			'meta_title' => 'Library preparation for Next Generation Sequencing (NGS) | Diagenode',
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			'name' => '次世代シーケンシング',
			'description' => '<div class="row">
<div class="small-12 medium-12 large-12 columns">
<h2 style="font-size: 22px;">DNA断片化、ライブラリー調製、自動化：NGSのワンストップショップ</h2>
<table class="small-12 medium-12 large-12 columns">
<tbody>
<tr>
<th class="small-12 medium-12 large-12 columns">
<h4>1. 断片化装置を選択してください：150 bp〜75 kbの範囲でDNAを断片化します。</h4>
</th>
</tr>
<tr style="background-color: #ffffff;">
<td class="small-12 medium-12 large-12 columns"></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns"><a href="../p/bioruptor-pico-sonication-device"><img src="https://www.diagenode.com/img/product/shearing_technologies/bioruptor_pico.jpg" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/megaruptor2-1-unit"><img src="https://www.diagenode.com/img/product/shearing_technologies/B06010001_megaruptor2.jpg" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/bioruptor-one-sonication-device"><img src="https://www.diagenode.com/img/product/shearing_technologies/br-one-profil.png" /></a></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns">5&mu;lまで断片化：150 bp〜2 kb<br />NGS DNAライブラリー調製およびFFPE核酸抽出に最適で、</td>
<td class="small-4 medium-4 large-4 columns">2 kb〜75 kbの範囲をできます。<br />メイトペアライブラリー調製および長いフラグメントDNAシーケンシングに最適で、この軽量デスクトップデバイスで</td>
<td class="small-4 medium-4 large-4 columns">20または50&mu;lの断片化が可能です。</td>
</tr>
</tbody>
</table>
<table class="small-12 medium-12 large-12 columns">
<tbody>
<tr>
<th class="small-8 medium-8 large-8 columns">
<h4>2. 最適化されたライブラリー調整キットを選択してください。</h4>
</th>
<th class="small-4 medium-4 large-4 columns">
<h4>3. ライブラリー前処理自動化を選択して、比類のないデータ再現性を実感</h4>
</th>
</tr>
<tr style="background-color: #ffffff;">
<td class="small-12 medium-12 large-12 columns"></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns"><a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns"><img src="https://www.diagenode.com/img/product/kits/microPlex_library_preparation.png" style="display: block; margin-left: auto; margin-right: auto;" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns"><img src="https://www.diagenode.com/img/product/kits/box_kit.jpg" style="display: block; margin-left: auto; margin-right: auto;" height="173" width="250" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/sx-8g-ip-star-compact-automated-system-1-unit"><img src="https://www.diagenode.com/img/product/automation/B03000002%20_ipstar_compact.png" style="display: block; margin-left: auto; margin-right: auto;" /></a></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns" style="text-align: center;">50pgの低入力：MicroPlex Library Preparation Kit</td>
<td class="small-4 medium-4 large-4 columns" style="text-align: center;">5ng以上：iDeal&nbsp;Library Preparation Kit</td>
<td class="small-4 medium-4 large-4 columns" style="text-align: center;">Achieve great NGS data easily</td>
</tr>
</tbody>
</table>
</div>
</div>
<blockquote>
<div class="row">
<div class="small-12 medium-12 large-12 columns"><span class="label" style="margin-bottom: 16px; margin-left: -22px; font-size: 15px;">DiagenodeがNGS研究にぴったりなプロバイダーである理由</span>
<p>Diagenodeは15年以上もエピジェネティクス研究に専念、専門としています。 ChIP研究クロマチン用のユニークな断片化システムの開発から始まり、 専門知識を活かし、5&mu;lのせん断体積まで可能で、NGS DNAライブラリーの調製に最適な最先端DNA断片化装置の開発にたどり着きました。 我々は以来、ChIP-seq、Methyl-seq、NGSライブラリー調製用キットを研究開発し、業界をリードする免疫沈降研究と同様に、ライブラリー調製を自動化および完結させる独自の自動化システムを開発にも成功しました。</p>
<ul>
<li>信頼されるせん断装置</li>
<li>様々なインプットからのライブラリ作成キット</li>
<li>独自の自動化デバイス</li>
</ul>
</div>
</div>
</blockquote>
<div class="row">
<div class="small-12 columns">
<ul class="accordion" data-accordion="">
<li class="accordion-navigation"><a href="#panel1a">次世代シーケンシングへの理解とその専門知識</a>
<div id="panel1a" class="content">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<p><strong>次世代シーケンシング (NGS)</strong> ）は、著しいスケールとハイスループットでシーケンシングを行い、1日に数十億もの塩基生成を可能にします。 NGSのハイスループットは迅速でありながら正確で、再現性のあるデータセットを実現し、さらにシーケンシング費用を削減します。 NGSは、ゲノムシーケンシング、ゲノム再シーケンシング、デノボシーケンシング、トランスクリプトームシーケンシング、その他にDNA-タンパク質相互作用の検出やエピゲノムなどを示します。 指数関数的に増加するシーケンシングデータの需要は、計算分析の障害や解釈、データストレージなどの課題を解決します。</p>
<p>アプリケーションおよび出発物質に応じて、数百万から数十億の鋳型DNA分子を大規模に並行してシーケンシングすることが可能です。その為に、異なる化学物質を使用するいくつかの市販のNGSプラットフォームを利用することができます。 NGSプラットフォームの種類によっては、事前準備とライブラリー作成が必要です。</p>
<p>NGSにとっても、特にデータ処理と分析に関した大きな課題はあります。第3世代技術はゲノミクス研究にさらに革命を起こすであろうと大きく期待されています。</p>
</div>
</div>
<div class="row">
<div class="small-6 medium-6 large-6 columns">
<p><strong>NGS アプリケーション</strong></p>
<ul>
<li>全ゲノム配列決定</li>
<li>デノボシーケンシング</li>
<li>標的配列</li>
<li>Exomeシーケンシング</li>
<li>トランスクリプトーム配列決定</li>
<li>ゲノム配列決定</li>
<li>ミトコンドリア配列決定</li>
<li>DNA-タンパク質相互作用（ChIP-seq</li>
<li>バリアント検出</li>
<li>ゲノム仕上げ</li>
</ul>
</div>
<div class="small-6 medium-6 large-6 columns">
<p><strong>研究分野におけるNGS:</strong></p>
<ul>
<li>腫瘍学</li>
<li>リプロダクティブ・ヘルス</li>
<li>法医学ゲノミクス</li>
<li>アグリゲノミックス</li>
<li>複雑な病気</li>
<li>微生物ゲノミクス</li>
<li>食品・環境ゲノミクス</li>
<li>創薬ゲノミクス - パーソナライズド・メディカル</li>
</ul>
</div>
<div class="small-12 medium-12 large-12 columns">
<p><strong>NGSの用語</strong></p>
<dl>
<dt>リード（読み取り）</dt>
<dd>この装置から得られた連続した単一のストレッチ</dd>
<dt>断片リード</dt>
<dd>フラグメントライブラリからの読み込み。 シーケンシングプラットフォームに応じて、読み取りは通常約100〜300bp。</dd>
<dt>断片ペアエンドリード</dt>
<dd>断片ライブラリーからDNA断片の各末端2つの読み取り。</dd>
<dt>メイトペアリード</dt>
<dd>大きなDNA断片（通常は予め定義されたサイズ範囲）の各末端から2つの読み取り。</dd>
<dt>カバレッジ（例）</dt>
<dd>30&times;適用範囲とは、参照ゲノム中の各塩基対が平均30回の読み取りを示す。</dd>
</dl>
</div>
</div>
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<h2>NGSプラットフォーム</h2>
<h3><a href="http://www.illumina.com" target="_blank">イルミナ</a></h3>
<p>イルミナは、クローン的に増幅された鋳型DNA（クラスター）上に位置する、蛍光標識された可逆的鎖ターミネーターヌクレオチドを用いた配列別合成技術を使用。 DNAクラスターは、ガラスフローセルの表面上に固定化され、 ワークフローは、4つのヌクレオチド（それぞれ異なる蛍光色素で標識された）の組み込み、4色イメージング、色素や末端基の切断、取り込み、イメージングなどを繰り返します。フローセルは大規模な並列配列決定を受ける。 この方法により、単一蛍光標識されたヌクレオチドの制御添加によるモノヌクレオチドのエラーを回避する可能性があります。 読み取りの長さは、通常約100〜150 bpです。</p>
<h3><a href="http://www.lifetechnologies.com" target="_blank">イオン トレント</a></h3>
<p>イオントレントは、半導体技術チップを用いて、合成中にヌクレオチドを取り込む際に放出されたプロトンを検出します。 これは、イオン球粒子と呼ばれるビーズの表面にエマルションPCR（emPCR）を使用し、リンクされた特定のアダプターを用いてDNA断片を増幅します。 各ビーズは1種類のDNA断片で覆われていて、異なるDNA断片を有するビーズは次いで、チップの陽子感知ウェル内に配置されます。 チップには一度に4つのヌクレオチドのうちの1つが浸水し、このプロセスは異なるヌクレオチドで15秒ごとに繰り返されます。 配列決定の間に4つの塩基の各々が1つずつ導入されます、組み込みの場合はプロトンが放出され、電圧信号が取り込みに比例して検出されます。.</p>
<h3><a href="http://www.pacificbiosciences.com" target="_blank">パシフィック バイオサイエンス</a></h3>
<p>パシフィックバイオサイエンスでは、20kbを超える塩基対の読み取りも、単一分子リアルタイム（SMRT）シーケンシングによる構造および細胞タイプの変化を観察することができます。 このプラットフォームでは、超長鎖二本鎖DNA（dsDNA）断片が、Megaruptor（登録商標）のようなDiagenode装置を用いたランダムシアリングまたは目的の標的領域の増幅によって生成されます。 SMRTbellライブラリーは、ユニバーサルヘアピンアダプターをDNA断片の各末端に連結することによって生成します。 サイズ選択条件による洗浄ステップの後、配列決定プライマーをSMRTbellテンプレートにアニーリングし、鋳型DNAに結合したDNAポリメラーゼを含む配列決定を、蛍光標識ヌクレオチドの存在下で開始。 各塩基が取り込まれると、異なる蛍光のパルスをリアルタイムで検出します。</p>
<h3><a href="https://nanoporetech.com" target="_blank">オックスフォード ナノポア</a></h3>
<p>Oxford Nanoporeは、単一のDNA分子配列決定に基づく技術を開発します。その技術により生物学的分子、すなわちDNAが一群の電気抵抗性高分子膜として位置するナノスケールの孔（ナノ細孔）またはその近くを通過し、イオン電流が変化します。 この変化に関する情報は、例えば4つのヌクレオチド（AまたはG r CまたはT）ならびに修飾されたヌクレオチドすべてを区別することによって分子情報に訳されます。 シーケンシングミニオンデバイスのフローセルは、数百個のナノポアチャネルのセンサアレイを含みます。 DNAサンプルは、Diagenode社のMegaruptor（登録商標）を用いてランダムシアリングによって生成され得る超長鎖DNAフラグメントが必要です。</p>
<h3><a href="http://www.lifetechnologies.com/be/en/home/life-science/sequencing/next-generation-sequencing/solid-next-generation-sequencing.html" target="_blank">SOLiD</a></h3>
<p>SOLiDは、ユニークな化学作用により、何千という個々のDNA分子の同時配列決定を可能にします。 それは、アダプター対ライブラリーのフラグメントが適切で、せん断されたゲノムDNAへのアダプターのライゲーションによるライブラリー作製から始まります。 次のステップでは、エマルジョンPCR（emPCR）を実施して、ビーズの表面上の個々の鋳型DNA分子をクローン的に増幅。 emPCRでは、個々の鋳型DNAをPCR試薬と混合し、水中油型エマルジョン内の疎水性シェルで囲まれた水性液滴内のプライマーコートビーズを、配列決定のためにロードするスライドガラスの表面にランダムに付着。 この技術は、シークエンシングプライマーへのライゲーションで競合する4つの蛍光標識されたジ塩基プローブのセットを使用します。</p>
<h3><a href="http://454.com/products/technology.asp" target="_blank">454</a></h3>
<p>454は、大規模並列パイロシーケンシングを利用しています。 始めに全ゲノムDNAまたは標的遺伝子断片の300〜800bp断片のライブラリー調製します。 次に、DNAフラグメントへのアダプターの付着および単一のDNA鎖の分離。 その後アダプターに連結されたDNAフラグメントをエマルジョンベースのクローン増幅（emPCR）で処理し、DNAライブラリーフラグメントをミクロンサイズのビーズ上に配置します。 各DNA結合ビーズを光ファイバーチップ上のウェルに入れ、器具に挿入します。 4つのDNAヌクレオチドは、配列決定操作中に固定された順序で連続して加えられ、並行して配列決定されます。</p>
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</div>
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			'meta_description' => 'Diagenode offers kits and DNA/RNA shearing technology prior to next-generation sequencing, many Next-generation sequencing platforms require preparation of the DNA.',
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			'description' => '<div class="row">
<div class="large-12 columns text-justify">
<p>Library preparation following ChIP can be challenging due to the limited amount of DNA recovered after ChIP. Diagenode has developed the optimal solutions for ChIP-seq using two different approaches: the ligation-based library preparation on purified DNA or the tagmentation-based ChIPmentation.</p>
</div>
</div>
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<li><a href="#panel1" class="tips portal button">Ligation-based library prep</a></li>
<li><a href="#panel2" class="tips portal button">ChIPmentation</a></li>
<li><a href="#panel3" class="tips portal button">Kit choice guide</a></li>
<li><a href="#panel4" class="tips portal button">Resources</a></li>
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<li class="accordion-navigation"><a href="#v5" style="color: #13b29c;"><i class="fa fa-caret-right"></i> Standard input library prep</a>
<div id="v5" class="content">
<div class="small-12 medium-12 large-12 columns">
<p>The <strong>iDeal Library Preparation Kit</strong> reliably converts DNA into indexed libraries for next-generation sequencing, with input amounts down to <strong>5 ng</strong>. Our kit offers a simple and fast workflow, high yields, and ready-to-sequence DNA on the Illumina platform.</p>
<div class="extra-spaced">
<h2>Features</h2>
<ul class="nobullet">
<li><i class="fa fa-arrow-circle-right"></i> <strong>Sample</strong>: Fragmented dsDNA</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Input</strong>: 5 ng &ndash; 1 &micro;g</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Fast protocol</strong>: 3 hours</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Easy processing</strong>: 3 steps</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Indexing</strong>: single indexes for multiplexing up to 24 samples</li>
<li><i class="fa fa-arrow-circle-right"></i> Manual and automated protocols available</li>
<li><i class="fa fa-arrow-circle-right"></i> Sequencing technology: Illumina</li>
</ul>
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<div class="extra-spaced">
<h2>Applications</h2>
<ul class="square">
<li>MeDIP-seq library prep</li>
<li>Genomic DNA sequencing</li>
<li>High input ChIP-seq</li>
</ul>
</div>
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<tr>
<td class="catalog_number"><span class="success label">C05010020</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns" style="color: #b21329;" target="_blank">iDeal Library Preparation Kit x24 (incl. Index Primer Set 1)</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010021</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/ideal-library-index-primer-set-2-24-rxns" style="color: #b21329;" target="_blank">Index Primer Set 2 (iDeal Lib. Prep Kit x24)</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/ideal-library-index-primer-set-2-24-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
</tbody>
</table>
</div>
</div>
</div>
</li>
</ul>
<ul class="accordion" data-accordion="">
<li class="accordion-navigation"><a href="#v4" style="color: #13b29c;"><i class="fa fa-caret-right"></i> Low input library prep</a>
<div id="v4" class="content active"><center><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" target="_blank"><img src="https://www.diagenode.com/img/banners/banner-microplex-v3-580.jpg" class="extra-spaced" /></a></center>
<div align="center"><a href="https://www.diagenode.com/pages/form-microplex3" class="center alert radius button extra-spaced"><i class="fa fa-info"></i> Contact us</a></div>
<div class="extra-spaced">
<p>Diagenode&rsquo;s <strong>MicroPlex Library Preparation kits</strong> have been extensively validated for ChIP-seq samples. Generated libraries are compatible with single-end or paired-end sequencing. MicroPlex chemistry (using stem-loop adapters ) is specifically developed and optimized to generate DNA libraries with high molecular complexity from the lowest input amounts. Only <strong>50 pg to 50 ng</strong> of fragmented double-stranded DNA is required for library preparation. The entire <strong>three-step workflow</strong> takes place in a <strong>single tube</strong> or well in about <strong>2 hours</strong>. No intermediate purification steps and no sample transfers are necessary to prevent handling errors and loss of valuable samples.</p>
</div>
<div class="extra-spaced">
<h2>Features</h2>
<ul class="nobullet">
<li><i class="fa fa-arrow-circle-right"></i> <strong>Sample</strong>: Fragmented dsDNA</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Low input</strong>: 50 pg &ndash; 50 ng</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Fast protocol</strong>: 2 hours</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Easy processing</strong>: 3 steps in 1 tube</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>No intermediate purification</strong></li>
<li><i class="fa fa-arrow-circle-right"></i> Sequencing technology: Illumina</li>
<li><i class="fa fa-arrow-circle-right"></i> Manual and automated protocols available</li>
</ul>
</div>
<div class="extra-spaced">
<h2>Applications</h2>
<ul class="square">
<li>ChIP-seq library prep from ChIP-derived DNA</li>
<li>Low input DNA sequencing</li>
</ul>
</div>
<h2>Two versions are available:</h2>
<ul class="accordion" data-accordion="">
<li class="accordion-navigation"><a href="#v2" style="color: #13b29c;"><i class="fa fa-caret-right"></i> MicroPlex Library Preparation Kit v2 with single indexes</a>
<div id="v2" class="content">
<p>The MicroPlex Library Preparation Kit v2 contains all necessary reagents including single indexes for multiplexing up to 48 samples using single barcoding.</p>
<h4>KITS</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C05010012</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns" style="color: #b21329;" target="_blank">MicroPlex Library Preparation Kit v2 (12 indexes)</a></td>
<td class="format">12 rxns</td>
<td><a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
</tbody>
</table>
</div>
</li>
<li class="accordion-navigation"><a href="#v3" style="color: #13b29c;"><i class="fa fa-caret-right"></i> MicroPlex Library Preparation Kit v3 with dual indexes &nbsp;&nbsp;<strong><span class="diacol">NEW!</span></strong></a>
<div id="v3" class="content active">
<p>In this version the library preparation reagents and the dual indexes are available separately allowing for the flexibility choosing the number of indexes. MicroPlex v3 has multiplexing capacities up to 384 samples.</p>
<h4>KITS</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C05010001</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" style="color: #b21329;" target="_blank">MicroPlex Library Preparation Kit v3 /48 rxns</a></td>
<td class="format">48 rxns</td>
<td><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010002</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-96-rxns" style="color: #b21329;" target="_blank">MicroPlex Library Preparation Kit v3 /96 rxns</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-96-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
</tbody>
</table>
<h4>DUAL INDEXES</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C05010003</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/24-dual-indexes-for-microplex-kit-v3-48-rxns" style="color: #b21329;" target="_blank">24 Dual indexes for MicroPlex Kit v3</a></td>
<td class="format">48 rxns</td>
<td><a href="https://www.diagenode.com/en/p/24-dual-indexes-for-microplex-kit-v3-48-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010004</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-1" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set I</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-1" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010005</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-2" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set II</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-2" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010006</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-3" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set III</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-3" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010007</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-4" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set IV</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-4" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
</tbody>
</table>
</div>
</li>
</ul>
</div>
</li>
</ul>
</div>
</div>
</div>
<div class="content active" id="panel2">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<div class="extra-spaced">
<p>The TAG Kit for ChIPmentation offers an optimized ChIP-seq library preparation solution based on tagmentation. This kit includes reagents for tagmentation-based library preparation integrated in the IP and is compatible with any ChIP protocol based on magnetic beads. The primer indexes for multiplexing&nbsp;must be purchased separately and are available as a reference: <a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" target="_blank">24 SI for ChIPmentation</a>, Cat. No. C01011031. Alternatively, for histone marks, Diagenode proposes the complete solution (including all buffers for ChIP, tagmentation and multiplexing): <a href="https://www.diagenode.com/en/p/manual-chipmentation-kit-for-histones-24-rxns" target="_blank">ChIPmentation for Histones</a>.</p>
</div>
<div class="extra-spaced">
<h2>Features</h2>
<ul class="nobullet">
<li><i class="fa fa-arrow-circle-right"></i> Sample: chromatin-antibody-magnetic beads complexes</li>
<li><i class="fa fa-arrow-circle-right"></i> Input: chromatin from 5 K &ndash; 4 M cells</li>
<li><i class="fa fa-arrow-circle-right"></i> Easy and fast protocol</li>
<li><i class="fa fa-arrow-circle-right"></i> Compatible with any ChIP protocol based on magnetic beads</li>
<li><i class="fa fa-arrow-circle-right"></i> No adapter dimers</li>
<li><i class="fa fa-arrow-circle-right"></i> Sequencing technology: Illumina</li>
</ul>
</div>
<div class="extra-spaced">
<h2>Applications</h2>
<p class="lead"><em><strong>TAG kit for ChIPmentation</strong></em></p>
<ul class="square">
<li>ChIPmentation library preparation</li>
</ul>
<p class="lead"><em><strong>24 SI for for ChIPmentation</strong></em></p>
<ul class="square">
<li>ChIPmentation library preparation</li>
<li>Tagmentation-based library preparation methods like ATAC-seq, CUT&amp;Tag</li>
</ul>
</div>
<h4>KITS</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C01011030</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/tag-kit-for-chipmentation-24" style="color: #b21329;" target="_blank">TAG Kit for ChIPmentation</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/tag-kit-for-chipmentation-24" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C01011031</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" style="color: #b21329;" target="_blank">24 SI for ChIPmentation</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
</tbody>
</table>
</div>
</div>
</div>
<div class="content" id="panel3">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<div class="extra-spaced">
<h3 class="text-center diacol"><em>How to choose your library preparation kit?</em></h3>
</div>
<table class="noborder">
<tbody>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Sample</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Chromatin-antibody-beads complex</p>
</td>
<td colspan="2">
<p class="text-center" style="font-size: 15px;">Purified DNA</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Purified DNA</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td colspan="2"><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Application</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">ChIPmentation</p>
</td>
<td colspan="2">
<p class="text-center" style="font-size: 15px;">ChIP-seq library prep<br /> Low input DNA sequencing</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">MeDIP-seq library prep<br /> Genomic DNA sequencing<br /> High input ChIP-seq</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td colspan="2"><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Input</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Chromatin: 5 K to 4 M cells</p>
</td>
<td colspan="2&quot;">
<p class="text-center" style="font-size: 15px;">DNA: 50 pg &ndash; 50 ng</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">DNA: 5 ng &ndash; 1 &micro;g</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow-45-left.png" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow-45-right.png" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Multiplexing</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 24 samples</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 384 samples</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 48 samples</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 24 samples</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Indexes</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Single indexes (SI)</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Dual indexes (DI)</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Single indexes (SI)</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Single indexes (SI)</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Kit</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>TAG Kit for ChIPmentation</strong><br /> (indexes not included in the kit)</p>
<p class="text-center"><strong>Kit</strong><br /> <a href="https://www.diagenode.com/en/p/tag-kit-for-chipmentation-24" target="_blank">C01011030 &ndash; 24 rxns</a></p>
<p class="text-center"><strong>Single indexes</strong><br /> <a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" target="_blank">C01011031 &ndash; 24 SI/24 rxns</a></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>MicroPlex Library Preparation Kit v3</strong><br />(dual indexes not included in the kit)</p>
<p class="text-center"><strong>Kit</strong><br /> <a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" target="_blank">C05010001 - 48 rxns</a><br /> <a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-96-rxns" target="_blank">C05010002 - 96 rxns</a></p>
<br />
<p class="text-center"><strong>Unique dual indexes</strong><br /> <a href="https://www.diagenode.com/en/p/24-unique-dual-indexes-for-microplex-kit-v3-set1" target="_blank">C05010008 - Set I 24 UDI / 24 rxns</a><br /> <a href="https://www.diagenode.com/en/p/24-unique-dual-indexes-for-microplex-kit-v3-set2" target="_blank">C05010009 - Set II 24 UDI/ 24 rxns</a></p>
<p class="text-center"><strong>Dual indexes</strong><br /> <a href="https://www.diagenode.com/en/p/24-dual-indexes-for-microplex-kit-v3-48-rxns" target="_blank">C05010003 - 24 DI/ 48 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-1" target="_blank">C05010004 - Set I 96 DI/ 96 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-2" target="_blank">C05010005 - Set II 96 DI/ 96 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-3" target="_blank">C05010006 - Set III 96 DI/ 96 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-4" target="_blank">C05010007 - Set IV 96 DI/ 96 rxns</a></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>MicroPlex Library Preparation Kit v2</strong><br />(single indexes included in the kit)</p>
<p class="text-center"><a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns" target="_blank">C05010012 - 12 SI/ 12 rxns</a><br /> <a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x48-12-indices-48-rxns" target="_blank">C05010013 - 12 SI/ 48 rxns</a></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>iDeal Library Preparation Kit</strong><br />(Set 1 of indexes included in the kit)</p>
<p class="text-center"><a href="https://www.diagenode.com/en/p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns" target="_blank">C05010020 - 12 SI/ 24 rxns</a></p>
<p class="text-center" style="font-size: 15px;"><strong>Index Primer Set 2</strong></p>
<p class="text-center"><a href="https://www.diagenode.com/en/p/ideal-library-index-primer-set-2-24-rxns" target="_blank">C05010021 - 12 SI/ 24 rxns</a></p>
</td>
</tr>
</tbody>
</table>
</div>
</div>
</div>
<div class="content" id="panel4">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<p>Combined chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) has become the gold standard to investigate genome-wide epigenetic profiles. However, ChIP from a limited amount of cells has been a challenge. Here we provide a complete and robust workflow solution for successful ChIP-seq from small numbers of cells using the True MicroChIP kit and MicroPlex Library Preparation kit.</p>
<blockquote><span class="label-green" style="margin-bottom: 16px; margin-left: -22px;">APPLICATION NOTE</span>
<div class="row">
<div class="small-12 medium-6 large-6 columns"><center><img src="https://www.diagenode.com/img/categories/microplex/chip-efficiency-on-10000-cells.jpg" /></center>
<p><small><em>ChIP efficiency on 10,000 cells</em></small></p>
</div>
<div class="small-12 medium-6 large-6 columns">
<p><strong>From minuscule amounts to magnificent results:</strong><br /> reliable ChIP-seq data from 10,000 cells with the True MicroChIP&trade; and the MicroPlex Library Preparation&trade; kits.</p>
<a href="https://www.diagenode.com/files/application_notes/True_MicroChIP_and_MicroPlex_kits_Application_Note.pdf" class="details small button" target="_blank">DOWNLOAD</a></div>
</div>
</blockquote>
<blockquote><span class="label-green" style="margin-bottom: 16px; margin-left: -22px;">APPLICATION NOTE</span>
<div class="row">
<div class="small-12 medium-6 large-6 columns"><center><img src="https://www.diagenode.com/img/categories/microplex/quality-control-check.jpg" /></center>
<p class="text-left"><small><em>Quality control check of a ChIP-seq library on the Fragment Analyzer. High Efficiency ChIP performed on 10,000 cells</em></small></p>
</div>
<div class="small-12 medium-6 large-6 columns">
<p class="text-left"><strong>Best Workflow Practices for ChIP-seq Analysis with Small Samples</strong></p>
<a href="https://www.diagenode.com/files/application_notes/Diagenode_AATI_Joint.pdf" class="details small button" target="_blank">DOWNLOAD</a></div>
</div>
</blockquote>
</div>
</div>
</div>
<div class="content" id="panel5">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<div class="extra-spaced">
<h2>TAG Kit for ChIPmentation</h2>
<ol>
<li><strong>What is the difference between tagmentation and ChIPmentation?</strong><br />Tagmentation is a reaction where an enzyme (a transposase) cleaves DNA and incorporates sequencing adaptors at the ends of the fragments in one step. In our ChIPmentation technology we combine chromatin immunoprecipitation and tagmentation in one streamlined workflow where the tagmentation step occurs directly on chromatin.<br /><br /></li>
<li><strong>What is the expected concentration of ChIPmentation libraries?</strong><br />The concentration of libraries that you need to reach will depend on the sensitivity of the machine and kits that you will use to perform the quality control and the sequencing of your libraries. Usually a concentration of 4-8 ng/&mu;l is enough for a quality control using the Qubit High Sensitivity assay (ThermoFischer Scientific) and the High Sensitivity chip for BioAnalyzer (Agilent) and for sequencing on Illumina HiSeq3000/4000.<br /><br /></li>
<li><strong>Does the ChIPmentation approach work on plants?</strong><br />Our ChIPmentation solution has been validated on human cells and we do not have any data on plants. It should be compatible. We would recommend using our Universal Plant ChIP Kit in combination with the TAG Kit for ChIPmentation and the 24 SI for ChIPmentation.<br /><br /></li>
<li><strong>What is the size of the fragments after the tagmentation?</strong><br />The size of the fragments at the end of the ChIPmentation protocol can vary depending on many parameters like the shearing efficiency, the antibody used or the tagmentation time. However, with our standard protocol we usually obtain a library peak which is around 200-300 bp (see example of results at the end of the manual). If many fragments larger than 500 bp are present , the best would be to contact your sequencing provider to ask what their requirements are, because it can vary depending on the sequencer. If you want to remove the large fragments you can use the size selection protocol described in the manual.<br /><br /></li>
<li><strong>What is the size of the adapters?</strong><br />The sum of the adapters is 128 bp.</li>
</ol>
</div>
<div class="extra-spaced">
<h2>MicroPlex Library Preparation Kit</h2>
<ol>
<li><strong>Can I use the available Illumina primers and validate them with the MicroPlex Kit v2?</strong><br /> Although the final flanking sequences of MicroPlex are the same as those used by Illumina, the PCR primers are not identical and part of them is supplied with the buffer. For this reason Illumina primers will not work as substitute.<br /><br /></li>
<li><strong>The BioAnalyzer profile of purified library shows the presence of low molecular weight peaks (primers/adaptors) in the samples. Should I re- purify the samples or they can be used directly to the sequencing? If the second purification is recommended, which ratio sample/AMPure beads should I use?</strong><br /> You can do a second round of purification using 1:1 ratio of AMPure beads to sample and this should get rid of the majority of the dimers.<br /><br /></li>
<li><strong>I am going to use the MicroPlex Library Preparation Kit v2 on ChIP samples . Our thermocycler has ramp rate 1.5&deg;/s max while the protocol recommends using a ramp rate 3 to 5&deg;/s. How would this affect the library prep?</strong><br /> We have not used a thermocycler with a ramp rate of 1.5 &deg;C, which seems faster than most of thermocyclers. Too fast of a ramp rate may affect the primer annealing and ligation steps.<br /><br /></li>
<li><strong>What is the function of the replication stop site in the adapter loops?</strong><br /> The replication stop site in the adaptor loops function to stop the polymerase from continuing to copy the rest of the stem loop.<br /><br /></li>
<li><strong>I want to do ChIP-seq. Which ChIP-seq kit can I use for sample preparation prior to Microplex Library Preparation Kit v2?</strong><br /> In our portfolio there are several ChIP-seq kits compatible with Microplex Library Preparation Kit v2. Depending on your sample type and target studied you can use the following kits: iDeal ChIP-seq Kit for Transcription Factors (Cat. No. C01010055), iDeal ChIP-seq Kit for Histones (Cat. No. C01010051), True MicroChIP kit (Cat. No. C01010130), Universal Plant ChIP-seq Kit (Cat. No. C01010152). All these kits exist in manual and automated versions.<br /><br /></li>
<li><strong>Is Microplex Library Preparation Kit v2 compatible with exome enrichment methods?</strong><br /> Microplex Library Preparation Kit v2 is compatible with major exome and target enrichment products, including Agilent SureSelect<sup>&reg;</sup>, Roche NimbleGen<sup>&reg;</sup> SeqCap<sup>&reg;</sup> EZ and custom panels.<br /><br /></li>
<li><strong>What is the nick that is mentioned in the kit method overview?</strong><br /> The nick is simply a gap between a stem adaptor and 3&rsquo; DNA end, as shown on the schema in the kit method overview.<br /><br /></li>
<li><strong>Are the indexes of the MicroPlex library preparation kit v2 located at i5 or i7?</strong><br /> The libraries generated with the MicroPlex kit v2 contain indices located at i7.<br /><br /></li>
<li><strong>Is there a need to use custom index read primers for the sequencing to read the 8nt iPCRtags?</strong><br /> There is no need for using custom Sequencing primer to sequence MicroPlex libraires. MicroPlex libraries can be sequenced using standard Illumina Sequencing kits and protocols.<br /><br /></li>
<li><strong>What is the advantage of using stem-loop adapter in the MicroPlex kit?</strong><br /> There are several advantages of using stem-loop adaptors. First of all, stem-loop adaptors prevent from self-ligation thus increases the ligation efficiency between the adapter and DNA fragment. Moreover, the background is reduced using ds adaptors with no single-stranded tails. Finally, adaptor-adaptor ligation is reduced using blocked 5&rsquo; ends.<br /><br /></li>
</ol>
</div>
<div class="extra-spaced">
<h2>IDeal Library Preparation Kit</h2>
<ol>
<li><strong>Are the index from the iDeal library Prep kit compatible with the MicroPlex library prep kit?</strong><br /> No, it is important to use only the indexes provided in the MicroPlex kit to ensure proper library preparation with this kit</li>
</ol>
</div>
</div>
</div>
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<p><span>MicroPlex v2 builds on the innovative MicroPlex chemistry to generate DNA libraries with expanded multiplexing capability and with even greater diversity. Kits contain up to 48 Illumina</span><span>&reg; </span><span>-compatible indexes. MicroPlex v2 can be used in DNA- seq, RNA-seq, or ChIP-seq and offers robust target enrichment performance with all of the leading platforms. </span></p>
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			'name' => 'True MicroChIP and MicroPlex kits',
			'description' => '<p><span>From minuscule amounts to magnificent results: reliable ChIP-seq data from 10,000 cells with the True MicroChIP</span>&trade; <span>and the MicroPlex Library Preparation</span>&trade; <span>kits. </span></p>',
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			'id' => '16',
			'name' => 'ChIP kit results with True MicroChIP kit',
			'description' => '<p style="text-align: justify;"><span>Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become the gold standard for whole-genome mapping of protein-DNA interactions. However, conventional ChIP protocols require abundant amounts of starting material (at least hundreds of thousands of cells per immunoprecipitation) limiting the application for the ChIP technology to few cell samples. </span></p>',
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			'id' => '4843',
			'name' => 'Differentiation block in acute myeloid leukemia regulated by intronicsequences of FTO',
			'authors' => 'Camera  F. et al.',
			'description' => '<p>Iroquois transcription factor gene IRX3 is highly expressed in 20&acirc;&euro;&ldquo;30\% of acute myeloid leukemia (AML) and contributes to the pathognomonic differentiation block. Intron 8 FTO sequences &acirc;&circ;&frac14;220kB downstream of IRX3 exhibit histone acetylation, DNA methylation, and contacts with the IRX3 promoter, which correlate with IRX3 expression. Deletion of these intronic elements confirms a role in positively regulating IRX3. RNAseq revealed long non-coding (lnc) transcripts arising from this locus. FTO-lncAML knockdown (KD) induced differentiation of AML cells, loss of clonogenic activity, and reduced FTO intron 8:IRX3 promoter contacts. While both FTO-lncAML KD and IRX3 KD induced differentiation, FTO-lncAML but not IRX3 KD led to HOXA downregulation suggesting transcript activity in trans. FTO-lncAMLhigh AML samples expressed higher levels of HOXA and lower levels of differentiation genes. Thus, a regulatory module in FTO intron 8 consisting of clustered enhancer elements and a long non-coding RNA is active in human AML, impeding myeloid differentiation.</p>',
			'date' => '2023-08-01',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S2589004223013962',
			'doi' => '10.1016/j.isci.2023.107319',
			'modified' => '2023-08-01 14:14:01',
			'created' => '2023-08-01 15:59:38',
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		(int) 1 => array(
			'id' => '4851',
			'name' => 'Supraphysiological Androgens Promote the Tumor Suppressive Activity of the Androgen Receptor Through cMYC Repression and Recruitment of the DREAM Complex',
			'authors' => 'Nyquist  M. et al.',
			'description' => '<p>The androgen receptor (AR) pathway regulates key cell survival programs in prostate epithelium. The AR represents a near-universal driver and therapeutic vulnerability in metastatic prostate cancer, and targeting AR has a remarkable therapeutic index. Though most approaches directed toward AR focus on inhibiting AR signaling, laboratory and now clinical data have shown that high dose, supraphysiological androgen treatment (SPA) results in growth repression and improved outcomes in subsets of prostate cancer patients. A better understanding of the mechanisms contributing to SPA response and resistance could help guide patient selection and combination therapies to improve efficacy. To characterize SPA signaling, we integrated metrics of gene expression changes induced by SPA together with cistrome data and protein-interactomes. These analyses indicated that the Dimerization partner, RB-like, E2F and Multi-vulval class B (DREAM) complex mediates growth repression and downregulation of E2F targets in response to SPA. Notably, prostate cancers with complete genomic loss of RB1 responded to SPA treatment whereas loss of DREAM complex components such as RBL1/2 promoted resistance. Overexpression of MYC resulted in complete resistance to SPA and attenuated the SPA/AR-mediated repression of E2F target genes. These findings support a model of SPA-mediated growth repression that relies on the negative regulation of MYC by AR leading to repression of E2F1 signaling via the DREAM complex. The integrity of MYC signaling and DREAM complex assembly may consequently serve as determinants of SPA responses and as pathways mediating SPA resistance.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/37352376/',
			'doi' => '10.1158/0008-5472.CAN-22-2613',
			'modified' => '2023-08-01 18:09:31',
			'created' => '2023-08-01 15:59:38',
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		(int) 2 => array(
			'id' => '4852',
			'name' => 'In skeletal muscle and neural crest cells, SMCHD1 regulates biologicalpathways relevant for Bosma syndrome and facioscapulohumeral dystrophyphenotype.',
			'authors' => 'Laberthonnière  C. et al.',
			'description' => '<p>Many genetic syndromes are linked to mutations in genes encoding factors that guide chromatin organization. Among them, several distinct rare genetic diseases are linked to mutations in SMCHD1 that encodes the structural maintenance of chromosomes flexible hinge domain containing 1 chromatin-associated factor. In humans, its function as well as the impact of its mutations remains poorly defined. To fill this gap, we determined the episignature associated with heterozygous SMCHD1 variants in primary cells and cell lineages derived from induced pluripotent stem cells for Bosma arhinia and microphthalmia syndrome (BAMS) and type 2 facioscapulohumeral dystrophy (FSHD2). In human tissues, SMCHD1 regulates the distribution of methylated CpGs, H3K27 trimethylation and CTCF at repressed chromatin but also at euchromatin. Based on the exploration of tissues affected either in FSHD or in BAMS, i.e. skeletal muscle fibers and neural crest stem cells, respectively, our results emphasize multiple functions for SMCHD1, in chromatin compaction, chromatin insulation and gene regulation with variable targets or phenotypical outcomes. We concluded that in rare genetic diseases, SMCHD1 variants impact gene expression in two ways: (i) by changing the chromatin context at a number of euchromatin loci or (ii) by directly regulating some loci encoding master transcription factors required for cell fate determination and tissue differentiation.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37334829',
			'doi' => '10.1093/nar/gkad523',
			'modified' => '2023-08-01 14:35:38',
			'created' => '2023-08-01 15:59:38',
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		),
		(int) 3 => array(
			'id' => '4861',
			'name' => 'Hypomethylation and overexpression of Th17-associated genes is ahallmark of intestinal CD4+ lymphocytes in Crohn's disease.',
			'authors' => 'Sun  Z. et al.',
			'description' => '<p>BACKGROUND: The development of Crohn's disease (CD) involves immune cell signaling pathways regulated by epigenetic modifications. Aberrant DNA methylation has been identified in peripheral blood and bulk intestinal tissue from CD patients. However, the DNA methylome of disease-associated intestinal CD4 + lymphocytes has not been evaluated. MATERIALS AND METHODS: Genome-wide DNA methylation sequencing was performed from terminal ileum CD4 + cells from 21 CD patients and 12 age and sex matched controls. Data was analyzed for differentially methylated CpGs (DMCs) and methylated regions (DMRs). Integration was performed with RNA-sequencing data to evaluate the functional impact of DNA methylation changes on gene expression. DMRs were overlapped with regions of differentially open chromatin (by ATAC-seq) and CCCTC-binding factor (CTCF) binding sites (by ChIP-seq) between peripherally-derived Th17 and Treg cells. RESULTS: CD4+ cells in CD patients had significantly increased DNA methylation compared to those from the controls. A total of 119,051 DMCs and 8,113 DMRs were detected. While hyper-methylated genes were mostly related to cell metabolism and homeostasis, hypomethylated genes were significantly enriched within the Th17 signaling pathway. The differentially enriched ATAC regions in Th17 cells (compared to Tregs) were hypomethylated in CD patients, suggesting heightened Th17 activity. There was significant overlap between hypomethylated DNA regions and CTCF-associated binding sites. CONCLUSIONS: The methylome of CD patients demonstrate an overall dominant hypermethylation yet hypomethylation is more concentrated in proinflammatory pathways, including Th17 differentiation. Hypomethylation of Th17-related genes associated with areas of open chromatin and CTCF binding sites constitutes a hallmark of CD-associated intestinal CD4 + cells.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37280154',
			'doi' => '10.1093/ecco-jcc/jjad093',
			'modified' => '2023-08-01 14:52:39',
			'created' => '2023-08-01 15:59:38',
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		(int) 4 => 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',
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			'id' => '4782',
			'name' => 'Transient suppression of SUMOylation in embryonic stem cells generatesembryo-like structures.',
			'authors' => 'Cossec  J-C. et al.',
			'description' => '<p>Recent advances in synthetic embryology have opened new avenues for understanding the complex events controlling mammalian peri-implantation development. Here, we show that mouse embryonic stem cells (ESCs) solely exposed to chemical inhibition of SUMOylation generate embryo-like structures comprising anterior neural and trunk-associated regions. HypoSUMOylation-instructed ESCs give rise to spheroids that self-organize into gastrulating structures containing cell types spatially and functionally related to embryonic and extraembryonic compartments. Alternatively, spheroids cultured in a droplet microfluidic device form elongated structures that undergo axial organization reminiscent of natural embryo morphogenesis. Single-cell transcriptomics reveals various cellular lineages, including properly positioned anterior neuronal cell types and paraxial mesoderm segmented into somite-like structures. Transient SUMOylation suppression gradually increases DNA methylation genome wide and repressive mark deposition at Nanog. Interestingly, cell-to-cell variations in SUMOylation levels occur during early embryogenesis. Our approach provides a proof of principle for potentially powerful strategies to explore early embryogenesis by targeting chromatin roadblocks of cell fate change.</p>',
			'date' => '2023-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37061916',
			'doi' => '10.1016/j.celrep.2023.112380',
			'modified' => '2023-06-13 09:20:06',
			'created' => '2023-05-05 12:34:24',
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		(int) 6 => array(
			'id' => '4693',
			'name' => 'ZEB1 controls a lineage-specific transcriptional program essential formelanoma cell state transitions',
			'authors' => 'Tang  Y. et al.',
			'description' => '<p>Cell plasticity sustains intra-tumor heterogeneity and treatment resistance in melanoma. Deciphering the transcriptional mechanisms governing reversible phenotypic transitions between proliferative/differentiated and invasive/stem-like states is required in order to design novel therapeutic strategies. EMT-inducing transcription factors, extensively known for their role in metastasis in carcinoma, display cell-type specific functions in melanoma, with a decreased ZEB2/ZEB1 expression ratio fostering adaptive resistance to targeted therapies. While ZEB1 direct target genes have been well characterized in carcinoma models, they remain unknown in melanoma. Here, we performed a genome-wide characterization of ZEB1 transcriptional targets, by combining ChIP-sequencing and RNA-sequencing, upon phenotype switching in melanoma models. We identified and validated ZEB1 binding peaks in the promoter of key lineage-specific genes related to melanoma cell identity. Comparative analyses with breast carcinoma cells demonstrated melanoma-specific ZEB1 binding, further supporting lineage specificity. Gain- or loss-of-function of ZEB1, combined with functional analyses, further demonstrated that ZEB1 negatively regulates proliferative/melanocytic programs and positively regulates both invasive and stem-like programs. We then developed single-cell spatial multiplexed analyses to characterize melanoma cell states with respect to ZEB1/ZEB2 expression in human melanoma samples. We characterized the intra-tumoral heterogeneity of ZEB1 and ZEB2 and further validated ZEB1 increased expression in invasive cells, but also in stem-like cells, highlighting its relevance in vivo in both populations. Overall, our results define ZEB1 as a major transcriptional regulator of cell states transitions and provide a better understanding of lineage-specific transcriptional programs sustaining intra-tumor heterogeneity in melanoma.</p>',
			'date' => '2023-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2023.02.10.526467',
			'doi' => '10.1101/2023.02.10.526467',
			'modified' => '2023-04-14 09:11:23',
			'created' => '2023-02-28 12:19:11',
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		),
		(int) 7 => 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',
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		(int) 8 => array(
			'id' => '4710',
			'name' => 'Mechanisms and function of de novo DNA methylation in placentaldevelopment reveals an essential role for DNMT3B.',
			'authors' => 'Andrews  S. et al.',
			'description' => '<p>DNA methylation is a repressive epigenetic modification that is essential for development, exemplified by the embryonic and perinatal lethality observed in mice lacking de novo DNA methyltransferases (DNMTs). Here we characterise the role for DNMT3A, 3B and 3L in gene regulation and development of the mouse placenta. We find that each DNMT establishes unique aspects of the placental methylome through targeting to distinct chromatin features. Loss of Dnmt3b results in de-repression of germline genes in trophoblast lineages and impaired formation of the maternal-foetal interface in the placental labyrinth. Using Sox2-Cre to delete Dnmt3b in the embryo, leaving expression intact in placental cells, the placental phenotype was rescued and, consequently, the embryonic lethality, as Dnmt3b null embryos could now survive to birth. We conclude that de novo DNA methylation by DNMT3B during embryogenesis is principally required to regulate placental development and function, which in turn is critical for embryo survival.</p>',
			'date' => '2023-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36690623',
			'doi' => '10.1038/s41467-023-36019-9',
			'modified' => '2023-04-05 08:38:12',
			'created' => '2023-02-28 12:19:11',
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		),
		(int) 9 => array(
			'id' => '4651',
			'name' => 'TCDD induces multigenerational alterations in the expression ofmicroRNA in the thymus through epigenetic modifications',
			'authors' => 'Singh  Narendra P et al.',
			'description' => '<p>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, is an environmental contaminant that is known for mediating toxicity across generations. However, whether TCDD can induce multigenerational changes in the expression of miRNAs (miRs) has not been previously studied. In the current study, we investigated the effect of administration of TCDD in pregnant mice (F0) on gestational day 14, on the expression of miRs in the thymus of F0 and subsequent generations (F1 and F2). Of the 3200 miRs screened, 160 miRs were dysregulated similarly in F0, F1, and F2 generations while 46 miRs were differentially altered in F0-F2 generations. Pathway analysis revealed that the changes in miR signature profile mediated by TCDD affected the genes that regulate cell signaling, apoptosis, thymic atrophy, cancer, immunosuppression, and other physiological pathways. A significant number of miRs that showed altered expression exhibited dioxin response elements (DRE) on their promoters. Focusing on one such miR, namely miR-203 that expressed DREs and was induced across F0-F2 by TCDD, promoter analysis showed that one of the DREs expressed by miR-203 was functional to TCDD-mediated upregulation. Also, the histone methylation status of H3K4me3 in the miR-203 promoter was significantly increased near the transcriptional start site (TSS) in TCDD-treated thymocytes across F0-F2 generations. Genome-wide ChIP-seq study suggested that TCDD may cause alterations in histone methylation in certain genes across the three generations. Together, the current study demonstrates that gestational exposure to TCDD can alter the expression of miRs in F0 through direct activation of DREs as well as across F0, F1, and F2 generations through epigenetic pathways.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://academic.oup.com/pnasnexus/advance-article/doi/10.1093/pnasnexus/pgac290/6886578',
			'doi' => 'https://doi.org/10.1093/pnasnexus/pgac290',
			'modified' => '2023-03-13 10:55:36',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 10 => array(
			'id' => '4632',
			'name' => 'The histone acetyltransferase KAT6A is recruited to unmethylatedCpG islands via a DNA binding winged helix domain.',
			'authors' => 'Weber  L.M. et al.',
			'description' => '<p>The lysine acetyltransferase KAT6A (MOZ, MYST3) belongs to the MYST family of chromatin regulators, facilitating histone acetylation. Dysregulation of KAT6A has been implicated in developmental syndromes and the onset of acute myeloid leukemia (AML). Previous work suggests that KAT6A is recruited to its genomic targets by a combinatorial function of histone binding PHD fingers, transcription factors and chromatin binding interaction partners. Here, we demonstrate that a winged helix (WH) domain at the very N-terminus of KAT6A specifically interacts with unmethylated CpG motifs. This DNA binding function leads to the association of KAT6A with unmethylated CpG islands (CGIs) genome-wide. Mutation of the essential amino acids for DNA binding completely abrogates the enrichment of KAT6A at CGIs. In contrast, deletion of a second WH domain or the histone tail binding PHD fingers only subtly influences the binding of KAT6A to CGIs. Overexpression of a KAT6A WH1 mutant has a dominant negative effect on H3K9 histone acetylation, which is comparable to the effects upon overexpression of a KAT6A HAT domain mutant. Taken together, our work revealed a previously unrecognized chromatin recruitment mechanism of KAT6A, offering a new perspective on the role of KAT6A in gene regulation and human diseases.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36537216',
			'doi' => '10.1093/nar/gkac1188',
			'modified' => '2023-03-28 09:01:38',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 11 => array(
			'id' => '4629',
			'name' => 'Polyglutamine-expanded ATXN7 alters a specific epigenetic signatureunderlying photoreceptor identity gene expression in SCA7 mouseretinopathy.',
			'authors' => 'Niewiadomska-Cimicka  A.et al.',
			'description' => '<p>BACKGROUND: Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder that primarily affects the cerebellum and retina. SCA7 is caused by a polyglutamine expansion in the ATXN7 protein, a subunit of the transcriptional coactivator SAGA that acetylates histone H3 to deposit narrow H3K9ac mark at DNA regulatory elements of active genes. Defective histone acetylation has been presented as a possible cause for gene deregulation in SCA7 mouse models. However, the topography of acetylation defects at the whole genome level and its relationship to changes in gene expression remain to be determined. METHODS: We performed deep RNA-sequencing and chromatin immunoprecipitation coupled to high-throughput sequencing to examine the genome-wide correlation between gene deregulation and alteration of the active transcription marks, e.g. SAGA-related H3K9ac, CBP-related H3K27ac and RNA polymerase II (RNAPII), in a SCA7 mouse retinopathy model. RESULTS: Our analyses revealed that active transcription marks are reduced at most gene promoters in SCA7 retina, while a limited number of genes show changes in expression. We found that SCA7 retinopathy is caused by preferential downregulation of hundreds of highly expressed genes that define morphological and physiological identities of mature photoreceptors. We further uncovered that these photoreceptor genes harbor unusually broad H3K9ac profiles spanning the entire gene bodies and have a low RNAPII pausing. This broad H3K9ac signature co-occurs with other features that delineate superenhancers, including broad H3K27ac, binding sites for photoreceptor specific transcription factors and expression of enhancer-related non-coding RNAs (eRNAs). In SCA7 retina, downregulated photoreceptor genes show decreased H3K9 and H3K27 acetylation and eRNA expression as well as increased RNAPII pausing, suggesting that superenhancer-related features are altered. CONCLUSIONS: Our study thus provides evidence that distinctive epigenetic configurations underlying high expression of cell-type specific genes are preferentially impaired in SCA7, resulting in a defect in the maintenance of identity features of mature photoreceptors. Our results also suggest that continuous SAGA-driven acetylation plays a role in preserving post-mitotic neuronal identity.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36539812',
			'doi' => '10.1186/s12929-022-00892-1',
			'modified' => '2023-03-28 09:07:19',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 12 => array(
			'id' => '4575',
			'name' => 'Intranasal administration of Acinetobacter lwoffii in a murine model ofasthma induces IL-6-mediated protection associated with cecal microbiotachanges.',
			'authors' => 'Alashkar A. B. et al.',
			'description' => '<p>BACKGROUND: Early-life exposure to certain environmental bacteria including Acinetobacter lwoffii (AL) has been implicated in protection from chronic inflammatory diseases including asthma later in life. However, the underlying mechanisms at the immune-microbe interface remain largely unknown. METHODS: The effects of repeated intranasal AL exposure on local and systemic innate immune responses were investigated in wild-type and Il6 , Il10 , and Il17 mice exposed to ovalbumin-induced allergic airway inflammation. Those investigations were expanded by microbiome analyses. To assess for AL-associated changes in gene expression, the picture arising from animal data was supplemented by in vitro experiments of macrophage and T-cell responses, yielding expression and epigenetic data. RESULTS: The asthma preventive effect of AL was confirmed in the lung. Repeated intranasal AL administration triggered a proinflammatory immune response particularly characterized by elevated levels of IL-6, and consequently, IL-6 induced IL-10 production in CD4 T-cells. Both IL-6 and IL-10, but not IL-17, were required for asthma protection. AL had a profound impact on the gene regulatory landscape of CD4 T-cells which could be largely recapitulated by recombinant IL-6. AL administration also induced marked changes in the gastrointestinal microbiome but not in the lung microbiome. By comparing the effects on the microbiota according to mouse genotype and AL-treatment status, we have identified microbial taxa that were associated with either disease protection or activity. CONCLUSION: These experiments provide a novel mechanism of Acinetobacter lwoffii-induced asthma protection operating through IL-6-mediated epigenetic activation of IL-10 production and with associated effects on the intestinal microbiome.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36458896',
			'doi' => '10.1111/all.15606',
			'modified' => '2023-04-11 10:23:07',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 13 => array(
			'id' => '4535',
			'name' => 'Identification of genomic binding sites and direct target genes for thetranscription factor DDIT3/CHOP.',
			'authors' => 'Osman  A. et al.',
			'description' => '<p>DDIT3 is a tightly regulated basic leucine zipper (bZIP) transcription factor and key regulator in cellular stress responses. It is involved in a variety of pathological conditions and may cause cell cycle block and apoptosis. It is also implicated in differentiation of some specialized cell types and as an oncogene in several types of cancer. DDIT3 is believed to act as a dominant-negative inhibitor by forming heterodimers with other bZIP transcription factors, preventing their DNA binding and transactivating functions. DDIT3 has, however, been reported to bind DNA and regulate target genes. Here, we employed ChIP sequencing combined with microarray-based expression analysis to identify direct binding motifs and target genes of DDIT3. The results reveal DDIT3 binding to motifs similar to other bZIP transcription factors, known to form heterodimers with DDIT3. Binding to a class III satellite DNA repeat sequence was also detected. DDIT3 acted as a DNA-binding transcription factor and bound mainly to the promotor region of regulated genes. ChIP sequencing analysis of histone H3K27 methylation and acetylation showed a strong overlap between H3K27-acetylated marks and DDIT3 binding. These results support a role for DDIT3 as a transcriptional regulator of H3K27ac-marked genes in transcriptionally active chromatin.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36402425',
			'doi' => '10.1016/j.yexcr.2022.113418',
			'modified' => '2022-11-25 08:47:49',
			'created' => '2022-11-24 08:49:52',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 14 => array(
			'id' => '4494',
			'name' => 'Cryptococcal Hsf3 controls intramitochondrial ROS homeostasis byregulating the respiratory process.',
			'authors' => 'Gao  X.et al.',
			'description' => '<p>Mitochondrial quality control prevents accumulation of intramitochondrial-derived reactive oxygen species (mtROS), thereby protecting cells against DNA damage, genome instability, and programmed cell death. However, underlying mechanisms are incompletely understood, particularly in fungal species. Here, we show that Cryptococcus neoformans heat shock factor 3 (CnHsf3) exhibits an atypical function in regulating mtROS independent of the unfolded protein response. CnHsf3 acts in nuclei and mitochondria, and nuclear- and mitochondrial-targeting signals are required for its organelle-specific functions. It represses the expression of genes involved in the tricarboxylic acid cycle while promoting expression of genes involved in electron transfer chain. In addition, CnHsf3 responds to multiple intramitochondrial stresses; this response is mediated by oxidation of the cysteine residue on its DNA binding domain, which enhances DNA binding. Our results reveal a function of HSF proteins in regulating mtROS homeostasis that is independent of the unfolded protein response.</p>',
			'date' => '2022-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36109512',
			'doi' => '10.1038/s41467-022-33168-1',
			'modified' => '2022-11-18 12:43:17',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 15 => array(
			'id' => '4496',
			'name' => 'Dominant role of DNA methylation over H3K9me3 for IAP silencingin endoderm.',
			'authors' => 'Wang  Z. et al.',
			'description' => '<p>Silencing of endogenous retroviruses (ERVs) is largely mediated by repressive chromatin modifications H3K9me3 and DNA methylation. On ERVs, these modifications are mainly deposited by the histone methyltransferase Setdb1 and by the maintenance DNA methyltransferase Dnmt1. Knock-out of either Setdb1 or Dnmt1 leads to ERV de-repression in various cell types. However, it is currently not known if H3K9me3 and DNA methylation depend on each other for ERV silencing. Here we show that conditional knock-out of Setdb1 in mouse embryonic endoderm results in ERV de-repression in visceral endoderm (VE) descendants and does not occur in definitive endoderm (DE). Deletion of Setdb1 in VE progenitors results in loss of H3K9me3 and reduced DNA methylation of Intracisternal A-particle (IAP) elements, consistent with up-regulation of this ERV family. In DE, loss of Setdb1 does not affect H3K9me3 nor DNA methylation, suggesting Setdb1-independent pathways for maintaining these modifications. Importantly, Dnmt1 knock-out results in IAP de-repression in both visceral and definitive endoderm cells, while H3K9me3 is unaltered. Thus, our data suggest a dominant role of DNA methylation over H3K9me3 for IAP silencing in endoderm cells. Our findings suggest that Setdb1-meditated H3K9me3 is not sufficient for IAP silencing, but rather critical for maintaining high DNA methylation.</p>',
			'date' => '2022-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36123357',
			'doi' => '10.1038/s41467-022-32978-7',
			'modified' => '2022-11-21 10:26:30',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 16 => array(
			'id' => '4415',
			'name' => 'HDAC1 and PRC2 mediate combinatorial control in SPI1/PU.1-dependentgene repression in murine erythroleukaemia.',
			'authors' => 'Gregoricchio  S. et al.',
			'description' => '<p>Although originally described as transcriptional activator, SPI1/PU.1, a major player in haematopoiesis whose alterations are associated with haematological malignancies, has the ability to repress transcription. Here, we investigated the mechanisms underlying gene repression in the erythroid lineage, in which SPI1 exerts an oncogenic function by blocking differentiation. We show that SPI1 represses genes by binding active enhancers that are located in intergenic or gene body regions. HDAC1 acts as a cooperative mediator of SPI1-induced transcriptional repression by deacetylating SPI1-bound enhancers in a subset of genes, including those involved in erythroid differentiation. Enhancer deacetylation impacts on promoter acetylation, chromatin accessibility and RNA pol II occupancy. In addition to the activities of HDAC1, polycomb repressive complex 2 (PRC2) reinforces gene repression by depositing H3K27me3 at promoter sequences when SPI1 is located at enhancer sequences. Moreover, our study identified a synergistic relationship between PRC2 and HDAC1 complexes in mediating the transcriptional repression activity of SPI1, ultimately inducing synergistic adverse effects on leukaemic cell survival. Our results highlight the importance of the mechanism underlying transcriptional repression in leukemic cells, involving complex functional connections between SPI1 and the epigenetic regulators PRC2 and HDAC1.</p>',
			'date' => '2022-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35871293',
			'doi' => '10.1093/nar/gkac613',
			'modified' => '2022-09-15 08:59:26',
			'created' => '2022-09-08 16:32:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 17 => array(
			'id' => '4516',
			'name' => 'Dual role of histone variant H3.3B in spermatogenesis: positiveregulation of piRNA transcription and implication in X-chromosomeinactivation.',
			'authors' => 'Fontaine  E. et al.',
			'description' => '<p>The histone variant H3.3 is encoded by two distinct genes, H3f3a and H3f3b, exhibiting identical amino-acid sequence. H3.3 is required for spermatogenesis, but the molecular mechanism of its spermatogenic function remains obscure. Here, we have studied the role of each one of H3.3A and H3.3B proteins in spermatogenesis. We have generated transgenic conditional knock-out/knock-in (cKO/KI) epitope-tagged FLAG-FLAG-HA-H3.3B (H3.3BHA) and FLAG-FLAG-HA-H3.3A (H3.3AHA) mouse lines. We show that H3.3B, but not H3.3A, is required for spermatogenesis and male fertility. Analysis of the molecular mechanism unveils that the absence of H3.3B led to alterations in the meiotic/post-meiotic transition. Genome-wide RNA-seq reveals that the depletion of H3.3B in meiotic cells is associated with increased expression of the whole sex X and Y chromosomes as well as of both RLTR10B and RLTR10B2 retrotransposons. In contrast, the absence of H3.3B resulted in down-regulation of the expression of piRNA clusters. ChIP-seq experiments uncover that RLTR10B and RLTR10B2 retrotransposons, the whole sex chromosomes and the piRNA clusters are markedly enriched of H3.3. Taken together, our data dissect the molecular mechanism of H3.3B functions during spermatogenesis and demonstrate that H3.3B, depending on its chromatin localization, is involved in either up-regulation or down-regulation of expression of defined large chromatin regions.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35766398',
			'doi' => '10.1093/nar/gkac541',
			'modified' => '2022-11-24 08:51:34',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 18 => array(
			'id' => '4393',
			'name' => 'TBX2 acts as a potent transcriptional silencer of tumour suppressor genesthrough interaction with the CoREST complex to sustain theproliferation of breast cancers.',
			'authors' => 'McIntyre  A.J. et al.',
			'description' => '<p>Chromosome 17q23 amplification occurs in 20\% of primary breast tumours and is associated with poor outcome. The TBX2 gene is located on 17q23 and is often over-expressed in this breast tumour subset. TBX2 is an anti-senescence gene, promoting cell growth and survival through repression of Tumour Suppressor Genes (TSGs), such as NDRG1 and CST6. Previously we found that TBX2 cooperates with the PRC2 complex to repress several TSGs, and that PRC2 inhibition restored NDRG1 expression to impede cellular proliferation. Here, we now identify CoREST proteins, LSD1 and ZNF217, as novel interactors of TBX2. Genetic or pharmacological targeting of CoREST emulated TBX2 loss, inducing NDRG1 expression and abolishing breast cancer growth in vitro and in vivo. Furthermore, we uncover that TBX2/CoREST targeting of NDRG1 is achieved by recruitment of TBX2 to the NDRG1 promoter by Sp1, the abolishment of which resulted in NDRG1 upregulation and diminished cancer cell proliferation. Through ChIP-seq we reveal that 30\% of TBX2-bound promoters are shared with ZNF217 and identify novel targets repressed by TBX2/CoREST; of these targets a lncRNA, LINC00111, behaves as a negative regulator of cell proliferation. Overall, these data indicate that inhibition of CoREST proteins represents a promising therapeutic intervention for TBX2-addicted breast tumours.</p>',
			'date' => '2022-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35687133',
			'doi' => '10.1093/nar/gkac494',
			'modified' => '2022-08-11 14:23:06',
			'created' => '2022-08-11 12:14:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 19 => array(
			'id' => '4836',
			'name' => 'Caffeine intake exerts dual genome-wide effects on hippocampal metabolismand learning-dependent transcription.',
			'authors' => 'Paiva  I. et al.',
			'description' => '<p>Caffeine is the most widely consumed psychoactive substance in the world. Strikingly, the molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal omics techniques. Our results revealed that chronic caffeine exerts concerted pleiotropic effects in the hippocampus at the epigenomic, proteomic, and metabolomic levels. Caffeine lowered metabolism-related processes (e.g., at the level of metabolomics and gene expression) in bulk tissue, while it induced neuron-specific epigenetic changes at synaptic transmission/plasticity-related genes and increased experience-driven transcriptional activity. Altogether, these findings suggest that regular caffeine intake improves the signal-to-noise ratio during information encoding, in part through fine-tuning of metabolic genes, while boosting the salience of information processing during learning in neuronal circuits.</p>',
			'date' => '2022-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35536645',
			'doi' => '10.1172/JCI149371',
			'modified' => '2023-08-01 13:52:29',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 20 => 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) 21 => 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) 22 => 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) 23 => array(
			'id' => '4217',
			'name' => 'CREBBP/EP300 acetyltransferase inhibition disrupts FOXA1-bound enhancers to inhibit the proliferation of ER+ breast cancer cells.',
			'authors' => 'Bommi-Reddy A. et al.',
			'description' => '<p><span>Therapeutic targeting of the estrogen receptor (ER) is a clinically validated approach for estrogen receptor positive breast cancer (ER+ BC), but sustained response is limited by acquired resistance. Targeting the transcriptional coactivators required for estrogen receptor activity represents an alternative approach that is not subject to the same limitations as targeting estrogen receptor itself. In this report we demonstrate that the acetyltransferase activity of coactivator paralogs CREBBP/EP300 represents a promising therapeutic target in ER+ BC. Using the potent and selective inhibitor CPI-1612, we show that CREBBP/EP300 acetyltransferase inhibition potently suppresses in vitro and in vivo growth of breast cancer cell line models and acts in a manner orthogonal to directly targeting ER. CREBBP/EP300 acetyltransferase inhibition suppresses ER-dependent transcription by targeting lineage-specific enhancers defined by the pioneer transcription factor FOXA1. These results validate CREBBP/EP300 acetyltransferase activity as a viable target for clinical development in ER+ breast cancer.</span></p>',
			'date' => '2022-03-30',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/35353838/',
			'doi' => '10.1371/journal.pone.0262378',
			'modified' => '2022-04-12 10:56:54',
			'created' => '2022-04-12 10:56:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 24 => array(
			'id' => '4235',
			'name' => 'NuA4 and H2A.Z control environmental responses and autotrophicgrowth in Arabidopsis',
			'authors' => 'Bieluszewski T. et al.',
			'description' => '<p>Nucleosomal acetyltransferase of H4 (NuA4) is an essential transcriptional coactivator in eukaryotes, but remains poorly characterized in plants. Here, we describe Arabidopsis homologs of the NuA4 scaffold proteins Enhancer of Polycomb-Like 1 (AtEPL1) and Esa1-Associated Factor 1 (AtEAF1). Loss of AtEAF1 results in inhibition of growth and chloroplast development. These effects are stronger in the Atepl1 mutant and are further enhanced by loss of Golden2-Like (GLK) transcription factors, suggesting that NuA4 activates nuclear plastid genes alongside GLK. We demonstrate that AtEPL1 is necessary for nucleosomal acetylation of histones H4 and H2A.Z by NuA4 in vitro. These chromatin marks are diminished genome-wide in Atepl1, while another active chromatin mark, H3K9 acetylation (H3K9ac), is locally enhanced. Expression of many chloroplast-related genes depends on NuA4, as they are downregulated with loss of H4ac and H2A.Zac. Finally, we demonstrate that NuA4 promotes H2A.Z deposition and by doing so prevents spurious activation of stress response genes.</p>',
			'date' => '2022-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35022409',
			'doi' => '10.1038/s41467-021-27882-5',
			'modified' => '2022-05-19 17:02:00',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 25 => array(
			'id' => '4772',
			'name' => 'Three classes of epigenomic regulators converge to hyperactivate theessential maternal gene deadhead within a heterochromatin mini-domain.',
			'authors' => 'Torres-Campana  D. et al.',
			'description' => '<p>The formation of a diploid zygote is a highly complex cellular process that is entirely controlled by maternal gene products stored in the egg cytoplasm. This highly specialized transcriptional program is tightly controlled at the chromatin level in the female germline. As an extreme case in point, the massive and specific ovarian expression of the essential thioredoxin Deadhead (DHD) is critically regulated in Drosophila by the histone demethylase Lid and its partner, the histone deacetylase complex Sin3A/Rpd3, via yet unknown mechanisms. Here, we identified Snr1 and Mod(mdg4) as essential for dhd expression and investigated how these epigenomic effectors act with Lid and Sin3A to hyperactivate dhd. Using Cut\&amp;Run chromatin profiling with a dedicated data analysis procedure, we found that dhd is intriguingly embedded in an H3K27me3/H3K9me3-enriched mini-domain flanked by DNA regulatory elements, including a dhd promoter-proximal element essential for its expression. Surprisingly, Lid, Sin3a, Snr1 and Mod(mdg4) impact H3K27me3 and this regulatory element in distinct manners. However, we show that these effectors activate dhd independently of H3K27me3/H3K9me3, and that dhd remains silent in the absence of these marks. Together, our study demonstrates an atypical and critical role for chromatin regulators Lid, Sin3A, Snr1 and Mod(mdg4) to trigger tissue-specific hyperactivation within a unique heterochromatin mini-domain.</p>',
			'date' => '2022-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759638/',
			'doi' => '10.1371/journal.pgen.1009615',
			'modified' => '2023-04-17 09:46:00',
			'created' => '2023-04-14 13:41:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 26 => 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) 27 => array(
			'id' => '4245',
			'name' => 'Decreased PRC2 activity supports the survival of basal-like breastcancer cells to cytotoxic treatments',
			'authors' => 'Mieczkowska IK et al.',
			'description' => '<p>Breast cancer (BC) is the most common cancer occurring in women but also rarely develops in men. Recent advances in early diagnosis and development of targeted therapies have greatly improved the survival rate of BC patients. However, the basal-like BC subtype (BLBC), largely overlapping with the triple-negative BC subtype (TNBC), lacks such drug targets and conventional cytotoxic chemotherapies often remain the only treatment option. Thus, the development of resistance to cytotoxic therapies has fatal consequences. To assess the involvement of epigenetic mechanisms and their therapeutic potential increasing cytotoxic drug efficiency, we combined high-throughput RNA- and ChIP-sequencing analyses in BLBC cells. Tumor cells surviving chemotherapy upregulated transcriptional programs of epithelial-to-mesenchymal transition (EMT) and stemness. To our surprise, the same cells showed a pronounced reduction of polycomb repressive complex 2 (PRC2) activity via downregulation of its subunits Ezh2, Suz12, Rbbp7 and Mtf2. Mechanistically, loss of PRC2 activity leads to the de-repression of a set of genes through an epigenetic switch from repressive H3K27me3 to activating H3K27ac mark at regulatory regions. We identified Nfatc1 as an upregulated gene upon loss of PRC2 activity and directly implicated in the transcriptional changes happening upon survival to chemotherapy. Blocking NFATc1 activation reduced epithelial-to-mesenchymal transition, aggressiveness, and therapy resistance of BLBC cells. Our data demonstrate a previously unknown function of PRC2 maintaining low Nfatc1 expression levels and thereby repressing aggressiveness and therapy resistance in BLBC.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34845197',
			'doi' => '10.1038/s41419-021-04407-y',
			'modified' => '2022-05-20 09:21:56',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 28 => array(
			'id' => '4276',
			'name' => 'Ago1 controls myogenic differentiation by regulating eRNA-mediatedCBP-guided epigenome reprogramming.',
			'authors' => 'Fallatah Bodor et al.',
			'description' => '<p>The role of chromatin-associated RNAi components in the nucleus of mammalian cells and in particular in the context of developmental programs remains to be elucidated. Here, we investigate the function of nuclear Argonaute 1 (Ago1) in gene expression regulation during skeletal muscle differentiation. We show that Ago1 is required for activation of the myogenic program by supporting chromatin modification mediated by developmental enhancer activation. Mechanistically, we demonstrate that Ago1 directly controls global H3K27 acetylation (H3K27ac) by regulating enhancer RNA (eRNA)-CREB-binding protein (CBP) acetyltransferase interaction, a key step in enhancer-driven gene activation. In particular, we show that Ago1 is specifically required for myogenic differentiation 1 (MyoD) and downstream myogenic gene activation, whereas its depletion leads to failure of CBP acetyltransferase activation and blocking of the myogenic program. Our work establishes a role of the mammalian enhancer-associated RNAi component Ago1 in epigenome regulation and activation of developmental programs.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.celrep.2021.110066',
			'doi' => '10.1016/j.celrep.2021.110066',
			'modified' => '2022-05-23 09:53:14',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 29 => array(
			'id' => '4833',
			'name' => 'Extensive NEUROG3 occupancy in the human pancreatic endocrine generegulatory network.',
			'authors' => 'Schreiber  V. et al.',
			'description' => '<p>OBJECTIVE: Mice lacking the bHLH transcription factor (TF) Neurog3 do not form pancreatic islet cells, including insulin-secreting beta cells, the absence of which leads to diabetes. In humans, homozygous mutations of NEUROG3 manifest with neonatal or childhood diabetes. Despite this critical role in islet cell development, the precise function of and downstream genetic programs regulated directly by NEUROG3 remain elusive. Therefore, we mapped genome-wide NEUROG3 occupancy in human induced pluripotent stem cell (hiPSC)-derived endocrine progenitors and determined NEUROG3 dependency of associated genes to uncover direct targets. METHODS: We generated a novel hiPSC line (NEUROG3-HA-P2A-Venus) where NEUROG3 is HA-tagged and fused to a self-cleaving fluorescent VENUS reporter. We used the CUT\&amp;RUN technique to map NEUROG3 occupancy and epigenetic marks in pancreatic endocrine progenitors (PEP) that were differentiated from this hiPSC line. We integrated NEUROG3 occupancy data with chromatin status and gene expression in PEPs as well as their NEUROG3-dependence. In addition, we investigated whether NEUROG3 binds type 2 diabetes mellitus (T2DM)-associated variants at the PEP stage. RESULTS: CUT\&amp;RUN revealed a total of 863 NEUROG3 binding sites assigned to 1263 unique genes. NEUROG3 occupancy was found at promoters as well as at distant cis-regulatory elements that frequently overlapped within PEP active enhancers. De novo motif analyses defined a NEUROG3 consensus binding motif and suggested potential co-regulation of NEUROG3 target genes by FOXA or RFX transcription factors. We found that 22\% of the genes downregulated in NEUROG3 PEPs, and 10\% of genes enriched in NEUROG3-Venus positive endocrine cells were bound by NEUROG3 and thus likely to be directly regulated. NEUROG3 binds to 138 transcription factor genes, some with important roles in islet cell development or function, such as NEUROD1, PAX4, NKX2-2, SOX4, MLXIPL, LMX1B, RFX3, and NEUROG3 itself, and many others with unknown islet function. Unexpectedly, we uncovered that NEUROG3 targets genes critical for insulin secretion in beta cells (e.g., GCK, ABCC8/KCNJ11, CACNA1A, CHGA, SCG2, SLC30A8, and PCSK1). Thus, analysis of NEUROG3 occupancy suggests that the transient expression of NEUROG3 not only promotes islet destiny in uncommitted pancreatic progenitors, but could also initiate endocrine programs essential for beta cell function. Lastly, we identified eight T2DM risk SNPs within NEUROG3-bound regions. CONCLUSION: Mapping NEUROG3 genome occupancy in PEPs uncovered unexpectedly broad, direct control of the endocrine genes, raising novel hypotheses on how this master regulator controls islet and beta cell differentiation.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.04.14.439685',
			'doi' => '10.1016/j.molmet.2021.101313',
			'modified' => '2023-08-01 13:46:35',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 30 => array(
			'id' => '4285',
			'name' => 'Alveolar macrophages from persons living with HIV show impairedepigenetic response to Mycobacterium tuberculosis.',
			'authors' => 'Correa-Macedo Wilian et al.',
			'description' => '<p>Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV and antiretroviral therapy (ART) impact on the anti-mycobacterial response of AM is not known. To investigate the impact of HIV and ART on the transcriptomic and epigenetic response of AM to Mtb, we obtained AM by bronchoalveolar lavage from 20 PLWH receiving ART, 16 control subjects who were HIV-free (HC), and 14 subjects who received ART as pre-exposure prophylaxis (PrEP) to prevent HIV infection. Following in-vitro challenge with Mtb, AM from each group displayed overlapping but distinct profiles of significantly up- and down-regulated genes in response to Mtb. Comparatively, AM isolated from both PLWH and PrEP subjects presented a substantially weaker transcriptional response. In addition, AM from HC subjects challenged with Mtb responded with pronounced chromatin accessibility changes while AM obtained from PLWH and PrEP subjects displayed no significant changes in their chromatin state. Collectively, these results revealed a stronger adverse effect of ART than HIV on the epigenetic landscape and transcriptional responsiveness of AM.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/34473646/',
			'doi' => '10.1172/JCI148013',
			'modified' => '2022-05-24 09:08:39',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 31 => 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) 32 => array(
			'id' => '4304',
			'name' => 'The related coactivator complexes SAGA and ATAC control embryonicstem cell self-renewal through acetyltransferase-independent mechanisms',
			'authors' => 'Fischer Veronique et al.',
			'description' => '<p>SUMMARY SAGA (Spt-Ada-Gcn5 acetyltransferase) and ATAC (Ada-two-A-containing) are two related coactivator complexes, sharing the same histone acetyltransferase (HAT) subunit. The HAT activities of SAGA and ATAC are required for metazoan development, but the role of these complexes in RNA polymerase II transcription is less understood. To determine whether SAGA and ATAC have redundant or specific functions, we compare the effects of HAT inactivation in each complex with that of inactivation of either SAGA or ATAC core subunits in mouse embryonic stem cells (ESCs). We show that core subunits of SAGA or ATAC are required for complex assembly and mouse ESC growth and self-renewal. Surprisingly, depletion of HAT module subunits causes a global decrease in histone H3K9 acetylation, but does not result in significant phenotypic or transcriptional defects. Thus, our results indicate that SAGA and ATAC are differentially required for self-renewal of mouse ESCs by regulating transcription through different pathways in a HAT-independent manner.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34433046',
			'doi' => '10.1016/j.celrep.2021.109598',
			'modified' => '2022-05-30 09:57:39',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 33 => array(
			'id' => '4345',
			'name' => 'Altered Chromatin States Drive Cryptic Transcription in AgingMammalian Stem Cells.',
			'authors' => 'McCauley Brenna S et al.',
			'description' => '<p>A repressive chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation suppresses cryptic transcription in embryonic stem cells. Cryptic transcription is elevated with age in yeast and nematodes, and reducing it extends yeast lifespan, though whether this occurs in mammals is unknown. We show that cryptic transcription is elevated in aged mammalian stem cells, including murine hematopoietic stem cells (mHSCs) and neural stem cells (NSCs) and human mesenchymal stem cells (hMSCs). Precise mapping allowed quantification of age-associated cryptic transcription in hMSCs aged . Regions with significant age-associated cryptic transcription have a unique chromatin signature: decreased H3K36me3 and increased H3K4me1, H3K4me3, and H3K27ac with age. Genomic regions undergoing such changes resemble known promoter sequences and are bound by TBP even in young cells. Hence, the more permissive chromatin state at intragenic cryptic promoters likely underlies increased cryptic transcription in aged mammalian stem cells.</p>',
			'date' => '2021-08-01',
			'pmid' => 'https://doi.org/10.1038%2Fs43587-021-00091-x',
			'doi' => '10.1038/s43587-021-00091-x',
			'modified' => '2022-06-22 12:30:19',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 34 => array(
			'id' => '4333',
			'name' => 'Metabolically controlled histone H4K5 acylation/acetylation ratiodrives BRD4 genomic distribution.',
			'authors' => 'Gao M. et al.',
			'description' => '<p>In addition to acetylation, histones are modified by a series of competing longer-chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions hinder our understanding of histone acylations' specific roles. Here, by using an acute lymphoblastic leukemia (ALL) cell model and blasts from individuals with B-precusor ALL (B-ALL), we demonstrate a role of mitochondrial activity in controlling the histone acylation/acetylation ratio, especially at histone H4 lysine 5 (H4K5). An increase in the ratio of non-acetyl acylations (crotonylation or butyrylation) over acetylation on H4K5 weakens bromodomain containing protein 4 (BRD4) bromodomain-dependent chromatin interaction and enhances BRD4 nuclear mobility and availability for binding transcription start site regions of active genes. Our data suggest that the metabolism-driven control of the histone acetylation/longer-chain acylation(s) ratio could be a common mechanism regulating the bromodomain factors' functional genomic distribution.</p>',
			'date' => '2021-07-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.celrep.2021.109460',
			'doi' => '10.1016/j.celrep.2021.109460',
			'modified' => '2022-08-03 16:14:09',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 35 => array(
			'id' => '4341',
			'name' => 'Heterogeneity of neurons reprogrammed from spinal cord astrocytes by theproneural factors Ascl1 and Neurogenin2',
			'authors' => 'Kempf J. et al. ',
			'description' => '<p>Summary Astrocytes are a viable source for generating new neurons via direct conversion. However, little is known about the neurogenic cascades triggered in astrocytes from different regions of the CNS. Here, we examine the transcriptome induced by the proneural factors Ascl1 and Neurog2 in spinal cord-derived astrocytes in vitro. Each factor initially elicits different neurogenic programs that later converge to a V2 interneuron-like state. Intriguingly, patch sequencing (patch-seq) shows no overall correlation between functional properties and the transcriptome of the heterogenous induced neurons, except for K-channels. For example, some neurons with fully mature electrophysiological properties still express astrocyte genes, thus calling for careful molecular and functional analysis. Comparing the transcriptomes of spinal cord- and cerebral-cortex-derived astrocytes reveals profound differences, including developmental patterning cues maintained in vitro. These relate to the distinct neuronal identity elicited by Ascl1 and Neurog2 reflecting their developmental functions in subtype specification of the respective CNS region.</p>',
			'date' => '2021-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34289357',
			'doi' => '10.1016/j.celrep.2021.109409',
			'modified' => '2022-08-03 16:29:33',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 36 => 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) 37 => 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) 38 => array(
			'id' => '4147',
			'name' => 'Waves of sumoylation support transcription dynamics during adipocytedifferentiation',
			'authors' => 'Zhao, X. et al.',
			'description' => '<p>Tight control of gene expression networks required for adipose tissue formation and plasticity is essential for adaptation to energy needs and environmental cues. However, little is known about the mechanisms that orchestrate the dramatic transcriptional changes leading to adipocyte differentiation. We investigated the regulation of nascent transcription by the sumoylation pathway during adipocyte differentiation using SLAMseq and ChIPseq. We discovered that the sumoylation pathway has a dual function in differentiation; it supports the initial downregulation of pre-adipocyte-specific genes, while it promotes the establishment of the mature adipocyte transcriptional program. By characterizing sumoylome dynamics in differentiating adipocytes by mass spectrometry, we found that sumoylation of specific transcription factors like Ppar&gamma;/RXR and their co-factors is associated with the transcription of adipogenic genes. Our data demonstrate that the sumoylation pathway coordinates the rewiring of transcriptional networks required for formation of functional adipocytes. This study also provides an in-depth resource of gene transcription dynamics, SUMO-regulated genes and sumoylation sites during adipogenesis.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.02.20.432084',
			'doi' => '10.1101/2021.02.20.432084',
			'modified' => '2021-12-14 09:23:28',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 39 => array(
			'id' => '4192',
			'name' => 'Polycomb Repressive Complex 2 and KRYPTONITE regulate pathogen-inducedprogrammed cell death in Arabidopsis.',
			'authors' => 'Dvořák Tomaštíková E. et al.',
			'description' => '<p>The Polycomb Repressive Complex 2 (PRC2) is well-known for its role in controlling developmental transitions by suppressing the premature expression of key developmental regulators. Previous work revealed that PRC2 also controls the onset of senescence, a form of developmental programmed cell death (PCD) in plants. Whether the induction of PCD in response to stress is similarly suppressed by the PRC2 remained largely unknown. In this study, we explored whether PCD triggered in response to immunity- and disease-promoting pathogen effectors is associated with changes in the distribution of the PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) modification in Arabidopsis thaliana. We furthermore tested the distribution of the heterochromatic histone mark H3K9me2, which is established, to a large extent, by the H3K9 methyltransferase KRYPTONITE, and occupies chromatin regions generally not targeted by PRC2. We report that effector-induced PCD caused major changes in the distribution of both repressive epigenetic modifications and that both modifications have a regulatory role and impact on the onset of PCD during pathogen infection. Our work highlights that the transition to pathogen-induced PCD is epigenetically controlled, revealing striking similarities to developmental PCD.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33566101',
			'doi' => '10.1093/plphys/kiab035',
			'modified' => '2022-01-06 14:12:23',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 40 => array(
			'id' => '4273',
			'name' => 'An integrated multi-omics analysis identifies prognostic molecularsubtypes of non-muscle-invasive bladder cancer',
			'authors' => 'Lindskrog Sia Viborg et al.',
			'description' => '<p>The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n&thinsp;=&thinsp;834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33863885',
			'doi' => '10.1038/s41467-021-22465-w',
			'modified' => '2022-05-23 09:49:43',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 41 => 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) 42 => array(
			'id' => '4109',
			'name' => 'VPRBP functions downstream of the androgen receptor and OGT to restrict p53 activation in prostate cancer ',
			'authors' => 'Poulose N. et al. ',
			'description' => '<p>Androgen receptor (AR) is a major driver of prostate cancer (PCa) initiation and progression. O-GlcNAc transferase (OGT), the enzyme that catalyses the covalent addition of UDP-N-acetylglucosamine (UDP-GlcNAc) to serine and threonine residues of proteins, is often up-regulated in PCa with its expression correlated with high Gleason score. In this study we have identified an AR and OGT co-regulated factor, VPRBP/DCAF1. We show that VPRBP is regulated by the AR at the transcript level, and by OGT at the protein level. In human tissue samples, VPRBP protein expression correlated with AR amplification, OGT overexpression and poor prognosis. VPRBP knockdown in prostate cancer cells led to a significant decrease in cell proliferation, p53 stabilization, nucleolar fragmentation and increased p53 recruitment to the chromatin. In conclusion, we have shown that VPRBP/DCAF1 promotes prostate cancer cell proliferation by restraining p53 activation under the influence of the AR and OGT.</p>',
			'date' => '2021-02-21',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/2021.02.28.433236v1',
			'doi' => '',
			'modified' => '2021-07-07 11:59:15',
			'created' => '2021-07-07 11:59:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 43 => array(
			'id' => '4124',
			'name' => 'JAZF1, A Novel p400/TIP60/NuA4 Complex Member, Regulates H2A.ZAcetylation at Regulatory Regions.',
			'authors' => 'Procida, Tara and Friedrich, Tobias and Jack, Antonia P M and Peritore,Martina and Bönisch, Clemens and Eberl, H Christian and Daus, Nadine andKletenkov, Konstantin and Nist, Andrea and Stiewe, Thorsten and Borggrefe,Tilman and Mann, Matthias and Bartk',
			'description' => '<p>Histone variants differ in amino acid sequence, expression timing and genomic localization sites from canonical histones and convey unique functions to eukaryotic cells. Their tightly controlled spatial and temporal deposition into specific chromatin regions is accomplished by dedicated chaperone and/or remodeling complexes. While quantitatively identifying the chaperone complexes of many human H2A variants by using mass spectrometry, we also found additional members of the known H2A.Z chaperone complexes p400/TIP60/NuA4 and SRCAP. We discovered JAZF1, a nuclear/nucleolar protein, as a member of a p400 sub-complex containing MBTD1 but excluding ANP32E. Depletion of JAZF1 results in transcriptome changes that affect, among other pathways, ribosome biogenesis. To identify the underlying molecular mechanism contributing to JAZF1's function in gene regulation, we performed genome-wide ChIP-seq analyses. Interestingly, depletion of JAZF1 leads to reduced H2A.Z acetylation levels at &gt; 1000 regulatory sites without affecting H2A.Z nucleosome positioning. Since JAZF1 associates with the histone acetyltransferase TIP60, whose depletion causes a correlated H2A.Z deacetylation of several JAZF1-targeted enhancer regions, we speculate that JAZF1 acts as chromatin modulator by recruiting TIP60's enzymatic activity. Altogether, this study uncovers JAZF1 as a member of a TIP60-containing p400 chaperone complex orchestrating H2A.Z acetylation at regulatory regions controlling the expression of genes, many of which are involved in ribosome biogenesis.</p>',
			'date' => '2021-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33445503',
			'doi' => '10.3390/ijms22020678',
			'modified' => '2021-12-07 10:00:44',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 44 => array(
			'id' => '4153',
			'name' => 'Epigenetic impairment and blunted transcriptional response to Mycobacteriumtuberculosis of alveolar macrophages from persons living with HIV',
			'authors' => 'Correa-Macedo, W. et al.',
			'description' => '<p>Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV and antiretroviral therapy (ART) impact on the anti-mycobacterial response of AM is not known. To investigate the impact of HIV and ART on the transcriptomic and epigenetic response of AM to Mtb, we obtained AM by bronchoalveolar lavage from 20 PLWH receiving ART, 16 control subjects who were HIV-free (HC), and 14 subjects who received ART as pre-exposure prophylaxis (PrEP) to prevent HIV infection. Following in-vitro challenge with Mtb, AM from each group displayed overlapping but distinct profiles of significantly up- and down-regulated genes in response to Mtb. Compared to HC subjects, AM isolated from PLWH and PrEP subjects presented a substantially weaker transcriptional response. Further investigation of chromatin structure revealed that AM from control subjects challenged with Mtb responded with pronounced accessibility changes in over ten thousand regions. In stark contrast, AM obtained from PLWH and PrEP subjects displayed no significant changes in their chromatin state in response to Mtb. Collectively, these results revealed a previously unknown adverse effect of ART on the epigenetic landscape and transcriptional responsiveness of AM.</p>',
			'date' => '2021-01-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.01.26.21250318',
			'doi' => '10.1101/2021.01.26.21250318',
			'modified' => '2021-12-16 10:35:21',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 45 => array(
			'id' => '4179',
			'name' => 'Histone demethylase JMJD2B/KDM4B regulates transcriptional program viadistinctive epigenetic targets and protein interactors for the maintenanceof trophoblast stem cells.',
			'authors' => 'Mak, Kylie Hin-Man et al.',
			'description' => '<p>Trophoblast stem cell (TSC) is crucial to the formation of placenta in mammals. Histone demethylase JMJD2 (also known as KDM4) family proteins have been previously shown to support self-renewal and differentiation of stem cells. However, their roles in the context of the trophoblast lineage remain unclear. Here, we find that knockdown of Jmjd2b resulted in differentiation of TSCs, suggesting an indispensable role of JMJD2B/KDM4B in maintaining the stemness. Through the integration of transcriptome and ChIP-seq profiling data, we show that JMJD2B is associated with a loss of H3K36me3 in a subset of embryonic lineage genes which are marked by H3K9me3 for stable repression. By characterizing the JMJD2B binding motifs and other transcription factor binding datasets, we discover that JMJD2B forms a protein complex with AP-2 family transcription factor TFAP2C and histone demethylase LSD1. The JMJD2B-TFAP2C-LSD1 complex predominantly occupies active gene promoters, whereas the TFAP2C-LSD1 complex is located at putative enhancers, suggesting that these proteins mediate enhancer-promoter interaction for gene regulation. We conclude that JMJD2B is vital to the TSC transcriptional program and safeguards the trophoblast cell fate via distinctive protein interactors and epigenetic targets.</p>',
			'date' => '2021-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33441614',
			'doi' => '10.1038/s41598-020-79601-7',
			'modified' => '2021-12-21 16:43:16',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 46 => array(
			'id' => '4038',
			'name' => 'Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture.',
			'authors' => 'Yusufova, Nevin and Kloetgen, Andreas and Teater, Matt and Osunsade,Adewola and Camarillo, Jeannie M and Chin, Christopher R and Doane, AshleyS and Venters, Bryan J and Portillo-Ledesma, Stephanie and Conway, Josephand Phillip, Jude M and Elemento, Oli',
			'description' => '<p>Linker histone H1 proteins bind to nucleosomes and facilitate chromatin compaction, although their biological functions are poorly understood. Mutations in the genes that encode H1 isoforms B-E (H1B, H1C, H1D and H1E; also known as H1-5, H1-2, H1-3 and H1-4, respectively) are highly recurrent in B&nbsp;cell lymphomas, but the pathogenic relevance of these mutations to cancer and the mechanisms that are involved are unknown. Here we show that lymphoma-associated H1 alleles are genetic driver mutations in lymphomas. Disruption of H1 function results in a profound architectural remodelling of the genome, which is characterized by large-scale yet focal shifts of chromatin from a compacted to a relaxed state. This decompaction drives distinct changes in epigenetic states, primarily owing to a gain of histone H3 dimethylation at lysine 36 (H3K36me2) and/or loss of repressive H3 trimethylation at lysine 27 (H3K27me3). These changes unlock the expression of stem cell genes that are normally silenced during early development. In mice, loss of H1c and H1e (also known as H1f2 and H1f4, respectively) conferred germinal centre B&nbsp;cells with enhanced fitness and self-renewal properties, ultimately leading to aggressive lymphomas with an increased repopulating potential. Collectively, our data indicate that H1 proteins are normally required to sequester early developmental genes into architecturally inaccessible genomic compartments. We also establish H1 as a bona fide tumour suppressor and show that mutations in H1 drive malignant transformation primarily through three-dimensional genome reorganization, which leads to epigenetic reprogramming and derepression of developmentally silenced genes.</p>',
			'date' => '2020-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33299181',
			'doi' => '10.1038/s41586-020-3017-y',
			'modified' => '2021-02-18 17:15:52',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 47 => array(
			'id' => '4056',
			'name' => 'Multi-omic comparison of Alzheimer's variants in human ESC-derivedmicroglia reveals convergence at APOE.',
			'authors' => 'Liu, Tongfei and Zhu, Bing and Liu, Yan and Zhang, Xiaoming and Yin, Junand Li, Xiaoguang and Jiang, LuLin and Hodges, Andrew P and Rosenthal, SaraBrin and Zhou, Lisa and Yancey, Joel and McQuade, Amanda and Blurton-Jones,Mathew and Tanzi, Rudolph E an',
			'description' => '<p>Variations in many genes linked to sporadic Alzheimer's disease (AD) show abundant expression in microglia, but relationships among these genes remain largely elusive. Here, we establish isogenic human ESC-derived microglia-like cell lines (hMGLs) harboring AD variants in CD33, INPP5D, SORL1, and TREM2 loci and curate a comprehensive atlas comprising ATAC-seq, ChIP-seq, RNA-seq, and proteomics datasets. AD-like expression signatures are observed in AD mutant SORL1 and TREM2 hMGLs, while integrative multi-omic analysis of combined epigenetic and expression datasets indicates up-regulation of APOE as a convergent pathogenic node. We also observe cross-regulatory relationships between SORL1 and TREM2, in which SORL1R744X hMGLs induce TREM2 expression to enhance APOE expression. AD-associated SORL1 and TREM2 mutations also impaired hMGL A&beta; uptake in an APOE-dependent manner in vitro and attenuated A&beta; uptake/clearance in mouse AD brain xenotransplants. Using this modeling and analysis platform for human microglia, we provide new insight into epistatic interactions in AD genes and demonstrate convergence of microglial AD genes at the APOE locus.</p>',
			'date' => '2020-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32941599',
			'doi' => '10.1084/jem.20200474',
			'modified' => '2021-02-19 17:18:23',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 48 => array(
			'id' => '4060',
			'name' => 'A genetic variant controls interferon-β gene expression in human myeloidcells by preventing C/EBP-β binding on a conserved enhancer.',
			'authors' => 'Assouvie, Anaïs and Rotival, Maxime and Hamroune, Juliette and Busso,Didier and Romeo, Paul-Henri and Quintana-Murci, Lluis and Rousselet,Germain',
			'description' => '<p>Interferon &beta; (IFN-&beta;) is a cytokine that induces a global antiviral proteome, and regulates the adaptive immune response to infections and tumors. Its effects strongly depend on its level and timing of expression. Therefore, the transcription of its coding gene IFNB1 is strictly controlled. We have previously shown that in mice, the TRIM33 protein restrains Ifnb1 transcription in activated myeloid cells through an upstream inhibitory sequence called ICE. Here, we show that the deregulation of Ifnb1 expression observed in murine Trim33-/- macrophages correlates with abnormal looping of both ICE and the Ifnb1 gene to a 100 kb downstream region overlapping the Ptplad2/Hacd4 gene. This region is a predicted myeloid super-enhancer in which we could characterize 3 myeloid-specific active enhancers, one of which (E5) increases the response of the Ifnb1 promoter to activation. In humans, the orthologous region contains several single nucleotide polymorphisms (SNPs) known to be associated with decreased expression of IFNB1 in activated monocytes, and loops to the IFNB1 gene. The strongest association is found for the rs12553564 SNP, located in the E5 orthologous region. The minor allele of rs12553564 disrupts a conserved C/EBP-&beta; binding motif, prevents binding of C/EBP-&beta;, and abolishes the activation-induced enhancer activity of E5. Altogether, these results establish a link between a genetic variant preventing binding of a transcription factor and a higher order phenotype, and suggest that the frequent minor allele (around 30\% worldwide) might be associated with phenotypes regulated by IFN-&beta; expression in myeloid cells.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33147208',
			'doi' => '10.1371/journal.pgen.1009090',
			'modified' => '2021-02-19 17:29:34',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 49 => 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) 50 => array(
			'id' => '4210',
			'name' => 'Trans- and cis-acting effects of Firre on epigenetic features of theinactive X chromosome.',
			'authors' => 'Fang, He and Bonora, Giancarlo and Lewandowski, Jordan P and Thakur,Jitendra and Filippova, Galina N and Henikoff, Steven and Shendure, Jay andDuan, Zhijun and Rinn, John L and Deng, Xinxian and Noble, William S andDisteche, Christine M',
			'description' => '<p>Firre encodes a lncRNA involved in nuclear organization. Here, we show that Firre RNA expressed from the active X chromosome maintains histone H3K27me3 enrichment on the inactive X chromosome (Xi) in somatic cells. This trans-acting effect involves SUZ12, reflecting interactions between Firre RNA and components of the Polycomb repressive complexes. Without Firre RNA, H3K27me3 decreases on the Xi and the&nbsp;Xi-perinucleolar location is disrupted, possibly due to decreased CTCF binding on the Xi. We also observe widespread gene dysregulation, but not on the Xi. These effects are measurably rescued by ectopic expression of mouse or human Firre/FIRRE transgenes, supporting conserved trans-acting roles. We also find that the compact 3D structure of the Xi partly depends on the Firre locus and its RNA. In common lymphoid progenitors and T-cells Firre exerts a cis-acting effect on maintenance of H3K27me3 in a 26&thinsp;Mb region around the locus, demonstrating cell type-specific trans- and cis-acting roles of this lncRNA.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33247132',
			'doi' => '10.1038/s41467-020-19879-3',
			'modified' => '2022-01-13 15:03:45',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 51 => array(
			'id' => '4048',
			'name' => 'The histone H2B ubiquitin ligase RNF40 is required for HER2-drivenmammary tumorigenesis.',
			'authors' => 'Wegwitz, Florian and Prokakis, Evangelos and Pejkovska, Anastasija andKosinsky, Robyn Laura and Glatzel, Markus and Pantel, Klaus and Wikman,Harriet and Johnsen, Steven A',
			'description' => '<p>The HER2-positive breast cancer subtype (HER2-BC) displays a particularly aggressive behavior. Anti-HER2 therapies have significantly improved the survival of patients with HER2-BC. However, a large number of patients become refractory to current targeted therapies, necessitating the development of new treatment strategies. Epigenetic regulators are commonly misregulated in cancer and represent attractive molecular therapeutic targets. Monoubiquitination of histone 2B (H2Bub1) by the heterodimeric ubiquitin ligase complex RNF20/RNF40 has been described to have tumor suppressor functions and loss of H2Bub1 has been associated with cancer progression. In this study, we utilized human tumor samples, cell culture models, and a mammary carcinoma mouse model with tissue-specific Rnf40 deletion and identified an unexpected tumor-supportive role of RNF40 in HER2-BC. We demonstrate that RNF40-driven H2B monoubiquitination is essential for transcriptional activation of RHO/ROCK/LIMK pathway components and proper actin-cytoskeleton dynamics through a trans-histone crosstalk with histone 3 lysine 4 trimethylation (H3K4me3). Collectively, this work demonstrates a previously unknown essential role of RNF40 in HER2-BC, revealing the H2B monoubiquitination axis as a possible tumor context-dependent therapeutic target in breast cancer.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33070155',
			'doi' => '10.1038/s41419-020-03081-w',
			'modified' => '2021-02-19 14:03:18',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 52 => array(
			'id' => '4065',
			'name' => 'Polycomb Repressive Complex 2-mediated histone modification H3K27me3 isassociated with embryogenic potential in Norway spruce.',
			'authors' => 'Nakamura, Miyuki and Batista, Rita A and Köhler, Claudia and Hennig, Lars',
			'description' => '<p>Epigenetic reprogramming during germ cell formation is essential to gain pluripotency and thus embryogenic potential. The histone modification H3K27me3, which is catalysed by the Polycomb repressive complex 2 (PRC2), regulates important developmental processes in both plants and animals, and defects in PRC2 components cause pleiotropic developmental abnormalities. Nevertheless, the role of H3K27me3 in determining embryogenic potential in gymnosperms is still elusive. To address this, we generated H3K27me3 profiles of Norway spruce (Picea abies) embryonic callus and non-embryogenic callus using CUT\&amp;RUN, which is a powerful method for chromatin profiling. Here, we show that H3K27me3 mainly accumulated in genic regions in the Norway spruce genome, similarly to what is observed in other plant species. Interestingly, H3K27me3 levels in embryonic callus were much lower than those in the other examined tissues, but markedly increased upon embryo induction. These results show that H3K27me3 levels are associated with the embryogenic potential of a given tissue, and that the early phase of somatic embryogenesis is accompanied by changes in H3K27me3 levels. Thus, our study provides novel insights into the role of this epigenetic mark in spruce embryogenesis and reinforces the importance of PRC2 as a key regulator of cell fate determination across different plant species.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32894759',
			'doi' => '10.1093/jxb/eraa365',
			'modified' => '2021-02-19 17:45:29',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 53 => array(
			'id' => '4384',
			'name' => 'Age-associated cryptic transcription in mammalian stem cells is linked topermissive chromatin at cryptic promoters',
			'authors' => 'McCauley  B. S. et al.',
			'description' => '<p>Suppressing spurious cryptic transcription by a repressive intragenic chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation is critical for maintaining self-renewal capacity in mouse embryonic stem cells. In yeast and nematodes, such cryptic transcription is elevated with age, and reducing the levels of age-associated cryptic transcription extends yeast lifespan. Whether cryptic transcription is also increased during mammalian aging is unknown. We show for the first time an age-associated elevation in cryptic transcription in several stem cell populations, including murine hematopoietic stem cells (mHSCs) and neural stem cells (NSCs) and human mesenchymal stem cells (hMSCs). Using DECAP-seq, we mapped and quantified age-associated cryptic transcription in hMSCs aged in vitro. Regions with significant age-associated cryptic transcription have a unique chromatin signature: decreased H3K36me3 and increased H3K4me1, H3K4me3, and H3K27ac with age. Furthermore, genomic regions undergoing such age-dependent chromatin changes resemble known promoter sequences and are bound by the promoter-associated protein TBP even in young cells. Hence, the more permissive chromatin state at intragenic cryptic promoters likely underlies the increase of cryptic transcription in aged mammalian stem cells.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://europepmc.org/article/ppr/ppr221829',
			'doi' => '10.21203/rs.3.rs-82156/v1',
			'modified' => '2022-08-04 16:24:46',
			'created' => '2022-08-04 14:55:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 54 => array(
			'id' => '4076',
			'name' => 'RNF40 exerts stage-dependent functions in differentiating osteoblasts andis essential for bone cell crosstalk.',
			'authors' => 'Najafova, Zeynab and Liu, Peng and Wegwitz, Florian and Ahmad, Mubashir andTamon, Liezel and Kosinsky, Robyn Laura and Xie, Wanhua and Johnsen, StevenA and Tuckermann, Jan',
			'description' => '<p>The role of histone ubiquitination in directing cell lineage specification is only poorly understood. Our previous work indicated a role of the histone 2B ubiquitin ligase RNF40 in controlling osteoblast differentiation in vitro. Here, we demonstrate that RNF40 has a stage-dependent function in controlling osteoblast differentiation in vivo. RNF40 expression is essential for early stages of lineage specification, but is dispensable in mature osteoblasts. Paradoxically, while osteoblast-specific RNF40 deletion led to impaired bone formation, it also resulted in increased bone mass due to impaired bone cell crosstalk. Loss of RNF40 resulted in decreased osteoclast number and function through modulation of&nbsp;RANKL expression in OBs. Mechanistically, we demonstrate that&nbsp;Tnfsf11 (encoding RANKL)&nbsp;is an important target gene of H2B monoubiquitination. These data reveal an important role of RNF40-mediated H2B monoubiquitination in bone formation and remodeling and provide a basis for exploring this pathway for the treatment of conditions such as osteoporosis or cancer-associated osteolysis.</p>',
			'date' => '2020-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32901120',
			'doi' => '10.1038/s41418-020-00614-w',
			'modified' => '2021-02-19 18:10:55',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 55 => 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) 56 => array(
			'id' => '4010',
			'name' => 'Combined treatment with CBP and BET inhibitors reverses inadvertentactivation of detrimental super enhancer programs in DIPG cells.',
			'authors' => 'Wiese, M and Hamdan, FH and Kubiak, K and Diederichs, C and Gielen, GHand Nussbaumer, G and Carcaboso, AM and Hulleman, E and Johnsen, SA andKramm, CM',
			'description' => '<p>Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation. Hyperacetylation in DIPG favors the action of the Bromodomain and Extra-Terminal (BET) protein BRD4, and leads to the reprogramming of the enhancer landscape contributing to the activation of DIPG super enhancer-driven oncogenes. The activity of the acetyltransferase CREB-binding protein (CBP) is enhanced by BRD4 and associated with acetylation of nucleosomes at super enhancers (SE). In addition, CBP contributes to transcriptional activation through its function as a scaffold and protein bridge. Monotherapy with either a CBP (ICG-001) or BET inhibitor (JQ1) led to the reduction of tumor-related characteristics. Interestingly, combined treatment induced strong cytotoxic effects in H3.3K27M-mutated DIPG cell lines. RNA sequencing and chromatin immunoprecipitation revealed that these effects were caused by the inactivation of DIPG SE-controlled tumor-related genes. However, single treatment with ICG-001 or JQ1, respectively, led to activation of a subgroup of detrimental super enhancers. Combinatorial treatment reversed the inadvertent activation of these super enhancers and rescued the effect of ICG-001 and JQ1 single treatment on enhancer-driven oncogenes in H3K27M-mutated DIPG, but not in H3 wild-type pedHGG cells. In conclusion, combinatorial treatment with CBP and BET inhibitors is highly efficient in H3K27M-mutant DIPG due to reversal of inadvertent activation of detrimental SE programs in comparison with monotherapy.</p>',
			'date' => '2020-08-21',
			'pmid' => 'http://www.pubmed.gov/32826850',
			'doi' => '10.1038/s41419-020-02800-7',
			'modified' => '2020-12-18 13:25:09',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 57 => array(
			'id' => '4011',
			'name' => 'Exploring the virulence gene interactome with CRISPR/dCas9 in the humanmalaria parasite.',
			'authors' => 'Bryant, JM and Baumgarten, S and Dingli, F and Loew, D and Sinha, A andClaës, A and Preiser, PR and Dedon, PC and Scherf, A',
			'description' => '<p>Mutually exclusive expression of the var multigene family is key to immune evasion and pathogenesis in Plasmodium falciparum, but few factors have been shown to play a direct role. We adapted a CRISPR-based proteomics approach to identify novel factors associated with var genes in their natural chromatin context. Catalytically inactive Cas9 ("dCas9") was targeted to var gene regulatory elements, immunoprecipitated, and analyzed with mass spectrometry. Known and novel factors were enriched including structural proteins, DNA helicases, and chromatin remodelers. Functional characterization of PfISWI, an evolutionarily divergent putative chromatin remodeler enriched at the var gene promoter, revealed a role in transcriptional activation. Proteomics of PfISWI identified several proteins enriched at the var gene promoter such as acetyl-CoA synthetase, a putative MORC protein, and an ApiAP2 transcription factor. These findings validate the CRISPR/dCas9 proteomics method and define a new var gene-associated chromatin complex. This study establishes a tool for targeted chromatin purification of unaltered genomic loci and identifies novel chromatin-associated factors potentially involved in transcriptional control and/or chromatin organization of virulence genes in the human malaria parasite.</p>',
			'date' => '2020-08-02',
			'pmid' => 'http://www.pubmed.gov/32816370',
			'doi' => 'https://dx.doi.org/10.15252%2Fmsb.20209569',
			'modified' => '2020-12-18 13:26:33',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 58 => array(
			'id' => '4024',
			'name' => 'Tissue-Specific In Vivo Biotin Chromatin Immunoprecipitation withSequencing in Zebrafish and Chicken',
			'authors' => 'Lukoseviciute, Martyna and Ling, Irving T.C. and Senanayake, Upeka andCandido-Ferreira, Ivan and Taylor, Gunes and Williams, Ruth M. andSauka-Spengler, Tatjana',
			'description' => '<p>Chromatin immunoprecipitation with sequencing (ChIP-seq) has been instrumental in understanding transcription factor (TF) binding during gene regulation. ChIP-seq requires specific antibodies against desired TFs, which are not available for numerous species. Here, we describe a tissue-specific biotin ChIP-seq protocol for zebrafish and chicken embryos which utilizes AVI tagging of TFs, permitting their biotinylation by a co-expressed nuclear biotin ligase. Subsequently, biotinylated factors can be precipitated with streptavidin beads, enabling the user to construct TF genome-wide binding landscapes like conventional ChIP-seq methods.</p>',
			'date' => '2020-07-31',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S2666166720300538',
			'doi' => '10.1016/j.xpro.2020.100066',
			'modified' => '2020-12-16 17:50:09',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 59 => array(
			'id' => '4026',
			'name' => 'The gut microbiome switches mutant p53 from tumour-suppressive tooncogenic.',
			'authors' => 'Kadosh, E and Snir-Alkalay, I and Venkatachalam, A and May, S and Lasry, Aand Elyada, E and Zinger, A and Shaham, M and Vaalani, G and Mernberger, Mand Stiewe, T and Pikarsky, E and Oren, M and Ben-Neriah, Y',
			'description' => '<p>Somatic mutations in p53, which inactivate the tumour-suppressor function of p53 and often confer oncogenic gain-of-function properties, are very common in cancer. Here we studied the effects of hotspot gain-of-function mutations in Trp53 (the gene that encodes p53 in mice) in mouse models of WNT-driven intestinal cancer caused by Csnk1a1 deletion or Apc mutation. Cancer in these models is known to be facilitated by loss of p53. We found that mutant versions of p53 had contrasting effects in different segments of the gut: in the distal gut, mutant p53 had the expected oncogenic effect; however, in the proximal gut and in tumour organoids it had a pronounced tumour-suppressive effect. In the tumour-suppressive mode, mutant p53 eliminated dysplasia and tumorigenesis in Csnk1a1-deficient and Apc mice, and promoted normal growth and differentiation of tumour organoids derived from these mice. In these settings, mutant p53 was more effective than wild-type p53 at inhibiting tumour formation. Mechanistically, the tumour-suppressive effects of mutant p53 were driven by disruption of the WNT pathway, through preventing the binding of TCF4 to chromatin. Notably, this tumour-suppressive effect was completely abolished by the gut microbiome. Moreover, a single metabolite derived from the gut microbiota-gallic acid-could reproduce the entire effect of the microbiome. Supplementing gut-sterilized p53-mutant mice and p53-mutant organoids with gallic acid reinstated the TCF4-chromatin interaction and the hyperactivation of WNT, thus conferring a malignant phenotype to the organoids and throughout the gut. Our study demonstrates the substantial plasticity of a cancer mutation and highlights the role of the microenvironment in determining its functional outcome.</p>',
			'date' => '2020-07-29',
			'pmid' => 'http://www.pubmed.gov/32728212',
			'doi' => '10.1038/s41586-020-2541-0',
			'modified' => '2020-12-16 17:52:28',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 60 => array(
			'id' => '3992',
			'name' => 'Egr2-guided histone H2B monoubiquitination is required for peripheral nervous system myelination.',
			'authors' => 'Wüst HM, Wegener A, Fröb F, Hartwig AC, Wegwitz F, Kari V, Schimmel M, Tamm ER, Johnsen SA, Wegner M, Sock E',
			'description' => '<p>Schwann cells are the nerve ensheathing cells of the peripheral nervous system. Absence, loss and malfunction of Schwann cells or their myelin sheaths lead to peripheral neuropathies such as Charcot-Marie-Tooth disease in humans. During Schwann cell development and myelination chromatin is dramatically modified. However, impact and functional relevance of these modifications are poorly understood. Here, we analyzed histone H2B monoubiquitination as one such chromatin modification by conditionally deleting the Rnf40 subunit of the responsible E3 ligase in mice. Rnf40-deficient Schwann cells were arrested immediately before myelination or generated abnormally thin, unstable myelin, resulting in a peripheral neuropathy characterized by hypomyelination and progressive axonal degeneration. By combining sequencing techniques with functional studies we show that H2B monoubiquitination does not influence global gene expression patterns, but instead ensures selective high expression of myelin and lipid biosynthesis genes and proper repression of immaturity genes. This requires the specific recruitment of the Rnf40-containing E3 ligase by Egr2, the central transcriptional regulator of peripheral myelination, to its target genes. Our study identifies histone ubiquitination as essential for Schwann cell myelination and unravels new disease-relevant links between chromatin modifications and transcription factors in the underlying regulatory network.</p>',
			'date' => '2020-07-16',
			'pmid' => 'http://www.pubmed.gov/32672815',
			'doi' => '10.1093/nar/gkaa606',
			'modified' => '2020-09-01 15:02:28',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 61 => array(
			'id' => '4031',
			'name' => 'Battle of the sex chromosomes: competition between X- and Y-chromosomeencoded proteins for partner interaction and chromatin occupancy drivesmulti-copy gene expression and evolution in muroid rodents.',
			'authors' => 'Moretti, C and Blanco, M and Ialy-Radio, C and Serrentino, ME and Gobé,C and Friedman, R and Battail, C and Leduc, M and Ward, MA and Vaiman, Dand Tores, F and Cocquet, J',
			'description' => '<p>Transmission distorters (TDs) are genetic elements that favor their own transmission to the detriments of others. Slx/Slxl1 (Sycp3-like-X-linked and Slx-like1) and Sly (Sycp3-like-Y-linked) are TDs which have been co-amplified on the X and Y chromosomes of Mus species. They are involved in an intragenomic conflict in which each favors its own transmission, resulting in sex ratio distortion of the progeny when Slx/Slxl1 vs. Sly copy number is unbalanced. They are specifically expressed in male postmeiotic gametes (spermatids) and have opposite effects on gene expression: Sly knockdown leads to the upregulation of hundreds of spermatid-expressed genes, while Slx/Slxl1-deficiency downregulates them. When both Slx/Slxl1 and Sly are knocked-down, sex ratio distortion and gene deregulation are corrected. Slx/Slxl1 and Sly are, therefore, in competition but the molecular mechanism remains unknown. By comparing their chromatin binding profiles and protein partners, we show that SLX/SLXL1 and SLY proteins compete for interaction with H3K4me3-reader SSTY1 (Spermiogenesis-specific-transcript-on-the-Y1) at the promoter of thousands of genes to drive their expression, and that the opposite effect they have on gene expression is mediated by different abilities to recruit SMRT/N-Cor transcriptional complex. Their target genes are predominantly spermatid-specific multicopy genes encoded by the sex chromosomes and the autosomal Speer/Takusan. Many of them have co-amplified with Slx/Slxl1/Sly but also Ssty during muroid rodent evolution. Overall, we identify Ssty as a key element of the X vs. Y intragenomic conflict, which may have influenced gene content and hybrid sterility beyond Mus lineage since Ssty amplification on the Y pre-dated that of Slx/Slxl1/Sly.</p>',
			'date' => '2020-07-13',
			'pmid' => 'http://www.pubmed.gov/32658962',
			'doi' => '10.1093/molbev/msaa175/5870835',
			'modified' => '2020-12-18 13:27:51',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 62 => array(
			'id' => '3948',
			'name' => '2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters hepatic polyunsaturated fatty acid metabolism and eicosanoid biosynthesis in female Sprague-Dawley rats.',
			'authors' => 'Doskey CM, Fader KA, Nault R, Lydic T, Matthews J, Potter D, Sharratt B, Williams K, Zacharewski T',
			'description' => '<p>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent aryl hydrocarbon receptor (AhR) agonist that elicits a broad spectrum of dose-dependent hepatic effects including lipid accumulation, inflammation, and fibrosis. To determine the role of inflammatory lipid mediators in TCDD-mediated hepatotoxicity, eicosanoid metabolism was investigated. Female Sprague-Dawley (SD) rats were orally gavaged with sesame oil vehicle or 0.01-10&nbsp;&mu;g/kg TCDD every 4&nbsp;days for 28&nbsp;days. Hepatic RNA-Seq data was integrated with untargeted metabolomics of liver, serum, and urine, revealing dose-dependent changes in linoleic acid (LA) and arachidonic acid (AA) metabolism. TCDD also elicited dose-dependent differential gene expression associated with the cyclooxygenase, lipoxygenase, and cytochrome P450 epoxidation/hydroxylation pathways with corresponding changes in &omega;-6 (e.g. AA and LA) and &omega;-3 polyunsaturated fatty acids (PUFAs), as well as associated eicosanoid metabolites. Overall, TCDD increased the ratio of &omega;-6 to &omega;-3 PUFAs. Phospholipase A2 (Pla2g12a) was induced consistent with increased AA metabolism, while AA utilization by induced lipoxygenases Alox5 and Alox15 increased leukotrienes (LTs). More specifically, TCDD increased pro-inflammatory eicosanoids including leukotriene LTB, and LTB, known to recruit neutrophils to damaged tissue. Dose-response modeling suggests the cytochrome P450 hydroxylase/epoxygenase and lipoxygenase pathways are more sensitive to TCDD than the cyclooxygenase pathway. Hepatic AhR ChIP-Seq analysis found little enrichment within the regulatory regions of differentially expressed genes (DEGs) involved in eicosanoid biosynthesis, suggesting TCDD-elicited dysregulation of eicosanoid metabolism is a downstream effect of AhR activation. Overall, these results suggest alterations in eicosanoid metabolism may play a key role in TCDD-elicited hepatotoxicity associated with the progression of steatosis to steatohepatitis.</p>',
			'date' => '2020-07-01',
			'pmid' => 'http://www.pubmed.gov/32387183',
			'doi' => '10.1016/j.taap.2020.115034',
			'modified' => '2020-08-17 10:04:38',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 63 => 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) 64 => array(
			'id' => '3981',
			'name' => 'Vulnerability of drug-resistant EML4-ALK rearranged lung cancer to transcriptional inhibition.',
			'authors' => 'Paliouras AR, Buzzetti M, Shi L, Donaldson IJ, Magee P, Sahoo S, Leong HS, Fassan M, Carter M, Di Leva G, Krebs MG, Blackhall F, Lovly CM, Garofalo M',
			'description' => '<p>A subset of lung adenocarcinomas is driven by the EML4-ALK translocation. Even though ALK inhibitors in the clinic lead to excellent initial responses, acquired resistance to these inhibitors due to on-target mutations or parallel pathway alterations is a major clinical challenge. Exploring these mechanisms of resistance, we found that EML4-ALK cells parental or resistant to crizotinib, ceritinib or alectinib are remarkably sensitive to inhibition of CDK7/12 with THZ1 and CDK9 with alvocidib or dinaciclib. These compounds robustly induce apoptosis through transcriptional inhibition and downregulation of anti-apoptotic genes. Importantly, alvocidib reduced tumour progression in xenograft mouse models. In summary, our study takes advantage of the transcriptional addiction hypothesis to propose a new treatment strategy for a subset of patients with acquired resistance to first-, second- and third-generation ALK inhibitors.</p>',
			'date' => '2020-06-17',
			'pmid' => 'http://www.pubmed.gov/32558295',
			'doi' => 'https://doi.org/10.15252/emmm.201911099',
			'modified' => '2020-09-01 15:20:40',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 65 => array(
			'id' => '3975',
			'name' => 'Removal of H2Aub1 by ubiquitin-specific proteases 12 and 13 is required for stable Polycomb-mediated gene repression in Arabidopsis.',
			'authors' => 'Kralemann LEM, Liu S, Trejo-Arellano MS, Muñoz-Viana R, Köhler C, Hennig L',
			'description' => '<p>BACKGROUND: Stable gene repression is essential for normal growth and development. Polycomb repressive complexes 1 and 2 (PRC1&amp;2) are involved in this process by establishing monoubiquitination of histone 2A (H2Aub1) and subsequent trimethylation of lysine 27 of histone 3 (H3K27me3). Previous work proposed that H2Aub1 removal by the ubiquitin-specific proteases 12 and 13 (UBP12 and UBP13) is part of the repressive PRC1&amp;2 system, but its functional role remains elusive. RESULTS: We show that UBP12 and UBP13 work together with PRC1, PRC2, and EMF1 to repress genes involved in stimulus response. We find that PRC1-mediated H2Aub1 is associated with gene responsiveness, and its repressive function requires PRC2 recruitment. We further show that the requirement of PRC1 for PRC2 recruitment depends on the initial expression status of genes. Lastly, we demonstrate that removal of H2Aub1 by UBP12/13 prevents loss of H3K27me3, consistent with our finding that the H3K27me3 demethylase REF6 is positively associated with H2Aub1. CONCLUSIONS: Our data allow us to propose a model in which deposition of H2Aub1 permits genes to switch between repression and activation by H3K27me3 deposition and removal. Removal of H2Aub1 by UBP12/13 is required to achieve stable PRC2-mediated repression.</p>',
			'date' => '2020-06-16',
			'pmid' => 'http://www.pubmed.gov/32546254',
			'doi' => '10.1186/s13059-020-02062-8',
			'modified' => '2020-08-12 09:23:32',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 66 => array(
			'id' => '3969',
			'name' => 'Delineating the early transcriptional specification of the mammalian trachea and esophagus.',
			'authors' => 'Kuwahara A, Lewis AE, Coombes C, Leung FS, Percharde M, Bush JO',
			'description' => '<p>The genome-scale transcriptional programs that specify the mammalian trachea and esophagus are unknown. Though NKX2-1 and SOX2 are hypothesized to be co-repressive master regulators of tracheoesophageal fates, this is untested at a whole transcriptomic scale and their downstream networks remain unidentified. By combining single-cell RNA-sequencing with bulk RNA-sequencing of mutants and NKX2-1 ChIP-sequencing in mouse embryos, we delineate the NKX2-1 transcriptional program in tracheoesophageal specification, and discover that the majority of the tracheal and esophageal transcriptome is NKX2-1 independent. To decouple the NKX2-1 transcriptional program from regulation by SOX2, we interrogate the expression of newly-identified tracheal and esophageal markers in / compound mutants. Finally, we discover that NKX2-1 binds directly to and and regulates their expression to control mesenchymal specification to cartilage and smooth muscle, coupling epithelial identity with mesenchymal specification. These findings create a new framework for understanding early tracheoesophageal fate specification at the genome-wide level.</p>',
			'date' => '2020-06-09',
			'pmid' => 'http://www.pubmed.gov/32515350',
			'doi' => '10.7554/eLife.55526',
			'modified' => '2020-08-12 09:32:02',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 67 => array(
			'id' => '3950',
			'name' => 'Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response.',
			'authors' => 'Béguelin W, Teater M, Meydan C, Hoehn KB, Phillip JM, Soshnev AA, Venturutti L, Rivas MA, Calvo-Fernández MT, Gutierrez J, Camarillo JM, Takata K, Tarte K, Kelleher NL, Steidl C, Mason CE, Elemento O, Allis CD, Kleinstein SH, Melnick AM',
			'description' => '<p>Follicular lymphomas (FLs) are slow-growing, indolent tumors containing extensive follicular dendritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations. Paradoxically, FLs originate from highly proliferative germinal center (GC) B cells with proliferation strictly dependent on interactions with T follicular helper cells. Herein, we show that EZH2 mutations initiate FL by attenuating GC B cell requirement for T&nbsp;cell help and driving slow expansion of GC centrocytes that become enmeshed with and dependent on FDCs. By impairing T&nbsp;cell help, mutant EZH2 prevents induction of proliferative MYC programs. Thus, EZH2 mutation fosters malignant transformation by epigenetically reprograming B cells to form an aberrant immunological niche that reflects characteristic features of human FLs, explaining how indolent tumors arise from GC B cells.</p>',
			'date' => '2020-05-11',
			'pmid' => 'http://www.pubmed.gov/32396861',
			'doi' => '10.1016/j.ccell.2020.04.004',
			'modified' => '2020-08-17 09:56:58',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 68 => array(
			'id' => '4206',
			'name' => 'H2A.Z is dispensable for both basal and activated transcription inpost-mitotic mouse muscles.',
			'authors' => 'Belotti E. et al.',
			'description' => '<p>While the histone variant H2A.Z is known to be required for mitosis, it is also enriched in nucleosomes surrounding the transcription start site of active promoters, implicating H2A.Z in transcription. However, evidence obtained so far mainly rely on correlational data generated in actively dividing cells. We have exploited a paradigm in which transcription is uncoupled from the cell cycle by developing an in vivo system to inactivate H2A.Z in terminally differentiated post-mitotic muscle cells. ChIP-seq, RNA-seq and ATAC-seq experiments performed on H2A.Z KO post-mitotic muscle cells show that this histone variant is neither required to maintain nor to activate transcription. Altogether, this study provides in vivo evidence that in the absence of mitosis H2A.Z is dispensable for transcription and that the enrichment of H2A.Z on active promoters is a marker but not an active driver of transcription.</p>',
			'date' => '2020-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32266374',
			'doi' => '10.1093/nar/gkaa157',
			'modified' => '2022-01-13 13:46:38',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 69 => array(
			'id' => '3922',
			'name' => 'Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes.',
			'authors' => 'Crespo M, Damont A, Blanco M, Lastrucci E, Kennani SE, Ialy-Radio C, Khattabi LE, Terrier S, Louwagie M, Kieffer-Jaquinod S, Hesse AM, Bruley C, Chantalat S, Govin J, Fenaille F, Battail C, Cocquet J, Pflieger D',
			'description' => '<p>Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and crotonylation on histones H3 and H4 during mouse spermatogenesis. Lysine crotonylation appeared to be of significant abundance compared to acetylation, particularly on Lys27 of histone H3 (H3K27cr) that accumulates in sperm in a cleaved form of H3. We identified the genomic localization of H3K27cr and studied its effects on transcription compared to the classical active mark H3K27ac at promoters and distal enhancers. The presence of both marks was strongly associated with highest gene expression. Assessment of their co-localization with transcription regulators (SLY, SOX30) and chromatin-binding proteins (BRD4, BRDT, BORIS and CTCF) indicated systematic highest binding when both active marks were present and different selective binding when present alone at chromatin. H3K27cr and H3K27ac finally mark the building of some sperm super-enhancers. This integrated analysis of omics data provides an unprecedented level of understanding of gene expression regulation by H3K27cr in comparison to H3K27ac, and reveals both synergistic and specific actions of each histone modification.</p>',
			'date' => '2020-03-17',
			'pmid' => 'http://www.pubmed.gov/32182340',
			'doi' => '10.1093/nar/gkaa163',
			'modified' => '2020-08-17 10:56:19',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 70 => array(
			'id' => '3917',
			'name' => 'Anti-adipogenic signals at the onset of obesity-related inflammation in white adipose tissue.',
			'authors' => 'Caputo T, Tran VDT, Bararpour N, Winkler C, Aguileta G, Trang KB, Giordano Attianese GMP, Wilson A, Thomas A, Pagni M, Guex N, Desvergne B, Gilardi F',
			'description' => '<p>Chronic inflammation that affects primarily metabolic organs, such as white adipose tissue (WAT), is considered as a major cause of human obesity-associated co-morbidities. However, the molecular mechanisms initiating this inflammation in WAT are poorly understood. By combining transcriptomics, ChIP-seq and modeling approaches, we studied the global early and late responses to a high-fat diet (HFD) in visceral (vWAT) and subcutaneous (scWAT) AT, the first being more prone to obesity-induced inflammation. HFD rapidly triggers proliferation of adipocyte precursors within vWAT. However, concomitant antiadipogenic signals limit vWAT hyperplastic expansion by interfering with the differentiation of proliferating adipocyte precursors. Conversely, in scWAT, residing beige adipocytes lose their oxidizing properties and allow storage of excessive fatty acids. This phase is followed by tissue hyperplastic growth and increased angiogenic signals, which further enable scWAT expansion without generating inflammation. Our data indicate that scWAT and vWAT differential ability to modulate adipocyte number and differentiation in response to obesogenic stimuli has a crucial impact on the different susceptibility to obesity-related inflammation of these adipose tissue depots.</p>',
			'date' => '2020-03-11',
			'pmid' => 'http://www.pubmed.gov/32157317',
			'doi' => '10.1007/s00018-020-03485-z',
			'modified' => '2020-08-17 11:01:57',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 71 => array(
			'id' => '3888',
			'name' => 'HDAC3 functions as a positive regulator in Notch signal transduction.',
			'authors' => 'Ferrante F, Giaimo BD, Bartkuhn M, Zimmermann T, Close V, Mertens D, Nist A, Stiewe T, Meier-Soelch J, Kracht M, Just S, Klöble P, Oswald F, Borggrefe T',
			'description' => '<p>Aberrant Notch signaling plays a pivotal role in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL). Amplitude and duration of the Notch response is controlled by ubiquitin-dependent proteasomal degradation of the Notch1 intracellular domain (NICD1), a hallmark of the leukemogenic process. Here, we show that HDAC3 controls NICD1 acetylation levels directly affecting NICD1 protein stability. Either genetic loss-of-function of HDAC3 or nanomolar concentrations of HDAC inhibitor apicidin lead to downregulation of Notch target genes accompanied by a local reduction of histone acetylation. Importantly, an HDAC3-insensitive NICD1 mutant is more stable but biologically less active. Collectively, these data show a new HDAC3- and acetylation-dependent mechanism that may be exploited to treat Notch1-dependent leukemias.</p>',
			'date' => '2020-02-28',
			'pmid' => 'http://www.pubmed.gov/32107550',
			'doi' => '10.1093/nar/gkaa088',
			'modified' => '2020-03-20 17:21:31',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 72 => array(
			'id' => '3860',
			'name' => 'Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon.',
			'authors' => 'Zambusi A, Pelin Burhan Ö, Di Giaimo R, Schmid B, Ninkovic J',
			'description' => '<p>Granulins (GRN) are secreted factors that promote neuronal survival and regulate inflammation in various pathological conditions. However, their roles in physiological conditions in the brain remain poorly understood. To address this knowledge gap, we analysed the telencephalon in Grn-deficient zebrafish and identified morphological and transcriptional changes in microglial cells, indicative of a pro-inflammatory phenotype in the absence of any insult. Unexpectedly, activated mutant microglia shared part of their transcriptional signature with aged human microglia. Furthermore, transcriptome profiles of the entire telencephali isolated from young Grn-deficient animals showed remarkable similarities with the profiles of the telencephali isolated from aged wildtype animals. Additionally, 50% of differentially regulated genes during aging were regulated in the telencephalon of young Grn-deficient animals compared to their wildtype littermates. Importantly, the telencephalon transcriptome in young Grn-deficent animals changed only mildly with aging, further suggesting premature aging of Grn-deficient brain. Indeed, Grn loss led to decreased neurogenesis and oligodendrogenesis, and to shortening of telomeres at young ages, to an extent comparable to that observed during aging. Altogether, our data demonstrate a role of Grn in regulating aging kinetics in the zebrafish telencephalon, thus providing a valuable tool for the development of new therapeutic approaches to treat age-associated pathologies.</p>',
			'date' => '2020-02-03',
			'pmid' => 'http://www.pubmed.gov/32028681',
			'doi' => '10.3390/cells9020350',
			'modified' => '2020-03-20 17:55:13',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 73 => array(
			'id' => '3872',
			'name' => 'An inferred fitness consequence map of the rice genome.',
			'authors' => 'Joly-Lopez Z, Platts AE, Gulko B, Choi JY, Groen SC, Zhong X, Siepel A, Purugganan MD',
			'description' => '<p>The extent to which sequence variation impacts plant fitness is poorly understood. High-resolution maps detailing the constraint acting on the genome, especially in regulatory sites, would be beneficial as functional annotation of noncoding sequences remains sparse. Here, we present a fitness consequence (fitCons) map for rice (Oryza sativa). We inferred fitCons scores (&rho;) for 246 inferred genome classes derived from nine functional genomic and epigenomic datasets, including chromatin accessibility, messenger RNA/small RNA transcription, DNA methylation, histone modifications and engaged RNA polymerase activity. These were integrated with genome-wide polymorphism and divergence data from 1,477 rice accessions and 11 reference genome sequences in the Oryzeae. We found &rho; to be multimodal, with ~9% of the rice genome falling into classes where more than half of the bases would probably have a fitness consequence if mutated. Around 2% of the rice genome showed evidence of weak negative selection, frequently at candidate regulatory sites, including a novel set of 1,000 potentially active enhancer elements. This fitCons map provides perspective on the evolutionary forces associated with genome diversity, aids in genome annotation and can guide crop breeding programs.</p>',
			'date' => '2020-02-02',
			'pmid' => 'http://www.pubmed.gov/32042156',
			'doi' => '10.1038/s41477-019-0589-3',
			'modified' => '2020-03-20 17:43:24',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 74 => array(
			'id' => '3850',
			'name' => 'Dual-initiation promoters with intertwined canonical and TCT/TOP transcription start sites diversify transcript processing.',
			'authors' => 'Nepal C, Hadzhiev Y, Balwierz P, Tarifeño-Saldivia E, Cardenas R, Wragg JW, Suzuki AM, Carninci P, Peers B, Lenhard B, Andersen JB, Müller F',
			'description' => '<p>Variations in transcription start site (TSS) selection reflect diversity of preinitiation complexes and can impact on post-transcriptional RNA fates. Most metazoan polymerase II-transcribed genes carry canonical initiation with pyrimidine/purine (YR) dinucleotide, while translation machinery-associated genes carry polypyrimidine initiator (5'-TOP or TCT). By addressing the developmental regulation of TSS selection in zebrafish we uncovered a class of dual-initiation promoters in thousands of genes, including snoRNA host genes. 5'-TOP/TCT initiation is intertwined with canonical initiation and used divergently in hundreds of dual-initiation promoters during maternal to zygotic transition. Dual-initiation in snoRNA host genes selectively generates host and snoRNA with often different spatio-temporal expression. Dual-initiation promoters are pervasive in human and fruit fly, reflecting evolutionary conservation. We propose that dual-initiation on shared promoters represents a composite promoter architecture, which can function both coordinately and divergently to diversify RNAs.</p>',
			'date' => '2020-01-10',
			'pmid' => 'http://www.pubmed.gov/31924754',
			'doi' => '10.1038/s41467-019-13687-0',
			'modified' => '2020-02-13 11:09:58',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 75 => 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) 76 => 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) 77 => array(
			'id' => '3845',
			'name' => 'Combinatorial action of NF-Y and TALE at embryonic enhancers defines distinct gene expression programs during zygotic genome activation in zebrafish.',
			'authors' => 'Stanney W, Ladam F, Donaldson IJ, Parsons TJ, Maehr R, Bobola N, Sagerström CG',
			'description' => '<p>Animal embryogenesis is initiated by maternal factors, but zygotic genome activation (ZGA) shifts regulatory control to the embryo during blastula stages. ZGA is thought to be mediated by maternally provided transcription factors (TFs), but few such TFs have been identified in vertebrates. Here we report that NF-Y and TALE TFs bind zebrafish genomic elements associated with developmental control genes already at ZGA. In particular, co-regulation by NF-Y and TALE is associated with broadly acting genes involved in transcriptional control, while regulation by either NF-Y or TALE defines genes in specific developmental processes, such that NF-Y controls a cilia gene expression program while TALE controls expression of hox genes. We also demonstrate that NF-Y and TALE-occupied genomic elements function as enhancers during embryogenesis. We conclude that combinatorial use of NF-Y and TALE at developmental enhancers permits the establishment of distinct gene expression programs at zebrafish ZGA.</p>',
			'date' => '2019-12-17',
			'pmid' => 'http://www.pubmed.gov/31862379',
			'doi' => '10.1016/j.ydbio.2019.12.003',
			'modified' => '2020-02-20 11:13:27',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 78 => array(
			'id' => '3819',
			'name' => 'Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites.',
			'authors' => 'Hammam E, Ananda G, Sinha A, Scheidig-Benatar C, Bohec M, Preiser PR, Dedon PC, Scherf A, Vembar SS',
			'description' => '<p>DNA cytosine modifications are key epigenetic regulators of cellular processes in mammalian cells, with their misregulation leading to varied disease states. In the human malaria parasite Plasmodium falciparum, a unicellular eukaryotic pathogen, little is known about the predominant cytosine modifications, cytosine methylation (5mC) and hydroxymethylation (5hmC). Here, we report the first identification of a hydroxymethylcytosine-like (5hmC-like) modification in P. falciparum asexual blood stages using a suite of biochemical methods. In contrast to mammalian cells, we report 5hmC-like levels in the P. falciparum genome of 0.2-0.4%, which are significantly higher than the methylated cytosine (mC) levels of 0.01-0.05%. Immunoprecipitation of hydroxymethylated DNA followed by next generation sequencing (hmeDIP-seq) revealed that 5hmC-like modifications are enriched in gene bodies with minimal dynamic changes during asexual development. Moreover, levels of the 5hmC-like base in gene bodies positively correlated to transcript levels, with more than 2000 genes stably marked with this modification throughout asexual development. Our work highlights the existence of a new predominant cytosine DNA modification pathway in P. falciparum and opens up exciting avenues for gene regulation research and the development of antimalarials.</p>',
			'date' => '2019-11-28',
			'pmid' => 'http://www.pubmed.gov/31777939',
			'doi' => '10.1093/nar/gkz1093.',
			'modified' => '2020-02-25 13:47:09',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 79 => array(
			'id' => '3820',
			'name' => 'A stress-responsive enhancer induces dynamic drug resistance in acute myeloid leukemia.',
			'authors' => 'Williams MS, Amaral FM, Simeoni F, Somervaille TC',
			'description' => '<p>The drug efflux pump ABCB1 is a key driver of chemoresistance, and high expression predicts for treatment failure in acute myeloid leukemia (AML). In this study, we identified and functionally validated the network of enhancers that controls expression of ABCB1. We show that exposure of leukemia cells to daunorubicin activated an integrated stress response-like transcriptional program to induce ABCB1 through remodeling and activation of an ATF4-bound, stress-responsive enhancer. Protracted stress primed enhancers for rapid increases in activity following re-exposure of cells to daunorubicin, providing an epigenetic memory of prior drug treatment. In primary human AML, exposure of fresh blast cells to daunorubicin activated the stress-responsive enhancer and led to dose-dependent induction of ABCB1. Dynamic induction of ABCB1 by diverse stressors, including chemotherapy, facilitated escape of leukemia cells from targeted third-generation ABCB1 inhibition, providing an explanation for the failure of ABCB1 inhibitors in clinical trials. Stress-induced up regulation of ABCB1 was mitigated by combined use of pharmacologic inhibitors U0126 and ISRIB, which inhibit stress signalling and have potential for use as adjuvants to enhance the activity of ABCB1 inhibitors.</p>',
			'date' => '2019-11-26',
			'pmid' => 'http://www.pubmed.gov/31770110',
			'doi' => '/',
			'modified' => '2020-02-25 13:46:19',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 80 => array(
			'id' => '3810',
			'name' => 'Distinct CoREST complexes act in a cell-type-specific manner.',
			'authors' => 'Mačinković I, Theofel I, Hundertmark T, Kovač K, Awe S, Lenz J, Forné I, Lamp B, Nist A, Imhof A, Stiewe T, Renkawitz-Pohl R, Rathke C, Brehm A',
			'description' => '<p>CoREST has been identified as a subunit of several protein complexes that generate transcriptionally repressive chromatin structures during development. However, a comprehensive analysis of the CoREST interactome has not been carried out. We use proteomic approaches to define the interactomes of two dCoREST isoforms, dCoREST-L and dCoREST-M, in Drosophila. We identify three distinct histone deacetylase complexes built around a common dCoREST/dRPD3 core: A dLSD1/dCoREST complex, the LINT complex and a dG9a/dCoREST complex. The latter two complexes can incorporate both dCoREST isoforms. By contrast, the dLSD1/dCoREST complex exclusively assembles with the dCoREST-L isoform. Genome-wide studies show that the three dCoREST complexes associate with chromatin predominantly at promoters. Transcriptome analyses in S2 cells and testes reveal that different cell lineages utilize distinct dCoREST complexes to maintain cell-type-specific gene expression programmes: In macrophage-like S2 cells, LINT represses germ line-related genes whereas other dCoREST complexes are largely dispensable. By contrast, in testes, the dLSD1/dCoREST complex prevents transcription of germ line-inappropriate genes and is essential for spermatogenesis and fertility, whereas depletion of other dCoREST complexes has no effect. Our study uncovers three distinct dCoREST complexes that function in a lineage-restricted fashion to repress specific sets of genes thereby maintaining cell-type-specific gene expression programmes.</p>',
			'date' => '2019-11-08',
			'pmid' => 'http://www.pubmed.gov/31701127',
			'doi' => '10.1093/nar/gkz1050',
			'modified' => '2019-12-05 11:02:22',
			'created' => '2019-12-02 15:25:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 81 => array(
			'id' => '3782',
			'name' => 'Residual apoptotic activity of a tumorigenic p53 mutant improves cancer therapy responses.',
			'authors' => 'Timofeev O, Klimovich B, Schneikert J, Wanzel M, Pavlakis E, Noll J, Mutlu S, Elmshäuser S, Nist A, Mernberger M, Lamp B, Wenig U, Brobeil A, Gattenlöhner S, Köhler K, Stiewe T',
			'description' => '<p>Engineered p53 mutant mice are valuable tools for delineating p53 functions in tumor suppression and cancer therapy. Here, we have introduced the R178E mutation into the Trp53 gene of mice to specifically ablate the cooperative nature of p53 DNA binding. Trp53 mice show no detectable target gene regulation and, at first sight, are largely indistinguishable from Trp53 mice. Surprisingly, stabilization of p53 in Mdm2 mice nevertheless triggers extensive apoptosis, indicative of residual wild-type activities. Although this apoptotic activity suffices to trigger lethality of Trp53 ;Mdm2 embryos, it proves insufficient for suppression of spontaneous and oncogene-driven tumorigenesis. Trp53 mice develop tumors indistinguishably from Trp53 mice and tumors retain and even stabilize the p53 protein, further attesting to the lack of significant tumor suppressor activity. However, Trp53 tumors exhibit remarkably better chemotherapy responses than Trp53 ones, resulting in enhanced eradication of p53-mutated tumor cells. Together, this provides genetic proof-of-principle evidence that a p53 mutant can be highly tumorigenic and yet retain apoptotic activity which provides a survival benefit in the context of cancer therapy.</p>',
			'date' => '2019-09-04',
			'pmid' => 'http://www.pubmed.gov/31483066',
			'doi' => '10.15252/embj.2019102096',
			'modified' => '2019-10-02 16:50:40',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 82 => array(
			'id' => '3759',
			'name' => 'EOMES interacts with RUNX3 and BRG1 to promote innate memory cell formation through epigenetic reprogramming.',
			'authors' => 'Istaces N, Splittgerber M, Lima Silva V, Nguyen M, Thomas S, Le A, Achouri Y, Calonne E, Defrance M, Fuks F, Goriely S, Azouz A',
			'description' => '<p>Memory CD8 T cells have the ability to provide lifelong immunity against pathogens. Although memory features generally arise after challenge with a foreign antigen, na&iuml;ve CD8 single positive (SP) thymocytes may acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associated with the induction of the T-box transcription factor Eomesodermin (EOMES). However, the underlying molecular mechanisms remain ill-defined. Using epigenomic profiling, we show that these innate memory CD8SP cells acquire only a portion of the active enhancer repertoire of conventional memory cells. This reprograming is secondary to EOMES recruitment, mostly to RUNX3-bound enhancers. Furthermore, EOMES is found within chromatin-associated complexes containing BRG1 and promotes the recruitment of this chromatin remodelling factor. Also, the in vivo acquisition of EOMES-dependent program is BRG1-dependent. In conclusion, our results support a strong epigenetic basis for the EOMES-driven establishment of CD8 T cell innate memory program.</p>',
			'date' => '2019-07-24',
			'pmid' => 'http://www.pubmed.gov/31341159',
			'doi' => '10.1038/s41467-019-11233-6',
			'modified' => '2019-10-03 10:06:15',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 83 => 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) 84 => array(
			'id' => '3743',
			'name' => 'ARID1A facilitates KRAS signaling-regulated enhancer activity in an AP1-dependent manner in colorectal cancer cells.',
			'authors' => 'Sen M, Wang X, Hamdan FH, Rapp J, Eggert J, Kosinsky RL, Wegwitz F, Kutschat AP, Younesi FS, Gaedcke J, Grade M, Hessmann E, Papantonis A, Strӧbel P, Johnsen SA',
			'description' => '<p>BACKGROUND: ARID1A (AT-rich interactive domain-containing protein 1A) is a subunit of the BAF chromatin remodeling complex and plays roles in transcriptional regulation and DNA damage response. Mutations in ARID1A that lead to inactivation or&nbsp;loss of expression are frequent and widespread across many cancer types including colorectal cancer (CRC). A tumor suppressor role of ARID1A has been established in a number of tumor types including CRC where the genetic inactivation of Arid1a alone led to the formation of invasive colorectal adenocarcinomas in mice. Mechanistically, ARID1A has been described to largely function through the regulation of enhancer activity. METHODS: To mimic ARID1A-deficient colorectal cancer, we used CRISPR/Cas9-mediated gene editing to inactivate the ARID1A gene in established colorectal cancer cell lines. We integrated gene expression analyses with genome-wide ARID1A occupancy and epigenomic mapping data to decipher ARID1A-dependent transcriptional regulatory mechanisms. RESULTS: Interestingly, we found that CRC cell lines harboring KRAS mutations are critically dependent on ARID1A function. In the absence of ARID1A, proliferation of these cell lines is severely impaired, suggesting an essential role for ARID1A in this context. Mechanistically, we showed that ARID1A acts as a co-factor at enhancers occupied by AP1 transcription factors acting downstream of the MEK/ERK pathway. Consistently, loss of ARID1A led to a disruption of KRAS/AP1-dependent enhancer activity, accompanied by a downregulation of expression of the associated target genes. CONCLUSIONS: We identify a previously unknown context-dependent tumor-supporting function of ARID1A in CRC downstream of KRAS signaling. Upon the loss of ARID1A in KRAS-mutated cells, enhancers that are co-occupied by ARID1A and the AP1 transcription factors become inactive, thereby leading to decreased target gene expression. Thus, targeting of the BAF complex in KRAS-mutated CRC may offer a unique, previously unknown, context-dependent therapeutic option in CRC.</p>',
			'date' => '2019-06-19',
			'pmid' => 'http://www.pubmed.gov/31217031',
			'doi' => '10.1186/s13148-019-0690-5',
			'modified' => '2019-08-06 16:37:28',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 85 => array(
			'id' => '3631',
			'name' => 'Guidelines for optimized gene knockout using CRISPR/Cas9',
			'authors' => 'Campenhout CV et al.',
			'description' => '<p>CRISPR/Cas9 technology has evolved as the most powerful approach to generate genetic models both for fundamental and preclinical research. Despite its apparent simplicity, the outcome of a genome-editing experiment can be substantially impacted by technical parameters and biological considerations. Here, we present guidelines and tools to optimize CRISPR/Cas9 genome-targeting efficiency and specificity. The nature of the target locus, the design of the single guide RNA and the choice of the delivery method should all be carefully considered prior to a genome-editing experiment. Different methods can also be used to detect off-target cleavages and decrease the risk of unwanted mutations. Together, these optimized tools and proper controls are essential to the assessment of CRISPR/Cas9 genome-editing experiments.</p>',
			'date' => '2019-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/31039627',
			'doi' => '10.2144/btn-2018-0187',
			'modified' => '2019-05-09 15:37:50',
			'created' => '2019-05-09 15:37:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 86 => array(
			'id' => '3710',
			'name' => 'BRCA1 mutations attenuate super-enhancer function and chromatin looping in haploinsufficient human breast epithelial cells.',
			'authors' => 'Zhang X, Wang Y, Chiang HC, Hsieh YP, Lu C, Park BH, Jatoi I, Jin VX, Hu Y, Li R',
			'description' => '<p>BACKGROUND: BRCA1-associated breast cancer originates from luminal progenitor cells. BRCA1 functions in multiple biological processes, including double-strand break repair, replication stress suppression, transcriptional regulation, and chromatin reorganization. While non-malignant cells carrying cancer-predisposing BRCA1 mutations exhibit increased genomic instability, it remains unclear whether BRCA1 haploinsufficiency affects transcription and chromatin dynamics in breast epithelial cells. METHODS: H3K27ac-associated super-enhancers were compared in primary breast epithelial cells from BRCA1 mutation carriers (BRCA1) and non-carriers (BRCA1). Non-tumorigenic MCF10A breast epithelial cells with engineered BRCA1 haploinsufficiency were used to confirm the H3K27ac changes. The impact of BRCA1 mutations on enhancer function and enhancer-promoter looping was assessed in MCF10A cells. RESULTS: Here, we show that primary mammary epithelial cells from women with BRCA1 mutations display significant loss of H3K27ac-associated super-enhancers. These BRCA1-dependent super-enhancers are enriched with binding motifs for the GATA family. Non-tumorigenic BRCA1 MCF10A cells recapitulate the H3K27ac loss. Attenuated histone mark and enhancer activity in these BRCA1 MCF10A cells can be partially restored with wild-type BRCA1. Furthermore, chromatin conformation analysis demonstrates impaired enhancer-promoter looping in BRCA1 MCF10A cells. CONCLUSIONS: H3K27ac-associated super-enhancer loss is a previously unappreciated functional deficiency in ostensibly normal BRCA1 mutation-carrying breast epithelium. Our findings offer new mechanistic insights into BRCA1 mutation-associated transcriptional and epigenetic abnormality in breast epithelial cells and tissue/cell lineage-specific tumorigenesis.</p>',
			'date' => '2019-04-17',
			'pmid' => 'http://www.pubmed.gov/30995943',
			'doi' => '10.1186/s13058-019-1132-1',
			'modified' => '2019-07-05 14:32:42',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 87 => array(
			'id' => '3613',
			'name' => 'Point mutations in the PDX1 transactivation domain impair human β-cell development and function.',
			'authors' => 'Wang X, Sterr M, Ansarullah , Burtscher I, Böttcher A, Beckenbauer J, Siehler J, Meitinger T, Häring HU, Staiger H, Cernilogar FM, Schotta G, Irmler M, Beckers J, Wright CVE, Bakhti M, Lickert H',
			'description' => '<p>OBJECTIVE: Hundreds of missense mutations in the coding region of PDX1 exist; however, if these mutations predispose to diabetes mellitus is unknown. METHODS: In this study, we screened a large cohort of subjects with increased risk for diabetes and identified two subjects with impaired glucose tolerance carrying common, heterozygous, missense mutations in the PDX1 coding region leading to single amino acid exchanges (P33T, C18R) in its transactivation domain. We generated iPSCs from patients with heterozygous PDX1, PDX1 mutations and engineered isogenic cell lines carrying homozygous PDX1, PDX1 mutations and a heterozygous PDX1 loss-of-function mutation (PDX1). RESULTS: Using an in&nbsp;vitro &beta;-cell differentiation protocol, we demonstrated that both, heterozygous PDX1, PDX1 and homozygous PDX1, PDX1 mutations impair &beta;-cell differentiation and function. Furthermore, PDX1 and PDX1 mutations reduced differentiation efficiency of pancreatic progenitors (PPs), due to downregulation of PDX1-bound genes, including transcription factors MNX1 and PDX1 as well as insulin resistance gene CES1. Additionally, both PDX1 and PDX1 mutations in PPs reduced the expression of PDX1-bound genes including the long-noncoding RNA, MEG3 and the imprinted gene NNAT, both involved in insulin synthesis and secretion. CONCLUSIONS: Our results reveal mechanistic details of how common coding mutations in PDX1 impair human pancreatic endocrine lineage formation and &beta;-cell function and contribute to the predisposition for diabetes.</p>',
			'date' => '2019-03-20',
			'pmid' => 'http://www.pubmed.gov/30930126',
			'doi' => '10.1016/j.molmet.2019.03.006',
			'modified' => '2019-04-17 14:43:53',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 88 => 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) 89 => array(
			'id' => '3727',
			'name' => 'Transcriptome-wide dynamics of extensive m6A mRNA methylation during Plasmodium falciparum blood-stage development',
			'authors' => 'Sebastian Baumgarten, Jessica M. Bryant, Ameya Sinha, Thibaud Reyser, Peter R. Preiser, Peter C. Dedon, Artur Scherf',
			'description' => '<p>Malaria pathogenesis results from the asexual replication of Plasmodium falciparum within human red blood cells, which relies on a precisely timed cascade of gene expression over a 48-hour life cycle. Although substantial post-transcriptional regulation of this hardwired program has been observed, it remains unclear how these processes are mediated on a transcriptome-wide level. To this end, we identified mRNA modifications in the P. falciparum transcriptome and performed a comprehensive characterization of N6-methyladenosine (m6A) over the course of blood stage development. Using mass spectrometry and m6A RNA sequencing, we demonstrate that m6A is highly developmentally regulated, exceeding m6A levels known in any other eukaryote. We identify an evolutionarily conserved m6A writer complex and show that knockdown of the putative m6A methyltransferase by CRISPR interference leads to increased levels of transcripts that normally contain m6A. In accordance, we find an inverse correlation between m6A status and mRNA stability or translational efficiency. Our data reveal the crucial role of extensive m6A mRNA methylation in dynamically fine-tuning the transcriptional program of a unicellular eukaryote as well as a new &lsquo;epitranscriptomic&rsquo; layer of gene regulation in malaria parasites.</p>',
			'date' => '2019-03-09',
			'pmid' => 'https://www.nature.com/articles/s41564-019-0521-7',
			'doi' => '10.1101/572891.',
			'modified' => '2022-05-18 19:27:33',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 90 => 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) 91 => array(
			'id' => '3662',
			'name' => 'NF-κB p65 dimerization and DNA-binding is important for inflammatory gene expression.',
			'authors' => 'Riedlinger T, Liefke R, Meier-Soelch J, Jurida L, Nist A, Stiewe T, Kracht M, Schmitz ML',
			'description' => '<p>Increasing evidence shows that many transcription factors execute important biologic functions independent from their DNA-binding capacity. The NF-&kappa;B p65 (RELA) subunit is a central regulator of innate immunity. Here, we investigated the relative functional contribution of p65 DNA-binding and dimerization in p65-deficient human and murine cells reconstituted with single amino acid mutants preventing either DNA-binding (p65 E/I) or dimerization (p65 FL/DD). DNA-binding of p65 was required for RelB-dependent stabilization of the NF-&kappa;B p100 protein. The antiapoptotic function of p65 and expression of the majority of TNF-&alpha;-induced genes were dependent on p65's ability to bind DNA and to dimerize. Chromatin immunoprecipitation with massively parallel DNA sequencing experiments revealed that impaired DNA-binding and dimerization strongly diminish the chromatin association of p65. However, there were also p65-independent TNF-&alpha;-inducible genes and a subgroup of p65 binding sites still allowed some residual chromatin association of the mutants. These sites were enriched in activator protein 1 (AP-1) binding motifs and showed increased chromatin accessibility and basal transcription. This suggests a mechanism of assisted p65 chromatin association that can be in part facilitated by chromatin priming and cooperativity with other transcription factors such as AP-1.-Riedlinger, T., Liefke, R., Meier-Soelch, J., Jurida, L., Nist, A., Stiewe, T., Kracht, M., Schmitz, M. L. NF-&kappa;B p65 dimerization and DNA-binding is important for inflammatory gene expression.</p>',
			'date' => '2019-03-01',
			'pmid' => 'http://www.pubmed.gov/30526044',
			'doi' => '10.1096/fj.201801638R',
			'modified' => '2019-07-01 11:42:50',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 92 => array(
			'id' => '3646',
			'name' => 'Differential regulation of RNA polymerase III genes during liver regeneration.',
			'authors' => 'Yeganeh M, Praz V, Carmeli C, Villeneuve D, Rib L, Guex N, Herr W, Delorenzi M, Hernandez N,  ',
			'description' => '<p>Mouse liver regeneration after partial hepatectomy involves cells in the remaining tissue synchronously entering the cell division cycle. We have used this system and H3K4me3, Pol II and Pol III profiling to characterize adaptations in Pol III transcription. Our results broadly define a class of genes close to H3K4me3 and Pol II peaks, whose Pol III occupancy is high and stable, and another class, distant from Pol II peaks, whose Pol III occupancy strongly increases after partial hepatectomy. Pol III regulation in the liver thus entails both highly expressed housekeeping genes and genes whose expression can adapt to increased demand.</p>',
			'date' => '2019-02-28',
			'pmid' => 'http://www.pubmed.gov/30597109',
			'doi' => '10.1093/nar/gky1282',
			'modified' => '2019-06-07 10:14:59',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 93 => array(
			'id' => '3678',
			'name' => 'CBX7 Induces Self-Renewal of Human Normal and Malignant Hematopoietic Stem and Progenitor Cells by Canonical and Non-canonical Interactions.',
			'authors' => 'Jung J, Buisman SC, Weersing E, Dethmers-Ausema A, Zwart E, Schepers H, Dekker MR, Lazare SS, Hammerl F, Skokova Y, Kooistra SM, Klauke K, Poot RA, Bystrykh LV, de Haan G',
			'description' => '<p>In this study, we demonstrate that, among all five CBX Polycomb proteins, only CBX7 possesses the ability to control self-renewal of human hematopoietic stem and progenitor cells (HSPCs). Xenotransplantation of CBX7-overexpressing HSPCs resulted in increased multi-lineage long-term engraftment and myelopoiesis.&nbsp;Gene expression and chromatin analyses revealed perturbations in genes involved in differentiation,&nbsp;DNA and chromatin maintenance, and cell cycle control. CBX7 is upregulated in acute myeloid leukemia (AML), and its genetic or pharmacological repression in AML cells inhibited proliferation and induced differentiation. Mass spectrometry analysis revealed several non-histone protein interactions between CBX7 and the H3K9 methyltransferases SETDB1, EHMT1, and EHMT2. These CBX7-binding proteins possess a trimethylated lysine peptide motif highly similar to the canonical CBX7 target H3K27me3. Depletion of SETDB1 in AML cells phenocopied repression of CBX7. We identify CBX7 as an important regulator of self-renewal and uncover non-canonical crosstalk between distinct pathways, revealing therapeutic opportunities for leukemia.</p>',
			'date' => '2019-02-12',
			'pmid' => 'http://www.pubmed.gov/30759399',
			'doi' => '10.1016/j.celrep.2019.01.050',
			'modified' => '2019-07-01 11:20:46',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 94 => array(
			'id' => '3659',
			'name' => 'Fluorescence-Activated Cell Sorting-Based Isolation and Characterization of Neural Stem Cells from the Adult Zebrafish Telencephalon.',
			'authors' => 'Di Giaimo R, Aschenbroich S, Ninkovic J',
			'description' => '<p>Adult mammalian brain, including humans, has rather limited addition of new neurons and poor regenerative capacity. In contrast, neural stem cells (NSC) with glial identity and neurogenesis are highly abundant throughout the adult zebrafish brain. Importantly, the activation of NSC and production of new neurons in response to injuries lead to the brain regeneration in zebrafish brain. Therefore, understanding of the molecular pathways regulating NSC behavior in response to injury is crucial in order to set the basis for experimental modification of these pathways in glial cells after injury in the mammalian brain and to elicit neuronal regeneration. Here, we describe the procedure that we successfully used to prospectively isolate NSCs from adult zebrafish telencephalon, extract RNA, and prepare cDNA libraries for next generation sequencing (NGS) and full transcriptome analysis as the first step toward understanding regulatory mechanisms leading to restorative neurogenesis in zebrafish. Moreover, we describe an alternative approach to analyze antigenic properties of NSC in the adult zebrafish brain using intracellular fluorescence activated cell sorting (FACS). We employ this method to analyze the number of proliferating NSCs positive for proliferating cell nuclear antigen (PCNA) in the prospectively isolated population of stem cells.</p>',
			'date' => '2019-01-09',
			'pmid' => 'http://www.pubmed.gov/30617972',
			'doi' => '10.1007/978-1-4939-9068-9_4,',
			'modified' => '2019-06-07 08:57:58',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 95 => array(
			'id' => '3651',
			'name' => 'DeltaNp63-dependent super enhancers define molecular identity in pancreatic cancer by an interconnected transcription factor network.',
			'authors' => 'Hamdan FH, Johnsen SA',
			'description' => '<p>Molecular subtyping of cancer offers tremendous promise for the optimization of a precision oncology approach to anticancer therapy. Recent advances in pancreatic cancer research uncovered various molecular subtypes with tumors expressing a squamous/basal-like gene expression signature displaying a worse prognosis. Through unbiased epigenome mapping, we identified deltaNp63 as a major driver of a gene signature in pancreatic cancer cell lines, which we report to faithfully represent the highly aggressive pancreatic squamous subtype observed in vivo, and display the specific epigenetic marking of genes associated with decreased survival. Importantly, depletion of deltaNp63 in these systems significantly decreased cell proliferation and gene expression patterns associated with a squamous subtype and transcriptionally mimicked a subtype switch. Using genomic localization data of deltaNp63 in pancreatic cancer cell lines coupled with epigenome mapping data from patient-derived xenografts, we uncovered that deltaNp63 mainly exerts its effects by activating subtype-specific super enhancers. Furthermore, we identified a group of 45 subtype-specific super enhancers that are associated with poorer prognosis and are highly dependent on deltaNp63. Genes associated with these enhancers included a network of transcription factors, including HIF1A, BHLHE40, and RXRA, which form a highly intertwined transcriptional regulatory network with deltaNp63 to further activate downstream genes associated with poor survival.</p>',
			'date' => '2018-12-26',
			'pmid' => 'http://www.pubmed.gov/30541891',
			'doi' => '10.1073/pnas.1812915116',
			'modified' => '2019-06-07 09:29:25',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 96 => array(
			'id' => '3610',
			'name' => 'The Aryl Hydrocarbon Receptor Pathway Defines the Time Frame for Restorative Neurogenesis.',
			'authors' => 'Di Giaimo R, Durovic T, Barquin P, Kociaj A, Lepko T, Aschenbroich S, Breunig CT, Irmler M, Cernilogar FM, Schotta G, Barbosa JS, Trümbach D, Baumgart EV, Neuner AM, Beckers J, Wurst W, Stricker SH, Ninkovic J',
			'description' => '<p>Zebrafish have a high capacity to replace lost neurons after brain injury. New neurons involved in repair are generated by a specific set of glial cells, known as ependymoglial cells. We analyze changes in the transcriptome of ependymoglial cells and their progeny after injury to infer the molecular pathways governing restorative neurogenesis. We identify the aryl hydrocarbon receptor (AhR) as a regulator of ependymoglia differentiation toward post-mitotic neurons. In&nbsp;vivo imaging shows that high AhR signaling promotes the direct conversion of a specific subset of ependymoglia into post-mitotic neurons, while low AhR signaling promotes ependymoglial proliferation. Interestingly, we observe the inactivation of AhR signaling shortly after injury followed by a return to the basal levels 7&nbsp;days post injury. Interference with timely AhR regulation after injury leads to aberrant restorative neurogenesis. Taken together, we identify AhR signaling as a crucial regulator of restorative neurogenesis timing in the zebrafish brain.</p>',
			'date' => '2018-12-18',
			'pmid' => 'http://www.pubmed.gov/30566853',
			'doi' => '10.1016/j.celrep.2018.11.055',
			'modified' => '2019-04-17 14:47:22',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 97 => array(
			'id' => '3649',
			'name' => 'Genome-wide identification of RETINOBLASTOMA RELATED 1 binding sites in Arabidopsis reveals novel DNA damage regulators.',
			'authors' => 'Bouyer D, Heese M, Chen P, Harashima H, Roudier F, Grüttner C, Schnittger A',
			'description' => '<p>Retinoblastoma (pRb) is a multifunctional regulator, which was likely present in the last common ancestor of all eukaryotes. The Arabidopsis pRb homolog RETINOBLASTOMA RELATED 1 (RBR1), similar to its animal counterparts, controls not only cell proliferation but is also implicated in developmental decisions, stress responses and maintenance of genome integrity. Although most functions of pRb-type proteins involve chromatin association, a genome-wide understanding of RBR1 binding sites in Arabidopsis is still missing. Here, we present a plant chromatin immunoprecipitation protocol optimized for genome-wide studies of indirectly DNA-bound proteins like RBR1. Our analysis revealed binding of Arabidopsis RBR1 to approximately 1000 genes and roughly 500 transposable elements, preferentially MITES. The RBR1-decorated genes broadly overlap with previously identified targets of two major transcription factors controlling the cell cycle, i.e. E2F and MYB3R3 and represent a robust inventory of RBR1-targets in dividing cells. Consistently, enriched motifs in the RBR1-marked domains include sequences related to the E2F consensus site and the MSA-core element bound by MYB3R transcription factors. Following up a key role of RBR1 in DNA damage response, we performed a meta-analysis combining the information about the RBR1-binding sites with genome-wide expression studies under DNA stress. As a result, we present the identification and mutant characterization of three novel genes required for growth upon genotoxic stress.</p>',
			'date' => '2018-11-01',
			'pmid' => 'http://www.pubmed.gov/30500810',
			'doi' => '10.1371/journal.',
			'modified' => '2019-06-07 10:12:16',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 98 => array(
			'id' => '3576',
			'name' => 'SUMO Safeguards Somatic and Pluripotent Cell Identities by Enforcing Distinct Chromatin States',
			'authors' => 'Cossec Jack-Christophe, Theurillat Ilan, Chica Claudia, Búa Aguín Sabela, Gaume Xavier, Andrieux Alexandra, Iturbide Ane, Jouvion Gregory, Li Han, Bossis Guillaume, Seeler Jacob-Sebastian, Torres-Padilla Maria-Elena, Dejean Anne',
			'description' => '<p>Understanding general principles that safeguard cellular identity should reveal critical insights into common mechanisms underlying specification of varied cell types. Here, we show that SUMO modification acts to stabilize cell fate in a variety of contexts. Hyposumoylation enhances pluripotency reprogramming in vitro and in vivo, increases lineage transdifferentiation, and facilitates leukemic cell differentiation. Suppressing sumoylation in embryonic stem cells (ESCs) promotes their conversion into 2-cell-embryo-like (2C-like) cells. During reprogramming to pluripotency, SUMO functions on fibroblastic enhancers to retain somatic transcription factors together with Oct4, Sox2, and Klf4, thus impeding somatic enhancer inactivation. In contrast, in ESCs, SUMO functions on heterochromatin to silence the 2C program, maintaining both proper H3K9me3 levels genome-wide and repression of the Dux locus by triggering recruitment of the sumoylated PRC1.6 and Kap/Setdb1 repressive complexes. Together, these studies show that SUMO acts on chromatin as a glue to stabilize key determinants of somatic and pluripotent states.</p>',
			'date' => '2018-10-25',
			'pmid' => 'http://www.pubmed.gov/30401455',
			'doi' => '10.1016/j.stem.2018.10.001',
			'modified' => '2019-07-22 09:18:55',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 99 => array(
			'id' => '3636',
			'name' => 'Caenorhabditis elegans sperm carry a histone-based epigenetic memory of both spermatogenesis and oogenesis.',
			'authors' => 'Tabuchi TM, Rechtsteiner A, Jeffers TE, Egelhofer TA, Murphy CT, Strome S',
			'description' => '<p>Paternal contributions to epigenetic inheritance are not well understood. Paternal contributions via marked nucleosomes are particularly understudied, in part because sperm in some organisms replace the majority of nucleosome packaging with protamine packaging. Here we report that in Caenorhabditis elegans sperm, the genome is packaged in nucleosomes and carries a histone-based epigenetic memory of genes expressed during spermatogenesis, which unexpectedly include genes well known for their expression during oogenesis. In sperm, genes with spermatogenesis-restricted expression are uniquely marked with both active and repressive marks, which may reflect a sperm-specific chromatin signature. We further demonstrate that epigenetic information provided by sperm is important and in fact sufficient to guide proper germ cell development in offspring. This study establishes one mode of paternal epigenetic inheritance and offers a potential mechanism for how the life experiences of fathers may impact the development and health of their descendants.</p>',
			'date' => '2018-10-17',
			'pmid' => 'http://www.pubmed.gov/30333496',
			'doi' => '10.1038/s41467-018-06236-8',
			'modified' => '2019-06-07 10:26:54',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 100 => array(
			'id' => '3556',
			'name' => 'PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex.',
			'authors' => 'Link S, Spitzer RMM, Sana M, Torrado M, Völker-Albert MC, Keilhauer EC, Burgold T, Pünzeler S, Low JKK, Lindström I, Nist A, Regnard C, Stiewe T, Hendrich B, Imhof A, Mann M, Mackay JP, Bartkuhn M, Hake SB',
			'description' => '<p>Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and cranial-facial development. Here, using in vitro assays, we show that distinct domains of PWWP2A mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly binds H3K36me3-containing gene bodies. Further, PWWP2A binds to an MTA1-specific subcomplex of the NuRD complex (M1HR), which consists solely of MTA1, HDAC1, and RBBP4/7, and excludes CHD, GATAD2 and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as a complex chromatin-binding protein that serves to direct the deacetylase complex M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels.</p>',
			'date' => '2018-10-16',
			'pmid' => 'http://www.pubmed.gov/30327463',
			'doi' => '10.1038/s41467-018-06665-5',
			'modified' => '2019-07-22 09:17:39',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 101 => array(
			'id' => '3498',
			'name' => 'Convergent evolution of complex genomic rearrangements in two fungal meiotic drive elements.',
			'authors' => 'Svedberg J, Hosseini S, Chen J, Vogan AA, Mozgova I, Hennig L, Manitchotpisit P, Abusharekh A, Hammond TM, Lascoux M, Johannesson H',
			'description' => '<p>Meiotic drive is widespread in nature. The conflict it generates is expected to be an important motor for evolutionary change and innovation. In this study, we investigated the genomic consequences of two large multi-gene meiotic drive elements, Sk-2 and Sk-3, found in the filamentous ascomycete Neurospora intermedia. Using long-read sequencing, we generated the first complete and well-annotated genome assemblies of large, highly diverged, non-recombining regions associated with meiotic drive elements. Phylogenetic analysis shows that, even though Sk-2 and Sk-3 are located in the same chromosomal region, they do not form sister clades, suggesting independent origins or at least a long evolutionary separation. We conclude that they have in a convergent manner accumulated similar patterns of tandem inversions and dense repeat clusters, presumably in response to similar needs to create linkage between genes causing drive and resistance.</p>',
			'date' => '2018-10-12',
			'pmid' => 'http://www.pubmed.gov/30315196',
			'doi' => '10.1038/s41467-018-06562-x',
			'modified' => '2019-07-22 09:20:24',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 102 => array(
			'id' => '3507',
			'name' => 'Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclones.',
			'authors' => 'de Boer B, Prick J, Pruis MG, Keane P, Imperato MR, Jaques J, Brouwers-Vos AZ, Hogeling SM, Woolthuis CM, Nijk MT, Diepstra A, Wandinger S, Versele M, Attar RM, Cockerill PN, Huls G, Vellenga E, Mulder AB, Bonifer C, Schuringa JJ',
			'description' => '<p>Intra-tumor heterogeneity caused by clonal evolution is a major problem in cancer treatment. To address this problem, we performed label-free quantitative proteomics on primary acute myeloid leukemia (AML) samples. We identified 50 leukemia-enriched plasma membrane proteins enabling the prospective isolation of genetically distinct subclones from individual AML patients. Subclones differed in their regulatory phenotype, drug sensitivity, growth, and engraftment behavior, as determined by RNA sequencing, DNase I hypersensitive site mapping, transcription factor occupancy analysis, in&nbsp;vitro culture, and xenograft transplantation. Finally, we show that these markers can be used to identify and longitudinally track distinct leukemic clones in patients in routine diagnostics. Our study describes a strategy for a major improvement in stratifying cancer diagnosis and treatment.</p>',
			'date' => '2018-10-08',
			'pmid' => 'http://www.pubmed.gov/30245083',
			'doi' => '10.1016/j.ccell.2018.08.014',
			'modified' => '2019-02-27 16:26:01',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 103 => array(
			'id' => '3505',
			'name' => 'Genomic Location of PRMT6-Dependent H3R2 Methylation Is Linked to the Transcriptional Outcome of Associated Genes.',
			'authors' => 'Bouchard C, Sahu P, Meixner M, Nötzold RR, Rust MB, Kremmer E, Feederle R, Hart-Smith G, Finkernagel F, Bartkuhn M, Savai Pullamsetti S, Nist A, Stiewe T, Philipsen S, Bauer UM',
			'description' => '<p>Protein arginine methyltransferase 6 (PRMT6) catalyzes asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a). This mark has been reported to associate with silent genes. Here, we use a cell model&nbsp;of neural differentiation, which upon PRMT6 knockout exhibits proliferation and differentiation defects. Strikingly, we detect PRMT6-dependent H3R2me2a at active genes, both at promoter and enhancer sites. Loss of H3R2me2a from promoter sites leads to enhanced KMT2A binding and H3K4me3 deposition together with increased target gene transcription, supporting a repressive nature of H3R2me2a. At enhancers, H3R2me2a peaks co-localize with the active enhancer marks H3K4me1 and H3K27ac. Here, loss of H3R2me2a results in reduced KMT2D binding and H3K4me1/H3K27ac deposition together with decreased transcription of associated genes, indicating that H3R2me2a also exerts activation functions. Our work suggests that PRMT6 via H3R2me2a interferes with the deposition of adjacent histone marks and modulates the activity of important differentiation-associated genes by opposing transcriptional effects.</p>',
			'date' => '2018-09-18',
			'pmid' => 'http://www.pubmed.gov/30232013',
			'doi' => '10.1016/j.celrep.2018.08.052',
			'modified' => '2019-02-28 10:05:16',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 104 => array(
			'id' => '3599',
			'name' => 'Enhancer-driven transcriptional regulation is a potential key determinant for human visceral and subcutaneous adipocytes.',
			'authors' => 'Liefke R, Bokelmann K, Ghadimi BM, Dango S',
			'description' => '<p>Obesity is characterized by the excess of body fat leading to impaired health. Abdominal fat is particularly harmful and is associated with cardiovascular and metabolic diseases and cancer. In contrast, subcutaneous fat is generally considered less detrimental. The mechanisms that establish the cellular characteristics of these distinct fat types in humans are not fully understood. Here, we explored whether differences of their gene regulatory mechanisms can be investigated in vitro. For this purpose, we in vitro differentiated human visceral and subcutaneous pre-adipocytes into mature adipocytes and obtained their gene expression profiles and genome-wide H3K4me3, H3K9me3 and H3K27ac patterns. Subsequently, we compared those data with public gene expression data from visceral and subcutaneous fat tissues. We found that the in vitro differentiated adipocytes show significant differences in their transcriptional landscapes, which correlate with biological pathways that are characteristic for visceral and subcutaneous fat tissues, respectively. Unexpectedly, visceral adipocyte enhancers are rich on motifs for transcription factors involved in the Hippo-YAP pathway, cell growth and inflammation, which are not typically associated with adipocyte function. In contrast, enhancers of subcutaneous adipocytes show enrichment of motifs for common adipogenic transcription factors, such as C/EBP, NFI and PPAR&gamma;, implicating substantially disparate gene regulatory networks in visceral and subcutaneous adipocytes. Consistent with the role in obesity, predominantly the histone modification pattern of visceral adipocytes is linked to obesity-associated diseases. Thus, this work suggests that the properties of visceral and subcutaneous fat tissues can be studied in vitro and provides preliminary insights into their gene regulatory processes.</p>',
			'date' => '2018-06-30',
			'pmid' => 'http://www.pubmed.gov/29966764',
			'doi' => '10.1016/j.bbagrm.2018.06.007',
			'modified' => '2019-04-17 15:05:35',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 105 => array(
			'id' => '3621',
			'name' => 'Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx.',
			'authors' => 'Hensel KO, Cantner F, Bangert F, Wirth S, Postberg J',
			'description' => '<p>BACKGROUND: In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of cccDNA and HBx remains unexplored. RESULTS: To identify virus-host genome interactions and the underlying nuclear landscape for the first time, we combined circular chromosome conformation capture (4C) with RNA-seq and ChIP-seq. Moreover, we studied HBx-binding to HBV episomes. In HBV-positive HepaRG hepatocytes, we observed preferential association of HBV episomes and HBx with actively transcribed nuclear domains on the host genome correlating in size with constrained topological units of chromatin. Interestingly, HBx alone occupied transcribed chromatin domains. Silencing of native HBx caused reduced episomal HBV stability. CONCLUSIONS: As part of the HBV episome, HBx might stabilize HBV episomal nuclear localization. Our observations may contribute to the understanding of long-term episomal stability and the facilitation of viral persistence. The exact mechanism by which HBx contributes to HBV nuclear persistence warrants further investigations.</p>',
			'date' => '2018-06-22',
			'pmid' => 'http://www.pubmed.gov/29933745',
			'doi' => '10.1186/s13072-018-0204-2',
			'modified' => '2019-05-16 11:23:59',
			'created' => '2019-04-25 11:11:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 106 => array(
			'id' => '3503',
			'name' => 'Genome-wide rules of nucleosome phasing',
			'authors' => 'Sandro Baldi, Dhawal S. Jain1, Lisa Harpprecht1, Angelika Zabel1, Marion Scheibe, Falk Butter, Tobias Straub and Peter B. Becker',
			'description' => '<p>Regular successions of positioned nucleosomes &ndash; phased nucleosome arrays (PNAs) &ndash; are predominantly known from transcriptional start sites (TSS). It is unclear whether PNAs occur elsewhere in the genome. To generate a comprehensive inventory of PNAs for Drosophila, we applied spectral analysis to nucleosome maps and identified thousands of PNAs throughout the genome. About half of them are not near TSS and strongly enriched for a novel sequence motif. Through genome-wide reconstitution of physiological chromatin in Drosophila embryo extracts we uncovered the molecular basis of PNA formation. We identified Phaser, an unstudied zinc finger protein that positions nucleosomes flanking the new motif. It also revealed how the global activity of the chromatin remodeler CHRAC/ACF, together with local barrier elements, generates islands of regular phasing throughout the genome. Our work demonstrates the potential of chromatin assembly by embryo extracts as a powerful tool to reconstitute chromatin features on a global scale in vitro.</p>',
			'date' => '2018-06-13',
			'pmid' => 'https://doi.org/10.1101/093666',
			'doi' => '10.1101/093666.',
			'modified' => '2019-02-28 10:28:59',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 107 => array(
			'id' => '3562',
			'name' => 'Insulin promoter in human pancreatic β cells contacts diabetes susceptibility loci and regulates genes affecting insulin metabolism.',
			'authors' => 'Jian X, Felsenfeld G',
			'description' => '<p>Both type 1 and type 2 diabetes involve a complex interplay between genetic, epigenetic, and environmental factors. Our laboratory has been interested in the physical interactions, in nuclei of human pancreatic &beta; cells, between the insulin ( gene and other genes that are involved in insulin metabolism. We have identified, using Circularized Chromosome Conformation Capture (4C), many physical contacts in a human pancreatic &beta; cell line between the promoter on chromosome 11 and sites on most other chromosomes. Many of these contacts are associated with type 1 or type 2 diabetes susceptibility loci. To determine whether physical contact is correlated with an ability of the locus to affect expression of these genes, we knock down expression by targeting the promoter; 259 genes are either up or down-regulated. Of these, 46 make physical contact with We analyze a subset of the contacted genes and show that all are associated with acetylation of histone H3 lysine 27, a marker of actively expressed genes. To demonstrate the usefulness of this approach in revealing regulatory pathways, we identify from among the contacted sites the previously uncharacterized gene and show that it plays an important role in controlling the effect of somatostatin-28 on insulin secretion. These results are consistent with models in which clustering of genes supports transcriptional activity. This may be a particularly important mechanism in pancreatic &beta; cells and in other cells where a small subset of genes is expressed at high levels.</p>',
			'date' => '2018-05-15',
			'pmid' => 'http://www.pubmed.gov/29712868',
			'doi' => '10.1073/pnas.1803146115',
			'modified' => '2019-03-25 11:27:48',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 108 => array(
			'id' => '3578',
			'name' => 'Modulation of gene transcription and epigenetics of colon carcinoma cells by bacterial membrane vesicles.',
			'authors' => 'Vdovikova S, Gilfillan S, Wang S, Dongre M, Wai SN, Hurtado A',
			'description' => '<p>Interactions between bacteria and colon cancer cells influence the transcription of the host cell. Yet is it undetermined whether the bacteria itself or the communication between the host and bacteria is responsible for the genomic changes in the eukaryotic cell. Now, we have investigated the genomic and epigenetic consequences of co-culturing colorectal carcinoma cells with membrane vesicles from pathogenic bacteria Vibrio cholerae and non-pathogenic commensal bacteria Escherichia coli. Our study reveals that membrane vesicles from pathogenic and commensal bacteria have a global impact on the gene expression of colon-carcinoma cells. The changes in gene expression correlate positively with both epigenetic changes and chromatin accessibility of promoters at transcription start sites of genes induced by both types of membrane vesicles. Moreover, we have demonstrated that membrane vesicles obtained only from V. cholerae induced the expression of genes associated with epithelial cell differentiation. Altogether, our study suggests that the observed genomic changes in host cells might be due to specific components of membrane vesicles and do not require communication by direct contact with the bacteria.</p>',
			'date' => '2018-05-09',
			'pmid' => 'http://www.pubmed.gov/29743643',
			'doi' => '10.1038/s41598-018-25308-9',
			'modified' => '2019-04-17 15:56:24',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 109 => array(
			'id' => '3459',
			'name' => 'Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI as a co-repressor for RUNX1.',
			'authors' => 'Feld C, Sahu P, Frech M, Finkernagel F, Nist A, Stiewe T, Bauer UM, Neubauer A',
			'description' => '<p>SKI is a transcriptional co-regulator and overexpressed in various human tumors, for example in acute myeloid leukemia (AML). SKI contributes to the origin and maintenance of the leukemic phenotype. Here, we use ChIP-seq and RNA-seq analysis to identify the epigenetic alterations induced by SKI overexpression in AML cells. We show that approximately two thirds of differentially expressed genes are up-regulated upon SKI deletion, of which &gt;40% harbor SKI binding sites in their proximity, primarily in enhancer regions. Gene ontology analysis reveals that many of the differentially expressed genes are annotated to hematopoietic cell differentiation and inflammatory response, corroborating our finding that SKI contributes to a myeloid differentiation block in HL60 cells. We find that SKI peaks are enriched for RUNX1 consensus motifs, particularly in up-regulated SKI targets upon SKI deletion. RUNX1 ChIP-seq displays that nearly 70% of RUNX1 binding sites overlap with SKI peaks, mainly at enhancer regions. SKI and RUNX1 occupy the same genomic sites and cooperate in gene silencing. Our work demonstrates for the first time the predominant co-repressive function of SKI in AML cells on a genome-wide scale and uncovers the transcription factor RUNX1 as an important mediator of SKI-dependent transcriptional repression.</p>',
			'date' => '2018-04-20',
			'pmid' => 'http://www.pubmed.gov/29471413',
			'doi' => '10.1093/nar/gky119',
			'modified' => '2019-02-15 21:13:23',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 110 => array(
			'id' => '3539',
			'name' => 'A long range distal enhancer controls temporal fine-tuning of PAX6 expression in neuronal precursors.',
			'authors' => 'Lacomme M, Medevielle F, Bourbon HM, Thierion E, Kleinjan DJ, Roussat M, Pituello F, Bel-Vialar S',
			'description' => '<p>Proper embryonic development relies on a tight control of spatial and temporal gene expression profiles in a highly regulated manner. One good example is the ON/OFF switching of the transcription factor PAX6 that governs important steps of neurogenesis. In the neural tube PAX6 expression is initiated in neural progenitors through the positive action of retinoic acid signaling and downregulated in neuronal precursors by the bHLH transcription factor NEUROG2. How these two regulatory inputs are integrated at the molecular level to properly fine tune temporal PAX6 expression is not known. In this study we identified and characterized a 940-bp long distal cis-regulatory module (CRM), located far away from the PAX6 transcription unit and which conveys positive input from RA signaling pathway and indirect repressive signal(s) from NEUROG2. These opposing regulatory signals are integrated through HOMZ, a 94 bp core region within E940 which is evolutionarily conserved in distant organisms such as the zebrafish. We show that within HOMZ, NEUROG2 and RA exert their opposite temporal activities through a short 60 bp region containing a functional RA-responsive element (RARE). We propose a model in which retinoic acid receptors (RARs) and NEUROG2 repressive target(s) compete on the same DNA motif to fine tune temporal PAX6 expression during the course of spinal neurogenesis.</p>',
			'date' => '2018-04-15',
			'pmid' => 'http://www.pubmed.gov/29486153',
			'doi' => '10.1016/j.ydbio.2018.02.015',
			'modified' => '2019-02-28 10:42:57',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 111 => array(
			'id' => '3432',
			'name' => 'HDAC1 and HDAC2 Modulate TGF-β Signaling during Endothelial-to-Hematopoietic Transition.',
			'authors' => 'Thambyrajah R, Fadlullah MZH, Proffitt M, Patel R, Cowley SM, Kouskoff V, Lacaud G',
			'description' => '<p>The first hematopoietic stem and progenitor cells are generated during development from hemogenic endothelium (HE) through trans-differentiation. The molecular mechanisms underlying this endothelial-to-hematopoietic transition (EHT) remain poorly understood. Here, we explored the role of the epigenetic regulators HDAC1 and HDAC2 in the emergence of these first blood cells in&nbsp;vitro and in&nbsp;vivo. Loss of either of these epigenetic silencers through conditional genetic deletion reduced hematopoietic transition from HE, while combined deletion was incompatible with blood generation. We investigated the molecular basis of HDAC1 and HDAC2 requirement and identified TGF-&beta; signaling as one of the pathways controlled by HDAC1 and HDAC2. Accordingly, we experimentally demonstrated that activation of this pathway in HE cells reinforces hematopoietic development. Altogether, our results establish that HDAC1 and HDAC2 modulate TGF-&beta; signaling and suggest that stimulation of this pathway in HE cells would be beneficial for production of hematopoietic cells for regenerative therapies.</p>',
			'date' => '2018-04-10',
			'pmid' => 'http://www.pubmed.gov/29641990',
			'doi' => '10.1016/j.stemcr.2018.03.011',
			'modified' => '2018-12-31 11:55:16',
			'created' => '2018-12-04 09:51:07',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 112 => array(
			'id' => '3468',
			'name' => 'EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma.',
			'authors' => 'Gorthi A, Romero JC, Loranc E, Cao L, Lawrence LA, Goodale E, Iniguez AB, Bernard X, Masamsetti VP, Roston S, Lawlor ER, Toretsky JA, Stegmaier K, Lessnick SL, Chen Y, Bishop AJR',
			'description' => '<p>Ewing sarcoma is an aggressive paediatric cancer of the bone and soft tissue. It results from a chromosomal translocation, predominantly t(11;22)(q24:q12), that fuses the N-terminal transactivation domain of the constitutively expressed EWSR1 protein with the C-terminal DNA binding domain of the rarely expressed FLI1 protein. Ewing sarcoma is highly sensitive to genotoxic agents such as etoposide, but the underlying molecular basis of this sensitivity is unclear. Here we show that Ewing sarcoma cells display alterations in regulation of damage-induced transcription, accumulation of R-loops and increased replication stress. In addition, homologous recombination is impaired in Ewing sarcoma owing to an enriched interaction between BRCA1 and the elongating transcription machinery. Finally, we uncover a role for EWSR1 in the transcriptional response to damage, suppressing R-loops and promoting homologous recombination. Our findings improve the current understanding of EWSR1 function, elucidate the mechanistic basis of the sensitivity of Ewing sarcoma to chemotherapy (including PARP1 inhibitors) and highlight a class of BRCA-deficient-like tumours.</p>',
			'date' => '2018-03-15',
			'pmid' => 'http://www.pubmed.gov/29513652',
			'doi' => '10.1038/nature25748',
			'modified' => '2019-02-15 21:16:23',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 113 => array(
			'id' => '3533',
			'name' => 'A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.',
			'authors' => 'Zanghì G, Vembar SS, Baumgarten S, Ding S, Guizetti J, Bryant JM, Mattei D, Jensen ATR, Rénia L, Goh YS, Sauerwein R, Hermsen CC, Franetich JF, Bordessoulles M, Silvie O, Soulard V, Scatton O, Chen P, Mecheri S, Mazier D, Scherf A',
			'description' => '<p>Heterochromatin plays a central role in the process of immune evasion, pathogenesis, and transmission of the malaria parasite Plasmodium falciparum during blood stage infection. Here, we use ChIP sequencing to demonstrate that sporozoites from mosquito salivary glands expand heterochromatin at subtelomeric regions to silence blood-stage-specific&nbsp;genes. Our data also revealed that heterochromatin enrichment is predictive of the transcription status of clonally variant genes members that mediate cytoadhesion in blood stage parasites. A specific member (here called NF54var) of the var gene family remains euchromatic, and the resultant PfEMP1 (NF54_SpzPfEMP1) is expressed at the&nbsp;sporozoite surface. NF54_SpzPfEMP1-specific antibodies efficiently block hepatocyte infection in&nbsp;a strain-specific manner. Furthermore, human volunteers immunized with infective sporozoites developed antibodies against NF54_SpzPfEMP1. Overall, we show that the epigenetic signature of var genes is reset in mosquito stages. Moreover, the identification of a strain-specific sporozoite PfEMP1 is highly relevant for vaccine design based on sporozoites.</p>',
			'date' => '2018-03-13',
			'pmid' => 'http://www.pubmed.gov/29539423',
			'doi' => '10.1016/j.celrep.2018.02.075',
			'modified' => '2019-02-28 10:47:11',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 114 => array(
			'id' => '3444',
			'name' => 'Genome-wide analysis of PDX1 target genes in human pancreatic progenitors.',
			'authors' => 'Wang X, Sterr M, Burtscher I, Chen S, Hieronimus A, Machicao F, Staiger H, Häring HU, Lederer G, Meitinger T, Cernilogar FM, Schotta G, Irmler M, Beckers J, Hrabě de Angelis M, Ray M, Wright CVE, Bakhti M, Lickert H',
			'description' => '<p>OBJECTIVE: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing &beta;-cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Also, comparative studies of PDX1 binding patterns in pancreatic progenitors and adult &beta;-cells have not been conducted so far. Furthermore, many studies reported the association between single nucleotide polymorphisms (SNPs) and T2DM, and it has been shown that islet enhancers are enriched in T2DM-associated SNPs. Whether regions, harboring T2DM-associated SNPs are PDX1 bound and active at the pancreatic progenitor stage has not been reported so far. METHODS: In this study, we have generated a novel induced pluripotent stem cell (iPSC) line that efficiently differentiates into human pancreatic progenitors (PPs). Furthermore, PDX1 and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) was used to identify PDX1 transcriptional targets and active enhancer and promoter regions. To address potential differences in the function of PDX1 during development and adulthood, we compared PDX1 binding profiles from PPs and adult islets. Moreover, combining ChIP-seq and GWAS meta-analysis data we identified T2DM-associated SNPs in PDX1 binding sites and active chromatin regions. RESULTS: ChIP-seq for PDX1 revealed a total of 8088 PDX1-bound regions that map to 5664 genes in iPSC-derived PPs. The PDX1 target regions include important pancreatic TFs, such as PDX1 itself, RFX6, HNF1B, and MEIS1, which were activated during the differentiation process as revealed by the active chromatin mark H3K27ac and mRNA expression profiling, suggesting that auto-regulatory feedback regulation maintains PDX1 expression and initiates a pancreatic TF program. Remarkably, we identified several PDX1 target genes that have not been reported in the literature in human so far, including RFX3, required for ciliogenesis and endocrine differentiation in mouse, and the ligand of the Notch receptor DLL1, which is important for endocrine induction and tip-trunk patterning. The comparison of PDX1 profiles from PPs and adult human islets identified sets of stage-specific target genes, associated with early pancreas development and adult &beta;-cell function, respectively. Furthermore, we found an enrichment of T2DM-associated SNPs in active chromatin regions from iPSC-derived PPs. Two of these SNPs fall into PDX1 occupied sites that are located in the intronic regions of TCF7L2 and HNF1B. Both of these genes are key transcriptional regulators of endocrine induction and mutations in cis-regulatory regions predispose to diabetes. CONCLUSIONS: Our data provide stage-specific target genes of PDX1 during in&nbsp;vitro differentiation of stem cells into pancreatic progenitors that could be useful to identify pathways and molecular targets that predispose for diabetes. In addition, we show that T2DM-associated SNPs are enriched in active chromatin regions at the pancreatic progenitor stage, suggesting that the susceptibility to T2DM might originate from imperfect execution of a &beta;-cell developmental program.</p>',
			'date' => '2018-03-01',
			'pmid' => 'http://www.pubmed.gov/29396371',
			'doi' => '10.1016/j.molmet.2018.01.011',
			'modified' => '2019-02-15 21:27:03',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 115 => array(
			'id' => '3543',
			'name' => 'A multi-omics study of the grapevine-downy mildew (Plasmopara viticola) pathosystem unveils a complex protein coding- and noncoding-based arms race during infection.',
			'authors' => 'Brilli M, Asquini E, Moser M, Bianchedi PL, Perazzolli M, Si-Ammour A',
			'description' => '<p>Fungicides are applied intensively to prevent downy mildew infections of grapevines (Vitis vinifera) with high impact on the environment. In order to develop alternative strategies we sequenced the genome of the oomycete pathogen Plasmopara viticola causing this disease. We show that it derives from a Phytophthora-like ancestor that switched to obligate biotrophy by losing genes involved in nitrogen metabolism and &gamma;-Aminobutyric acid catabolism. By combining multiple omics approaches we characterized the pathosystem and identified a RxLR effector that trigger an immune response in the wild species V. riparia. This effector is an ideal marker to screen novel grape resistant varieties. Our study reveals an unprecedented bidirectional noncoding RNA-based mechanism that, in one direction might be fundamental for P. viticola to proficiently infect its host, and in the other might reduce the effects of the infection on the plant.</p>',
			'date' => '2018-01-15',
			'pmid' => 'http://www.pubmed.gov/29335535',
			'doi' => '10.1038/s41598-018-19158-8',
			'modified' => '2019-02-28 11:00:21',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 116 => array(
			'id' => '3445',
			'name' => 'BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis.',
			'authors' => 'Kaufmann E, Sanz J, Dunn JL, Khan N, Mendonça LE, Pacis A, Tzelepis F, Pernet E, Dumaine A, Grenier JC, Mailhot-Léonard F, Ahmed E, Belle J, Besla R, Mazer B, King IL, Nijnik A, Robbins CS, Barreiro LB, Divangahi M',
			'description' => '<p>The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and&nbsp;location for generating such innate memory responses in&nbsp;vivo remain unknown. Here, we show that access of Bacillus Calmette-Gu&eacute;rin (BCG) to the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), leading to local cell&nbsp;expansion and enhanced myelopoiesis at the&nbsp;expense of lymphopoiesis. Importantly, BCG-educated HSCs generate epigenetically modified macrophages that provide significantly better protection against virulent M.&nbsp;tuberculosis infection than na&iuml;ve macrophages. By using parabiotic and chimeric mice, as well as adoptive transfer approaches, we demonstrate that training of the monocyte/macrophage lineage via BCG-induced HSC reprogramming is sustainable in&nbsp;vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.</p>',
			'date' => '2018-01-11',
			'pmid' => 'http://www.pubmed.gov/29328912',
			'doi' => '10.1016/j.cell.2017.12.031',
			'modified' => '2019-02-15 21:32:25',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 117 => 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) 118 => array(
			'id' => '3355',
			'name' => 'Functional dissection of Drosophila melanogaster SUUR protein influence on H3K27me3 profile',
			'authors' => 'Posukh O. V. et al.',
			'description' => '<div id="__sec1" class="sec sec-first">
<h3>Background</h3>
<p id="Par1" class="p p-first-last">In eukaryotes, heterochromatin replicates late in S phase of the cell cycle and contains specific covalent modifications of histones. <em>SuUR</em> mutation found in Drosophila makes heterochromatin replicate earlier than in wild type and reduces the level of repressive histone modifications. SUUR protein was shown to be associated with moving replication forks, apparently through the interaction with PCNA. The biological process underlying the effects of SUUR on replication and composition of heterochromatin remains unknown.</p>
</div>
<div id="__sec2" class="sec">
<h3>Results</h3>
<p id="Par2" class="p p-first-last">Here we performed a functional dissection of SUUR protein effects on H3K27me3 level. Using hidden Markow model-based algorithm we revealed <em>SuUR</em>-sensitive chromosomal regions that demonstrated unusual characteristics: They do not contain Polycomb and require SUUR function to sustain H3K27me3 level. We tested the role of SUUR protein in the mechanisms that could affect H3K27me3 histone levels in these regions. We found that SUUR does not affect the initial H3K27me3 pattern formation in embryogenesis or Polycomb distribution in the chromosomes. We also ruled out the possible effect of SUUR on histone genes expression and its involvement in DSB repair.</p>
</div>
<div id="__sec3" class="sec">
<h3>Conclusions</h3>
<p id="Par3" class="p p-first-last">Obtained results support the idea that SUUR protein contributes to the heterochromatin maintenance during the chromosome replication. A model that explains major SUUR-associated phenotypes is proposed.</p>
</div>',
			'date' => '2017-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709859/',
			'doi' => '',
			'modified' => '2018-04-05 12:28:59',
			'created' => '2018-04-05 12:28:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 119 => array(
			'id' => '3305',
			'name' => 'An endosiRNA-Based Repression Mechanism Counteracts Transposon Activation during Global DNA Demethylation in Embryonic Stem Cells',
			'authors' => 'Berrens R.V. et al.',
			'description' => '<p>Erasure of DNA methylation and repressive chromatin marks in the mammalian germline leads to risk of transcriptional activation of transposable elements (TEs). Here, we used mouse embryonic stem cells (ESCs) to identify an endosiRNA-based mechanism involved in suppression of TE transcription. In ESCs with DNA demethylation induced by acute deletion of Dnmt1, we saw an increase in sense transcription at TEs, resulting in an abundance of sense/antisense transcripts leading to high levels of ARGONAUTE2 (AGO2)-bound small RNAs. Inhibition of Dicer or Ago2 expression revealed that small RNAs are involved in an immediate response to demethylation-induced transposon activation, while the deposition of repressive histone marks follows as a chronic response. In&nbsp;vivo, we also found TE-specific endosiRNAs present during primordial germ cell development. Our results suggest that antisense TE transcription is a "trap" that elicits an endosiRNA response to restrain acute transposon activity during epigenetic reprogramming in the mammalian germline.</p>',
			'date' => '2017-11-02',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29100015',
			'doi' => '',
			'modified' => '2018-01-03 10:17:40',
			'created' => '2018-01-03 10:17:40',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 120 => array(
			'id' => '3281',
			'name' => 'Epigenome profiling and editing of neocortical progenitor cells during development',
			'authors' => 'Albert M. et al.',
			'description' => '<p>The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resolution are required. Here, we present genomewide histone methylation maps for distinct neural cell populations in the developing mouse neocortex. Using different chromatin features, we identify potential novel regulators of cortical NPCs. Moreover, we identify extensive H3K27me3 changes between NPC subtypes coinciding with major developmental and cell biological transitions. Interestingly, we detect dynamic H3K27me3 changes on promoters of several crucial transcription factors, including the basal progenitor regulator <i>Eomes</i> We use catalytically inactive Cas9 fused with the histone methyltransferase Ezh2 to edit H3K27me3 at the <i>Eomes</i> locus <i>in&nbsp;vivo</i>, which results in reduced Tbr2 expression and lower basal progenitor abundance, underscoring the relevance of dynamic H3K27me3 changes during neocortex development. Taken together, we provide a rich resource of neocortical histone methylation data and outline an approach to investigate its contribution to the regulation of selected genes during neocortical development.</p>',
			'date' => '2017-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28765163',
			'doi' => '',
			'modified' => '2017-10-17 10:25:58',
			'created' => '2017-10-17 10:25:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 121 => array(
			'id' => '3250',
			'name' => 'Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles',
			'authors' => 'Marincevic-Zuniga Y. et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL). In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts.</abstracttext></p>
<h4>METHODS:</h4>
<p><abstracttext label="METHODS" nlmcategory="METHODS">We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">We identified 64 unique fusion events distributed among 80 individual patients, of which over 50% have not previously been reported in ALL. Although the majority of the fusion genes were found only in a single patient, we identified several recurrent fusion gene families defined by promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5, and ZNF384, or recurrent fusion genes, such as DUX4-IGH. Our data show that patients harboring these fusion genes displayed characteristic genome-wide DNA methylation and gene expression signatures in addition to distinct patterns in single nucleotide variants and recurrent copy number alterations.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">Our study delineates the fusion gene landscape in pediatric ALL, including both known and novel fusion genes, and highlights fusion gene families with shared molecular etiologies, which may provide additional information for prognosis and therapeutic options in the future.</abstracttext></p>
</div>',
			'date' => '2017-08-14',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28806978',
			'doi' => '',
			'modified' => '2017-09-26 09:49:39',
			'created' => '2017-09-26 09:49:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 122 => array(
			'id' => '3259',
			'name' => 'Dynamics of RNA Polymerase II Pausing and Bivalent Histone H3 Methylation during Neuronal Differentiation in Brain Development',
			'authors' => 'Liu J. et al.',
			'description' => '<p>During cellular differentiation, genes important for differentiation are expected to be silent in stem/progenitor cells yet can be readily activated. RNA polymerase II (Pol II) pausing and bivalent chromatin marks are two paradigms suited for establishing such a poised state of gene expression; however, their specific contributions in development are not well understood. Here we characterized Pol II pausing and H3K4me3/H3K27me3 marks in neural progenitor cells (NPCs) and their daughter neurons purified from the developing mouse cortex. We show that genes paused in NPCs or neurons are characteristic of respective cellular functions important for each cell type, although pausing and pause release were not correlated with gene activation. Bivalent chromatin marks poised the marked genes&nbsp;in NPCs for activation in neurons. Interestingly, we&nbsp;observed a positive correlation between H3K27me3 and paused Pol II. This study thus reveals cell type-specific Pol II pausing and gene activation-associated bivalency during mammalian neuronal differentiation.</p>',
			'date' => '2017-08-08',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28793256',
			'doi' => '',
			'modified' => '2017-10-05 11:17:11',
			'created' => '2017-10-05 11:17:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 123 => 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) 124 => array(
			'id' => '3282',
			'name' => 'Krox20 hindbrain regulation incorporates multiple modes of cooperation between cis-acting elements',
			'authors' => 'Thierion E. et al.',
			'description' => '<p>Developmental genes can harbour multiple transcriptional enhancers that act simultaneously or in succession to achieve robust and precise spatiotemporal expression. However, the mechanisms underlying cooperation between cis-acting elements are poorly documented, notably in vertebrates. The mouse gene Krox20 encodes a transcription factor required for the specification of two segments (rhombomeres) of the developing hindbrain. In rhombomere 3, Krox20 is subject to direct positive feedback governed by an autoregulatory enhancer, element A. In contrast, a second enhancer, element C, distant by 70 kb, is active from the initiation of transcription independent of the presence of the KROX20 protein. Here, using both enhancer knock-outs and investigations of chromatin organisation, we show that element C possesses a dual activity: besides its classical enhancer function, it is also permanently required in cis to potentiate the autoregulatory activity of element A, by increasing its chromatin accessibility. This work uncovers a novel, asymmetrical, long-range mode of cooperation between cis-acting elements that might be essential to avoid promiscuous activation of positive autoregulatory elements.</p>',
			'date' => '2017-07-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28749941',
			'doi' => '',
			'modified' => '2017-10-23 17:38:21',
			'created' => '2017-10-23 17:38:21',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 125 => array(
			'id' => '3261',
			'name' => 'Ectopic application of the repressive histone modification H3K9me2 establishes post-zygotic reproductive isolation in Arabidopsis thaliana',
			'authors' => 'Jiang H. et al.',
			'description' => '<p>Hybrid seed lethality as a consequence of interspecies or interploidy hybridizations is a major mechanism of reproductive isolation in plants. This mechanism is manifested in the endosperm, a dosage-sensitive tissue supporting embryo growth. Deregulated expression of imprinted genes such as <em>ADMETOS</em> (<em>ADM</em>) underpin the interploidy hybridization barrier in <em>Arabidopsis thaliana</em>; however, the mechanisms of their action remained unknown. In this study, we show that ADM interacts with the AT hook domain protein AHL10 and the SET domain-containing SU(VAR)3&ndash;9 homolog SUVH9 and ectopically recruits the heterochromatic mark H3K9me2 to AT-rich transposable elements (TEs), causing deregulated expression of neighboring genes. Several hybrid incompatibility genes identified in <em>Drosophila</em> encode for dosage-sensitive heterochromatin-interacting proteins, which has led to the suggestion that hybrid incompatibilities evolve as a consequence of interspecies divergence of selfish DNA elements and their regulation. Our data show that imbalance of dosage-sensitive chromatin regulators underpins the barrier to interploidy hybridization in <em>Arabidopsis</em>, suggesting that reproductive isolation as a consequence of epigenetic regulation of TEs is a conserved feature in animals and plants.</p>',
			'date' => '2017-07-25',
			'pmid' => 'http://genesdev.cshlp.org/content/early/2017/07/25/gad.299347.117',
			'doi' => '',
			'modified' => '2017-10-05 11:34:59',
			'created' => '2017-10-05 11:34:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 126 => array(
			'id' => '3267',
			'name' => '2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: Alterations in biosynthesis, enterohepatic circulation, and microbial metabolism.',
			'authors' => 'Fader K. et al.',
			'description' => '<p>2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant which elicits hepatotoxicity through activation of the aryl hydrocarbon receptor (AhR). Male C57BL/6 mice orally gavaged with TCDD (0.01-30&thinsp;&micro;g/kg) every 4 days for 28 days exhibited bile duct proliferation and pericholangitis. Mass spectrometry analysis detected a 4.6-fold increase in total hepatic bile acid levels, despite the coordinated repression of genes involved in cholesterol and primary bile acid biosynthesis including Cyp7a1. Specifically, TCDD elicited a &gt;200-fold increase in taurolithocholic acid (TLCA), a potent G protein-coupled bile acid receptor 1 (GPBAR1) agonist associated with bile duct proliferation. Increased levels of microbial bile acid metabolism loci (bsh, baiCD) are consistent with accumulation of TLCA and other secondary bile acids. Fecal bile acids decreased 2.8-fold, suggesting enhanced intestinal reabsorption due to induction of ileal transporters (Slc10a2, Slc51a) and increases in whole gut transit time and intestinal permeability. Moreover, serum bile acids were increased 45.4-fold, consistent with blood-to-hepatocyte transporter repression (Slco1a1, Slc10a1, Slco2b1, Slco1b2, Slco1a4) and hepatocyte-to-blood transporter induction (Abcc4, Abcc3). These results suggest that systemic alterations in enterohepatic circulation, as well as host and microbiota bile acid metabolism, favor bile acid accumulation that contributes to AhR-mediated hepatotoxicity.</p>',
			'date' => '2017-07-19',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28725001',
			'doi' => '',
			'modified' => '2017-10-09 16:22:36',
			'created' => '2017-10-09 16:22:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 127 => 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) 128 => array(
			'id' => '3258',
			'name' => 'CRISPR/Cas9 Genome Editing Reveals That the Intron Is Not Essential for var2csa Gene Activation or Silencing in Plasmodium falciparum',
			'authors' => 'Bryant J.M. et al.',
			'description' => '<p id="p-4"><em>Plasmodium falciparum</em> relies on monoallelic expression of 1 of 60 <em>var</em> virulence genes for antigenic variation and host immune evasion. Each <em>var</em> gene contains a conserved intron which has been implicated in previous studies in both activation and repression of transcription via several epigenetic mechanisms, including interaction with the <em>var</em> promoter, production of long noncoding RNAs (lncRNAs), and localization to repressive perinuclear sites. However, functional studies have relied primarily on artificial expression constructs. Using the recently developed <em>P.&nbsp;falciparum</em> clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, we directly deleted the <em>var2csa P.&nbsp;falciparum</em> 3D7_1200600 (Pf3D7_1200600) endogenous intron, resulting in an intronless <em>var</em> gene in a natural, marker-free chromosomal context. Deletion of the <em>var2csa</em> intron resulted in an upregulation of transcription of the <em>var2csa</em> gene in ring-stage parasites and subsequent expression of the PfEMP1 protein in late-stage parasites. Intron deletion did not affect the normal temporal regulation and subsequent transcriptional silencing of the <em>var</em> gene in trophozoites but did result in increased rates of <em>var</em> gene switching in some mutant clones. Transcriptional repression of the intronless <em>var2csa</em> gene could be achieved via long-term culture or panning with the CD36 receptor, after which reactivation was possible with chondroitin sulfate A (CSA) panning. These data suggest that the <em>var2csa</em> intron is not required for silencing or activation in ring-stage parasites but point to a subtle role in regulation of switching within the <em>var</em> gene family.</p>
<p id="p-5"><strong>IMPORTANCE</strong> <em>Plasmodium falciparum</em> is the most virulent species of malaria parasite, causing high rates of morbidity and mortality in those infected. Chronic infection depends on an immune evasion mechanism termed antigenic variation, which in turn relies on monoallelic expression of 1 of ~60 <em>var</em> genes. Understanding antigenic variation and the transcriptional regulation of monoallelic expression is important for developing drugs and/or vaccines. The <em>var</em> gene family encodes the antigenic surface proteins that decorate infected erythrocytes. Until recently, studying the underlying genetic elements that regulate monoallelic expression in <em>P.&nbsp;falciparum</em> was difficult, and most studies relied on artificial systems such as episomal reporter genes. Our study was the first to use CRISPR/Cas9 genome editing for the functional study of an important, conserved genetic element of <em>var</em> genes&mdash;the intron&mdash;in an endogenous, episome-free manner. Our findings shed light on the role of the <em>var</em> gene intron in transcriptional regulation of monoallelic expression.</p>',
			'date' => '2017-07-11',
			'pmid' => 'http://mbio.asm.org/content/8/4/e00729-17.abstract',
			'doi' => '',
			'modified' => '2017-10-05 11:12:18',
			'created' => '2017-10-05 11:12:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 129 => array(
			'id' => '3218',
			'name' => 'Genome-wide mapping and analysis of aryl hydrocarbon receptor (AHR)- and aryl hydrocarbon receptor repressor (AHRR)-binding sites in human breast cancer cells',
			'authors' => 'Sunny Y. Yang, Shaimaa Ahmed, Somisetty V. Satheesh, Jason Matthews',
			'description' => '<p><span>The aryl hydrocarbon receptor (AHR) mediates the toxic actions of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-</span><em class="EmphasisTypeItalic ">&rho;</em><span>-dioxin (TCDD), and also plays roles in vascular development, the immune response, and cell cycle regulation. The AHR repressor (AHRR) is an AHR-regulated gene and a negative regulator of AHR; however, the mechanisms of AHRR-dependent repression of AHR are unclear. In this study, we compared the genome-wide binding profiles of AHR and AHRR in MCF-7 human breast cancer cells treated for 24&nbsp;h with TCDD using chromatin immunoprecipitation followed by next-generation sequencing (ChIP-Seq). We identified 3915 AHR- and 2811 AHRR-bound regions, of which 974 (35%) were common to both datasets. When these 24-h datasets were also compared with AHR-bound regions identified after 45&nbsp;min of TCDD treatment, 67% (1884) of AHRR-bound regions overlapped with those of AHR. This analysis identified 994 unique AHRR-bound regions. AHRR-bound regions mapped closer to promoter regions when compared with AHR-bound regions. The AHRE was identified and overrepresented in AHR:AHRR-co-bound regions, AHR-only regions, and AHRR-only regions. Candidate unique AHR- and AHRR-bound regions were validated by ChIP&ndash;qPCR and their ability to regulate gene expression was confirmed by luciferase reporter gene assays. Overall, this study reveals that AHR and AHRR exhibit similar but also distinct genome-wide binding profiles, supporting the notion that AHRR is a context- and gene-specific repressor of AHR activity.</span></p>',
			'date' => '2017-07-05',
			'pmid' => 'https://link.springer.com/article/10.1007/s00204-017-2022-x',
			'doi' => '10.1007/s00204-017-2022-x',
			'modified' => '2017-07-29 08:23:22',
			'created' => '2017-07-29 08:23:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 130 => 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) 131 => array(
			'id' => '3358',
			'name' => 'Characterization of the Polycomb-Group Mark H3K27me3 in Unicellular Algae',
			'authors' => 'Mikulski P. et al.',
			'description' => '<p>Polycomb Group (PcG) proteins mediate chromatin repression in plants and animals by catalyzing H3K27 methylation and H2AK118/119 mono-ubiquitination through the activity of the Polycomb repressive complex 2 (PRC2) and PRC1, respectively. PcG proteins were extensively studied in higher plants, but their function and target genes in unicellular branches of the green lineage remain largely unknown. To shed light on PcG function and <i>modus operandi</i> in a broad evolutionary context, we demonstrate phylogenetic relationship of core PRC1 and PRC2 proteins and H3K27me3 biochemical presence in several unicellular algae of different phylogenetic subclades. We focus then on one of the species, the model red alga <i>Cyanidioschizon merolae</i>, and show that H3K27me3 occupies both, genes and repetitive elements, and mediates the strength of repression depending on the differential occupancy over gene bodies. Furthermore, we report that H3K27me3 in <i>C. merolae</i> is enriched in telomeric and subtelomeric regions of the chromosomes and has unique preferential binding toward intein-containing genes involved in protein splicing. Thus, our study gives important insight for Polycomb-mediated repression in lower eukaryotes, uncovering a previously unknown link between H3K27me3 targets and protein splicing.</p>',
			'date' => '2017-04-26',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28491069',
			'doi' => '',
			'modified' => '2018-04-05 13:09:46',
			'created' => '2018-04-05 13:09:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 132 => 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) 133 => array(
			'id' => '3176',
			'name' => 'First landscape of binding to chromosomes for a domesticated mariner transposase in the human genome: diversity of genomic targets of SETMAR isoforms in two colorectal cell lines',
			'authors' => 'Antoine-Lorquin A. et al.',
			'description' => '<p>Setmar is a 3-exons gene coding a SET domain fused to a Hsmar1 transposase. Its different transcripts theoretically encode 8 isoforms with SET moieties differently spliced. In vitro, the largest isoform binds specifically to Hsmar1 DNA ends and with no specificity to DNA when it is associated with hPso4. In colon cell lines, we found they bind specifically to two chromosomal targets depending probably on the isoform, Hsmar1 ends and sites with no conserved motifs. We also discovered that the isoforms profile was different between cell lines and patient tissues, suggesting the isoforms encoded by this gene in healthy cells and their functions are currently not investigated.</p>',
			'date' => '2017-03-09',
			'pmid' => 'http://biorxiv.org/content/early/2017/03/09/115030',
			'doi' => '',
			'modified' => '2017-05-15 10:24:16',
			'created' => '2017-05-15 10:24:16',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 134 => array(
			'id' => '3156',
			'name' => 'Crebbp loss cooperates with Bcl2 over-expression to promote lymphoma in mice',
			'authors' => 'Idoia García-Ramírez, Saber Tadros, Inés González-Herrero, Alberto Martín-Lorenzo, Guillermo Rodríguez-Hernández, Dalia Moore, Lucía Ruiz-Roca, Oscar Blanco, Diego Alonso-López, Javier De Las Rivas, Keenan Hartert, Romain Duval, David Klinkebiel, Martin B',
			'description' => '<p><span>CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits in B-cell development and can cooperate with Bcl2 over-expression to promote B-cell lymphoma. Through transcriptional and epigenetic profiling of these B-cells we found that Crebbp inactivation was associated with broad transcriptional alterations, but no changes in the patterns of histone acetylation at the proximal regulatory regions of these genes. However, B-cells with Crebbp inactivation showed high expression of Myc and patterns of altered histone acetylation that were localized to intragenic regions, enriched for Myc DNA binding motifs, and showed Myc binding. Through the analysis of CREBBP mutations from a large cohort of primary human FL and DLBCL, we show a significant difference in the spectrum of CREBBP mutations in these two diseases, with higher frequencies of nonsense/frameshift mutations in DLBCL compared to FL. Together our data therefore provide important links between Crebbp inactivation and Bcl2 dependence, and show a role for Crebbp inactivation in the induction of Myc expression. We suggest this may parallel the role of CREBBP frameshift/nonsense mutations in DLBCL that result in loss of the protein, but may contrast the role of missense mutations in the lysine acetyltransferase domain that are more frequently observed in FL and yield an inactive protein.</span></p>',
			'date' => '2017-03-05',
			'pmid' => 'http://www.bloodjournal.org/content/early/2017/03/13/blood-2016-08-733469?sso-checked=true',
			'doi' => 'https://doi.org/10.1182/blood-2016-08-733469',
			'modified' => '2017-05-11 11:17:42',
			'created' => '2017-04-10 07:56:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 135 => array(
			'id' => '3151',
			'name' => 'Aorta macrophage inflammatory and epigenetic changes in a murine model of obstructive sleep apnea: Potential role of CD36.',
			'authors' => 'Cortese R. et al.',
			'description' => '<p>Obstructive sleep apnea (OSA) affects 8-10% of the population, is characterized by chronic intermittent hypoxia (CIH), and causally associates with cardiovascular morbidities. In CIH-exposed mice, closely mimicking the chronicity of human OSA, increased accumulation and proliferation of pro-inflammatory metabolic M1-like macrophages highly expressing CD36, emerged in aorta. Transcriptomic and MeDIP-seq approaches identified activation of pro-atherogenic pathways involving a complex interplay of histone modifications in functionally-relevant biological pathways, such as inflammation and oxidative stress in aorta macrophages. Discontinuation of CIH did not elicit significant improvements in aorta wall macrophage phenotype. However, CIH-induced aorta changes were absent in CD36 knockout mice, Our results provide mechanistic insights showing that CIH exposures during sleep in absence of concurrent pro-atherogenic settings (i.e., genetic propensity or dietary manipulation) lead to the recruitment of CD36(+)<sup>high</sup> macrophages to the aortic wall and trigger atherogenesis. Furthermore, long-term CIH-induced changes may not be reversible with usual OSA treatment.</p>',
			'date' => '2017-02-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28240319',
			'doi' => '',
			'modified' => '2017-03-28 09:16:02',
			'created' => '2017-03-28 09:16:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 136 => array(
			'id' => '3138',
			'name' => 'Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia',
			'authors' => 'Chen S. et al.',
			'description' => '<p>Severe neonatal hyperbilirubinemia (SNH) and the onset of bilirubin encephalopathy and kernicterus result in part from delayed expression of UDP-glucuronosyltransferase 1A1 (UGT1A1) and the inability to metabolize bilirubin. Although there is a good understanding of the early events after birth that lead to the rapid increase in serum bilirubin, the events that control delayed expression of UGT1A1 during development remain a mystery. Humanized <em>UGT1</em> (<em>hUGT1</em>) mice develop SNH spontaneously, which is linked to repression of both liver and intestinal UGT1A1. In this study, we report that deletion of intestinal nuclear receptor corepressor 1 (NCoR1) completely diminishes hyperbilirubinemia in <em>hUGT1</em> neonates because of intestinal <em>UGT1A1</em> gene derepression. Transcriptomic studies and immunohistochemistry analysis demonstrate that NCoR1 plays a major role in repressing developmental maturation of the intestines. Derepression is marked by accelerated metabolic and oxidative phosphorylation, drug metabolism, fatty acid metabolism, and intestinal maturation, events that are controlled predominantly by H3K27 acetylation. The control of NCoR1 function and derepression is linked to IKK&beta; function, as validated in <em>hUGT1</em> mice with targeted deletion of intestinal IKK&beta;. Physiological events during neonatal development that target activation of an IKK&beta;/NCoR1 loop in intestinal epithelial cells lead to derepression of genes involved in intestinal maturation and bilirubin detoxification. These findings provide a mechanism of NCoR1 in intestinal homeostasis during development and provide a key link to those events that control developmental repression of UGT1A1 and hyperbilirubinemia.</p>',
			'date' => '2017-02-21',
			'pmid' => 'http://www.pnas.org/content/114/8/E1432.abstract',
			'doi' => '',
			'modified' => '2017-03-21 17:48:23',
			'created' => '2017-03-21 17:48:23',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 137 => array(
			'id' => '3166',
			'name' => 'The Drosophila speciation factor HMR localizes to genomic insulator sites',
			'authors' => 'Gerland T.A. et al.',
			'description' => '<p>Hybrid incompatibility between Drosophila melanogaster and D. simulans is caused by a lethal interaction of the proteins encoded by the Hmr and Lhr genes. In D. melanogaster the loss of HMR results in mitotic defects, an increase in transcription of transposable elements and a deregulation of heterochromatic genes. To better understand the molecular mechanisms that mediate HMR's function, we measured genome-wide localization of HMR in D. melanogaster tissue culture cells by chromatin immunoprecipitation. Interestingly, we find HMR localizing to genomic insulator sites that can be classified into two groups. One group belongs to gypsy insulators and another one borders HP1a bound regions at active genes. The transcription of the latter group genes is strongly affected in larvae and ovaries of Hmr mutant flies. Our data suggest a novel link between HMR and insulator proteins, a finding that implicates a potential role for genome organization in the formation of species.</p>',
			'date' => '2017-02-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28207793',
			'doi' => '',
			'modified' => '2017-05-09 10:05:49',
			'created' => '2017-05-09 10:05:49',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 138 => array(
			'id' => '3357',
			'name' => 'Applying the INTACT method to purify endosperm nuclei and to generate parental-specific epigenome profiles.',
			'authors' => 'Moreno-Romero J. et al.',
			'description' => '<p>The early endosperm tissue of dicot species is very difficult to isolate by manual dissection. This protocol details how to apply the INTACT (isolation of nuclei tagged in specific cell types) system for isolating early endosperm nuclei of Arabidopsis at high purity and how to generate parental-specific epigenome profiles. As a Protocol Extension, this article describes an adaptation of an existing Nature Protocol that details the use of the INTACT method for purification of root nuclei. We address how to obtain the INTACT lines, generate the starting material and purify the nuclei. We describe a method that allows purity assessment, which has not been previously addressed. The purified nuclei can be used for ChIP and DNA bisulfite treatment followed by next-generation sequencing (seq) to study histone modifications and DNA methylation profiles, respectively. By using two different Arabidopsis accessions as parents that differ by a large number of single-nucleotide polymorphisms (SNPs), we were able to distinguish the parental origin of epigenetic modifications. Our protocol describes the only working method to our knowledge for generating parental-specific epigenome profiles of the early Arabidopsis endosperm. The complete protocol, from silique collection to finished libraries, can be completed in 2 d for bisulfite-seq (BS-seq) and 3 to 4 d for ChIP-seq experiments.This protocol is an extension to: Nat. Protoc. 6, 56-68 (2011); doi:10.1038/nprot.2010.175; published online 16 December 2010.</p>',
			'date' => '2017-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28055034',
			'doi' => '',
			'modified' => '2018-04-05 12:52:20',
			'created' => '2018-04-05 12:52:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 139 => array(
			'id' => '3042',
			'name' => 'BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire',
			'authors' => 'Najafova Z. et al.',
			'description' => '<p>Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4.</p>',
			'date' => '2016-09-19',
			'pmid' => 'http://nar.oxfordjournals.org/content/early/2016/09/19/nar.gkw826.abstract',
			'doi' => '',
			'modified' => '2016-10-10 09:58:41',
			'created' => '2016-10-10 09:49:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 140 => array(
			'id' => '3043',
			'name' => 'CTCF modulates Estrogen Receptor function through specific chromatin and nuclear matrix interactions',
			'authors' => 'Fiorito E. et al.',
			'description' => '<p>Enhancer regions and transcription start sites of estrogen-target regulated genes are connected by means of Estrogen Receptor long-range chromatin interactions. Yet, the complete molecular mechanisms controlling the transcriptional output of engaged enhancers and subsequent activation of coding genes remain elusive. Here, we report that CTCF binding to enhancer RNAs is enriched when breast cancer cells are stimulated with estrogen. CTCF binding to enhancer regions results in modulation of estrogen-induced gene transcription by preventing Estrogen Receptor chromatin binding and by hindering the formation of additional enhancer-promoter ER looping. Furthermore, the depletion of CTCF facilitates the expression of target genes associated with cell division and increases the rate of breast cancer cell proliferation. We have also uncovered a genomic network connecting loci enriched in cell cycle regulator genes to nuclear lamina that mediates the CTCF function. The nuclear lamina and chromatin interactions are regulated by estrogen-ER. We have observed that the chromatin loops formed when cells are treated with estrogen establish contacts with the nuclear lamina. Once there, the portion of CTCF associated with the nuclear lamina interacts with enhancer regions, limiting the formation of ER loops and the induction of genes present in the loop. Collectively, our results reveal an important, unanticipated interplay between CTCF and nuclear lamina to control the transcription of ER target genes, which has great implications in the rate of growth of breast cancer cells.</p>',
			'date' => '2016-09-15',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27638884',
			'doi' => '',
			'modified' => '2016-10-10 10:12:33',
			'created' => '2016-10-10 10:12:33',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 141 => array(
			'id' => '3052',
			'name' => 'PionX sites mark the X chromosome for dosage compensation',
			'authors' => 'Villa R et al.',
			'description' => '<p>The rules defining which small fraction of related DNA sequences can be selectively bound by a transcription factor are poorly understood. One of the most challenging tasks in DNA recognition is posed by dosage compensation systems that require the distinction between sex chromosomes and autosomes. In <i>Drosophila melanogaster</i>, the male-specific lethal dosage compensation complex (MSL-DCC) doubles the level of transcription from the single male X chromosome, but the nature of this selectivity is not known<sup><a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref1" title="Lucchesi, J. C. &amp; Kuroda, M. I. Dosage compensation in Drosophila. Cold Spring Harb. Perspect. Biol. 7, a019398 (2015)" id="ref-link-7">1</a></sup>. Previous efforts to identify X-chromosome-specific target sequences were unsuccessful as the identified MSL recognition elements lacked discriminative power<sup><a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref2" title="Alekseyenko, A. A. et al. A sequence motif within chromatin entry sites directs MSL establishment on the Drosophila X chromosome. Cell. 134, 599&ndash;609 (2008)" id="ref-link-8">2</a>, <a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref3" title="Straub, T., Grimaud, C., Gilfillan, G. D., Mitterweger, A. &amp; Becker, P. B. The chromosomal high-affinity binding sites for the Drosophila dosage compensation complex. PLoS Genet. 4, e1000302 (2008)" id="ref-link-9">3</a></sup>. Therefore, additional determinants such as co-factors, chromatin features, RNA and chromosome conformation have been proposed to refine targeting further<sup><a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref4" title="McElroy, K. A., Kang, H. &amp; Kuroda, M. I. Are we there yet? Initial targeting of the Male-Specific Lethal and Polycomb group chromatin complexes in Drosophila. Open Biol. 4, 140006 (2014)" id="ref-link-10">4</a></sup>. Here, using an <i>in vitro</i> genome-wide DNA binding assay, we show that recognition of the X chromosome is an intrinsic feature of the MSL-DCC. MSL2, the male-specific organizer of the complex, uses two distinct DNA interaction surfaces&mdash;the CXC and proline/basic-residue-rich domains&mdash;to identify complex DNA elements on the X chromosome. Specificity is provided by the CXC domain, which binds a novel motif defined by DNA sequence and shape. This motif characterizes a subclass of MSL2-binding sites, which we name PionX (pioneering sites on the X) as they appeared early during the recent evolution of an X chromosome in <i>D. miranda</i> and are the first chromosomal sites to be bound during <i>de novo</i> MSL-DCC assembly. Our data provide the first, to our knowledge, documented molecular mechanism through which the dosage compensation machinery distinguishes the X chromosome from an autosome. They highlight fundamental principles in the recognition of complex DNA elements by protein that will have a strong impact on many aspects of chromosome biology.</p>',
			'date' => '2016-08-31',
			'pmid' => 'http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html',
			'doi' => '',
			'modified' => '2016-10-24 14:23:31',
			'created' => '2016-10-24 14:23:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 142 => 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',
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			'id' => '2976',
			'name' => 'Deletion of Polycomb Repressive Complex 2 From Mouse Intestine Causes Loss of Stem Cells',
			'authors' => 'Koppens MA et al.',
			'description' => '<h4>BACKGROUND &amp; AIMS:</h4>
<p><abstracttext label="BACKGROUND &amp; AIMS" nlmcategory="OBJECTIVE">The polycomb repressive complex 2 (PRC2) regulates differentiation by contributing to repression of gene expression and thereby stabilizing the fate of stem cells and their progeny. PRC2 helps to maintain adult stem cell populations, but little is known about its functions in intestinal stem cells. We studied phenotypes of mice with intestine-specific deletion of the PRC2 proteins EED (a subunit required for PRC2 function) and EZH2 (a histone methyltransferase).</abstracttext></p>
<h4>METHODS:</h4>
<p><abstracttext label="METHODS" nlmcategory="METHODS">We performed studies of AhCre;EedLoxP/LoxP (EED knockout) mice and AhCre;Ezh2LoxP/LoxP (EZH2 knockout) mice, which have intestine-specific disruption in EED and EZH2, respectively. Small intestinal crypts were isolated and subsequently cultured to grow organoids. Intestines and organoids were analyzed by immunohistochemical, in situ hybridization, RNA sequence, and chromatin immunoprecipitation methods.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Intestines of EED knockout mice had massive crypt degeneration and lower numbers of proliferating cells, compared with wildtype control mice; Cdkn2a became derepressed and we detected increased levels of P21. We did not observe any differences between EZH2 knockout and control mice. Intestinal crypts from EED knockout mice had signs of aberrant differentiation of uncommitted crypt cells-these differentiated toward the secretory cell lineage. Furthermore, crypts from EED-knockout mice had impaired Wnt signaling and concomitant loss of intestinal stem cells; this phenotype was not reversed upon ectopic stimulation of Wnt and Notch signaling in organoids. Analysis of gene expression patterns from intestinal tissues of EED knockout mice revealed dysregulation of several genes involved in Wnt signaling. Wnt signaling was directly regulated by PRC2.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">In intestinal tissues of mice, PRC2 maintains small intestinal stem cells by promoting proliferation and preventing differentiation in the intestinal stem cell compartment. PRC2 controls expression of genes in multiple signaling pathways that regulate intestinal homeostasis.</abstracttext></p>',
			'date' => '2016-06-21',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27342214',
			'doi' => ' 10.1053/j.gastro.2016.06.020',
			'modified' => '2016-07-07 10:04:31',
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			'name' => 'Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells',
			'authors' => 'von Meyenn F et al.',
			'description' => '<p>Global demethylation is part of a conserved program of epigenetic reprogramming to naive pluripotency. The transition from primed hypermethylated embryonic stem cells (ESCs) to naive hypomethylated ones (serum-to-2i) is a valuable model system for epigenetic reprogramming. We present a mathematical model, which accurately predicts global DNA demethylation kinetics. Experimentally, we show that the main drivers of global demethylation are neither active mechanisms (Aicda, Tdg, and Tet1-3) nor the&nbsp;reduction of de novo methylation. UHRF1 protein, the essential targeting factor for DNMT1, is reduced upon transition to 2i, and so is recruitment of the maintenance methylation machinery to replication foci. Concurrently, there is global loss of H3K9me2, which is needed for chromatin binding of UHRF1. These mechanisms synergistically enforce global DNA hypomethylation in a replication-coupled fashion. Our observations establish the molecular mechanism for global demethylation in naive ESCs, which has key parallels with those operating in primordial germ cells and early embryos.</p>',
			'date' => '2016-05-25',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27237052',
			'doi' => '10.1016/j.molcel.2016.04.025',
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			'authors' => 'Moreno-Romero J et al.',
			'description' => '<p>Parental genomes in the endosperm are marked by differential DNA methylation and are therefore epigenetically distinct. This epigenetic asymmetry is established in the gametes and maintained after fertilization by unknown mechanisms. In this manuscript, we have addressed the key question whether parentally inherited differential DNA methylation affects <em>de novo</em> targeting of chromatin modifiers in the early endosperm. Our data reveal that polycomb-mediated H3 lysine 27 trimethylation (H3K27me3) is preferentially localized to regions that are targeted by the DNA glycosylase DEMETER (DME), mechanistically linking DNA hypomethylation to imprinted gene expression. Our data furthermore suggest an absence of <em>de novo </em>DNA methylation in the early endosperm, providing an explanation how DME-mediated hypomethylation of the maternal genome is maintained after fertilization. Lastly, we show that paternal-specific H3K27me3-marked regions are located at pericentromeric regions, suggesting that H3K27me3 and DNA methylation are not necessarily exclusive marks at pericentromeric regions in the endosperm.</p>',
			'date' => '2016-04-25',
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			'description' => '<p>We sheared the DNA on the Diagenode One and used the MicroPlex Library Preparation v2 Kit to create DNA libraries for whole genome sequencing of four plant species for which there is no reference genome available. Previous attempts with a commercial Tn5-transposase based method gave unsatisfactory results. However, the Diagenode MicroPlex kit was quicker, easier, and gave the expected profile of fragment sizes. In just 30 seconds of sonication, we obtained a fragment distribution centered at 270 bp. The library construction took only 2 hours with this kit. The library was sequenced in a NexSeq 550 in High-Output mode, giving 85% based with&gt;Q30.</p>',
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<p>Thanks Diagenode for saving my PhD!</p>',
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			'description' => '<p>There are so many ChIP-related products on the market, but I feel so lucky that I have been using the ones from Diagenode since I started my CHIP-seq project. I have used their <a href="../p/ideal-chip-seq-kit-for-transcription-factors-x100-100-rxns">iDeal CHIP-seq Kit for Transcription Factors</a> and <a href="../p/microplex-library-preparation-kit-v2-x48-12-indices-48-rxns">MicroPlex Library Prep Kit v2</a>. Both of them are fantastic and very reproducible. With the very-well written protocols, you will just be home and dry. Particularly, I want to thank the technical support, who is very patient, knowledgeable and extremely helpful. I would definitely recommend my colleagues to use the CHIP products from Diagenode.</p>',
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<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>
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<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>There are so many ChIP-related products on the market, but I feel so lucky that I have been using the ones from Diagenode since I started my CHIP-seq project. I have used their <a href="../p/ideal-chip-seq-kit-for-transcription-factors-x100-100-rxns">iDeal CHIP-seq Kit for Transcription Factors</a> and <a href="../p/microplex-library-preparation-kit-v2-x48-12-indices-48-rxns">MicroPlex Library Prep Kit v2</a>. Both of them are fantastic and very reproducible. With the very-well written protocols, you will just be home and dry. Particularly, I want to thank the technical support, who is very patient, knowledgeable and extremely helpful. I would definitely recommend my colleagues to use the CHIP products from Diagenode.</p><cite>Dr Kaiyu Lei, Faculty of Medicine, Department of Surgery & Cancer, Imperial College London</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>
<blockquote><p>The Diagenode MicroPlex kit is the quickest and most efficient way to make sequencing libraries, especially from samples with very low inputs. We regularly start with picogram amounts of ChIP material and produce excellent quality libraries that would be impossible to make using normal methods. Sequencing libraries made from the MicroPlex kit give us excellent results even in large genomes. The kit performs very well, and we will use the kit in the future for studies with low cell numbers or starting material.</p><cite>Dr. Morgan Sammons, Lab of Dr. Shelley Berger, University of Pennsylvania</cite></blockquote>
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$featured_testimonials = '<blockquote><span class="label-green" style="margin-bottom:16px;margin-left:-22px">TESTIMONIAL</span><p>We used the MicroPlex version 2 kit to generate libraries using ChIP DNA for several transcription factors and compared the results to a standard library generation protocol starting from 5ng of ChIP DNA. Even when we reduced the starting amount of DNA by 10-fold, the MicroPlex Kit produced the same high yields and quality of the libraries. As expected, the number of duplicate reads increased but 15 to 20 million unique reads were sufficient to achieve excellent enrichment data. We found that no information was lost, and the MicroPlex Kit helped produce data that was consistent with the standard protocol despite the lower input. On top of this, the MicroPlex Kit was extremely user-friendly and saved us time. The MicroPlex version 2 kit will make challenging ChIP-seq experiments that rely on very limited amount of starting material much easier with robust results.</p><cite>Katia Basso, PhD, Assistant Professor, Columbia University, New York</cite></blockquote>
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        <p><strong><input name="data[Cart][quantity]" placeholder="1" value="1" min="1" style="width:60px;display:inline" type="number" id="CartQuantity" required="required"/></strong>iDeal ChIP-seq kit for Transcription Factors個カートに追加。</p>

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<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;">
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<td style="width: 144px;"></td>
<td style="width: 267px; text-align: center;"><span style="font-weight: 400;">Amount per IP</span></td>
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<td style="width: 144px;">Cells</td>
<td style="width: 267px; text-align: center;"><strong>4,000,000</strong></td>
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<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>',
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<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>
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<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>',
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	'description' => '<p>Parental genomes in the endosperm are marked by differential DNA methylation and are therefore epigenetically distinct. This epigenetic asymmetry is established in the gametes and maintained after fertilization by unknown mechanisms. In this manuscript, we have addressed the key question whether parentally inherited differential DNA methylation affects <em>de novo</em> targeting of chromatin modifiers in the early endosperm. Our data reveal that polycomb-mediated H3 lysine 27 trimethylation (H3K27me3) is preferentially localized to regions that are targeted by the DNA glycosylase DEMETER (DME), mechanistically linking DNA hypomethylation to imprinted gene expression. Our data furthermore suggest an absence of <em>de novo </em>DNA methylation in the early endosperm, providing an explanation how DME-mediated hypomethylation of the maternal genome is maintained after fertilization. Lastly, we show that paternal-specific H3K27me3-marked regions are located at pericentromeric regions, suggesting that H3K27me3 and DNA methylation are not necessarily exclusive marks at pericentromeric regions in the endosperm.</p>',
	'date' => '2016-04-25',
	'pmid' => 'http://onlinelibrary.wiley.com/doi/10.15252/embj.201593534/abstract',
	'doi' => '10.15252/embj.201593534',
	'modified' => '2016-05-14 00:49:53',
	'created' => '2016-05-13 11:30:16',
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$externalLink = ' <a href="http://onlinelibrary.wiley.com/doi/10.15252/embj.201593534/abstract" target="_blank"><i class="fa fa-external-link"></i></a>'
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			'name' => 'MicroPlex Library Preparation Kit v2 (12 indices)',
			'description' => '<p><strong>ChIP-seq</strong><strong>専用に最適化</strong></p>
<p>MicroPlex Library Preparation&trade;kit は、ChIP-seq専用に検証されていて、ピコグラム単位の入力だけで索引付きライブラリー調製できる唯一のキットです。 <span><a href="http://www.diagenode.com/en/catalog/chromatin-function-74/chromatin-immunoprecipitation-75/manual-chip-kits-77/product/true-microchip-kit-x16-2532">True MicroChIP kit</a></span>と組み合わせることで、わずか10,000細胞でChIP-seqを行えます。細胞入力数、手順数、用品数が減少するだけでなく、結果までの時間も短縮できます！</p>',
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<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>
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<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>
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<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>',
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		'name' => 'MicroPlex Library Preparation Kit v2 (12 indices)',
		'description' => '<p><strong>ChIP-seq</strong><strong>専用に最適化</strong></p>
<p>MicroPlex Library Preparation&trade;kit は、ChIP-seq専用に検証されていて、ピコグラム単位の入力だけで索引付きライブラリー調製できる唯一のキットです。 <span><a href="http://www.diagenode.com/en/catalog/chromatin-function-74/chromatin-immunoprecipitation-75/manual-chip-kits-77/product/true-microchip-kit-x16-2532">True MicroChIP kit</a></span>と組み合わせることで、わずか10,000細胞でChIP-seqを行えます。細胞入力数、手順数、用品数が減少するだけでなく、結果までの時間も短縮できます！</p>',
		'label1' => '特徴',
		'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>',
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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)',
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			'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>',
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			'format' => '12 rxns',
			'catalog_number' => 'C05010012',
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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)',
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		'Product' => array(
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	'Related' => array(
		(int) 0 => 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>
<p>
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<div class="extra-spaced" align="center"></div>
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<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>
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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>',
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			'meta_title' => 'True MicroChIP-seq Kit | Diagenode C01010132',
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			'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.',
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			'name' => 'iDeal ChIP-seq kit for Transcription Factors',
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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>',
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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',
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			'meta_description' => 'iDeal ChIP-seq kit for Transcription Factors x24',
			'modified' => '2023-06-20 18:27:37',
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			'name' => 'DNA/RNA library preparation',
			'description' => '<div class="row">
<div class="small-12 medium-12 large-12 columns">
<p><span style="font-weight: 400;">Most of the major next-generation sequencing platforms require ligation of specific adaptor oligos to </span><a href="../applications/dna-rna-shearing"><span style="font-weight: 400;">fragmented DNA or RNA</span></a><span style="font-weight: 400;"> prior to sequencing</span></p>
<p><span style="font-weight: 400;">After input DNA has been fragmented, it is end-repaired and blunt-ended</span><span style="font-weight: 400;">. The next step is a A-tailing in which dAMP is added to the 3&acute; end of the blunt phosphorylated DNA fragments to prevent concatemerization and to allow the ligation of adaptors with complementary dT overhangs. In addition, barcoded adapters can be incorporated to facilitate multiplexing prior to or during amplification.</span></p>
<center><img src="https://www.diagenode.com/img/categories/library-prep/flux.png" /></center>
<p><span style="font-weight: 400;">Diagenode offers a comprehensive product portfolio for library preparation:<br /></span></p>
<strong><a href="https://www.diagenode.com/en/categories/Library-preparation-for-RNA-seq">D-Plex&nbsp;RNA-seq Library Preparation Kits</a></strong><br />
<p><span style="font-weight: 400;">Diagenode&rsquo;s new RNA-sequencing solutions utilize the innovative c</span><span style="font-weight: 400;">apture and a</span><span style="font-weight: 400;">mplification by t</span><span style="font-weight: 400;">ailing and s</span><span style="font-weight: 400;">witching&rdquo;</span><span style="font-weight: 400;">, a ligation-free method to produce DNA libraries for next generation sequencing from low input amounts of RNA. </span><span style="font-weight: 400;"></span><a href="../categories/Library-preparation-for-RNA-seq">Learn more</a></p>
<strong><a href="../categories/library-preparation-for-ChIP-seq">ChIP-seq and DNA sequencing library preparation solutions</a></strong><br />
<p><span style="font-weight: 400;">Our kits have been optimized for DNA library preparation used for next generation sequencing for a wide range of inputs. Using a simple three-step protocols, our</span><a href="http://www.diagenode.com/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns"><span style="font-weight: 400;"> </span></a><span style="font-weight: 400;">kits are an optimal choice for library preparation from DNA inputs down to 50 pg.&nbsp;</span><a href="../categories/library-preparation-for-ChIP-seq">Learn more</a></p>
<a href="../p/bioruptor-pico-sonication-device"><span style="font-weight: 400;"></span><strong>Bioruptor Pico - short fragments</strong></a><a href="../categories/library-preparation-for-ChIP-seq-and-DNA-sequencing"><span style="font-weight: 400;"></span></a><br />
<p><span style="font-weight: 400;"></span><span style="font-weight: 400;">Our well-cited Bioruptor Pico is the shearing device of choice for chromatin and DNA fragmentation. Obtain uniform and tight fragment distributions &nbsp;between 150bp -2kb. </span><a href="../p/bioruptor-pico-sonication-device">Learn more</a></p>
<strong><a href="../p/megaruptor2-1-unit"><span href="../p/bioruptor-pico-sonication-device">Megaruptor</span>&reg; - long fragments</a></strong><a href="../p/bioruptor-pico-sonication-device"><span style="font-weight: 400;"></span></a><a href="../categories/library-preparation-for-ChIP-seq-and-DNA-sequencing"><span style="font-weight: 400;"></span></a><br />
<p><span style="font-weight: 400;"></span><span style="font-weight: 400;">The Megaruptor is designed to shear DNA from 3kb-75kb for long-read sequencing.&nbsp; <a href="../p/megaruptor2-1-unit">Learn more</a></span></p>
<span href="../p/bioruptor-pico-sonication-device"></span><span style="font-weight: 400;"></span></div>
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			'meta_description' => 'Diagenode offers a comprehensive product portfolio for library preparation such as CATS RNA-seq Library Preparation Kits,ChIP-seq and DNA sequencing library preparation solutions',
			'meta_title' => 'Library preparation for Next Generation Sequencing (NGS) | Diagenode',
			'modified' => '2021-03-10 03:27:16',
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			'name' => '次世代シーケンシング',
			'description' => '<div class="row">
<div class="small-12 medium-12 large-12 columns">
<h2 style="font-size: 22px;">DNA断片化、ライブラリー調製、自動化：NGSのワンストップショップ</h2>
<table class="small-12 medium-12 large-12 columns">
<tbody>
<tr>
<th class="small-12 medium-12 large-12 columns">
<h4>1. 断片化装置を選択してください：150 bp〜75 kbの範囲でDNAを断片化します。</h4>
</th>
</tr>
<tr style="background-color: #ffffff;">
<td class="small-12 medium-12 large-12 columns"></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns"><a href="../p/bioruptor-pico-sonication-device"><img src="https://www.diagenode.com/img/product/shearing_technologies/bioruptor_pico.jpg" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/megaruptor2-1-unit"><img src="https://www.diagenode.com/img/product/shearing_technologies/B06010001_megaruptor2.jpg" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/bioruptor-one-sonication-device"><img src="https://www.diagenode.com/img/product/shearing_technologies/br-one-profil.png" /></a></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns">5&mu;lまで断片化：150 bp〜2 kb<br />NGS DNAライブラリー調製およびFFPE核酸抽出に最適で、</td>
<td class="small-4 medium-4 large-4 columns">2 kb〜75 kbの範囲をできます。<br />メイトペアライブラリー調製および長いフラグメントDNAシーケンシングに最適で、この軽量デスクトップデバイスで</td>
<td class="small-4 medium-4 large-4 columns">20または50&mu;lの断片化が可能です。</td>
</tr>
</tbody>
</table>
<table class="small-12 medium-12 large-12 columns">
<tbody>
<tr>
<th class="small-8 medium-8 large-8 columns">
<h4>2. 最適化されたライブラリー調整キットを選択してください。</h4>
</th>
<th class="small-4 medium-4 large-4 columns">
<h4>3. ライブラリー前処理自動化を選択して、比類のないデータ再現性を実感</h4>
</th>
</tr>
<tr style="background-color: #ffffff;">
<td class="small-12 medium-12 large-12 columns"></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns"><a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns"><img src="https://www.diagenode.com/img/product/kits/microPlex_library_preparation.png" style="display: block; margin-left: auto; margin-right: auto;" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns"><img src="https://www.diagenode.com/img/product/kits/box_kit.jpg" style="display: block; margin-left: auto; margin-right: auto;" height="173" width="250" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/sx-8g-ip-star-compact-automated-system-1-unit"><img src="https://www.diagenode.com/img/product/automation/B03000002%20_ipstar_compact.png" style="display: block; margin-left: auto; margin-right: auto;" /></a></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns" style="text-align: center;">50pgの低入力：MicroPlex Library Preparation Kit</td>
<td class="small-4 medium-4 large-4 columns" style="text-align: center;">5ng以上：iDeal&nbsp;Library Preparation Kit</td>
<td class="small-4 medium-4 large-4 columns" style="text-align: center;">Achieve great NGS data easily</td>
</tr>
</tbody>
</table>
</div>
</div>
<blockquote>
<div class="row">
<div class="small-12 medium-12 large-12 columns"><span class="label" style="margin-bottom: 16px; margin-left: -22px; font-size: 15px;">DiagenodeがNGS研究にぴったりなプロバイダーである理由</span>
<p>Diagenodeは15年以上もエピジェネティクス研究に専念、専門としています。 ChIP研究クロマチン用のユニークな断片化システムの開発から始まり、 専門知識を活かし、5&mu;lのせん断体積まで可能で、NGS DNAライブラリーの調製に最適な最先端DNA断片化装置の開発にたどり着きました。 我々は以来、ChIP-seq、Methyl-seq、NGSライブラリー調製用キットを研究開発し、業界をリードする免疫沈降研究と同様に、ライブラリー調製を自動化および完結させる独自の自動化システムを開発にも成功しました。</p>
<ul>
<li>信頼されるせん断装置</li>
<li>様々なインプットからのライブラリ作成キット</li>
<li>独自の自動化デバイス</li>
</ul>
</div>
</div>
</blockquote>
<div class="row">
<div class="small-12 columns">
<ul class="accordion" data-accordion="">
<li class="accordion-navigation"><a href="#panel1a">次世代シーケンシングへの理解とその専門知識</a>
<div id="panel1a" class="content">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<p><strong>次世代シーケンシング (NGS)</strong> ）は、著しいスケールとハイスループットでシーケンシングを行い、1日に数十億もの塩基生成を可能にします。 NGSのハイスループットは迅速でありながら正確で、再現性のあるデータセットを実現し、さらにシーケンシング費用を削減します。 NGSは、ゲノムシーケンシング、ゲノム再シーケンシング、デノボシーケンシング、トランスクリプトームシーケンシング、その他にDNA-タンパク質相互作用の検出やエピゲノムなどを示します。 指数関数的に増加するシーケンシングデータの需要は、計算分析の障害や解釈、データストレージなどの課題を解決します。</p>
<p>アプリケーションおよび出発物質に応じて、数百万から数十億の鋳型DNA分子を大規模に並行してシーケンシングすることが可能です。その為に、異なる化学物質を使用するいくつかの市販のNGSプラットフォームを利用することができます。 NGSプラットフォームの種類によっては、事前準備とライブラリー作成が必要です。</p>
<p>NGSにとっても、特にデータ処理と分析に関した大きな課題はあります。第3世代技術はゲノミクス研究にさらに革命を起こすであろうと大きく期待されています。</p>
</div>
</div>
<div class="row">
<div class="small-6 medium-6 large-6 columns">
<p><strong>NGS アプリケーション</strong></p>
<ul>
<li>全ゲノム配列決定</li>
<li>デノボシーケンシング</li>
<li>標的配列</li>
<li>Exomeシーケンシング</li>
<li>トランスクリプトーム配列決定</li>
<li>ゲノム配列決定</li>
<li>ミトコンドリア配列決定</li>
<li>DNA-タンパク質相互作用（ChIP-seq</li>
<li>バリアント検出</li>
<li>ゲノム仕上げ</li>
</ul>
</div>
<div class="small-6 medium-6 large-6 columns">
<p><strong>研究分野におけるNGS:</strong></p>
<ul>
<li>腫瘍学</li>
<li>リプロダクティブ・ヘルス</li>
<li>法医学ゲノミクス</li>
<li>アグリゲノミックス</li>
<li>複雑な病気</li>
<li>微生物ゲノミクス</li>
<li>食品・環境ゲノミクス</li>
<li>創薬ゲノミクス - パーソナライズド・メディカル</li>
</ul>
</div>
<div class="small-12 medium-12 large-12 columns">
<p><strong>NGSの用語</strong></p>
<dl>
<dt>リード（読み取り）</dt>
<dd>この装置から得られた連続した単一のストレッチ</dd>
<dt>断片リード</dt>
<dd>フラグメントライブラリからの読み込み。 シーケンシングプラットフォームに応じて、読み取りは通常約100〜300bp。</dd>
<dt>断片ペアエンドリード</dt>
<dd>断片ライブラリーからDNA断片の各末端2つの読み取り。</dd>
<dt>メイトペアリード</dt>
<dd>大きなDNA断片（通常は予め定義されたサイズ範囲）の各末端から2つの読み取り。</dd>
<dt>カバレッジ（例）</dt>
<dd>30&times;適用範囲とは、参照ゲノム中の各塩基対が平均30回の読み取りを示す。</dd>
</dl>
</div>
</div>
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<h2>NGSプラットフォーム</h2>
<h3><a href="http://www.illumina.com" target="_blank">イルミナ</a></h3>
<p>イルミナは、クローン的に増幅された鋳型DNA（クラスター）上に位置する、蛍光標識された可逆的鎖ターミネーターヌクレオチドを用いた配列別合成技術を使用。 DNAクラスターは、ガラスフローセルの表面上に固定化され、 ワークフローは、4つのヌクレオチド（それぞれ異なる蛍光色素で標識された）の組み込み、4色イメージング、色素や末端基の切断、取り込み、イメージングなどを繰り返します。フローセルは大規模な並列配列決定を受ける。 この方法により、単一蛍光標識されたヌクレオチドの制御添加によるモノヌクレオチドのエラーを回避する可能性があります。 読み取りの長さは、通常約100〜150 bpです。</p>
<h3><a href="http://www.lifetechnologies.com" target="_blank">イオン トレント</a></h3>
<p>イオントレントは、半導体技術チップを用いて、合成中にヌクレオチドを取り込む際に放出されたプロトンを検出します。 これは、イオン球粒子と呼ばれるビーズの表面にエマルションPCR（emPCR）を使用し、リンクされた特定のアダプターを用いてDNA断片を増幅します。 各ビーズは1種類のDNA断片で覆われていて、異なるDNA断片を有するビーズは次いで、チップの陽子感知ウェル内に配置されます。 チップには一度に4つのヌクレオチドのうちの1つが浸水し、このプロセスは異なるヌクレオチドで15秒ごとに繰り返されます。 配列決定の間に4つの塩基の各々が1つずつ導入されます、組み込みの場合はプロトンが放出され、電圧信号が取り込みに比例して検出されます。.</p>
<h3><a href="http://www.pacificbiosciences.com" target="_blank">パシフィック バイオサイエンス</a></h3>
<p>パシフィックバイオサイエンスでは、20kbを超える塩基対の読み取りも、単一分子リアルタイム（SMRT）シーケンシングによる構造および細胞タイプの変化を観察することができます。 このプラットフォームでは、超長鎖二本鎖DNA（dsDNA）断片が、Megaruptor（登録商標）のようなDiagenode装置を用いたランダムシアリングまたは目的の標的領域の増幅によって生成されます。 SMRTbellライブラリーは、ユニバーサルヘアピンアダプターをDNA断片の各末端に連結することによって生成します。 サイズ選択条件による洗浄ステップの後、配列決定プライマーをSMRTbellテンプレートにアニーリングし、鋳型DNAに結合したDNAポリメラーゼを含む配列決定を、蛍光標識ヌクレオチドの存在下で開始。 各塩基が取り込まれると、異なる蛍光のパルスをリアルタイムで検出します。</p>
<h3><a href="https://nanoporetech.com" target="_blank">オックスフォード ナノポア</a></h3>
<p>Oxford Nanoporeは、単一のDNA分子配列決定に基づく技術を開発します。その技術により生物学的分子、すなわちDNAが一群の電気抵抗性高分子膜として位置するナノスケールの孔（ナノ細孔）またはその近くを通過し、イオン電流が変化します。 この変化に関する情報は、例えば4つのヌクレオチド（AまたはG r CまたはT）ならびに修飾されたヌクレオチドすべてを区別することによって分子情報に訳されます。 シーケンシングミニオンデバイスのフローセルは、数百個のナノポアチャネルのセンサアレイを含みます。 DNAサンプルは、Diagenode社のMegaruptor（登録商標）を用いてランダムシアリングによって生成され得る超長鎖DNAフラグメントが必要です。</p>
<h3><a href="http://www.lifetechnologies.com/be/en/home/life-science/sequencing/next-generation-sequencing/solid-next-generation-sequencing.html" target="_blank">SOLiD</a></h3>
<p>SOLiDは、ユニークな化学作用により、何千という個々のDNA分子の同時配列決定を可能にします。 それは、アダプター対ライブラリーのフラグメントが適切で、せん断されたゲノムDNAへのアダプターのライゲーションによるライブラリー作製から始まります。 次のステップでは、エマルジョンPCR（emPCR）を実施して、ビーズの表面上の個々の鋳型DNA分子をクローン的に増幅。 emPCRでは、個々の鋳型DNAをPCR試薬と混合し、水中油型エマルジョン内の疎水性シェルで囲まれた水性液滴内のプライマーコートビーズを、配列決定のためにロードするスライドガラスの表面にランダムに付着。 この技術は、シークエンシングプライマーへのライゲーションで競合する4つの蛍光標識されたジ塩基プローブのセットを使用します。</p>
<h3><a href="http://454.com/products/technology.asp" target="_blank">454</a></h3>
<p>454は、大規模並列パイロシーケンシングを利用しています。 始めに全ゲノムDNAまたは標的遺伝子断片の300〜800bp断片のライブラリー調製します。 次に、DNAフラグメントへのアダプターの付着および単一のDNA鎖の分離。 その後アダプターに連結されたDNAフラグメントをエマルジョンベースのクローン増幅（emPCR）で処理し、DNAライブラリーフラグメントをミクロンサイズのビーズ上に配置します。 各DNA結合ビーズを光ファイバーチップ上のウェルに入れ、器具に挿入します。 4つのDNAヌクレオチドは、配列決定操作中に固定された順序で連続して加えられ、並行して配列決定されます。</p>
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			'meta_description' => 'Diagenode offers kits and DNA/RNA shearing technology prior to next-generation sequencing, many Next-generation sequencing platforms require preparation of the DNA.',
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<div class="large-12 columns text-justify">
<p>Library preparation following ChIP can be challenging due to the limited amount of DNA recovered after ChIP. Diagenode has developed the optimal solutions for ChIP-seq using two different approaches: the ligation-based library preparation on purified DNA or the tagmentation-based ChIPmentation.</p>
</div>
</div>
<div class="row extra-spaced">
<div class="large-12 columns"><center><a href="https://www.diagenode.com/en/pages/form-microplex-promo" target="_blank"></a></center></div>
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<div id="portal" class="main-portal">
<div class="portal-inner"><nav class="portal-nav">
<ul data-tab="" class="tips-menu">
<li><a href="#panel1" class="tips portal button">Ligation-based library prep</a></li>
<li><a href="#panel2" class="tips portal button">ChIPmentation</a></li>
<li><a href="#panel3" class="tips portal button">Kit choice guide</a></li>
<li><a href="#panel4" class="tips portal button">Resources</a></li>
<li><a href="#panel5" class="tips portal button">FAQs</a></li>
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<li class="accordion-navigation"><a href="#v5" style="color: #13b29c;"><i class="fa fa-caret-right"></i> Standard input library prep</a>
<div id="v5" class="content">
<div class="small-12 medium-12 large-12 columns">
<p>The <strong>iDeal Library Preparation Kit</strong> reliably converts DNA into indexed libraries for next-generation sequencing, with input amounts down to <strong>5 ng</strong>. Our kit offers a simple and fast workflow, high yields, and ready-to-sequence DNA on the Illumina platform.</p>
<div class="extra-spaced">
<h2>Features</h2>
<ul class="nobullet">
<li><i class="fa fa-arrow-circle-right"></i> <strong>Sample</strong>: Fragmented dsDNA</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Input</strong>: 5 ng &ndash; 1 &micro;g</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Fast protocol</strong>: 3 hours</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Easy processing</strong>: 3 steps</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Indexing</strong>: single indexes for multiplexing up to 24 samples</li>
<li><i class="fa fa-arrow-circle-right"></i> Manual and automated protocols available</li>
<li><i class="fa fa-arrow-circle-right"></i> Sequencing technology: Illumina</li>
</ul>
</div>
<div class="extra-spaced">
<h2>Applications</h2>
<ul class="square">
<li>MeDIP-seq library prep</li>
<li>Genomic DNA sequencing</li>
<li>High input ChIP-seq</li>
</ul>
</div>
<div class="extra-spaced">
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
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</tr>
</thead>
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<tr>
<td class="catalog_number"><span class="success label">C05010020</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns" style="color: #b21329;" target="_blank">iDeal Library Preparation Kit x24 (incl. Index Primer Set 1)</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
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<td class="catalog_number"><span class="success label">C05010021</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/ideal-library-index-primer-set-2-24-rxns" style="color: #b21329;" target="_blank">Index Primer Set 2 (iDeal Lib. Prep Kit x24)</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/ideal-library-index-primer-set-2-24-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
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<li class="accordion-navigation"><a href="#v4" style="color: #13b29c;"><i class="fa fa-caret-right"></i> Low input library prep</a>
<div id="v4" class="content active"><center><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" target="_blank"><img src="https://www.diagenode.com/img/banners/banner-microplex-v3-580.jpg" class="extra-spaced" /></a></center>
<div align="center"><a href="https://www.diagenode.com/pages/form-microplex3" class="center alert radius button extra-spaced"><i class="fa fa-info"></i> Contact us</a></div>
<div class="extra-spaced">
<p>Diagenode&rsquo;s <strong>MicroPlex Library Preparation kits</strong> have been extensively validated for ChIP-seq samples. Generated libraries are compatible with single-end or paired-end sequencing. MicroPlex chemistry (using stem-loop adapters ) is specifically developed and optimized to generate DNA libraries with high molecular complexity from the lowest input amounts. Only <strong>50 pg to 50 ng</strong> of fragmented double-stranded DNA is required for library preparation. The entire <strong>three-step workflow</strong> takes place in a <strong>single tube</strong> or well in about <strong>2 hours</strong>. No intermediate purification steps and no sample transfers are necessary to prevent handling errors and loss of valuable samples.</p>
</div>
<div class="extra-spaced">
<h2>Features</h2>
<ul class="nobullet">
<li><i class="fa fa-arrow-circle-right"></i> <strong>Sample</strong>: Fragmented dsDNA</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Low input</strong>: 50 pg &ndash; 50 ng</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Fast protocol</strong>: 2 hours</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Easy processing</strong>: 3 steps in 1 tube</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>No intermediate purification</strong></li>
<li><i class="fa fa-arrow-circle-right"></i> Sequencing technology: Illumina</li>
<li><i class="fa fa-arrow-circle-right"></i> Manual and automated protocols available</li>
</ul>
</div>
<div class="extra-spaced">
<h2>Applications</h2>
<ul class="square">
<li>ChIP-seq library prep from ChIP-derived DNA</li>
<li>Low input DNA sequencing</li>
</ul>
</div>
<h2>Two versions are available:</h2>
<ul class="accordion" data-accordion="">
<li class="accordion-navigation"><a href="#v2" style="color: #13b29c;"><i class="fa fa-caret-right"></i> MicroPlex Library Preparation Kit v2 with single indexes</a>
<div id="v2" class="content">
<p>The MicroPlex Library Preparation Kit v2 contains all necessary reagents including single indexes for multiplexing up to 48 samples using single barcoding.</p>
<h4>KITS</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C05010012</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns" style="color: #b21329;" target="_blank">MicroPlex Library Preparation Kit v2 (12 indexes)</a></td>
<td class="format">12 rxns</td>
<td><a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
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</tbody>
</table>
</div>
</li>
<li class="accordion-navigation"><a href="#v3" style="color: #13b29c;"><i class="fa fa-caret-right"></i> MicroPlex Library Preparation Kit v3 with dual indexes &nbsp;&nbsp;<strong><span class="diacol">NEW!</span></strong></a>
<div id="v3" class="content active">
<p>In this version the library preparation reagents and the dual indexes are available separately allowing for the flexibility choosing the number of indexes. MicroPlex v3 has multiplexing capacities up to 384 samples.</p>
<h4>KITS</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C05010001</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" style="color: #b21329;" target="_blank">MicroPlex Library Preparation Kit v3 /48 rxns</a></td>
<td class="format">48 rxns</td>
<td><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010002</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-96-rxns" style="color: #b21329;" target="_blank">MicroPlex Library Preparation Kit v3 /96 rxns</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-96-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
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</tbody>
</table>
<h4>DUAL INDEXES</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C05010003</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/24-dual-indexes-for-microplex-kit-v3-48-rxns" style="color: #b21329;" target="_blank">24 Dual indexes for MicroPlex Kit v3</a></td>
<td class="format">48 rxns</td>
<td><a href="https://www.diagenode.com/en/p/24-dual-indexes-for-microplex-kit-v3-48-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010004</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-1" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set I</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-1" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010005</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-2" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set II</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-2" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010006</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-3" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set III</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-3" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010007</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-4" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set IV</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-4" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
</tbody>
</table>
</div>
</li>
</ul>
</div>
</li>
</ul>
</div>
</div>
</div>
<div class="content active" id="panel2">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<div class="extra-spaced">
<p>The TAG Kit for ChIPmentation offers an optimized ChIP-seq library preparation solution based on tagmentation. This kit includes reagents for tagmentation-based library preparation integrated in the IP and is compatible with any ChIP protocol based on magnetic beads. The primer indexes for multiplexing&nbsp;must be purchased separately and are available as a reference: <a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" target="_blank">24 SI for ChIPmentation</a>, Cat. No. C01011031. Alternatively, for histone marks, Diagenode proposes the complete solution (including all buffers for ChIP, tagmentation and multiplexing): <a href="https://www.diagenode.com/en/p/manual-chipmentation-kit-for-histones-24-rxns" target="_blank">ChIPmentation for Histones</a>.</p>
</div>
<div class="extra-spaced">
<h2>Features</h2>
<ul class="nobullet">
<li><i class="fa fa-arrow-circle-right"></i> Sample: chromatin-antibody-magnetic beads complexes</li>
<li><i class="fa fa-arrow-circle-right"></i> Input: chromatin from 5 K &ndash; 4 M cells</li>
<li><i class="fa fa-arrow-circle-right"></i> Easy and fast protocol</li>
<li><i class="fa fa-arrow-circle-right"></i> Compatible with any ChIP protocol based on magnetic beads</li>
<li><i class="fa fa-arrow-circle-right"></i> No adapter dimers</li>
<li><i class="fa fa-arrow-circle-right"></i> Sequencing technology: Illumina</li>
</ul>
</div>
<div class="extra-spaced">
<h2>Applications</h2>
<p class="lead"><em><strong>TAG kit for ChIPmentation</strong></em></p>
<ul class="square">
<li>ChIPmentation library preparation</li>
</ul>
<p class="lead"><em><strong>24 SI for for ChIPmentation</strong></em></p>
<ul class="square">
<li>ChIPmentation library preparation</li>
<li>Tagmentation-based library preparation methods like ATAC-seq, CUT&amp;Tag</li>
</ul>
</div>
<h4>KITS</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C01011030</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/tag-kit-for-chipmentation-24" style="color: #b21329;" target="_blank">TAG Kit for ChIPmentation</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/tag-kit-for-chipmentation-24" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C01011031</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" style="color: #b21329;" target="_blank">24 SI for ChIPmentation</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
</tbody>
</table>
</div>
</div>
</div>
<div class="content" id="panel3">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<div class="extra-spaced">
<h3 class="text-center diacol"><em>How to choose your library preparation kit?</em></h3>
</div>
<table class="noborder">
<tbody>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Sample</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Chromatin-antibody-beads complex</p>
</td>
<td colspan="2">
<p class="text-center" style="font-size: 15px;">Purified DNA</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Purified DNA</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td colspan="2"><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Application</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">ChIPmentation</p>
</td>
<td colspan="2">
<p class="text-center" style="font-size: 15px;">ChIP-seq library prep<br /> Low input DNA sequencing</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">MeDIP-seq library prep<br /> Genomic DNA sequencing<br /> High input ChIP-seq</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td colspan="2"><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Input</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Chromatin: 5 K to 4 M cells</p>
</td>
<td colspan="2&quot;">
<p class="text-center" style="font-size: 15px;">DNA: 50 pg &ndash; 50 ng</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">DNA: 5 ng &ndash; 1 &micro;g</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow-45-left.png" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow-45-right.png" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Multiplexing</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 24 samples</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 384 samples</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 48 samples</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 24 samples</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Indexes</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Single indexes (SI)</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Dual indexes (DI)</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Single indexes (SI)</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Single indexes (SI)</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Kit</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>TAG Kit for ChIPmentation</strong><br /> (indexes not included in the kit)</p>
<p class="text-center"><strong>Kit</strong><br /> <a href="https://www.diagenode.com/en/p/tag-kit-for-chipmentation-24" target="_blank">C01011030 &ndash; 24 rxns</a></p>
<p class="text-center"><strong>Single indexes</strong><br /> <a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" target="_blank">C01011031 &ndash; 24 SI/24 rxns</a></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>MicroPlex Library Preparation Kit v3</strong><br />(dual indexes not included in the kit)</p>
<p class="text-center"><strong>Kit</strong><br /> <a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" target="_blank">C05010001 - 48 rxns</a><br /> <a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-96-rxns" target="_blank">C05010002 - 96 rxns</a></p>
<br />
<p class="text-center"><strong>Unique dual indexes</strong><br /> <a href="https://www.diagenode.com/en/p/24-unique-dual-indexes-for-microplex-kit-v3-set1" target="_blank">C05010008 - Set I 24 UDI / 24 rxns</a><br /> <a href="https://www.diagenode.com/en/p/24-unique-dual-indexes-for-microplex-kit-v3-set2" target="_blank">C05010009 - Set II 24 UDI/ 24 rxns</a></p>
<p class="text-center"><strong>Dual indexes</strong><br /> <a href="https://www.diagenode.com/en/p/24-dual-indexes-for-microplex-kit-v3-48-rxns" target="_blank">C05010003 - 24 DI/ 48 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-1" target="_blank">C05010004 - Set I 96 DI/ 96 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-2" target="_blank">C05010005 - Set II 96 DI/ 96 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-3" target="_blank">C05010006 - Set III 96 DI/ 96 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-4" target="_blank">C05010007 - Set IV 96 DI/ 96 rxns</a></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>MicroPlex Library Preparation Kit v2</strong><br />(single indexes included in the kit)</p>
<p class="text-center"><a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns" target="_blank">C05010012 - 12 SI/ 12 rxns</a><br /> <a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x48-12-indices-48-rxns" target="_blank">C05010013 - 12 SI/ 48 rxns</a></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>iDeal Library Preparation Kit</strong><br />(Set 1 of indexes included in the kit)</p>
<p class="text-center"><a href="https://www.diagenode.com/en/p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns" target="_blank">C05010020 - 12 SI/ 24 rxns</a></p>
<p class="text-center" style="font-size: 15px;"><strong>Index Primer Set 2</strong></p>
<p class="text-center"><a href="https://www.diagenode.com/en/p/ideal-library-index-primer-set-2-24-rxns" target="_blank">C05010021 - 12 SI/ 24 rxns</a></p>
</td>
</tr>
</tbody>
</table>
</div>
</div>
</div>
<div class="content" id="panel4">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<p>Combined chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) has become the gold standard to investigate genome-wide epigenetic profiles. However, ChIP from a limited amount of cells has been a challenge. Here we provide a complete and robust workflow solution for successful ChIP-seq from small numbers of cells using the True MicroChIP kit and MicroPlex Library Preparation kit.</p>
<blockquote><span class="label-green" style="margin-bottom: 16px; margin-left: -22px;">APPLICATION NOTE</span>
<div class="row">
<div class="small-12 medium-6 large-6 columns"><center><img src="https://www.diagenode.com/img/categories/microplex/chip-efficiency-on-10000-cells.jpg" /></center>
<p><small><em>ChIP efficiency on 10,000 cells</em></small></p>
</div>
<div class="small-12 medium-6 large-6 columns">
<p><strong>From minuscule amounts to magnificent results:</strong><br /> reliable ChIP-seq data from 10,000 cells with the True MicroChIP&trade; and the MicroPlex Library Preparation&trade; kits.</p>
<a href="https://www.diagenode.com/files/application_notes/True_MicroChIP_and_MicroPlex_kits_Application_Note.pdf" class="details small button" target="_blank">DOWNLOAD</a></div>
</div>
</blockquote>
<blockquote><span class="label-green" style="margin-bottom: 16px; margin-left: -22px;">APPLICATION NOTE</span>
<div class="row">
<div class="small-12 medium-6 large-6 columns"><center><img src="https://www.diagenode.com/img/categories/microplex/quality-control-check.jpg" /></center>
<p class="text-left"><small><em>Quality control check of a ChIP-seq library on the Fragment Analyzer. High Efficiency ChIP performed on 10,000 cells</em></small></p>
</div>
<div class="small-12 medium-6 large-6 columns">
<p class="text-left"><strong>Best Workflow Practices for ChIP-seq Analysis with Small Samples</strong></p>
<a href="https://www.diagenode.com/files/application_notes/Diagenode_AATI_Joint.pdf" class="details small button" target="_blank">DOWNLOAD</a></div>
</div>
</blockquote>
</div>
</div>
</div>
<div class="content" id="panel5">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<div class="extra-spaced">
<h2>TAG Kit for ChIPmentation</h2>
<ol>
<li><strong>What is the difference between tagmentation and ChIPmentation?</strong><br />Tagmentation is a reaction where an enzyme (a transposase) cleaves DNA and incorporates sequencing adaptors at the ends of the fragments in one step. In our ChIPmentation technology we combine chromatin immunoprecipitation and tagmentation in one streamlined workflow where the tagmentation step occurs directly on chromatin.<br /><br /></li>
<li><strong>What is the expected concentration of ChIPmentation libraries?</strong><br />The concentration of libraries that you need to reach will depend on the sensitivity of the machine and kits that you will use to perform the quality control and the sequencing of your libraries. Usually a concentration of 4-8 ng/&mu;l is enough for a quality control using the Qubit High Sensitivity assay (ThermoFischer Scientific) and the High Sensitivity chip for BioAnalyzer (Agilent) and for sequencing on Illumina HiSeq3000/4000.<br /><br /></li>
<li><strong>Does the ChIPmentation approach work on plants?</strong><br />Our ChIPmentation solution has been validated on human cells and we do not have any data on plants. It should be compatible. We would recommend using our Universal Plant ChIP Kit in combination with the TAG Kit for ChIPmentation and the 24 SI for ChIPmentation.<br /><br /></li>
<li><strong>What is the size of the fragments after the tagmentation?</strong><br />The size of the fragments at the end of the ChIPmentation protocol can vary depending on many parameters like the shearing efficiency, the antibody used or the tagmentation time. However, with our standard protocol we usually obtain a library peak which is around 200-300 bp (see example of results at the end of the manual). If many fragments larger than 500 bp are present , the best would be to contact your sequencing provider to ask what their requirements are, because it can vary depending on the sequencer. If you want to remove the large fragments you can use the size selection protocol described in the manual.<br /><br /></li>
<li><strong>What is the size of the adapters?</strong><br />The sum of the adapters is 128 bp.</li>
</ol>
</div>
<div class="extra-spaced">
<h2>MicroPlex Library Preparation Kit</h2>
<ol>
<li><strong>Can I use the available Illumina primers and validate them with the MicroPlex Kit v2?</strong><br /> Although the final flanking sequences of MicroPlex are the same as those used by Illumina, the PCR primers are not identical and part of them is supplied with the buffer. For this reason Illumina primers will not work as substitute.<br /><br /></li>
<li><strong>The BioAnalyzer profile of purified library shows the presence of low molecular weight peaks (primers/adaptors) in the samples. Should I re- purify the samples or they can be used directly to the sequencing? If the second purification is recommended, which ratio sample/AMPure beads should I use?</strong><br /> You can do a second round of purification using 1:1 ratio of AMPure beads to sample and this should get rid of the majority of the dimers.<br /><br /></li>
<li><strong>I am going to use the MicroPlex Library Preparation Kit v2 on ChIP samples . Our thermocycler has ramp rate 1.5&deg;/s max while the protocol recommends using a ramp rate 3 to 5&deg;/s. How would this affect the library prep?</strong><br /> We have not used a thermocycler with a ramp rate of 1.5 &deg;C, which seems faster than most of thermocyclers. Too fast of a ramp rate may affect the primer annealing and ligation steps.<br /><br /></li>
<li><strong>What is the function of the replication stop site in the adapter loops?</strong><br /> The replication stop site in the adaptor loops function to stop the polymerase from continuing to copy the rest of the stem loop.<br /><br /></li>
<li><strong>I want to do ChIP-seq. Which ChIP-seq kit can I use for sample preparation prior to Microplex Library Preparation Kit v2?</strong><br /> In our portfolio there are several ChIP-seq kits compatible with Microplex Library Preparation Kit v2. Depending on your sample type and target studied you can use the following kits: iDeal ChIP-seq Kit for Transcription Factors (Cat. No. C01010055), iDeal ChIP-seq Kit for Histones (Cat. No. C01010051), True MicroChIP kit (Cat. No. C01010130), Universal Plant ChIP-seq Kit (Cat. No. C01010152). All these kits exist in manual and automated versions.<br /><br /></li>
<li><strong>Is Microplex Library Preparation Kit v2 compatible with exome enrichment methods?</strong><br /> Microplex Library Preparation Kit v2 is compatible with major exome and target enrichment products, including Agilent SureSelect<sup>&reg;</sup>, Roche NimbleGen<sup>&reg;</sup> SeqCap<sup>&reg;</sup> EZ and custom panels.<br /><br /></li>
<li><strong>What is the nick that is mentioned in the kit method overview?</strong><br /> The nick is simply a gap between a stem adaptor and 3&rsquo; DNA end, as shown on the schema in the kit method overview.<br /><br /></li>
<li><strong>Are the indexes of the MicroPlex library preparation kit v2 located at i5 or i7?</strong><br /> The libraries generated with the MicroPlex kit v2 contain indices located at i7.<br /><br /></li>
<li><strong>Is there a need to use custom index read primers for the sequencing to read the 8nt iPCRtags?</strong><br /> There is no need for using custom Sequencing primer to sequence MicroPlex libraires. MicroPlex libraries can be sequenced using standard Illumina Sequencing kits and protocols.<br /><br /></li>
<li><strong>What is the advantage of using stem-loop adapter in the MicroPlex kit?</strong><br /> There are several advantages of using stem-loop adaptors. First of all, stem-loop adaptors prevent from self-ligation thus increases the ligation efficiency between the adapter and DNA fragment. Moreover, the background is reduced using ds adaptors with no single-stranded tails. Finally, adaptor-adaptor ligation is reduced using blocked 5&rsquo; ends.<br /><br /></li>
</ol>
</div>
<div class="extra-spaced">
<h2>IDeal Library Preparation Kit</h2>
<ol>
<li><strong>Are the index from the iDeal library Prep kit compatible with the MicroPlex library prep kit?</strong><br /> No, it is important to use only the indexes provided in the MicroPlex kit to ensure proper library preparation with this kit</li>
</ol>
</div>
</div>
</div>
</div>
</div>
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<p><span>MicroPlex v2 builds on the innovative MicroPlex chemistry to generate DNA libraries with expanded multiplexing capability and with even greater diversity. Kits contain up to 48 Illumina</span><span>&reg; </span><span>-compatible indexes. MicroPlex v2 can be used in DNA- seq, RNA-seq, or ChIP-seq and offers robust target enrichment performance with all of the leading platforms. </span></p>
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			'description' => '<p style="text-align: justify;"><span>Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become the gold standard for whole-genome mapping of protein-DNA interactions. However, conventional ChIP protocols require abundant amounts of starting material (at least hundreds of thousands of cells per immunoprecipitation) limiting the application for the ChIP technology to few cell samples. </span></p>',
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			'modified' => '2018-04-17 11:52:29',
			'created' => '2018-03-15 15:50:34',
			'ProductsImage' => array(
				[maximum depth reached]
			)
		)
	),
	'Promotion' => array(),
	'Protocol' => array(),
	'Publication' => array(
		(int) 0 => array(
			'id' => '4843',
			'name' => 'Differentiation block in acute myeloid leukemia regulated by intronicsequences of FTO',
			'authors' => 'Camera  F. et al.',
			'description' => '<p>Iroquois transcription factor gene IRX3 is highly expressed in 20&acirc;&euro;&ldquo;30\% of acute myeloid leukemia (AML) and contributes to the pathognomonic differentiation block. Intron 8 FTO sequences &acirc;&circ;&frac14;220kB downstream of IRX3 exhibit histone acetylation, DNA methylation, and contacts with the IRX3 promoter, which correlate with IRX3 expression. Deletion of these intronic elements confirms a role in positively regulating IRX3. RNAseq revealed long non-coding (lnc) transcripts arising from this locus. FTO-lncAML knockdown (KD) induced differentiation of AML cells, loss of clonogenic activity, and reduced FTO intron 8:IRX3 promoter contacts. While both FTO-lncAML KD and IRX3 KD induced differentiation, FTO-lncAML but not IRX3 KD led to HOXA downregulation suggesting transcript activity in trans. FTO-lncAMLhigh AML samples expressed higher levels of HOXA and lower levels of differentiation genes. Thus, a regulatory module in FTO intron 8 consisting of clustered enhancer elements and a long non-coding RNA is active in human AML, impeding myeloid differentiation.</p>',
			'date' => '2023-08-01',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S2589004223013962',
			'doi' => '10.1016/j.isci.2023.107319',
			'modified' => '2023-08-01 14:14:01',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 1 => array(
			'id' => '4851',
			'name' => 'Supraphysiological Androgens Promote the Tumor Suppressive Activity of the Androgen Receptor Through cMYC Repression and Recruitment of the DREAM Complex',
			'authors' => 'Nyquist  M. et al.',
			'description' => '<p>The androgen receptor (AR) pathway regulates key cell survival programs in prostate epithelium. The AR represents a near-universal driver and therapeutic vulnerability in metastatic prostate cancer, and targeting AR has a remarkable therapeutic index. Though most approaches directed toward AR focus on inhibiting AR signaling, laboratory and now clinical data have shown that high dose, supraphysiological androgen treatment (SPA) results in growth repression and improved outcomes in subsets of prostate cancer patients. A better understanding of the mechanisms contributing to SPA response and resistance could help guide patient selection and combination therapies to improve efficacy. To characterize SPA signaling, we integrated metrics of gene expression changes induced by SPA together with cistrome data and protein-interactomes. These analyses indicated that the Dimerization partner, RB-like, E2F and Multi-vulval class B (DREAM) complex mediates growth repression and downregulation of E2F targets in response to SPA. Notably, prostate cancers with complete genomic loss of RB1 responded to SPA treatment whereas loss of DREAM complex components such as RBL1/2 promoted resistance. Overexpression of MYC resulted in complete resistance to SPA and attenuated the SPA/AR-mediated repression of E2F target genes. These findings support a model of SPA-mediated growth repression that relies on the negative regulation of MYC by AR leading to repression of E2F1 signaling via the DREAM complex. The integrity of MYC signaling and DREAM complex assembly may consequently serve as determinants of SPA responses and as pathways mediating SPA resistance.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/37352376/',
			'doi' => '10.1158/0008-5472.CAN-22-2613',
			'modified' => '2023-08-01 18:09:31',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 2 => array(
			'id' => '4852',
			'name' => 'In skeletal muscle and neural crest cells, SMCHD1 regulates biologicalpathways relevant for Bosma syndrome and facioscapulohumeral dystrophyphenotype.',
			'authors' => 'Laberthonnière  C. et al.',
			'description' => '<p>Many genetic syndromes are linked to mutations in genes encoding factors that guide chromatin organization. Among them, several distinct rare genetic diseases are linked to mutations in SMCHD1 that encodes the structural maintenance of chromosomes flexible hinge domain containing 1 chromatin-associated factor. In humans, its function as well as the impact of its mutations remains poorly defined. To fill this gap, we determined the episignature associated with heterozygous SMCHD1 variants in primary cells and cell lineages derived from induced pluripotent stem cells for Bosma arhinia and microphthalmia syndrome (BAMS) and type 2 facioscapulohumeral dystrophy (FSHD2). In human tissues, SMCHD1 regulates the distribution of methylated CpGs, H3K27 trimethylation and CTCF at repressed chromatin but also at euchromatin. Based on the exploration of tissues affected either in FSHD or in BAMS, i.e. skeletal muscle fibers and neural crest stem cells, respectively, our results emphasize multiple functions for SMCHD1, in chromatin compaction, chromatin insulation and gene regulation with variable targets or phenotypical outcomes. We concluded that in rare genetic diseases, SMCHD1 variants impact gene expression in two ways: (i) by changing the chromatin context at a number of euchromatin loci or (ii) by directly regulating some loci encoding master transcription factors required for cell fate determination and tissue differentiation.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37334829',
			'doi' => '10.1093/nar/gkad523',
			'modified' => '2023-08-01 14:35:38',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 3 => array(
			'id' => '4861',
			'name' => 'Hypomethylation and overexpression of Th17-associated genes is ahallmark of intestinal CD4+ lymphocytes in Crohn's disease.',
			'authors' => 'Sun  Z. et al.',
			'description' => '<p>BACKGROUND: The development of Crohn's disease (CD) involves immune cell signaling pathways regulated by epigenetic modifications. Aberrant DNA methylation has been identified in peripheral blood and bulk intestinal tissue from CD patients. However, the DNA methylome of disease-associated intestinal CD4 + lymphocytes has not been evaluated. MATERIALS AND METHODS: Genome-wide DNA methylation sequencing was performed from terminal ileum CD4 + cells from 21 CD patients and 12 age and sex matched controls. Data was analyzed for differentially methylated CpGs (DMCs) and methylated regions (DMRs). Integration was performed with RNA-sequencing data to evaluate the functional impact of DNA methylation changes on gene expression. DMRs were overlapped with regions of differentially open chromatin (by ATAC-seq) and CCCTC-binding factor (CTCF) binding sites (by ChIP-seq) between peripherally-derived Th17 and Treg cells. RESULTS: CD4+ cells in CD patients had significantly increased DNA methylation compared to those from the controls. A total of 119,051 DMCs and 8,113 DMRs were detected. While hyper-methylated genes were mostly related to cell metabolism and homeostasis, hypomethylated genes were significantly enriched within the Th17 signaling pathway. The differentially enriched ATAC regions in Th17 cells (compared to Tregs) were hypomethylated in CD patients, suggesting heightened Th17 activity. There was significant overlap between hypomethylated DNA regions and CTCF-associated binding sites. CONCLUSIONS: The methylome of CD patients demonstrate an overall dominant hypermethylation yet hypomethylation is more concentrated in proinflammatory pathways, including Th17 differentiation. Hypomethylation of Th17-related genes associated with areas of open chromatin and CTCF binding sites constitutes a hallmark of CD-associated intestinal CD4 + cells.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37280154',
			'doi' => '10.1093/ecco-jcc/jjad093',
			'modified' => '2023-08-01 14:52:39',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 4 => 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) 5 => array(
			'id' => '4782',
			'name' => 'Transient suppression of SUMOylation in embryonic stem cells generatesembryo-like structures.',
			'authors' => 'Cossec  J-C. et al.',
			'description' => '<p>Recent advances in synthetic embryology have opened new avenues for understanding the complex events controlling mammalian peri-implantation development. Here, we show that mouse embryonic stem cells (ESCs) solely exposed to chemical inhibition of SUMOylation generate embryo-like structures comprising anterior neural and trunk-associated regions. HypoSUMOylation-instructed ESCs give rise to spheroids that self-organize into gastrulating structures containing cell types spatially and functionally related to embryonic and extraembryonic compartments. Alternatively, spheroids cultured in a droplet microfluidic device form elongated structures that undergo axial organization reminiscent of natural embryo morphogenesis. Single-cell transcriptomics reveals various cellular lineages, including properly positioned anterior neuronal cell types and paraxial mesoderm segmented into somite-like structures. Transient SUMOylation suppression gradually increases DNA methylation genome wide and repressive mark deposition at Nanog. Interestingly, cell-to-cell variations in SUMOylation levels occur during early embryogenesis. Our approach provides a proof of principle for potentially powerful strategies to explore early embryogenesis by targeting chromatin roadblocks of cell fate change.</p>',
			'date' => '2023-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37061916',
			'doi' => '10.1016/j.celrep.2023.112380',
			'modified' => '2023-06-13 09:20:06',
			'created' => '2023-05-05 12:34:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 6 => array(
			'id' => '4693',
			'name' => 'ZEB1 controls a lineage-specific transcriptional program essential formelanoma cell state transitions',
			'authors' => 'Tang  Y. et al.',
			'description' => '<p>Cell plasticity sustains intra-tumor heterogeneity and treatment resistance in melanoma. Deciphering the transcriptional mechanisms governing reversible phenotypic transitions between proliferative/differentiated and invasive/stem-like states is required in order to design novel therapeutic strategies. EMT-inducing transcription factors, extensively known for their role in metastasis in carcinoma, display cell-type specific functions in melanoma, with a decreased ZEB2/ZEB1 expression ratio fostering adaptive resistance to targeted therapies. While ZEB1 direct target genes have been well characterized in carcinoma models, they remain unknown in melanoma. Here, we performed a genome-wide characterization of ZEB1 transcriptional targets, by combining ChIP-sequencing and RNA-sequencing, upon phenotype switching in melanoma models. We identified and validated ZEB1 binding peaks in the promoter of key lineage-specific genes related to melanoma cell identity. Comparative analyses with breast carcinoma cells demonstrated melanoma-specific ZEB1 binding, further supporting lineage specificity. Gain- or loss-of-function of ZEB1, combined with functional analyses, further demonstrated that ZEB1 negatively regulates proliferative/melanocytic programs and positively regulates both invasive and stem-like programs. We then developed single-cell spatial multiplexed analyses to characterize melanoma cell states with respect to ZEB1/ZEB2 expression in human melanoma samples. We characterized the intra-tumoral heterogeneity of ZEB1 and ZEB2 and further validated ZEB1 increased expression in invasive cells, but also in stem-like cells, highlighting its relevance in vivo in both populations. Overall, our results define ZEB1 as a major transcriptional regulator of cell states transitions and provide a better understanding of lineage-specific transcriptional programs sustaining intra-tumor heterogeneity in melanoma.</p>',
			'date' => '2023-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2023.02.10.526467',
			'doi' => '10.1101/2023.02.10.526467',
			'modified' => '2023-04-14 09:11:23',
			'created' => '2023-02-28 12:19:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 7 => 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) 8 => array(
			'id' => '4710',
			'name' => 'Mechanisms and function of de novo DNA methylation in placentaldevelopment reveals an essential role for DNMT3B.',
			'authors' => 'Andrews  S. et al.',
			'description' => '<p>DNA methylation is a repressive epigenetic modification that is essential for development, exemplified by the embryonic and perinatal lethality observed in mice lacking de novo DNA methyltransferases (DNMTs). Here we characterise the role for DNMT3A, 3B and 3L in gene regulation and development of the mouse placenta. We find that each DNMT establishes unique aspects of the placental methylome through targeting to distinct chromatin features. Loss of Dnmt3b results in de-repression of germline genes in trophoblast lineages and impaired formation of the maternal-foetal interface in the placental labyrinth. Using Sox2-Cre to delete Dnmt3b in the embryo, leaving expression intact in placental cells, the placental phenotype was rescued and, consequently, the embryonic lethality, as Dnmt3b null embryos could now survive to birth. We conclude that de novo DNA methylation by DNMT3B during embryogenesis is principally required to regulate placental development and function, which in turn is critical for embryo survival.</p>',
			'date' => '2023-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36690623',
			'doi' => '10.1038/s41467-023-36019-9',
			'modified' => '2023-04-05 08:38:12',
			'created' => '2023-02-28 12:19:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 9 => array(
			'id' => '4651',
			'name' => 'TCDD induces multigenerational alterations in the expression ofmicroRNA in the thymus through epigenetic modifications',
			'authors' => 'Singh  Narendra P et al.',
			'description' => '<p>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, is an environmental contaminant that is known for mediating toxicity across generations. However, whether TCDD can induce multigenerational changes in the expression of miRNAs (miRs) has not been previously studied. In the current study, we investigated the effect of administration of TCDD in pregnant mice (F0) on gestational day 14, on the expression of miRs in the thymus of F0 and subsequent generations (F1 and F2). Of the 3200 miRs screened, 160 miRs were dysregulated similarly in F0, F1, and F2 generations while 46 miRs were differentially altered in F0-F2 generations. Pathway analysis revealed that the changes in miR signature profile mediated by TCDD affected the genes that regulate cell signaling, apoptosis, thymic atrophy, cancer, immunosuppression, and other physiological pathways. A significant number of miRs that showed altered expression exhibited dioxin response elements (DRE) on their promoters. Focusing on one such miR, namely miR-203 that expressed DREs and was induced across F0-F2 by TCDD, promoter analysis showed that one of the DREs expressed by miR-203 was functional to TCDD-mediated upregulation. Also, the histone methylation status of H3K4me3 in the miR-203 promoter was significantly increased near the transcriptional start site (TSS) in TCDD-treated thymocytes across F0-F2 generations. Genome-wide ChIP-seq study suggested that TCDD may cause alterations in histone methylation in certain genes across the three generations. Together, the current study demonstrates that gestational exposure to TCDD can alter the expression of miRs in F0 through direct activation of DREs as well as across F0, F1, and F2 generations through epigenetic pathways.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://academic.oup.com/pnasnexus/advance-article/doi/10.1093/pnasnexus/pgac290/6886578',
			'doi' => 'https://doi.org/10.1093/pnasnexus/pgac290',
			'modified' => '2023-03-13 10:55:36',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 10 => array(
			'id' => '4632',
			'name' => 'The histone acetyltransferase KAT6A is recruited to unmethylatedCpG islands via a DNA binding winged helix domain.',
			'authors' => 'Weber  L.M. et al.',
			'description' => '<p>The lysine acetyltransferase KAT6A (MOZ, MYST3) belongs to the MYST family of chromatin regulators, facilitating histone acetylation. Dysregulation of KAT6A has been implicated in developmental syndromes and the onset of acute myeloid leukemia (AML). Previous work suggests that KAT6A is recruited to its genomic targets by a combinatorial function of histone binding PHD fingers, transcription factors and chromatin binding interaction partners. Here, we demonstrate that a winged helix (WH) domain at the very N-terminus of KAT6A specifically interacts with unmethylated CpG motifs. This DNA binding function leads to the association of KAT6A with unmethylated CpG islands (CGIs) genome-wide. Mutation of the essential amino acids for DNA binding completely abrogates the enrichment of KAT6A at CGIs. In contrast, deletion of a second WH domain or the histone tail binding PHD fingers only subtly influences the binding of KAT6A to CGIs. Overexpression of a KAT6A WH1 mutant has a dominant negative effect on H3K9 histone acetylation, which is comparable to the effects upon overexpression of a KAT6A HAT domain mutant. Taken together, our work revealed a previously unrecognized chromatin recruitment mechanism of KAT6A, offering a new perspective on the role of KAT6A in gene regulation and human diseases.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36537216',
			'doi' => '10.1093/nar/gkac1188',
			'modified' => '2023-03-28 09:01:38',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 11 => array(
			'id' => '4629',
			'name' => 'Polyglutamine-expanded ATXN7 alters a specific epigenetic signatureunderlying photoreceptor identity gene expression in SCA7 mouseretinopathy.',
			'authors' => 'Niewiadomska-Cimicka  A.et al.',
			'description' => '<p>BACKGROUND: Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder that primarily affects the cerebellum and retina. SCA7 is caused by a polyglutamine expansion in the ATXN7 protein, a subunit of the transcriptional coactivator SAGA that acetylates histone H3 to deposit narrow H3K9ac mark at DNA regulatory elements of active genes. Defective histone acetylation has been presented as a possible cause for gene deregulation in SCA7 mouse models. However, the topography of acetylation defects at the whole genome level and its relationship to changes in gene expression remain to be determined. METHODS: We performed deep RNA-sequencing and chromatin immunoprecipitation coupled to high-throughput sequencing to examine the genome-wide correlation between gene deregulation and alteration of the active transcription marks, e.g. SAGA-related H3K9ac, CBP-related H3K27ac and RNA polymerase II (RNAPII), in a SCA7 mouse retinopathy model. RESULTS: Our analyses revealed that active transcription marks are reduced at most gene promoters in SCA7 retina, while a limited number of genes show changes in expression. We found that SCA7 retinopathy is caused by preferential downregulation of hundreds of highly expressed genes that define morphological and physiological identities of mature photoreceptors. We further uncovered that these photoreceptor genes harbor unusually broad H3K9ac profiles spanning the entire gene bodies and have a low RNAPII pausing. This broad H3K9ac signature co-occurs with other features that delineate superenhancers, including broad H3K27ac, binding sites for photoreceptor specific transcription factors and expression of enhancer-related non-coding RNAs (eRNAs). In SCA7 retina, downregulated photoreceptor genes show decreased H3K9 and H3K27 acetylation and eRNA expression as well as increased RNAPII pausing, suggesting that superenhancer-related features are altered. CONCLUSIONS: Our study thus provides evidence that distinctive epigenetic configurations underlying high expression of cell-type specific genes are preferentially impaired in SCA7, resulting in a defect in the maintenance of identity features of mature photoreceptors. Our results also suggest that continuous SAGA-driven acetylation plays a role in preserving post-mitotic neuronal identity.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36539812',
			'doi' => '10.1186/s12929-022-00892-1',
			'modified' => '2023-03-28 09:07:19',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 12 => array(
			'id' => '4575',
			'name' => 'Intranasal administration of Acinetobacter lwoffii in a murine model ofasthma induces IL-6-mediated protection associated with cecal microbiotachanges.',
			'authors' => 'Alashkar A. B. et al.',
			'description' => '<p>BACKGROUND: Early-life exposure to certain environmental bacteria including Acinetobacter lwoffii (AL) has been implicated in protection from chronic inflammatory diseases including asthma later in life. However, the underlying mechanisms at the immune-microbe interface remain largely unknown. METHODS: The effects of repeated intranasal AL exposure on local and systemic innate immune responses were investigated in wild-type and Il6 , Il10 , and Il17 mice exposed to ovalbumin-induced allergic airway inflammation. Those investigations were expanded by microbiome analyses. To assess for AL-associated changes in gene expression, the picture arising from animal data was supplemented by in vitro experiments of macrophage and T-cell responses, yielding expression and epigenetic data. RESULTS: The asthma preventive effect of AL was confirmed in the lung. Repeated intranasal AL administration triggered a proinflammatory immune response particularly characterized by elevated levels of IL-6, and consequently, IL-6 induced IL-10 production in CD4 T-cells. Both IL-6 and IL-10, but not IL-17, were required for asthma protection. AL had a profound impact on the gene regulatory landscape of CD4 T-cells which could be largely recapitulated by recombinant IL-6. AL administration also induced marked changes in the gastrointestinal microbiome but not in the lung microbiome. By comparing the effects on the microbiota according to mouse genotype and AL-treatment status, we have identified microbial taxa that were associated with either disease protection or activity. CONCLUSION: These experiments provide a novel mechanism of Acinetobacter lwoffii-induced asthma protection operating through IL-6-mediated epigenetic activation of IL-10 production and with associated effects on the intestinal microbiome.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36458896',
			'doi' => '10.1111/all.15606',
			'modified' => '2023-04-11 10:23:07',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 13 => array(
			'id' => '4535',
			'name' => 'Identification of genomic binding sites and direct target genes for thetranscription factor DDIT3/CHOP.',
			'authors' => 'Osman  A. et al.',
			'description' => '<p>DDIT3 is a tightly regulated basic leucine zipper (bZIP) transcription factor and key regulator in cellular stress responses. It is involved in a variety of pathological conditions and may cause cell cycle block and apoptosis. It is also implicated in differentiation of some specialized cell types and as an oncogene in several types of cancer. DDIT3 is believed to act as a dominant-negative inhibitor by forming heterodimers with other bZIP transcription factors, preventing their DNA binding and transactivating functions. DDIT3 has, however, been reported to bind DNA and regulate target genes. Here, we employed ChIP sequencing combined with microarray-based expression analysis to identify direct binding motifs and target genes of DDIT3. The results reveal DDIT3 binding to motifs similar to other bZIP transcription factors, known to form heterodimers with DDIT3. Binding to a class III satellite DNA repeat sequence was also detected. DDIT3 acted as a DNA-binding transcription factor and bound mainly to the promotor region of regulated genes. ChIP sequencing analysis of histone H3K27 methylation and acetylation showed a strong overlap between H3K27-acetylated marks and DDIT3 binding. These results support a role for DDIT3 as a transcriptional regulator of H3K27ac-marked genes in transcriptionally active chromatin.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36402425',
			'doi' => '10.1016/j.yexcr.2022.113418',
			'modified' => '2022-11-25 08:47:49',
			'created' => '2022-11-24 08:49:52',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 14 => array(
			'id' => '4494',
			'name' => 'Cryptococcal Hsf3 controls intramitochondrial ROS homeostasis byregulating the respiratory process.',
			'authors' => 'Gao  X.et al.',
			'description' => '<p>Mitochondrial quality control prevents accumulation of intramitochondrial-derived reactive oxygen species (mtROS), thereby protecting cells against DNA damage, genome instability, and programmed cell death. However, underlying mechanisms are incompletely understood, particularly in fungal species. Here, we show that Cryptococcus neoformans heat shock factor 3 (CnHsf3) exhibits an atypical function in regulating mtROS independent of the unfolded protein response. CnHsf3 acts in nuclei and mitochondria, and nuclear- and mitochondrial-targeting signals are required for its organelle-specific functions. It represses the expression of genes involved in the tricarboxylic acid cycle while promoting expression of genes involved in electron transfer chain. In addition, CnHsf3 responds to multiple intramitochondrial stresses; this response is mediated by oxidation of the cysteine residue on its DNA binding domain, which enhances DNA binding. Our results reveal a function of HSF proteins in regulating mtROS homeostasis that is independent of the unfolded protein response.</p>',
			'date' => '2022-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36109512',
			'doi' => '10.1038/s41467-022-33168-1',
			'modified' => '2022-11-18 12:43:17',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 15 => array(
			'id' => '4496',
			'name' => 'Dominant role of DNA methylation over H3K9me3 for IAP silencingin endoderm.',
			'authors' => 'Wang  Z. et al.',
			'description' => '<p>Silencing of endogenous retroviruses (ERVs) is largely mediated by repressive chromatin modifications H3K9me3 and DNA methylation. On ERVs, these modifications are mainly deposited by the histone methyltransferase Setdb1 and by the maintenance DNA methyltransferase Dnmt1. Knock-out of either Setdb1 or Dnmt1 leads to ERV de-repression in various cell types. However, it is currently not known if H3K9me3 and DNA methylation depend on each other for ERV silencing. Here we show that conditional knock-out of Setdb1 in mouse embryonic endoderm results in ERV de-repression in visceral endoderm (VE) descendants and does not occur in definitive endoderm (DE). Deletion of Setdb1 in VE progenitors results in loss of H3K9me3 and reduced DNA methylation of Intracisternal A-particle (IAP) elements, consistent with up-regulation of this ERV family. In DE, loss of Setdb1 does not affect H3K9me3 nor DNA methylation, suggesting Setdb1-independent pathways for maintaining these modifications. Importantly, Dnmt1 knock-out results in IAP de-repression in both visceral and definitive endoderm cells, while H3K9me3 is unaltered. Thus, our data suggest a dominant role of DNA methylation over H3K9me3 for IAP silencing in endoderm cells. Our findings suggest that Setdb1-meditated H3K9me3 is not sufficient for IAP silencing, but rather critical for maintaining high DNA methylation.</p>',
			'date' => '2022-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36123357',
			'doi' => '10.1038/s41467-022-32978-7',
			'modified' => '2022-11-21 10:26:30',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 16 => array(
			'id' => '4415',
			'name' => 'HDAC1 and PRC2 mediate combinatorial control in SPI1/PU.1-dependentgene repression in murine erythroleukaemia.',
			'authors' => 'Gregoricchio  S. et al.',
			'description' => '<p>Although originally described as transcriptional activator, SPI1/PU.1, a major player in haematopoiesis whose alterations are associated with haematological malignancies, has the ability to repress transcription. Here, we investigated the mechanisms underlying gene repression in the erythroid lineage, in which SPI1 exerts an oncogenic function by blocking differentiation. We show that SPI1 represses genes by binding active enhancers that are located in intergenic or gene body regions. HDAC1 acts as a cooperative mediator of SPI1-induced transcriptional repression by deacetylating SPI1-bound enhancers in a subset of genes, including those involved in erythroid differentiation. Enhancer deacetylation impacts on promoter acetylation, chromatin accessibility and RNA pol II occupancy. In addition to the activities of HDAC1, polycomb repressive complex 2 (PRC2) reinforces gene repression by depositing H3K27me3 at promoter sequences when SPI1 is located at enhancer sequences. Moreover, our study identified a synergistic relationship between PRC2 and HDAC1 complexes in mediating the transcriptional repression activity of SPI1, ultimately inducing synergistic adverse effects on leukaemic cell survival. Our results highlight the importance of the mechanism underlying transcriptional repression in leukemic cells, involving complex functional connections between SPI1 and the epigenetic regulators PRC2 and HDAC1.</p>',
			'date' => '2022-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35871293',
			'doi' => '10.1093/nar/gkac613',
			'modified' => '2022-09-15 08:59:26',
			'created' => '2022-09-08 16:32:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 17 => array(
			'id' => '4516',
			'name' => 'Dual role of histone variant H3.3B in spermatogenesis: positiveregulation of piRNA transcription and implication in X-chromosomeinactivation.',
			'authors' => 'Fontaine  E. et al.',
			'description' => '<p>The histone variant H3.3 is encoded by two distinct genes, H3f3a and H3f3b, exhibiting identical amino-acid sequence. H3.3 is required for spermatogenesis, but the molecular mechanism of its spermatogenic function remains obscure. Here, we have studied the role of each one of H3.3A and H3.3B proteins in spermatogenesis. We have generated transgenic conditional knock-out/knock-in (cKO/KI) epitope-tagged FLAG-FLAG-HA-H3.3B (H3.3BHA) and FLAG-FLAG-HA-H3.3A (H3.3AHA) mouse lines. We show that H3.3B, but not H3.3A, is required for spermatogenesis and male fertility. Analysis of the molecular mechanism unveils that the absence of H3.3B led to alterations in the meiotic/post-meiotic transition. Genome-wide RNA-seq reveals that the depletion of H3.3B in meiotic cells is associated with increased expression of the whole sex X and Y chromosomes as well as of both RLTR10B and RLTR10B2 retrotransposons. In contrast, the absence of H3.3B resulted in down-regulation of the expression of piRNA clusters. ChIP-seq experiments uncover that RLTR10B and RLTR10B2 retrotransposons, the whole sex chromosomes and the piRNA clusters are markedly enriched of H3.3. Taken together, our data dissect the molecular mechanism of H3.3B functions during spermatogenesis and demonstrate that H3.3B, depending on its chromatin localization, is involved in either up-regulation or down-regulation of expression of defined large chromatin regions.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35766398',
			'doi' => '10.1093/nar/gkac541',
			'modified' => '2022-11-24 08:51:34',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 18 => array(
			'id' => '4393',
			'name' => 'TBX2 acts as a potent transcriptional silencer of tumour suppressor genesthrough interaction with the CoREST complex to sustain theproliferation of breast cancers.',
			'authors' => 'McIntyre  A.J. et al.',
			'description' => '<p>Chromosome 17q23 amplification occurs in 20\% of primary breast tumours and is associated with poor outcome. The TBX2 gene is located on 17q23 and is often over-expressed in this breast tumour subset. TBX2 is an anti-senescence gene, promoting cell growth and survival through repression of Tumour Suppressor Genes (TSGs), such as NDRG1 and CST6. Previously we found that TBX2 cooperates with the PRC2 complex to repress several TSGs, and that PRC2 inhibition restored NDRG1 expression to impede cellular proliferation. Here, we now identify CoREST proteins, LSD1 and ZNF217, as novel interactors of TBX2. Genetic or pharmacological targeting of CoREST emulated TBX2 loss, inducing NDRG1 expression and abolishing breast cancer growth in vitro and in vivo. Furthermore, we uncover that TBX2/CoREST targeting of NDRG1 is achieved by recruitment of TBX2 to the NDRG1 promoter by Sp1, the abolishment of which resulted in NDRG1 upregulation and diminished cancer cell proliferation. Through ChIP-seq we reveal that 30\% of TBX2-bound promoters are shared with ZNF217 and identify novel targets repressed by TBX2/CoREST; of these targets a lncRNA, LINC00111, behaves as a negative regulator of cell proliferation. Overall, these data indicate that inhibition of CoREST proteins represents a promising therapeutic intervention for TBX2-addicted breast tumours.</p>',
			'date' => '2022-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35687133',
			'doi' => '10.1093/nar/gkac494',
			'modified' => '2022-08-11 14:23:06',
			'created' => '2022-08-11 12:14:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 19 => array(
			'id' => '4836',
			'name' => 'Caffeine intake exerts dual genome-wide effects on hippocampal metabolismand learning-dependent transcription.',
			'authors' => 'Paiva  I. et al.',
			'description' => '<p>Caffeine is the most widely consumed psychoactive substance in the world. Strikingly, the molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal omics techniques. Our results revealed that chronic caffeine exerts concerted pleiotropic effects in the hippocampus at the epigenomic, proteomic, and metabolomic levels. Caffeine lowered metabolism-related processes (e.g., at the level of metabolomics and gene expression) in bulk tissue, while it induced neuron-specific epigenetic changes at synaptic transmission/plasticity-related genes and increased experience-driven transcriptional activity. Altogether, these findings suggest that regular caffeine intake improves the signal-to-noise ratio during information encoding, in part through fine-tuning of metabolic genes, while boosting the salience of information processing during learning in neuronal circuits.</p>',
			'date' => '2022-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35536645',
			'doi' => '10.1172/JCI149371',
			'modified' => '2023-08-01 13:52:29',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 20 => 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) 21 => 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) 22 => 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) 23 => array(
			'id' => '4217',
			'name' => 'CREBBP/EP300 acetyltransferase inhibition disrupts FOXA1-bound enhancers to inhibit the proliferation of ER+ breast cancer cells.',
			'authors' => 'Bommi-Reddy A. et al.',
			'description' => '<p><span>Therapeutic targeting of the estrogen receptor (ER) is a clinically validated approach for estrogen receptor positive breast cancer (ER+ BC), but sustained response is limited by acquired resistance. Targeting the transcriptional coactivators required for estrogen receptor activity represents an alternative approach that is not subject to the same limitations as targeting estrogen receptor itself. In this report we demonstrate that the acetyltransferase activity of coactivator paralogs CREBBP/EP300 represents a promising therapeutic target in ER+ BC. Using the potent and selective inhibitor CPI-1612, we show that CREBBP/EP300 acetyltransferase inhibition potently suppresses in vitro and in vivo growth of breast cancer cell line models and acts in a manner orthogonal to directly targeting ER. CREBBP/EP300 acetyltransferase inhibition suppresses ER-dependent transcription by targeting lineage-specific enhancers defined by the pioneer transcription factor FOXA1. These results validate CREBBP/EP300 acetyltransferase activity as a viable target for clinical development in ER+ breast cancer.</span></p>',
			'date' => '2022-03-30',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/35353838/',
			'doi' => '10.1371/journal.pone.0262378',
			'modified' => '2022-04-12 10:56:54',
			'created' => '2022-04-12 10:56:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 24 => array(
			'id' => '4235',
			'name' => 'NuA4 and H2A.Z control environmental responses and autotrophicgrowth in Arabidopsis',
			'authors' => 'Bieluszewski T. et al.',
			'description' => '<p>Nucleosomal acetyltransferase of H4 (NuA4) is an essential transcriptional coactivator in eukaryotes, but remains poorly characterized in plants. Here, we describe Arabidopsis homologs of the NuA4 scaffold proteins Enhancer of Polycomb-Like 1 (AtEPL1) and Esa1-Associated Factor 1 (AtEAF1). Loss of AtEAF1 results in inhibition of growth and chloroplast development. These effects are stronger in the Atepl1 mutant and are further enhanced by loss of Golden2-Like (GLK) transcription factors, suggesting that NuA4 activates nuclear plastid genes alongside GLK. We demonstrate that AtEPL1 is necessary for nucleosomal acetylation of histones H4 and H2A.Z by NuA4 in vitro. These chromatin marks are diminished genome-wide in Atepl1, while another active chromatin mark, H3K9 acetylation (H3K9ac), is locally enhanced. Expression of many chloroplast-related genes depends on NuA4, as they are downregulated with loss of H4ac and H2A.Zac. Finally, we demonstrate that NuA4 promotes H2A.Z deposition and by doing so prevents spurious activation of stress response genes.</p>',
			'date' => '2022-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35022409',
			'doi' => '10.1038/s41467-021-27882-5',
			'modified' => '2022-05-19 17:02:00',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 25 => array(
			'id' => '4772',
			'name' => 'Three classes of epigenomic regulators converge to hyperactivate theessential maternal gene deadhead within a heterochromatin mini-domain.',
			'authors' => 'Torres-Campana  D. et al.',
			'description' => '<p>The formation of a diploid zygote is a highly complex cellular process that is entirely controlled by maternal gene products stored in the egg cytoplasm. This highly specialized transcriptional program is tightly controlled at the chromatin level in the female germline. As an extreme case in point, the massive and specific ovarian expression of the essential thioredoxin Deadhead (DHD) is critically regulated in Drosophila by the histone demethylase Lid and its partner, the histone deacetylase complex Sin3A/Rpd3, via yet unknown mechanisms. Here, we identified Snr1 and Mod(mdg4) as essential for dhd expression and investigated how these epigenomic effectors act with Lid and Sin3A to hyperactivate dhd. Using Cut\&amp;Run chromatin profiling with a dedicated data analysis procedure, we found that dhd is intriguingly embedded in an H3K27me3/H3K9me3-enriched mini-domain flanked by DNA regulatory elements, including a dhd promoter-proximal element essential for its expression. Surprisingly, Lid, Sin3a, Snr1 and Mod(mdg4) impact H3K27me3 and this regulatory element in distinct manners. However, we show that these effectors activate dhd independently of H3K27me3/H3K9me3, and that dhd remains silent in the absence of these marks. Together, our study demonstrates an atypical and critical role for chromatin regulators Lid, Sin3A, Snr1 and Mod(mdg4) to trigger tissue-specific hyperactivation within a unique heterochromatin mini-domain.</p>',
			'date' => '2022-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759638/',
			'doi' => '10.1371/journal.pgen.1009615',
			'modified' => '2023-04-17 09:46:00',
			'created' => '2023-04-14 13:41:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 26 => 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) 27 => array(
			'id' => '4245',
			'name' => 'Decreased PRC2 activity supports the survival of basal-like breastcancer cells to cytotoxic treatments',
			'authors' => 'Mieczkowska IK et al.',
			'description' => '<p>Breast cancer (BC) is the most common cancer occurring in women but also rarely develops in men. Recent advances in early diagnosis and development of targeted therapies have greatly improved the survival rate of BC patients. However, the basal-like BC subtype (BLBC), largely overlapping with the triple-negative BC subtype (TNBC), lacks such drug targets and conventional cytotoxic chemotherapies often remain the only treatment option. Thus, the development of resistance to cytotoxic therapies has fatal consequences. To assess the involvement of epigenetic mechanisms and their therapeutic potential increasing cytotoxic drug efficiency, we combined high-throughput RNA- and ChIP-sequencing analyses in BLBC cells. Tumor cells surviving chemotherapy upregulated transcriptional programs of epithelial-to-mesenchymal transition (EMT) and stemness. To our surprise, the same cells showed a pronounced reduction of polycomb repressive complex 2 (PRC2) activity via downregulation of its subunits Ezh2, Suz12, Rbbp7 and Mtf2. Mechanistically, loss of PRC2 activity leads to the de-repression of a set of genes through an epigenetic switch from repressive H3K27me3 to activating H3K27ac mark at regulatory regions. We identified Nfatc1 as an upregulated gene upon loss of PRC2 activity and directly implicated in the transcriptional changes happening upon survival to chemotherapy. Blocking NFATc1 activation reduced epithelial-to-mesenchymal transition, aggressiveness, and therapy resistance of BLBC cells. Our data demonstrate a previously unknown function of PRC2 maintaining low Nfatc1 expression levels and thereby repressing aggressiveness and therapy resistance in BLBC.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34845197',
			'doi' => '10.1038/s41419-021-04407-y',
			'modified' => '2022-05-20 09:21:56',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 28 => array(
			'id' => '4276',
			'name' => 'Ago1 controls myogenic differentiation by regulating eRNA-mediatedCBP-guided epigenome reprogramming.',
			'authors' => 'Fallatah Bodor et al.',
			'description' => '<p>The role of chromatin-associated RNAi components in the nucleus of mammalian cells and in particular in the context of developmental programs remains to be elucidated. Here, we investigate the function of nuclear Argonaute 1 (Ago1) in gene expression regulation during skeletal muscle differentiation. We show that Ago1 is required for activation of the myogenic program by supporting chromatin modification mediated by developmental enhancer activation. Mechanistically, we demonstrate that Ago1 directly controls global H3K27 acetylation (H3K27ac) by regulating enhancer RNA (eRNA)-CREB-binding protein (CBP) acetyltransferase interaction, a key step in enhancer-driven gene activation. In particular, we show that Ago1 is specifically required for myogenic differentiation 1 (MyoD) and downstream myogenic gene activation, whereas its depletion leads to failure of CBP acetyltransferase activation and blocking of the myogenic program. Our work establishes a role of the mammalian enhancer-associated RNAi component Ago1 in epigenome regulation and activation of developmental programs.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.celrep.2021.110066',
			'doi' => '10.1016/j.celrep.2021.110066',
			'modified' => '2022-05-23 09:53:14',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 29 => array(
			'id' => '4833',
			'name' => 'Extensive NEUROG3 occupancy in the human pancreatic endocrine generegulatory network.',
			'authors' => 'Schreiber  V. et al.',
			'description' => '<p>OBJECTIVE: Mice lacking the bHLH transcription factor (TF) Neurog3 do not form pancreatic islet cells, including insulin-secreting beta cells, the absence of which leads to diabetes. In humans, homozygous mutations of NEUROG3 manifest with neonatal or childhood diabetes. Despite this critical role in islet cell development, the precise function of and downstream genetic programs regulated directly by NEUROG3 remain elusive. Therefore, we mapped genome-wide NEUROG3 occupancy in human induced pluripotent stem cell (hiPSC)-derived endocrine progenitors and determined NEUROG3 dependency of associated genes to uncover direct targets. METHODS: We generated a novel hiPSC line (NEUROG3-HA-P2A-Venus) where NEUROG3 is HA-tagged and fused to a self-cleaving fluorescent VENUS reporter. We used the CUT\&amp;RUN technique to map NEUROG3 occupancy and epigenetic marks in pancreatic endocrine progenitors (PEP) that were differentiated from this hiPSC line. We integrated NEUROG3 occupancy data with chromatin status and gene expression in PEPs as well as their NEUROG3-dependence. In addition, we investigated whether NEUROG3 binds type 2 diabetes mellitus (T2DM)-associated variants at the PEP stage. RESULTS: CUT\&amp;RUN revealed a total of 863 NEUROG3 binding sites assigned to 1263 unique genes. NEUROG3 occupancy was found at promoters as well as at distant cis-regulatory elements that frequently overlapped within PEP active enhancers. De novo motif analyses defined a NEUROG3 consensus binding motif and suggested potential co-regulation of NEUROG3 target genes by FOXA or RFX transcription factors. We found that 22\% of the genes downregulated in NEUROG3 PEPs, and 10\% of genes enriched in NEUROG3-Venus positive endocrine cells were bound by NEUROG3 and thus likely to be directly regulated. NEUROG3 binds to 138 transcription factor genes, some with important roles in islet cell development or function, such as NEUROD1, PAX4, NKX2-2, SOX4, MLXIPL, LMX1B, RFX3, and NEUROG3 itself, and many others with unknown islet function. Unexpectedly, we uncovered that NEUROG3 targets genes critical for insulin secretion in beta cells (e.g., GCK, ABCC8/KCNJ11, CACNA1A, CHGA, SCG2, SLC30A8, and PCSK1). Thus, analysis of NEUROG3 occupancy suggests that the transient expression of NEUROG3 not only promotes islet destiny in uncommitted pancreatic progenitors, but could also initiate endocrine programs essential for beta cell function. Lastly, we identified eight T2DM risk SNPs within NEUROG3-bound regions. CONCLUSION: Mapping NEUROG3 genome occupancy in PEPs uncovered unexpectedly broad, direct control of the endocrine genes, raising novel hypotheses on how this master regulator controls islet and beta cell differentiation.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.04.14.439685',
			'doi' => '10.1016/j.molmet.2021.101313',
			'modified' => '2023-08-01 13:46:35',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 30 => array(
			'id' => '4285',
			'name' => 'Alveolar macrophages from persons living with HIV show impairedepigenetic response to Mycobacterium tuberculosis.',
			'authors' => 'Correa-Macedo Wilian et al.',
			'description' => '<p>Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV and antiretroviral therapy (ART) impact on the anti-mycobacterial response of AM is not known. To investigate the impact of HIV and ART on the transcriptomic and epigenetic response of AM to Mtb, we obtained AM by bronchoalveolar lavage from 20 PLWH receiving ART, 16 control subjects who were HIV-free (HC), and 14 subjects who received ART as pre-exposure prophylaxis (PrEP) to prevent HIV infection. Following in-vitro challenge with Mtb, AM from each group displayed overlapping but distinct profiles of significantly up- and down-regulated genes in response to Mtb. Comparatively, AM isolated from both PLWH and PrEP subjects presented a substantially weaker transcriptional response. In addition, AM from HC subjects challenged with Mtb responded with pronounced chromatin accessibility changes while AM obtained from PLWH and PrEP subjects displayed no significant changes in their chromatin state. Collectively, these results revealed a stronger adverse effect of ART than HIV on the epigenetic landscape and transcriptional responsiveness of AM.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/34473646/',
			'doi' => '10.1172/JCI148013',
			'modified' => '2022-05-24 09:08:39',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 31 => 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) 32 => array(
			'id' => '4304',
			'name' => 'The related coactivator complexes SAGA and ATAC control embryonicstem cell self-renewal through acetyltransferase-independent mechanisms',
			'authors' => 'Fischer Veronique et al.',
			'description' => '<p>SUMMARY SAGA (Spt-Ada-Gcn5 acetyltransferase) and ATAC (Ada-two-A-containing) are two related coactivator complexes, sharing the same histone acetyltransferase (HAT) subunit. The HAT activities of SAGA and ATAC are required for metazoan development, but the role of these complexes in RNA polymerase II transcription is less understood. To determine whether SAGA and ATAC have redundant or specific functions, we compare the effects of HAT inactivation in each complex with that of inactivation of either SAGA or ATAC core subunits in mouse embryonic stem cells (ESCs). We show that core subunits of SAGA or ATAC are required for complex assembly and mouse ESC growth and self-renewal. Surprisingly, depletion of HAT module subunits causes a global decrease in histone H3K9 acetylation, but does not result in significant phenotypic or transcriptional defects. Thus, our results indicate that SAGA and ATAC are differentially required for self-renewal of mouse ESCs by regulating transcription through different pathways in a HAT-independent manner.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34433046',
			'doi' => '10.1016/j.celrep.2021.109598',
			'modified' => '2022-05-30 09:57:39',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 33 => array(
			'id' => '4345',
			'name' => 'Altered Chromatin States Drive Cryptic Transcription in AgingMammalian Stem Cells.',
			'authors' => 'McCauley Brenna S et al.',
			'description' => '<p>A repressive chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation suppresses cryptic transcription in embryonic stem cells. Cryptic transcription is elevated with age in yeast and nematodes, and reducing it extends yeast lifespan, though whether this occurs in mammals is unknown. We show that cryptic transcription is elevated in aged mammalian stem cells, including murine hematopoietic stem cells (mHSCs) and neural stem cells (NSCs) and human mesenchymal stem cells (hMSCs). Precise mapping allowed quantification of age-associated cryptic transcription in hMSCs aged . Regions with significant age-associated cryptic transcription have a unique chromatin signature: decreased H3K36me3 and increased H3K4me1, H3K4me3, and H3K27ac with age. Genomic regions undergoing such changes resemble known promoter sequences and are bound by TBP even in young cells. Hence, the more permissive chromatin state at intragenic cryptic promoters likely underlies increased cryptic transcription in aged mammalian stem cells.</p>',
			'date' => '2021-08-01',
			'pmid' => 'https://doi.org/10.1038%2Fs43587-021-00091-x',
			'doi' => '10.1038/s43587-021-00091-x',
			'modified' => '2022-06-22 12:30:19',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 34 => array(
			'id' => '4333',
			'name' => 'Metabolically controlled histone H4K5 acylation/acetylation ratiodrives BRD4 genomic distribution.',
			'authors' => 'Gao M. et al.',
			'description' => '<p>In addition to acetylation, histones are modified by a series of competing longer-chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions hinder our understanding of histone acylations' specific roles. Here, by using an acute lymphoblastic leukemia (ALL) cell model and blasts from individuals with B-precusor ALL (B-ALL), we demonstrate a role of mitochondrial activity in controlling the histone acylation/acetylation ratio, especially at histone H4 lysine 5 (H4K5). An increase in the ratio of non-acetyl acylations (crotonylation or butyrylation) over acetylation on H4K5 weakens bromodomain containing protein 4 (BRD4) bromodomain-dependent chromatin interaction and enhances BRD4 nuclear mobility and availability for binding transcription start site regions of active genes. Our data suggest that the metabolism-driven control of the histone acetylation/longer-chain acylation(s) ratio could be a common mechanism regulating the bromodomain factors' functional genomic distribution.</p>',
			'date' => '2021-07-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.celrep.2021.109460',
			'doi' => '10.1016/j.celrep.2021.109460',
			'modified' => '2022-08-03 16:14:09',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 35 => array(
			'id' => '4341',
			'name' => 'Heterogeneity of neurons reprogrammed from spinal cord astrocytes by theproneural factors Ascl1 and Neurogenin2',
			'authors' => 'Kempf J. et al. ',
			'description' => '<p>Summary Astrocytes are a viable source for generating new neurons via direct conversion. However, little is known about the neurogenic cascades triggered in astrocytes from different regions of the CNS. Here, we examine the transcriptome induced by the proneural factors Ascl1 and Neurog2 in spinal cord-derived astrocytes in vitro. Each factor initially elicits different neurogenic programs that later converge to a V2 interneuron-like state. Intriguingly, patch sequencing (patch-seq) shows no overall correlation between functional properties and the transcriptome of the heterogenous induced neurons, except for K-channels. For example, some neurons with fully mature electrophysiological properties still express astrocyte genes, thus calling for careful molecular and functional analysis. Comparing the transcriptomes of spinal cord- and cerebral-cortex-derived astrocytes reveals profound differences, including developmental patterning cues maintained in vitro. These relate to the distinct neuronal identity elicited by Ascl1 and Neurog2 reflecting their developmental functions in subtype specification of the respective CNS region.</p>',
			'date' => '2021-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34289357',
			'doi' => '10.1016/j.celrep.2021.109409',
			'modified' => '2022-08-03 16:29:33',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 36 => 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) 37 => 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) 38 => array(
			'id' => '4147',
			'name' => 'Waves of sumoylation support transcription dynamics during adipocytedifferentiation',
			'authors' => 'Zhao, X. et al.',
			'description' => '<p>Tight control of gene expression networks required for adipose tissue formation and plasticity is essential for adaptation to energy needs and environmental cues. However, little is known about the mechanisms that orchestrate the dramatic transcriptional changes leading to adipocyte differentiation. We investigated the regulation of nascent transcription by the sumoylation pathway during adipocyte differentiation using SLAMseq and ChIPseq. We discovered that the sumoylation pathway has a dual function in differentiation; it supports the initial downregulation of pre-adipocyte-specific genes, while it promotes the establishment of the mature adipocyte transcriptional program. By characterizing sumoylome dynamics in differentiating adipocytes by mass spectrometry, we found that sumoylation of specific transcription factors like Ppar&gamma;/RXR and their co-factors is associated with the transcription of adipogenic genes. Our data demonstrate that the sumoylation pathway coordinates the rewiring of transcriptional networks required for formation of functional adipocytes. This study also provides an in-depth resource of gene transcription dynamics, SUMO-regulated genes and sumoylation sites during adipogenesis.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.02.20.432084',
			'doi' => '10.1101/2021.02.20.432084',
			'modified' => '2021-12-14 09:23:28',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 39 => array(
			'id' => '4192',
			'name' => 'Polycomb Repressive Complex 2 and KRYPTONITE regulate pathogen-inducedprogrammed cell death in Arabidopsis.',
			'authors' => 'Dvořák Tomaštíková E. et al.',
			'description' => '<p>The Polycomb Repressive Complex 2 (PRC2) is well-known for its role in controlling developmental transitions by suppressing the premature expression of key developmental regulators. Previous work revealed that PRC2 also controls the onset of senescence, a form of developmental programmed cell death (PCD) in plants. Whether the induction of PCD in response to stress is similarly suppressed by the PRC2 remained largely unknown. In this study, we explored whether PCD triggered in response to immunity- and disease-promoting pathogen effectors is associated with changes in the distribution of the PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) modification in Arabidopsis thaliana. We furthermore tested the distribution of the heterochromatic histone mark H3K9me2, which is established, to a large extent, by the H3K9 methyltransferase KRYPTONITE, and occupies chromatin regions generally not targeted by PRC2. We report that effector-induced PCD caused major changes in the distribution of both repressive epigenetic modifications and that both modifications have a regulatory role and impact on the onset of PCD during pathogen infection. Our work highlights that the transition to pathogen-induced PCD is epigenetically controlled, revealing striking similarities to developmental PCD.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33566101',
			'doi' => '10.1093/plphys/kiab035',
			'modified' => '2022-01-06 14:12:23',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 40 => array(
			'id' => '4273',
			'name' => 'An integrated multi-omics analysis identifies prognostic molecularsubtypes of non-muscle-invasive bladder cancer',
			'authors' => 'Lindskrog Sia Viborg et al.',
			'description' => '<p>The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n&thinsp;=&thinsp;834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33863885',
			'doi' => '10.1038/s41467-021-22465-w',
			'modified' => '2022-05-23 09:49:43',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 41 => 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) 42 => array(
			'id' => '4109',
			'name' => 'VPRBP functions downstream of the androgen receptor and OGT to restrict p53 activation in prostate cancer ',
			'authors' => 'Poulose N. et al. ',
			'description' => '<p>Androgen receptor (AR) is a major driver of prostate cancer (PCa) initiation and progression. O-GlcNAc transferase (OGT), the enzyme that catalyses the covalent addition of UDP-N-acetylglucosamine (UDP-GlcNAc) to serine and threonine residues of proteins, is often up-regulated in PCa with its expression correlated with high Gleason score. In this study we have identified an AR and OGT co-regulated factor, VPRBP/DCAF1. We show that VPRBP is regulated by the AR at the transcript level, and by OGT at the protein level. In human tissue samples, VPRBP protein expression correlated with AR amplification, OGT overexpression and poor prognosis. VPRBP knockdown in prostate cancer cells led to a significant decrease in cell proliferation, p53 stabilization, nucleolar fragmentation and increased p53 recruitment to the chromatin. In conclusion, we have shown that VPRBP/DCAF1 promotes prostate cancer cell proliferation by restraining p53 activation under the influence of the AR and OGT.</p>',
			'date' => '2021-02-21',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/2021.02.28.433236v1',
			'doi' => '',
			'modified' => '2021-07-07 11:59:15',
			'created' => '2021-07-07 11:59:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 43 => array(
			'id' => '4124',
			'name' => 'JAZF1, A Novel p400/TIP60/NuA4 Complex Member, Regulates H2A.ZAcetylation at Regulatory Regions.',
			'authors' => 'Procida, Tara and Friedrich, Tobias and Jack, Antonia P M and Peritore,Martina and Bönisch, Clemens and Eberl, H Christian and Daus, Nadine andKletenkov, Konstantin and Nist, Andrea and Stiewe, Thorsten and Borggrefe,Tilman and Mann, Matthias and Bartk',
			'description' => '<p>Histone variants differ in amino acid sequence, expression timing and genomic localization sites from canonical histones and convey unique functions to eukaryotic cells. Their tightly controlled spatial and temporal deposition into specific chromatin regions is accomplished by dedicated chaperone and/or remodeling complexes. While quantitatively identifying the chaperone complexes of many human H2A variants by using mass spectrometry, we also found additional members of the known H2A.Z chaperone complexes p400/TIP60/NuA4 and SRCAP. We discovered JAZF1, a nuclear/nucleolar protein, as a member of a p400 sub-complex containing MBTD1 but excluding ANP32E. Depletion of JAZF1 results in transcriptome changes that affect, among other pathways, ribosome biogenesis. To identify the underlying molecular mechanism contributing to JAZF1's function in gene regulation, we performed genome-wide ChIP-seq analyses. Interestingly, depletion of JAZF1 leads to reduced H2A.Z acetylation levels at &gt; 1000 regulatory sites without affecting H2A.Z nucleosome positioning. Since JAZF1 associates with the histone acetyltransferase TIP60, whose depletion causes a correlated H2A.Z deacetylation of several JAZF1-targeted enhancer regions, we speculate that JAZF1 acts as chromatin modulator by recruiting TIP60's enzymatic activity. Altogether, this study uncovers JAZF1 as a member of a TIP60-containing p400 chaperone complex orchestrating H2A.Z acetylation at regulatory regions controlling the expression of genes, many of which are involved in ribosome biogenesis.</p>',
			'date' => '2021-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33445503',
			'doi' => '10.3390/ijms22020678',
			'modified' => '2021-12-07 10:00:44',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 44 => array(
			'id' => '4153',
			'name' => 'Epigenetic impairment and blunted transcriptional response to Mycobacteriumtuberculosis of alveolar macrophages from persons living with HIV',
			'authors' => 'Correa-Macedo, W. et al.',
			'description' => '<p>Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV and antiretroviral therapy (ART) impact on the anti-mycobacterial response of AM is not known. To investigate the impact of HIV and ART on the transcriptomic and epigenetic response of AM to Mtb, we obtained AM by bronchoalveolar lavage from 20 PLWH receiving ART, 16 control subjects who were HIV-free (HC), and 14 subjects who received ART as pre-exposure prophylaxis (PrEP) to prevent HIV infection. Following in-vitro challenge with Mtb, AM from each group displayed overlapping but distinct profiles of significantly up- and down-regulated genes in response to Mtb. Compared to HC subjects, AM isolated from PLWH and PrEP subjects presented a substantially weaker transcriptional response. Further investigation of chromatin structure revealed that AM from control subjects challenged with Mtb responded with pronounced accessibility changes in over ten thousand regions. In stark contrast, AM obtained from PLWH and PrEP subjects displayed no significant changes in their chromatin state in response to Mtb. Collectively, these results revealed a previously unknown adverse effect of ART on the epigenetic landscape and transcriptional responsiveness of AM.</p>',
			'date' => '2021-01-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.01.26.21250318',
			'doi' => '10.1101/2021.01.26.21250318',
			'modified' => '2021-12-16 10:35:21',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 45 => array(
			'id' => '4179',
			'name' => 'Histone demethylase JMJD2B/KDM4B regulates transcriptional program viadistinctive epigenetic targets and protein interactors for the maintenanceof trophoblast stem cells.',
			'authors' => 'Mak, Kylie Hin-Man et al.',
			'description' => '<p>Trophoblast stem cell (TSC) is crucial to the formation of placenta in mammals. Histone demethylase JMJD2 (also known as KDM4) family proteins have been previously shown to support self-renewal and differentiation of stem cells. However, their roles in the context of the trophoblast lineage remain unclear. Here, we find that knockdown of Jmjd2b resulted in differentiation of TSCs, suggesting an indispensable role of JMJD2B/KDM4B in maintaining the stemness. Through the integration of transcriptome and ChIP-seq profiling data, we show that JMJD2B is associated with a loss of H3K36me3 in a subset of embryonic lineage genes which are marked by H3K9me3 for stable repression. By characterizing the JMJD2B binding motifs and other transcription factor binding datasets, we discover that JMJD2B forms a protein complex with AP-2 family transcription factor TFAP2C and histone demethylase LSD1. The JMJD2B-TFAP2C-LSD1 complex predominantly occupies active gene promoters, whereas the TFAP2C-LSD1 complex is located at putative enhancers, suggesting that these proteins mediate enhancer-promoter interaction for gene regulation. We conclude that JMJD2B is vital to the TSC transcriptional program and safeguards the trophoblast cell fate via distinctive protein interactors and epigenetic targets.</p>',
			'date' => '2021-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33441614',
			'doi' => '10.1038/s41598-020-79601-7',
			'modified' => '2021-12-21 16:43:16',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 46 => array(
			'id' => '4038',
			'name' => 'Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture.',
			'authors' => 'Yusufova, Nevin and Kloetgen, Andreas and Teater, Matt and Osunsade,Adewola and Camarillo, Jeannie M and Chin, Christopher R and Doane, AshleyS and Venters, Bryan J and Portillo-Ledesma, Stephanie and Conway, Josephand Phillip, Jude M and Elemento, Oli',
			'description' => '<p>Linker histone H1 proteins bind to nucleosomes and facilitate chromatin compaction, although their biological functions are poorly understood. Mutations in the genes that encode H1 isoforms B-E (H1B, H1C, H1D and H1E; also known as H1-5, H1-2, H1-3 and H1-4, respectively) are highly recurrent in B&nbsp;cell lymphomas, but the pathogenic relevance of these mutations to cancer and the mechanisms that are involved are unknown. Here we show that lymphoma-associated H1 alleles are genetic driver mutations in lymphomas. Disruption of H1 function results in a profound architectural remodelling of the genome, which is characterized by large-scale yet focal shifts of chromatin from a compacted to a relaxed state. This decompaction drives distinct changes in epigenetic states, primarily owing to a gain of histone H3 dimethylation at lysine 36 (H3K36me2) and/or loss of repressive H3 trimethylation at lysine 27 (H3K27me3). These changes unlock the expression of stem cell genes that are normally silenced during early development. In mice, loss of H1c and H1e (also known as H1f2 and H1f4, respectively) conferred germinal centre B&nbsp;cells with enhanced fitness and self-renewal properties, ultimately leading to aggressive lymphomas with an increased repopulating potential. Collectively, our data indicate that H1 proteins are normally required to sequester early developmental genes into architecturally inaccessible genomic compartments. We also establish H1 as a bona fide tumour suppressor and show that mutations in H1 drive malignant transformation primarily through three-dimensional genome reorganization, which leads to epigenetic reprogramming and derepression of developmentally silenced genes.</p>',
			'date' => '2020-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33299181',
			'doi' => '10.1038/s41586-020-3017-y',
			'modified' => '2021-02-18 17:15:52',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 47 => array(
			'id' => '4056',
			'name' => 'Multi-omic comparison of Alzheimer's variants in human ESC-derivedmicroglia reveals convergence at APOE.',
			'authors' => 'Liu, Tongfei and Zhu, Bing and Liu, Yan and Zhang, Xiaoming and Yin, Junand Li, Xiaoguang and Jiang, LuLin and Hodges, Andrew P and Rosenthal, SaraBrin and Zhou, Lisa and Yancey, Joel and McQuade, Amanda and Blurton-Jones,Mathew and Tanzi, Rudolph E an',
			'description' => '<p>Variations in many genes linked to sporadic Alzheimer's disease (AD) show abundant expression in microglia, but relationships among these genes remain largely elusive. Here, we establish isogenic human ESC-derived microglia-like cell lines (hMGLs) harboring AD variants in CD33, INPP5D, SORL1, and TREM2 loci and curate a comprehensive atlas comprising ATAC-seq, ChIP-seq, RNA-seq, and proteomics datasets. AD-like expression signatures are observed in AD mutant SORL1 and TREM2 hMGLs, while integrative multi-omic analysis of combined epigenetic and expression datasets indicates up-regulation of APOE as a convergent pathogenic node. We also observe cross-regulatory relationships between SORL1 and TREM2, in which SORL1R744X hMGLs induce TREM2 expression to enhance APOE expression. AD-associated SORL1 and TREM2 mutations also impaired hMGL A&beta; uptake in an APOE-dependent manner in vitro and attenuated A&beta; uptake/clearance in mouse AD brain xenotransplants. Using this modeling and analysis platform for human microglia, we provide new insight into epistatic interactions in AD genes and demonstrate convergence of microglial AD genes at the APOE locus.</p>',
			'date' => '2020-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32941599',
			'doi' => '10.1084/jem.20200474',
			'modified' => '2021-02-19 17:18:23',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 48 => array(
			'id' => '4060',
			'name' => 'A genetic variant controls interferon-β gene expression in human myeloidcells by preventing C/EBP-β binding on a conserved enhancer.',
			'authors' => 'Assouvie, Anaïs and Rotival, Maxime and Hamroune, Juliette and Busso,Didier and Romeo, Paul-Henri and Quintana-Murci, Lluis and Rousselet,Germain',
			'description' => '<p>Interferon &beta; (IFN-&beta;) is a cytokine that induces a global antiviral proteome, and regulates the adaptive immune response to infections and tumors. Its effects strongly depend on its level and timing of expression. Therefore, the transcription of its coding gene IFNB1 is strictly controlled. We have previously shown that in mice, the TRIM33 protein restrains Ifnb1 transcription in activated myeloid cells through an upstream inhibitory sequence called ICE. Here, we show that the deregulation of Ifnb1 expression observed in murine Trim33-/- macrophages correlates with abnormal looping of both ICE and the Ifnb1 gene to a 100 kb downstream region overlapping the Ptplad2/Hacd4 gene. This region is a predicted myeloid super-enhancer in which we could characterize 3 myeloid-specific active enhancers, one of which (E5) increases the response of the Ifnb1 promoter to activation. In humans, the orthologous region contains several single nucleotide polymorphisms (SNPs) known to be associated with decreased expression of IFNB1 in activated monocytes, and loops to the IFNB1 gene. The strongest association is found for the rs12553564 SNP, located in the E5 orthologous region. The minor allele of rs12553564 disrupts a conserved C/EBP-&beta; binding motif, prevents binding of C/EBP-&beta;, and abolishes the activation-induced enhancer activity of E5. Altogether, these results establish a link between a genetic variant preventing binding of a transcription factor and a higher order phenotype, and suggest that the frequent minor allele (around 30\% worldwide) might be associated with phenotypes regulated by IFN-&beta; expression in myeloid cells.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33147208',
			'doi' => '10.1371/journal.pgen.1009090',
			'modified' => '2021-02-19 17:29:34',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 49 => 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) 50 => array(
			'id' => '4210',
			'name' => 'Trans- and cis-acting effects of Firre on epigenetic features of theinactive X chromosome.',
			'authors' => 'Fang, He and Bonora, Giancarlo and Lewandowski, Jordan P and Thakur,Jitendra and Filippova, Galina N and Henikoff, Steven and Shendure, Jay andDuan, Zhijun and Rinn, John L and Deng, Xinxian and Noble, William S andDisteche, Christine M',
			'description' => '<p>Firre encodes a lncRNA involved in nuclear organization. Here, we show that Firre RNA expressed from the active X chromosome maintains histone H3K27me3 enrichment on the inactive X chromosome (Xi) in somatic cells. This trans-acting effect involves SUZ12, reflecting interactions between Firre RNA and components of the Polycomb repressive complexes. Without Firre RNA, H3K27me3 decreases on the Xi and the&nbsp;Xi-perinucleolar location is disrupted, possibly due to decreased CTCF binding on the Xi. We also observe widespread gene dysregulation, but not on the Xi. These effects are measurably rescued by ectopic expression of mouse or human Firre/FIRRE transgenes, supporting conserved trans-acting roles. We also find that the compact 3D structure of the Xi partly depends on the Firre locus and its RNA. In common lymphoid progenitors and T-cells Firre exerts a cis-acting effect on maintenance of H3K27me3 in a 26&thinsp;Mb region around the locus, demonstrating cell type-specific trans- and cis-acting roles of this lncRNA.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33247132',
			'doi' => '10.1038/s41467-020-19879-3',
			'modified' => '2022-01-13 15:03:45',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 51 => array(
			'id' => '4048',
			'name' => 'The histone H2B ubiquitin ligase RNF40 is required for HER2-drivenmammary tumorigenesis.',
			'authors' => 'Wegwitz, Florian and Prokakis, Evangelos and Pejkovska, Anastasija andKosinsky, Robyn Laura and Glatzel, Markus and Pantel, Klaus and Wikman,Harriet and Johnsen, Steven A',
			'description' => '<p>The HER2-positive breast cancer subtype (HER2-BC) displays a particularly aggressive behavior. Anti-HER2 therapies have significantly improved the survival of patients with HER2-BC. However, a large number of patients become refractory to current targeted therapies, necessitating the development of new treatment strategies. Epigenetic regulators are commonly misregulated in cancer and represent attractive molecular therapeutic targets. Monoubiquitination of histone 2B (H2Bub1) by the heterodimeric ubiquitin ligase complex RNF20/RNF40 has been described to have tumor suppressor functions and loss of H2Bub1 has been associated with cancer progression. In this study, we utilized human tumor samples, cell culture models, and a mammary carcinoma mouse model with tissue-specific Rnf40 deletion and identified an unexpected tumor-supportive role of RNF40 in HER2-BC. We demonstrate that RNF40-driven H2B monoubiquitination is essential for transcriptional activation of RHO/ROCK/LIMK pathway components and proper actin-cytoskeleton dynamics through a trans-histone crosstalk with histone 3 lysine 4 trimethylation (H3K4me3). Collectively, this work demonstrates a previously unknown essential role of RNF40 in HER2-BC, revealing the H2B monoubiquitination axis as a possible tumor context-dependent therapeutic target in breast cancer.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33070155',
			'doi' => '10.1038/s41419-020-03081-w',
			'modified' => '2021-02-19 14:03:18',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 52 => array(
			'id' => '4065',
			'name' => 'Polycomb Repressive Complex 2-mediated histone modification H3K27me3 isassociated with embryogenic potential in Norway spruce.',
			'authors' => 'Nakamura, Miyuki and Batista, Rita A and Köhler, Claudia and Hennig, Lars',
			'description' => '<p>Epigenetic reprogramming during germ cell formation is essential to gain pluripotency and thus embryogenic potential. The histone modification H3K27me3, which is catalysed by the Polycomb repressive complex 2 (PRC2), regulates important developmental processes in both plants and animals, and defects in PRC2 components cause pleiotropic developmental abnormalities. Nevertheless, the role of H3K27me3 in determining embryogenic potential in gymnosperms is still elusive. To address this, we generated H3K27me3 profiles of Norway spruce (Picea abies) embryonic callus and non-embryogenic callus using CUT\&amp;RUN, which is a powerful method for chromatin profiling. Here, we show that H3K27me3 mainly accumulated in genic regions in the Norway spruce genome, similarly to what is observed in other plant species. Interestingly, H3K27me3 levels in embryonic callus were much lower than those in the other examined tissues, but markedly increased upon embryo induction. These results show that H3K27me3 levels are associated with the embryogenic potential of a given tissue, and that the early phase of somatic embryogenesis is accompanied by changes in H3K27me3 levels. Thus, our study provides novel insights into the role of this epigenetic mark in spruce embryogenesis and reinforces the importance of PRC2 as a key regulator of cell fate determination across different plant species.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32894759',
			'doi' => '10.1093/jxb/eraa365',
			'modified' => '2021-02-19 17:45:29',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 53 => array(
			'id' => '4384',
			'name' => 'Age-associated cryptic transcription in mammalian stem cells is linked topermissive chromatin at cryptic promoters',
			'authors' => 'McCauley  B. S. et al.',
			'description' => '<p>Suppressing spurious cryptic transcription by a repressive intragenic chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation is critical for maintaining self-renewal capacity in mouse embryonic stem cells. In yeast and nematodes, such cryptic transcription is elevated with age, and reducing the levels of age-associated cryptic transcription extends yeast lifespan. Whether cryptic transcription is also increased during mammalian aging is unknown. We show for the first time an age-associated elevation in cryptic transcription in several stem cell populations, including murine hematopoietic stem cells (mHSCs) and neural stem cells (NSCs) and human mesenchymal stem cells (hMSCs). Using DECAP-seq, we mapped and quantified age-associated cryptic transcription in hMSCs aged in vitro. Regions with significant age-associated cryptic transcription have a unique chromatin signature: decreased H3K36me3 and increased H3K4me1, H3K4me3, and H3K27ac with age. Furthermore, genomic regions undergoing such age-dependent chromatin changes resemble known promoter sequences and are bound by the promoter-associated protein TBP even in young cells. Hence, the more permissive chromatin state at intragenic cryptic promoters likely underlies the increase of cryptic transcription in aged mammalian stem cells.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://europepmc.org/article/ppr/ppr221829',
			'doi' => '10.21203/rs.3.rs-82156/v1',
			'modified' => '2022-08-04 16:24:46',
			'created' => '2022-08-04 14:55:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 54 => array(
			'id' => '4076',
			'name' => 'RNF40 exerts stage-dependent functions in differentiating osteoblasts andis essential for bone cell crosstalk.',
			'authors' => 'Najafova, Zeynab and Liu, Peng and Wegwitz, Florian and Ahmad, Mubashir andTamon, Liezel and Kosinsky, Robyn Laura and Xie, Wanhua and Johnsen, StevenA and Tuckermann, Jan',
			'description' => '<p>The role of histone ubiquitination in directing cell lineage specification is only poorly understood. Our previous work indicated a role of the histone 2B ubiquitin ligase RNF40 in controlling osteoblast differentiation in vitro. Here, we demonstrate that RNF40 has a stage-dependent function in controlling osteoblast differentiation in vivo. RNF40 expression is essential for early stages of lineage specification, but is dispensable in mature osteoblasts. Paradoxically, while osteoblast-specific RNF40 deletion led to impaired bone formation, it also resulted in increased bone mass due to impaired bone cell crosstalk. Loss of RNF40 resulted in decreased osteoclast number and function through modulation of&nbsp;RANKL expression in OBs. Mechanistically, we demonstrate that&nbsp;Tnfsf11 (encoding RANKL)&nbsp;is an important target gene of H2B monoubiquitination. These data reveal an important role of RNF40-mediated H2B monoubiquitination in bone formation and remodeling and provide a basis for exploring this pathway for the treatment of conditions such as osteoporosis or cancer-associated osteolysis.</p>',
			'date' => '2020-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32901120',
			'doi' => '10.1038/s41418-020-00614-w',
			'modified' => '2021-02-19 18:10:55',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 55 => 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) 56 => array(
			'id' => '4010',
			'name' => 'Combined treatment with CBP and BET inhibitors reverses inadvertentactivation of detrimental super enhancer programs in DIPG cells.',
			'authors' => 'Wiese, M and Hamdan, FH and Kubiak, K and Diederichs, C and Gielen, GHand Nussbaumer, G and Carcaboso, AM and Hulleman, E and Johnsen, SA andKramm, CM',
			'description' => '<p>Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation. Hyperacetylation in DIPG favors the action of the Bromodomain and Extra-Terminal (BET) protein BRD4, and leads to the reprogramming of the enhancer landscape contributing to the activation of DIPG super enhancer-driven oncogenes. The activity of the acetyltransferase CREB-binding protein (CBP) is enhanced by BRD4 and associated with acetylation of nucleosomes at super enhancers (SE). In addition, CBP contributes to transcriptional activation through its function as a scaffold and protein bridge. Monotherapy with either a CBP (ICG-001) or BET inhibitor (JQ1) led to the reduction of tumor-related characteristics. Interestingly, combined treatment induced strong cytotoxic effects in H3.3K27M-mutated DIPG cell lines. RNA sequencing and chromatin immunoprecipitation revealed that these effects were caused by the inactivation of DIPG SE-controlled tumor-related genes. However, single treatment with ICG-001 or JQ1, respectively, led to activation of a subgroup of detrimental super enhancers. Combinatorial treatment reversed the inadvertent activation of these super enhancers and rescued the effect of ICG-001 and JQ1 single treatment on enhancer-driven oncogenes in H3K27M-mutated DIPG, but not in H3 wild-type pedHGG cells. In conclusion, combinatorial treatment with CBP and BET inhibitors is highly efficient in H3K27M-mutant DIPG due to reversal of inadvertent activation of detrimental SE programs in comparison with monotherapy.</p>',
			'date' => '2020-08-21',
			'pmid' => 'http://www.pubmed.gov/32826850',
			'doi' => '10.1038/s41419-020-02800-7',
			'modified' => '2020-12-18 13:25:09',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 57 => array(
			'id' => '4011',
			'name' => 'Exploring the virulence gene interactome with CRISPR/dCas9 in the humanmalaria parasite.',
			'authors' => 'Bryant, JM and Baumgarten, S and Dingli, F and Loew, D and Sinha, A andClaës, A and Preiser, PR and Dedon, PC and Scherf, A',
			'description' => '<p>Mutually exclusive expression of the var multigene family is key to immune evasion and pathogenesis in Plasmodium falciparum, but few factors have been shown to play a direct role. We adapted a CRISPR-based proteomics approach to identify novel factors associated with var genes in their natural chromatin context. Catalytically inactive Cas9 ("dCas9") was targeted to var gene regulatory elements, immunoprecipitated, and analyzed with mass spectrometry. Known and novel factors were enriched including structural proteins, DNA helicases, and chromatin remodelers. Functional characterization of PfISWI, an evolutionarily divergent putative chromatin remodeler enriched at the var gene promoter, revealed a role in transcriptional activation. Proteomics of PfISWI identified several proteins enriched at the var gene promoter such as acetyl-CoA synthetase, a putative MORC protein, and an ApiAP2 transcription factor. These findings validate the CRISPR/dCas9 proteomics method and define a new var gene-associated chromatin complex. This study establishes a tool for targeted chromatin purification of unaltered genomic loci and identifies novel chromatin-associated factors potentially involved in transcriptional control and/or chromatin organization of virulence genes in the human malaria parasite.</p>',
			'date' => '2020-08-02',
			'pmid' => 'http://www.pubmed.gov/32816370',
			'doi' => 'https://dx.doi.org/10.15252%2Fmsb.20209569',
			'modified' => '2020-12-18 13:26:33',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 58 => array(
			'id' => '4024',
			'name' => 'Tissue-Specific In Vivo Biotin Chromatin Immunoprecipitation withSequencing in Zebrafish and Chicken',
			'authors' => 'Lukoseviciute, Martyna and Ling, Irving T.C. and Senanayake, Upeka andCandido-Ferreira, Ivan and Taylor, Gunes and Williams, Ruth M. andSauka-Spengler, Tatjana',
			'description' => '<p>Chromatin immunoprecipitation with sequencing (ChIP-seq) has been instrumental in understanding transcription factor (TF) binding during gene regulation. ChIP-seq requires specific antibodies against desired TFs, which are not available for numerous species. Here, we describe a tissue-specific biotin ChIP-seq protocol for zebrafish and chicken embryos which utilizes AVI tagging of TFs, permitting their biotinylation by a co-expressed nuclear biotin ligase. Subsequently, biotinylated factors can be precipitated with streptavidin beads, enabling the user to construct TF genome-wide binding landscapes like conventional ChIP-seq methods.</p>',
			'date' => '2020-07-31',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S2666166720300538',
			'doi' => '10.1016/j.xpro.2020.100066',
			'modified' => '2020-12-16 17:50:09',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 59 => array(
			'id' => '4026',
			'name' => 'The gut microbiome switches mutant p53 from tumour-suppressive tooncogenic.',
			'authors' => 'Kadosh, E and Snir-Alkalay, I and Venkatachalam, A and May, S and Lasry, Aand Elyada, E and Zinger, A and Shaham, M and Vaalani, G and Mernberger, Mand Stiewe, T and Pikarsky, E and Oren, M and Ben-Neriah, Y',
			'description' => '<p>Somatic mutations in p53, which inactivate the tumour-suppressor function of p53 and often confer oncogenic gain-of-function properties, are very common in cancer. Here we studied the effects of hotspot gain-of-function mutations in Trp53 (the gene that encodes p53 in mice) in mouse models of WNT-driven intestinal cancer caused by Csnk1a1 deletion or Apc mutation. Cancer in these models is known to be facilitated by loss of p53. We found that mutant versions of p53 had contrasting effects in different segments of the gut: in the distal gut, mutant p53 had the expected oncogenic effect; however, in the proximal gut and in tumour organoids it had a pronounced tumour-suppressive effect. In the tumour-suppressive mode, mutant p53 eliminated dysplasia and tumorigenesis in Csnk1a1-deficient and Apc mice, and promoted normal growth and differentiation of tumour organoids derived from these mice. In these settings, mutant p53 was more effective than wild-type p53 at inhibiting tumour formation. Mechanistically, the tumour-suppressive effects of mutant p53 were driven by disruption of the WNT pathway, through preventing the binding of TCF4 to chromatin. Notably, this tumour-suppressive effect was completely abolished by the gut microbiome. Moreover, a single metabolite derived from the gut microbiota-gallic acid-could reproduce the entire effect of the microbiome. Supplementing gut-sterilized p53-mutant mice and p53-mutant organoids with gallic acid reinstated the TCF4-chromatin interaction and the hyperactivation of WNT, thus conferring a malignant phenotype to the organoids and throughout the gut. Our study demonstrates the substantial plasticity of a cancer mutation and highlights the role of the microenvironment in determining its functional outcome.</p>',
			'date' => '2020-07-29',
			'pmid' => 'http://www.pubmed.gov/32728212',
			'doi' => '10.1038/s41586-020-2541-0',
			'modified' => '2020-12-16 17:52:28',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 60 => array(
			'id' => '3992',
			'name' => 'Egr2-guided histone H2B monoubiquitination is required for peripheral nervous system myelination.',
			'authors' => 'Wüst HM, Wegener A, Fröb F, Hartwig AC, Wegwitz F, Kari V, Schimmel M, Tamm ER, Johnsen SA, Wegner M, Sock E',
			'description' => '<p>Schwann cells are the nerve ensheathing cells of the peripheral nervous system. Absence, loss and malfunction of Schwann cells or their myelin sheaths lead to peripheral neuropathies such as Charcot-Marie-Tooth disease in humans. During Schwann cell development and myelination chromatin is dramatically modified. However, impact and functional relevance of these modifications are poorly understood. Here, we analyzed histone H2B monoubiquitination as one such chromatin modification by conditionally deleting the Rnf40 subunit of the responsible E3 ligase in mice. Rnf40-deficient Schwann cells were arrested immediately before myelination or generated abnormally thin, unstable myelin, resulting in a peripheral neuropathy characterized by hypomyelination and progressive axonal degeneration. By combining sequencing techniques with functional studies we show that H2B monoubiquitination does not influence global gene expression patterns, but instead ensures selective high expression of myelin and lipid biosynthesis genes and proper repression of immaturity genes. This requires the specific recruitment of the Rnf40-containing E3 ligase by Egr2, the central transcriptional regulator of peripheral myelination, to its target genes. Our study identifies histone ubiquitination as essential for Schwann cell myelination and unravels new disease-relevant links between chromatin modifications and transcription factors in the underlying regulatory network.</p>',
			'date' => '2020-07-16',
			'pmid' => 'http://www.pubmed.gov/32672815',
			'doi' => '10.1093/nar/gkaa606',
			'modified' => '2020-09-01 15:02:28',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 61 => array(
			'id' => '4031',
			'name' => 'Battle of the sex chromosomes: competition between X- and Y-chromosomeencoded proteins for partner interaction and chromatin occupancy drivesmulti-copy gene expression and evolution in muroid rodents.',
			'authors' => 'Moretti, C and Blanco, M and Ialy-Radio, C and Serrentino, ME and Gobé,C and Friedman, R and Battail, C and Leduc, M and Ward, MA and Vaiman, Dand Tores, F and Cocquet, J',
			'description' => '<p>Transmission distorters (TDs) are genetic elements that favor their own transmission to the detriments of others. Slx/Slxl1 (Sycp3-like-X-linked and Slx-like1) and Sly (Sycp3-like-Y-linked) are TDs which have been co-amplified on the X and Y chromosomes of Mus species. They are involved in an intragenomic conflict in which each favors its own transmission, resulting in sex ratio distortion of the progeny when Slx/Slxl1 vs. Sly copy number is unbalanced. They are specifically expressed in male postmeiotic gametes (spermatids) and have opposite effects on gene expression: Sly knockdown leads to the upregulation of hundreds of spermatid-expressed genes, while Slx/Slxl1-deficiency downregulates them. When both Slx/Slxl1 and Sly are knocked-down, sex ratio distortion and gene deregulation are corrected. Slx/Slxl1 and Sly are, therefore, in competition but the molecular mechanism remains unknown. By comparing their chromatin binding profiles and protein partners, we show that SLX/SLXL1 and SLY proteins compete for interaction with H3K4me3-reader SSTY1 (Spermiogenesis-specific-transcript-on-the-Y1) at the promoter of thousands of genes to drive their expression, and that the opposite effect they have on gene expression is mediated by different abilities to recruit SMRT/N-Cor transcriptional complex. Their target genes are predominantly spermatid-specific multicopy genes encoded by the sex chromosomes and the autosomal Speer/Takusan. Many of them have co-amplified with Slx/Slxl1/Sly but also Ssty during muroid rodent evolution. Overall, we identify Ssty as a key element of the X vs. Y intragenomic conflict, which may have influenced gene content and hybrid sterility beyond Mus lineage since Ssty amplification on the Y pre-dated that of Slx/Slxl1/Sly.</p>',
			'date' => '2020-07-13',
			'pmid' => 'http://www.pubmed.gov/32658962',
			'doi' => '10.1093/molbev/msaa175/5870835',
			'modified' => '2020-12-18 13:27:51',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 62 => array(
			'id' => '3948',
			'name' => '2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters hepatic polyunsaturated fatty acid metabolism and eicosanoid biosynthesis in female Sprague-Dawley rats.',
			'authors' => 'Doskey CM, Fader KA, Nault R, Lydic T, Matthews J, Potter D, Sharratt B, Williams K, Zacharewski T',
			'description' => '<p>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent aryl hydrocarbon receptor (AhR) agonist that elicits a broad spectrum of dose-dependent hepatic effects including lipid accumulation, inflammation, and fibrosis. To determine the role of inflammatory lipid mediators in TCDD-mediated hepatotoxicity, eicosanoid metabolism was investigated. Female Sprague-Dawley (SD) rats were orally gavaged with sesame oil vehicle or 0.01-10&nbsp;&mu;g/kg TCDD every 4&nbsp;days for 28&nbsp;days. Hepatic RNA-Seq data was integrated with untargeted metabolomics of liver, serum, and urine, revealing dose-dependent changes in linoleic acid (LA) and arachidonic acid (AA) metabolism. TCDD also elicited dose-dependent differential gene expression associated with the cyclooxygenase, lipoxygenase, and cytochrome P450 epoxidation/hydroxylation pathways with corresponding changes in &omega;-6 (e.g. AA and LA) and &omega;-3 polyunsaturated fatty acids (PUFAs), as well as associated eicosanoid metabolites. Overall, TCDD increased the ratio of &omega;-6 to &omega;-3 PUFAs. Phospholipase A2 (Pla2g12a) was induced consistent with increased AA metabolism, while AA utilization by induced lipoxygenases Alox5 and Alox15 increased leukotrienes (LTs). More specifically, TCDD increased pro-inflammatory eicosanoids including leukotriene LTB, and LTB, known to recruit neutrophils to damaged tissue. Dose-response modeling suggests the cytochrome P450 hydroxylase/epoxygenase and lipoxygenase pathways are more sensitive to TCDD than the cyclooxygenase pathway. Hepatic AhR ChIP-Seq analysis found little enrichment within the regulatory regions of differentially expressed genes (DEGs) involved in eicosanoid biosynthesis, suggesting TCDD-elicited dysregulation of eicosanoid metabolism is a downstream effect of AhR activation. Overall, these results suggest alterations in eicosanoid metabolism may play a key role in TCDD-elicited hepatotoxicity associated with the progression of steatosis to steatohepatitis.</p>',
			'date' => '2020-07-01',
			'pmid' => 'http://www.pubmed.gov/32387183',
			'doi' => '10.1016/j.taap.2020.115034',
			'modified' => '2020-08-17 10:04:38',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 63 => 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) 64 => array(
			'id' => '3981',
			'name' => 'Vulnerability of drug-resistant EML4-ALK rearranged lung cancer to transcriptional inhibition.',
			'authors' => 'Paliouras AR, Buzzetti M, Shi L, Donaldson IJ, Magee P, Sahoo S, Leong HS, Fassan M, Carter M, Di Leva G, Krebs MG, Blackhall F, Lovly CM, Garofalo M',
			'description' => '<p>A subset of lung adenocarcinomas is driven by the EML4-ALK translocation. Even though ALK inhibitors in the clinic lead to excellent initial responses, acquired resistance to these inhibitors due to on-target mutations or parallel pathway alterations is a major clinical challenge. Exploring these mechanisms of resistance, we found that EML4-ALK cells parental or resistant to crizotinib, ceritinib or alectinib are remarkably sensitive to inhibition of CDK7/12 with THZ1 and CDK9 with alvocidib or dinaciclib. These compounds robustly induce apoptosis through transcriptional inhibition and downregulation of anti-apoptotic genes. Importantly, alvocidib reduced tumour progression in xenograft mouse models. In summary, our study takes advantage of the transcriptional addiction hypothesis to propose a new treatment strategy for a subset of patients with acquired resistance to first-, second- and third-generation ALK inhibitors.</p>',
			'date' => '2020-06-17',
			'pmid' => 'http://www.pubmed.gov/32558295',
			'doi' => 'https://doi.org/10.15252/emmm.201911099',
			'modified' => '2020-09-01 15:20:40',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 65 => array(
			'id' => '3975',
			'name' => 'Removal of H2Aub1 by ubiquitin-specific proteases 12 and 13 is required for stable Polycomb-mediated gene repression in Arabidopsis.',
			'authors' => 'Kralemann LEM, Liu S, Trejo-Arellano MS, Muñoz-Viana R, Köhler C, Hennig L',
			'description' => '<p>BACKGROUND: Stable gene repression is essential for normal growth and development. Polycomb repressive complexes 1 and 2 (PRC1&amp;2) are involved in this process by establishing monoubiquitination of histone 2A (H2Aub1) and subsequent trimethylation of lysine 27 of histone 3 (H3K27me3). Previous work proposed that H2Aub1 removal by the ubiquitin-specific proteases 12 and 13 (UBP12 and UBP13) is part of the repressive PRC1&amp;2 system, but its functional role remains elusive. RESULTS: We show that UBP12 and UBP13 work together with PRC1, PRC2, and EMF1 to repress genes involved in stimulus response. We find that PRC1-mediated H2Aub1 is associated with gene responsiveness, and its repressive function requires PRC2 recruitment. We further show that the requirement of PRC1 for PRC2 recruitment depends on the initial expression status of genes. Lastly, we demonstrate that removal of H2Aub1 by UBP12/13 prevents loss of H3K27me3, consistent with our finding that the H3K27me3 demethylase REF6 is positively associated with H2Aub1. CONCLUSIONS: Our data allow us to propose a model in which deposition of H2Aub1 permits genes to switch between repression and activation by H3K27me3 deposition and removal. Removal of H2Aub1 by UBP12/13 is required to achieve stable PRC2-mediated repression.</p>',
			'date' => '2020-06-16',
			'pmid' => 'http://www.pubmed.gov/32546254',
			'doi' => '10.1186/s13059-020-02062-8',
			'modified' => '2020-08-12 09:23:32',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 66 => array(
			'id' => '3969',
			'name' => 'Delineating the early transcriptional specification of the mammalian trachea and esophagus.',
			'authors' => 'Kuwahara A, Lewis AE, Coombes C, Leung FS, Percharde M, Bush JO',
			'description' => '<p>The genome-scale transcriptional programs that specify the mammalian trachea and esophagus are unknown. Though NKX2-1 and SOX2 are hypothesized to be co-repressive master regulators of tracheoesophageal fates, this is untested at a whole transcriptomic scale and their downstream networks remain unidentified. By combining single-cell RNA-sequencing with bulk RNA-sequencing of mutants and NKX2-1 ChIP-sequencing in mouse embryos, we delineate the NKX2-1 transcriptional program in tracheoesophageal specification, and discover that the majority of the tracheal and esophageal transcriptome is NKX2-1 independent. To decouple the NKX2-1 transcriptional program from regulation by SOX2, we interrogate the expression of newly-identified tracheal and esophageal markers in / compound mutants. Finally, we discover that NKX2-1 binds directly to and and regulates their expression to control mesenchymal specification to cartilage and smooth muscle, coupling epithelial identity with mesenchymal specification. These findings create a new framework for understanding early tracheoesophageal fate specification at the genome-wide level.</p>',
			'date' => '2020-06-09',
			'pmid' => 'http://www.pubmed.gov/32515350',
			'doi' => '10.7554/eLife.55526',
			'modified' => '2020-08-12 09:32:02',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 67 => array(
			'id' => '3950',
			'name' => 'Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response.',
			'authors' => 'Béguelin W, Teater M, Meydan C, Hoehn KB, Phillip JM, Soshnev AA, Venturutti L, Rivas MA, Calvo-Fernández MT, Gutierrez J, Camarillo JM, Takata K, Tarte K, Kelleher NL, Steidl C, Mason CE, Elemento O, Allis CD, Kleinstein SH, Melnick AM',
			'description' => '<p>Follicular lymphomas (FLs) are slow-growing, indolent tumors containing extensive follicular dendritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations. Paradoxically, FLs originate from highly proliferative germinal center (GC) B cells with proliferation strictly dependent on interactions with T follicular helper cells. Herein, we show that EZH2 mutations initiate FL by attenuating GC B cell requirement for T&nbsp;cell help and driving slow expansion of GC centrocytes that become enmeshed with and dependent on FDCs. By impairing T&nbsp;cell help, mutant EZH2 prevents induction of proliferative MYC programs. Thus, EZH2 mutation fosters malignant transformation by epigenetically reprograming B cells to form an aberrant immunological niche that reflects characteristic features of human FLs, explaining how indolent tumors arise from GC B cells.</p>',
			'date' => '2020-05-11',
			'pmid' => 'http://www.pubmed.gov/32396861',
			'doi' => '10.1016/j.ccell.2020.04.004',
			'modified' => '2020-08-17 09:56:58',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 68 => array(
			'id' => '4206',
			'name' => 'H2A.Z is dispensable for both basal and activated transcription inpost-mitotic mouse muscles.',
			'authors' => 'Belotti E. et al.',
			'description' => '<p>While the histone variant H2A.Z is known to be required for mitosis, it is also enriched in nucleosomes surrounding the transcription start site of active promoters, implicating H2A.Z in transcription. However, evidence obtained so far mainly rely on correlational data generated in actively dividing cells. We have exploited a paradigm in which transcription is uncoupled from the cell cycle by developing an in vivo system to inactivate H2A.Z in terminally differentiated post-mitotic muscle cells. ChIP-seq, RNA-seq and ATAC-seq experiments performed on H2A.Z KO post-mitotic muscle cells show that this histone variant is neither required to maintain nor to activate transcription. Altogether, this study provides in vivo evidence that in the absence of mitosis H2A.Z is dispensable for transcription and that the enrichment of H2A.Z on active promoters is a marker but not an active driver of transcription.</p>',
			'date' => '2020-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32266374',
			'doi' => '10.1093/nar/gkaa157',
			'modified' => '2022-01-13 13:46:38',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 69 => array(
			'id' => '3922',
			'name' => 'Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes.',
			'authors' => 'Crespo M, Damont A, Blanco M, Lastrucci E, Kennani SE, Ialy-Radio C, Khattabi LE, Terrier S, Louwagie M, Kieffer-Jaquinod S, Hesse AM, Bruley C, Chantalat S, Govin J, Fenaille F, Battail C, Cocquet J, Pflieger D',
			'description' => '<p>Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and crotonylation on histones H3 and H4 during mouse spermatogenesis. Lysine crotonylation appeared to be of significant abundance compared to acetylation, particularly on Lys27 of histone H3 (H3K27cr) that accumulates in sperm in a cleaved form of H3. We identified the genomic localization of H3K27cr and studied its effects on transcription compared to the classical active mark H3K27ac at promoters and distal enhancers. The presence of both marks was strongly associated with highest gene expression. Assessment of their co-localization with transcription regulators (SLY, SOX30) and chromatin-binding proteins (BRD4, BRDT, BORIS and CTCF) indicated systematic highest binding when both active marks were present and different selective binding when present alone at chromatin. H3K27cr and H3K27ac finally mark the building of some sperm super-enhancers. This integrated analysis of omics data provides an unprecedented level of understanding of gene expression regulation by H3K27cr in comparison to H3K27ac, and reveals both synergistic and specific actions of each histone modification.</p>',
			'date' => '2020-03-17',
			'pmid' => 'http://www.pubmed.gov/32182340',
			'doi' => '10.1093/nar/gkaa163',
			'modified' => '2020-08-17 10:56:19',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 70 => array(
			'id' => '3917',
			'name' => 'Anti-adipogenic signals at the onset of obesity-related inflammation in white adipose tissue.',
			'authors' => 'Caputo T, Tran VDT, Bararpour N, Winkler C, Aguileta G, Trang KB, Giordano Attianese GMP, Wilson A, Thomas A, Pagni M, Guex N, Desvergne B, Gilardi F',
			'description' => '<p>Chronic inflammation that affects primarily metabolic organs, such as white adipose tissue (WAT), is considered as a major cause of human obesity-associated co-morbidities. However, the molecular mechanisms initiating this inflammation in WAT are poorly understood. By combining transcriptomics, ChIP-seq and modeling approaches, we studied the global early and late responses to a high-fat diet (HFD) in visceral (vWAT) and subcutaneous (scWAT) AT, the first being more prone to obesity-induced inflammation. HFD rapidly triggers proliferation of adipocyte precursors within vWAT. However, concomitant antiadipogenic signals limit vWAT hyperplastic expansion by interfering with the differentiation of proliferating adipocyte precursors. Conversely, in scWAT, residing beige adipocytes lose their oxidizing properties and allow storage of excessive fatty acids. This phase is followed by tissue hyperplastic growth and increased angiogenic signals, which further enable scWAT expansion without generating inflammation. Our data indicate that scWAT and vWAT differential ability to modulate adipocyte number and differentiation in response to obesogenic stimuli has a crucial impact on the different susceptibility to obesity-related inflammation of these adipose tissue depots.</p>',
			'date' => '2020-03-11',
			'pmid' => 'http://www.pubmed.gov/32157317',
			'doi' => '10.1007/s00018-020-03485-z',
			'modified' => '2020-08-17 11:01:57',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 71 => array(
			'id' => '3888',
			'name' => 'HDAC3 functions as a positive regulator in Notch signal transduction.',
			'authors' => 'Ferrante F, Giaimo BD, Bartkuhn M, Zimmermann T, Close V, Mertens D, Nist A, Stiewe T, Meier-Soelch J, Kracht M, Just S, Klöble P, Oswald F, Borggrefe T',
			'description' => '<p>Aberrant Notch signaling plays a pivotal role in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL). Amplitude and duration of the Notch response is controlled by ubiquitin-dependent proteasomal degradation of the Notch1 intracellular domain (NICD1), a hallmark of the leukemogenic process. Here, we show that HDAC3 controls NICD1 acetylation levels directly affecting NICD1 protein stability. Either genetic loss-of-function of HDAC3 or nanomolar concentrations of HDAC inhibitor apicidin lead to downregulation of Notch target genes accompanied by a local reduction of histone acetylation. Importantly, an HDAC3-insensitive NICD1 mutant is more stable but biologically less active. Collectively, these data show a new HDAC3- and acetylation-dependent mechanism that may be exploited to treat Notch1-dependent leukemias.</p>',
			'date' => '2020-02-28',
			'pmid' => 'http://www.pubmed.gov/32107550',
			'doi' => '10.1093/nar/gkaa088',
			'modified' => '2020-03-20 17:21:31',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 72 => array(
			'id' => '3860',
			'name' => 'Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon.',
			'authors' => 'Zambusi A, Pelin Burhan Ö, Di Giaimo R, Schmid B, Ninkovic J',
			'description' => '<p>Granulins (GRN) are secreted factors that promote neuronal survival and regulate inflammation in various pathological conditions. However, their roles in physiological conditions in the brain remain poorly understood. To address this knowledge gap, we analysed the telencephalon in Grn-deficient zebrafish and identified morphological and transcriptional changes in microglial cells, indicative of a pro-inflammatory phenotype in the absence of any insult. Unexpectedly, activated mutant microglia shared part of their transcriptional signature with aged human microglia. Furthermore, transcriptome profiles of the entire telencephali isolated from young Grn-deficient animals showed remarkable similarities with the profiles of the telencephali isolated from aged wildtype animals. Additionally, 50% of differentially regulated genes during aging were regulated in the telencephalon of young Grn-deficient animals compared to their wildtype littermates. Importantly, the telencephalon transcriptome in young Grn-deficent animals changed only mildly with aging, further suggesting premature aging of Grn-deficient brain. Indeed, Grn loss led to decreased neurogenesis and oligodendrogenesis, and to shortening of telomeres at young ages, to an extent comparable to that observed during aging. Altogether, our data demonstrate a role of Grn in regulating aging kinetics in the zebrafish telencephalon, thus providing a valuable tool for the development of new therapeutic approaches to treat age-associated pathologies.</p>',
			'date' => '2020-02-03',
			'pmid' => 'http://www.pubmed.gov/32028681',
			'doi' => '10.3390/cells9020350',
			'modified' => '2020-03-20 17:55:13',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 73 => array(
			'id' => '3872',
			'name' => 'An inferred fitness consequence map of the rice genome.',
			'authors' => 'Joly-Lopez Z, Platts AE, Gulko B, Choi JY, Groen SC, Zhong X, Siepel A, Purugganan MD',
			'description' => '<p>The extent to which sequence variation impacts plant fitness is poorly understood. High-resolution maps detailing the constraint acting on the genome, especially in regulatory sites, would be beneficial as functional annotation of noncoding sequences remains sparse. Here, we present a fitness consequence (fitCons) map for rice (Oryza sativa). We inferred fitCons scores (&rho;) for 246 inferred genome classes derived from nine functional genomic and epigenomic datasets, including chromatin accessibility, messenger RNA/small RNA transcription, DNA methylation, histone modifications and engaged RNA polymerase activity. These were integrated with genome-wide polymorphism and divergence data from 1,477 rice accessions and 11 reference genome sequences in the Oryzeae. We found &rho; to be multimodal, with ~9% of the rice genome falling into classes where more than half of the bases would probably have a fitness consequence if mutated. Around 2% of the rice genome showed evidence of weak negative selection, frequently at candidate regulatory sites, including a novel set of 1,000 potentially active enhancer elements. This fitCons map provides perspective on the evolutionary forces associated with genome diversity, aids in genome annotation and can guide crop breeding programs.</p>',
			'date' => '2020-02-02',
			'pmid' => 'http://www.pubmed.gov/32042156',
			'doi' => '10.1038/s41477-019-0589-3',
			'modified' => '2020-03-20 17:43:24',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 74 => array(
			'id' => '3850',
			'name' => 'Dual-initiation promoters with intertwined canonical and TCT/TOP transcription start sites diversify transcript processing.',
			'authors' => 'Nepal C, Hadzhiev Y, Balwierz P, Tarifeño-Saldivia E, Cardenas R, Wragg JW, Suzuki AM, Carninci P, Peers B, Lenhard B, Andersen JB, Müller F',
			'description' => '<p>Variations in transcription start site (TSS) selection reflect diversity of preinitiation complexes and can impact on post-transcriptional RNA fates. Most metazoan polymerase II-transcribed genes carry canonical initiation with pyrimidine/purine (YR) dinucleotide, while translation machinery-associated genes carry polypyrimidine initiator (5'-TOP or TCT). By addressing the developmental regulation of TSS selection in zebrafish we uncovered a class of dual-initiation promoters in thousands of genes, including snoRNA host genes. 5'-TOP/TCT initiation is intertwined with canonical initiation and used divergently in hundreds of dual-initiation promoters during maternal to zygotic transition. Dual-initiation in snoRNA host genes selectively generates host and snoRNA with often different spatio-temporal expression. Dual-initiation promoters are pervasive in human and fruit fly, reflecting evolutionary conservation. We propose that dual-initiation on shared promoters represents a composite promoter architecture, which can function both coordinately and divergently to diversify RNAs.</p>',
			'date' => '2020-01-10',
			'pmid' => 'http://www.pubmed.gov/31924754',
			'doi' => '10.1038/s41467-019-13687-0',
			'modified' => '2020-02-13 11:09:58',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 75 => 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) 76 => 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) 77 => array(
			'id' => '3845',
			'name' => 'Combinatorial action of NF-Y and TALE at embryonic enhancers defines distinct gene expression programs during zygotic genome activation in zebrafish.',
			'authors' => 'Stanney W, Ladam F, Donaldson IJ, Parsons TJ, Maehr R, Bobola N, Sagerström CG',
			'description' => '<p>Animal embryogenesis is initiated by maternal factors, but zygotic genome activation (ZGA) shifts regulatory control to the embryo during blastula stages. ZGA is thought to be mediated by maternally provided transcription factors (TFs), but few such TFs have been identified in vertebrates. Here we report that NF-Y and TALE TFs bind zebrafish genomic elements associated with developmental control genes already at ZGA. In particular, co-regulation by NF-Y and TALE is associated with broadly acting genes involved in transcriptional control, while regulation by either NF-Y or TALE defines genes in specific developmental processes, such that NF-Y controls a cilia gene expression program while TALE controls expression of hox genes. We also demonstrate that NF-Y and TALE-occupied genomic elements function as enhancers during embryogenesis. We conclude that combinatorial use of NF-Y and TALE at developmental enhancers permits the establishment of distinct gene expression programs at zebrafish ZGA.</p>',
			'date' => '2019-12-17',
			'pmid' => 'http://www.pubmed.gov/31862379',
			'doi' => '10.1016/j.ydbio.2019.12.003',
			'modified' => '2020-02-20 11:13:27',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 78 => array(
			'id' => '3819',
			'name' => 'Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites.',
			'authors' => 'Hammam E, Ananda G, Sinha A, Scheidig-Benatar C, Bohec M, Preiser PR, Dedon PC, Scherf A, Vembar SS',
			'description' => '<p>DNA cytosine modifications are key epigenetic regulators of cellular processes in mammalian cells, with their misregulation leading to varied disease states. In the human malaria parasite Plasmodium falciparum, a unicellular eukaryotic pathogen, little is known about the predominant cytosine modifications, cytosine methylation (5mC) and hydroxymethylation (5hmC). Here, we report the first identification of a hydroxymethylcytosine-like (5hmC-like) modification in P. falciparum asexual blood stages using a suite of biochemical methods. In contrast to mammalian cells, we report 5hmC-like levels in the P. falciparum genome of 0.2-0.4%, which are significantly higher than the methylated cytosine (mC) levels of 0.01-0.05%. Immunoprecipitation of hydroxymethylated DNA followed by next generation sequencing (hmeDIP-seq) revealed that 5hmC-like modifications are enriched in gene bodies with minimal dynamic changes during asexual development. Moreover, levels of the 5hmC-like base in gene bodies positively correlated to transcript levels, with more than 2000 genes stably marked with this modification throughout asexual development. Our work highlights the existence of a new predominant cytosine DNA modification pathway in P. falciparum and opens up exciting avenues for gene regulation research and the development of antimalarials.</p>',
			'date' => '2019-11-28',
			'pmid' => 'http://www.pubmed.gov/31777939',
			'doi' => '10.1093/nar/gkz1093.',
			'modified' => '2020-02-25 13:47:09',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 79 => array(
			'id' => '3820',
			'name' => 'A stress-responsive enhancer induces dynamic drug resistance in acute myeloid leukemia.',
			'authors' => 'Williams MS, Amaral FM, Simeoni F, Somervaille TC',
			'description' => '<p>The drug efflux pump ABCB1 is a key driver of chemoresistance, and high expression predicts for treatment failure in acute myeloid leukemia (AML). In this study, we identified and functionally validated the network of enhancers that controls expression of ABCB1. We show that exposure of leukemia cells to daunorubicin activated an integrated stress response-like transcriptional program to induce ABCB1 through remodeling and activation of an ATF4-bound, stress-responsive enhancer. Protracted stress primed enhancers for rapid increases in activity following re-exposure of cells to daunorubicin, providing an epigenetic memory of prior drug treatment. In primary human AML, exposure of fresh blast cells to daunorubicin activated the stress-responsive enhancer and led to dose-dependent induction of ABCB1. Dynamic induction of ABCB1 by diverse stressors, including chemotherapy, facilitated escape of leukemia cells from targeted third-generation ABCB1 inhibition, providing an explanation for the failure of ABCB1 inhibitors in clinical trials. Stress-induced up regulation of ABCB1 was mitigated by combined use of pharmacologic inhibitors U0126 and ISRIB, which inhibit stress signalling and have potential for use as adjuvants to enhance the activity of ABCB1 inhibitors.</p>',
			'date' => '2019-11-26',
			'pmid' => 'http://www.pubmed.gov/31770110',
			'doi' => '/',
			'modified' => '2020-02-25 13:46:19',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 80 => array(
			'id' => '3810',
			'name' => 'Distinct CoREST complexes act in a cell-type-specific manner.',
			'authors' => 'Mačinković I, Theofel I, Hundertmark T, Kovač K, Awe S, Lenz J, Forné I, Lamp B, Nist A, Imhof A, Stiewe T, Renkawitz-Pohl R, Rathke C, Brehm A',
			'description' => '<p>CoREST has been identified as a subunit of several protein complexes that generate transcriptionally repressive chromatin structures during development. However, a comprehensive analysis of the CoREST interactome has not been carried out. We use proteomic approaches to define the interactomes of two dCoREST isoforms, dCoREST-L and dCoREST-M, in Drosophila. We identify three distinct histone deacetylase complexes built around a common dCoREST/dRPD3 core: A dLSD1/dCoREST complex, the LINT complex and a dG9a/dCoREST complex. The latter two complexes can incorporate both dCoREST isoforms. By contrast, the dLSD1/dCoREST complex exclusively assembles with the dCoREST-L isoform. Genome-wide studies show that the three dCoREST complexes associate with chromatin predominantly at promoters. Transcriptome analyses in S2 cells and testes reveal that different cell lineages utilize distinct dCoREST complexes to maintain cell-type-specific gene expression programmes: In macrophage-like S2 cells, LINT represses germ line-related genes whereas other dCoREST complexes are largely dispensable. By contrast, in testes, the dLSD1/dCoREST complex prevents transcription of germ line-inappropriate genes and is essential for spermatogenesis and fertility, whereas depletion of other dCoREST complexes has no effect. Our study uncovers three distinct dCoREST complexes that function in a lineage-restricted fashion to repress specific sets of genes thereby maintaining cell-type-specific gene expression programmes.</p>',
			'date' => '2019-11-08',
			'pmid' => 'http://www.pubmed.gov/31701127',
			'doi' => '10.1093/nar/gkz1050',
			'modified' => '2019-12-05 11:02:22',
			'created' => '2019-12-02 15:25:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 81 => array(
			'id' => '3782',
			'name' => 'Residual apoptotic activity of a tumorigenic p53 mutant improves cancer therapy responses.',
			'authors' => 'Timofeev O, Klimovich B, Schneikert J, Wanzel M, Pavlakis E, Noll J, Mutlu S, Elmshäuser S, Nist A, Mernberger M, Lamp B, Wenig U, Brobeil A, Gattenlöhner S, Köhler K, Stiewe T',
			'description' => '<p>Engineered p53 mutant mice are valuable tools for delineating p53 functions in tumor suppression and cancer therapy. Here, we have introduced the R178E mutation into the Trp53 gene of mice to specifically ablate the cooperative nature of p53 DNA binding. Trp53 mice show no detectable target gene regulation and, at first sight, are largely indistinguishable from Trp53 mice. Surprisingly, stabilization of p53 in Mdm2 mice nevertheless triggers extensive apoptosis, indicative of residual wild-type activities. Although this apoptotic activity suffices to trigger lethality of Trp53 ;Mdm2 embryos, it proves insufficient for suppression of spontaneous and oncogene-driven tumorigenesis. Trp53 mice develop tumors indistinguishably from Trp53 mice and tumors retain and even stabilize the p53 protein, further attesting to the lack of significant tumor suppressor activity. However, Trp53 tumors exhibit remarkably better chemotherapy responses than Trp53 ones, resulting in enhanced eradication of p53-mutated tumor cells. Together, this provides genetic proof-of-principle evidence that a p53 mutant can be highly tumorigenic and yet retain apoptotic activity which provides a survival benefit in the context of cancer therapy.</p>',
			'date' => '2019-09-04',
			'pmid' => 'http://www.pubmed.gov/31483066',
			'doi' => '10.15252/embj.2019102096',
			'modified' => '2019-10-02 16:50:40',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 82 => array(
			'id' => '3759',
			'name' => 'EOMES interacts with RUNX3 and BRG1 to promote innate memory cell formation through epigenetic reprogramming.',
			'authors' => 'Istaces N, Splittgerber M, Lima Silva V, Nguyen M, Thomas S, Le A, Achouri Y, Calonne E, Defrance M, Fuks F, Goriely S, Azouz A',
			'description' => '<p>Memory CD8 T cells have the ability to provide lifelong immunity against pathogens. Although memory features generally arise after challenge with a foreign antigen, na&iuml;ve CD8 single positive (SP) thymocytes may acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associated with the induction of the T-box transcription factor Eomesodermin (EOMES). However, the underlying molecular mechanisms remain ill-defined. Using epigenomic profiling, we show that these innate memory CD8SP cells acquire only a portion of the active enhancer repertoire of conventional memory cells. This reprograming is secondary to EOMES recruitment, mostly to RUNX3-bound enhancers. Furthermore, EOMES is found within chromatin-associated complexes containing BRG1 and promotes the recruitment of this chromatin remodelling factor. Also, the in vivo acquisition of EOMES-dependent program is BRG1-dependent. In conclusion, our results support a strong epigenetic basis for the EOMES-driven establishment of CD8 T cell innate memory program.</p>',
			'date' => '2019-07-24',
			'pmid' => 'http://www.pubmed.gov/31341159',
			'doi' => '10.1038/s41467-019-11233-6',
			'modified' => '2019-10-03 10:06:15',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 83 => 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) 84 => array(
			'id' => '3743',
			'name' => 'ARID1A facilitates KRAS signaling-regulated enhancer activity in an AP1-dependent manner in colorectal cancer cells.',
			'authors' => 'Sen M, Wang X, Hamdan FH, Rapp J, Eggert J, Kosinsky RL, Wegwitz F, Kutschat AP, Younesi FS, Gaedcke J, Grade M, Hessmann E, Papantonis A, Strӧbel P, Johnsen SA',
			'description' => '<p>BACKGROUND: ARID1A (AT-rich interactive domain-containing protein 1A) is a subunit of the BAF chromatin remodeling complex and plays roles in transcriptional regulation and DNA damage response. Mutations in ARID1A that lead to inactivation or&nbsp;loss of expression are frequent and widespread across many cancer types including colorectal cancer (CRC). A tumor suppressor role of ARID1A has been established in a number of tumor types including CRC where the genetic inactivation of Arid1a alone led to the formation of invasive colorectal adenocarcinomas in mice. Mechanistically, ARID1A has been described to largely function through the regulation of enhancer activity. METHODS: To mimic ARID1A-deficient colorectal cancer, we used CRISPR/Cas9-mediated gene editing to inactivate the ARID1A gene in established colorectal cancer cell lines. We integrated gene expression analyses with genome-wide ARID1A occupancy and epigenomic mapping data to decipher ARID1A-dependent transcriptional regulatory mechanisms. RESULTS: Interestingly, we found that CRC cell lines harboring KRAS mutations are critically dependent on ARID1A function. In the absence of ARID1A, proliferation of these cell lines is severely impaired, suggesting an essential role for ARID1A in this context. Mechanistically, we showed that ARID1A acts as a co-factor at enhancers occupied by AP1 transcription factors acting downstream of the MEK/ERK pathway. Consistently, loss of ARID1A led to a disruption of KRAS/AP1-dependent enhancer activity, accompanied by a downregulation of expression of the associated target genes. CONCLUSIONS: We identify a previously unknown context-dependent tumor-supporting function of ARID1A in CRC downstream of KRAS signaling. Upon the loss of ARID1A in KRAS-mutated cells, enhancers that are co-occupied by ARID1A and the AP1 transcription factors become inactive, thereby leading to decreased target gene expression. Thus, targeting of the BAF complex in KRAS-mutated CRC may offer a unique, previously unknown, context-dependent therapeutic option in CRC.</p>',
			'date' => '2019-06-19',
			'pmid' => 'http://www.pubmed.gov/31217031',
			'doi' => '10.1186/s13148-019-0690-5',
			'modified' => '2019-08-06 16:37:28',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 85 => array(
			'id' => '3631',
			'name' => 'Guidelines for optimized gene knockout using CRISPR/Cas9',
			'authors' => 'Campenhout CV et al.',
			'description' => '<p>CRISPR/Cas9 technology has evolved as the most powerful approach to generate genetic models both for fundamental and preclinical research. Despite its apparent simplicity, the outcome of a genome-editing experiment can be substantially impacted by technical parameters and biological considerations. Here, we present guidelines and tools to optimize CRISPR/Cas9 genome-targeting efficiency and specificity. The nature of the target locus, the design of the single guide RNA and the choice of the delivery method should all be carefully considered prior to a genome-editing experiment. Different methods can also be used to detect off-target cleavages and decrease the risk of unwanted mutations. Together, these optimized tools and proper controls are essential to the assessment of CRISPR/Cas9 genome-editing experiments.</p>',
			'date' => '2019-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/31039627',
			'doi' => '10.2144/btn-2018-0187',
			'modified' => '2019-05-09 15:37:50',
			'created' => '2019-05-09 15:37:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 86 => array(
			'id' => '3710',
			'name' => 'BRCA1 mutations attenuate super-enhancer function and chromatin looping in haploinsufficient human breast epithelial cells.',
			'authors' => 'Zhang X, Wang Y, Chiang HC, Hsieh YP, Lu C, Park BH, Jatoi I, Jin VX, Hu Y, Li R',
			'description' => '<p>BACKGROUND: BRCA1-associated breast cancer originates from luminal progenitor cells. BRCA1 functions in multiple biological processes, including double-strand break repair, replication stress suppression, transcriptional regulation, and chromatin reorganization. While non-malignant cells carrying cancer-predisposing BRCA1 mutations exhibit increased genomic instability, it remains unclear whether BRCA1 haploinsufficiency affects transcription and chromatin dynamics in breast epithelial cells. METHODS: H3K27ac-associated super-enhancers were compared in primary breast epithelial cells from BRCA1 mutation carriers (BRCA1) and non-carriers (BRCA1). Non-tumorigenic MCF10A breast epithelial cells with engineered BRCA1 haploinsufficiency were used to confirm the H3K27ac changes. The impact of BRCA1 mutations on enhancer function and enhancer-promoter looping was assessed in MCF10A cells. RESULTS: Here, we show that primary mammary epithelial cells from women with BRCA1 mutations display significant loss of H3K27ac-associated super-enhancers. These BRCA1-dependent super-enhancers are enriched with binding motifs for the GATA family. Non-tumorigenic BRCA1 MCF10A cells recapitulate the H3K27ac loss. Attenuated histone mark and enhancer activity in these BRCA1 MCF10A cells can be partially restored with wild-type BRCA1. Furthermore, chromatin conformation analysis demonstrates impaired enhancer-promoter looping in BRCA1 MCF10A cells. CONCLUSIONS: H3K27ac-associated super-enhancer loss is a previously unappreciated functional deficiency in ostensibly normal BRCA1 mutation-carrying breast epithelium. Our findings offer new mechanistic insights into BRCA1 mutation-associated transcriptional and epigenetic abnormality in breast epithelial cells and tissue/cell lineage-specific tumorigenesis.</p>',
			'date' => '2019-04-17',
			'pmid' => 'http://www.pubmed.gov/30995943',
			'doi' => '10.1186/s13058-019-1132-1',
			'modified' => '2019-07-05 14:32:42',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 87 => array(
			'id' => '3613',
			'name' => 'Point mutations in the PDX1 transactivation domain impair human β-cell development and function.',
			'authors' => 'Wang X, Sterr M, Ansarullah , Burtscher I, Böttcher A, Beckenbauer J, Siehler J, Meitinger T, Häring HU, Staiger H, Cernilogar FM, Schotta G, Irmler M, Beckers J, Wright CVE, Bakhti M, Lickert H',
			'description' => '<p>OBJECTIVE: Hundreds of missense mutations in the coding region of PDX1 exist; however, if these mutations predispose to diabetes mellitus is unknown. METHODS: In this study, we screened a large cohort of subjects with increased risk for diabetes and identified two subjects with impaired glucose tolerance carrying common, heterozygous, missense mutations in the PDX1 coding region leading to single amino acid exchanges (P33T, C18R) in its transactivation domain. We generated iPSCs from patients with heterozygous PDX1, PDX1 mutations and engineered isogenic cell lines carrying homozygous PDX1, PDX1 mutations and a heterozygous PDX1 loss-of-function mutation (PDX1). RESULTS: Using an in&nbsp;vitro &beta;-cell differentiation protocol, we demonstrated that both, heterozygous PDX1, PDX1 and homozygous PDX1, PDX1 mutations impair &beta;-cell differentiation and function. Furthermore, PDX1 and PDX1 mutations reduced differentiation efficiency of pancreatic progenitors (PPs), due to downregulation of PDX1-bound genes, including transcription factors MNX1 and PDX1 as well as insulin resistance gene CES1. Additionally, both PDX1 and PDX1 mutations in PPs reduced the expression of PDX1-bound genes including the long-noncoding RNA, MEG3 and the imprinted gene NNAT, both involved in insulin synthesis and secretion. CONCLUSIONS: Our results reveal mechanistic details of how common coding mutations in PDX1 impair human pancreatic endocrine lineage formation and &beta;-cell function and contribute to the predisposition for diabetes.</p>',
			'date' => '2019-03-20',
			'pmid' => 'http://www.pubmed.gov/30930126',
			'doi' => '10.1016/j.molmet.2019.03.006',
			'modified' => '2019-04-17 14:43:53',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 88 => 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) 89 => array(
			'id' => '3727',
			'name' => 'Transcriptome-wide dynamics of extensive m6A mRNA methylation during Plasmodium falciparum blood-stage development',
			'authors' => 'Sebastian Baumgarten, Jessica M. Bryant, Ameya Sinha, Thibaud Reyser, Peter R. Preiser, Peter C. Dedon, Artur Scherf',
			'description' => '<p>Malaria pathogenesis results from the asexual replication of Plasmodium falciparum within human red blood cells, which relies on a precisely timed cascade of gene expression over a 48-hour life cycle. Although substantial post-transcriptional regulation of this hardwired program has been observed, it remains unclear how these processes are mediated on a transcriptome-wide level. To this end, we identified mRNA modifications in the P. falciparum transcriptome and performed a comprehensive characterization of N6-methyladenosine (m6A) over the course of blood stage development. Using mass spectrometry and m6A RNA sequencing, we demonstrate that m6A is highly developmentally regulated, exceeding m6A levels known in any other eukaryote. We identify an evolutionarily conserved m6A writer complex and show that knockdown of the putative m6A methyltransferase by CRISPR interference leads to increased levels of transcripts that normally contain m6A. In accordance, we find an inverse correlation between m6A status and mRNA stability or translational efficiency. Our data reveal the crucial role of extensive m6A mRNA methylation in dynamically fine-tuning the transcriptional program of a unicellular eukaryote as well as a new &lsquo;epitranscriptomic&rsquo; layer of gene regulation in malaria parasites.</p>',
			'date' => '2019-03-09',
			'pmid' => 'https://www.nature.com/articles/s41564-019-0521-7',
			'doi' => '10.1101/572891.',
			'modified' => '2022-05-18 19:27:33',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 90 => 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) 91 => array(
			'id' => '3662',
			'name' => 'NF-κB p65 dimerization and DNA-binding is important for inflammatory gene expression.',
			'authors' => 'Riedlinger T, Liefke R, Meier-Soelch J, Jurida L, Nist A, Stiewe T, Kracht M, Schmitz ML',
			'description' => '<p>Increasing evidence shows that many transcription factors execute important biologic functions independent from their DNA-binding capacity. The NF-&kappa;B p65 (RELA) subunit is a central regulator of innate immunity. Here, we investigated the relative functional contribution of p65 DNA-binding and dimerization in p65-deficient human and murine cells reconstituted with single amino acid mutants preventing either DNA-binding (p65 E/I) or dimerization (p65 FL/DD). DNA-binding of p65 was required for RelB-dependent stabilization of the NF-&kappa;B p100 protein. The antiapoptotic function of p65 and expression of the majority of TNF-&alpha;-induced genes were dependent on p65's ability to bind DNA and to dimerize. Chromatin immunoprecipitation with massively parallel DNA sequencing experiments revealed that impaired DNA-binding and dimerization strongly diminish the chromatin association of p65. However, there were also p65-independent TNF-&alpha;-inducible genes and a subgroup of p65 binding sites still allowed some residual chromatin association of the mutants. These sites were enriched in activator protein 1 (AP-1) binding motifs and showed increased chromatin accessibility and basal transcription. This suggests a mechanism of assisted p65 chromatin association that can be in part facilitated by chromatin priming and cooperativity with other transcription factors such as AP-1.-Riedlinger, T., Liefke, R., Meier-Soelch, J., Jurida, L., Nist, A., Stiewe, T., Kracht, M., Schmitz, M. L. NF-&kappa;B p65 dimerization and DNA-binding is important for inflammatory gene expression.</p>',
			'date' => '2019-03-01',
			'pmid' => 'http://www.pubmed.gov/30526044',
			'doi' => '10.1096/fj.201801638R',
			'modified' => '2019-07-01 11:42:50',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 92 => array(
			'id' => '3646',
			'name' => 'Differential regulation of RNA polymerase III genes during liver regeneration.',
			'authors' => 'Yeganeh M, Praz V, Carmeli C, Villeneuve D, Rib L, Guex N, Herr W, Delorenzi M, Hernandez N,  ',
			'description' => '<p>Mouse liver regeneration after partial hepatectomy involves cells in the remaining tissue synchronously entering the cell division cycle. We have used this system and H3K4me3, Pol II and Pol III profiling to characterize adaptations in Pol III transcription. Our results broadly define a class of genes close to H3K4me3 and Pol II peaks, whose Pol III occupancy is high and stable, and another class, distant from Pol II peaks, whose Pol III occupancy strongly increases after partial hepatectomy. Pol III regulation in the liver thus entails both highly expressed housekeeping genes and genes whose expression can adapt to increased demand.</p>',
			'date' => '2019-02-28',
			'pmid' => 'http://www.pubmed.gov/30597109',
			'doi' => '10.1093/nar/gky1282',
			'modified' => '2019-06-07 10:14:59',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 93 => array(
			'id' => '3678',
			'name' => 'CBX7 Induces Self-Renewal of Human Normal and Malignant Hematopoietic Stem and Progenitor Cells by Canonical and Non-canonical Interactions.',
			'authors' => 'Jung J, Buisman SC, Weersing E, Dethmers-Ausema A, Zwart E, Schepers H, Dekker MR, Lazare SS, Hammerl F, Skokova Y, Kooistra SM, Klauke K, Poot RA, Bystrykh LV, de Haan G',
			'description' => '<p>In this study, we demonstrate that, among all five CBX Polycomb proteins, only CBX7 possesses the ability to control self-renewal of human hematopoietic stem and progenitor cells (HSPCs). Xenotransplantation of CBX7-overexpressing HSPCs resulted in increased multi-lineage long-term engraftment and myelopoiesis.&nbsp;Gene expression and chromatin analyses revealed perturbations in genes involved in differentiation,&nbsp;DNA and chromatin maintenance, and cell cycle control. CBX7 is upregulated in acute myeloid leukemia (AML), and its genetic or pharmacological repression in AML cells inhibited proliferation and induced differentiation. Mass spectrometry analysis revealed several non-histone protein interactions between CBX7 and the H3K9 methyltransferases SETDB1, EHMT1, and EHMT2. These CBX7-binding proteins possess a trimethylated lysine peptide motif highly similar to the canonical CBX7 target H3K27me3. Depletion of SETDB1 in AML cells phenocopied repression of CBX7. We identify CBX7 as an important regulator of self-renewal and uncover non-canonical crosstalk between distinct pathways, revealing therapeutic opportunities for leukemia.</p>',
			'date' => '2019-02-12',
			'pmid' => 'http://www.pubmed.gov/30759399',
			'doi' => '10.1016/j.celrep.2019.01.050',
			'modified' => '2019-07-01 11:20:46',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 94 => array(
			'id' => '3659',
			'name' => 'Fluorescence-Activated Cell Sorting-Based Isolation and Characterization of Neural Stem Cells from the Adult Zebrafish Telencephalon.',
			'authors' => 'Di Giaimo R, Aschenbroich S, Ninkovic J',
			'description' => '<p>Adult mammalian brain, including humans, has rather limited addition of new neurons and poor regenerative capacity. In contrast, neural stem cells (NSC) with glial identity and neurogenesis are highly abundant throughout the adult zebrafish brain. Importantly, the activation of NSC and production of new neurons in response to injuries lead to the brain regeneration in zebrafish brain. Therefore, understanding of the molecular pathways regulating NSC behavior in response to injury is crucial in order to set the basis for experimental modification of these pathways in glial cells after injury in the mammalian brain and to elicit neuronal regeneration. Here, we describe the procedure that we successfully used to prospectively isolate NSCs from adult zebrafish telencephalon, extract RNA, and prepare cDNA libraries for next generation sequencing (NGS) and full transcriptome analysis as the first step toward understanding regulatory mechanisms leading to restorative neurogenesis in zebrafish. Moreover, we describe an alternative approach to analyze antigenic properties of NSC in the adult zebrafish brain using intracellular fluorescence activated cell sorting (FACS). We employ this method to analyze the number of proliferating NSCs positive for proliferating cell nuclear antigen (PCNA) in the prospectively isolated population of stem cells.</p>',
			'date' => '2019-01-09',
			'pmid' => 'http://www.pubmed.gov/30617972',
			'doi' => '10.1007/978-1-4939-9068-9_4,',
			'modified' => '2019-06-07 08:57:58',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 95 => array(
			'id' => '3651',
			'name' => 'DeltaNp63-dependent super enhancers define molecular identity in pancreatic cancer by an interconnected transcription factor network.',
			'authors' => 'Hamdan FH, Johnsen SA',
			'description' => '<p>Molecular subtyping of cancer offers tremendous promise for the optimization of a precision oncology approach to anticancer therapy. Recent advances in pancreatic cancer research uncovered various molecular subtypes with tumors expressing a squamous/basal-like gene expression signature displaying a worse prognosis. Through unbiased epigenome mapping, we identified deltaNp63 as a major driver of a gene signature in pancreatic cancer cell lines, which we report to faithfully represent the highly aggressive pancreatic squamous subtype observed in vivo, and display the specific epigenetic marking of genes associated with decreased survival. Importantly, depletion of deltaNp63 in these systems significantly decreased cell proliferation and gene expression patterns associated with a squamous subtype and transcriptionally mimicked a subtype switch. Using genomic localization data of deltaNp63 in pancreatic cancer cell lines coupled with epigenome mapping data from patient-derived xenografts, we uncovered that deltaNp63 mainly exerts its effects by activating subtype-specific super enhancers. Furthermore, we identified a group of 45 subtype-specific super enhancers that are associated with poorer prognosis and are highly dependent on deltaNp63. Genes associated with these enhancers included a network of transcription factors, including HIF1A, BHLHE40, and RXRA, which form a highly intertwined transcriptional regulatory network with deltaNp63 to further activate downstream genes associated with poor survival.</p>',
			'date' => '2018-12-26',
			'pmid' => 'http://www.pubmed.gov/30541891',
			'doi' => '10.1073/pnas.1812915116',
			'modified' => '2019-06-07 09:29:25',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 96 => array(
			'id' => '3610',
			'name' => 'The Aryl Hydrocarbon Receptor Pathway Defines the Time Frame for Restorative Neurogenesis.',
			'authors' => 'Di Giaimo R, Durovic T, Barquin P, Kociaj A, Lepko T, Aschenbroich S, Breunig CT, Irmler M, Cernilogar FM, Schotta G, Barbosa JS, Trümbach D, Baumgart EV, Neuner AM, Beckers J, Wurst W, Stricker SH, Ninkovic J',
			'description' => '<p>Zebrafish have a high capacity to replace lost neurons after brain injury. New neurons involved in repair are generated by a specific set of glial cells, known as ependymoglial cells. We analyze changes in the transcriptome of ependymoglial cells and their progeny after injury to infer the molecular pathways governing restorative neurogenesis. We identify the aryl hydrocarbon receptor (AhR) as a regulator of ependymoglia differentiation toward post-mitotic neurons. In&nbsp;vivo imaging shows that high AhR signaling promotes the direct conversion of a specific subset of ependymoglia into post-mitotic neurons, while low AhR signaling promotes ependymoglial proliferation. Interestingly, we observe the inactivation of AhR signaling shortly after injury followed by a return to the basal levels 7&nbsp;days post injury. Interference with timely AhR regulation after injury leads to aberrant restorative neurogenesis. Taken together, we identify AhR signaling as a crucial regulator of restorative neurogenesis timing in the zebrafish brain.</p>',
			'date' => '2018-12-18',
			'pmid' => 'http://www.pubmed.gov/30566853',
			'doi' => '10.1016/j.celrep.2018.11.055',
			'modified' => '2019-04-17 14:47:22',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 97 => array(
			'id' => '3649',
			'name' => 'Genome-wide identification of RETINOBLASTOMA RELATED 1 binding sites in Arabidopsis reveals novel DNA damage regulators.',
			'authors' => 'Bouyer D, Heese M, Chen P, Harashima H, Roudier F, Grüttner C, Schnittger A',
			'description' => '<p>Retinoblastoma (pRb) is a multifunctional regulator, which was likely present in the last common ancestor of all eukaryotes. The Arabidopsis pRb homolog RETINOBLASTOMA RELATED 1 (RBR1), similar to its animal counterparts, controls not only cell proliferation but is also implicated in developmental decisions, stress responses and maintenance of genome integrity. Although most functions of pRb-type proteins involve chromatin association, a genome-wide understanding of RBR1 binding sites in Arabidopsis is still missing. Here, we present a plant chromatin immunoprecipitation protocol optimized for genome-wide studies of indirectly DNA-bound proteins like RBR1. Our analysis revealed binding of Arabidopsis RBR1 to approximately 1000 genes and roughly 500 transposable elements, preferentially MITES. The RBR1-decorated genes broadly overlap with previously identified targets of two major transcription factors controlling the cell cycle, i.e. E2F and MYB3R3 and represent a robust inventory of RBR1-targets in dividing cells. Consistently, enriched motifs in the RBR1-marked domains include sequences related to the E2F consensus site and the MSA-core element bound by MYB3R transcription factors. Following up a key role of RBR1 in DNA damage response, we performed a meta-analysis combining the information about the RBR1-binding sites with genome-wide expression studies under DNA stress. As a result, we present the identification and mutant characterization of three novel genes required for growth upon genotoxic stress.</p>',
			'date' => '2018-11-01',
			'pmid' => 'http://www.pubmed.gov/30500810',
			'doi' => '10.1371/journal.',
			'modified' => '2019-06-07 10:12:16',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 98 => array(
			'id' => '3576',
			'name' => 'SUMO Safeguards Somatic and Pluripotent Cell Identities by Enforcing Distinct Chromatin States',
			'authors' => 'Cossec Jack-Christophe, Theurillat Ilan, Chica Claudia, Búa Aguín Sabela, Gaume Xavier, Andrieux Alexandra, Iturbide Ane, Jouvion Gregory, Li Han, Bossis Guillaume, Seeler Jacob-Sebastian, Torres-Padilla Maria-Elena, Dejean Anne',
			'description' => '<p>Understanding general principles that safeguard cellular identity should reveal critical insights into common mechanisms underlying specification of varied cell types. Here, we show that SUMO modification acts to stabilize cell fate in a variety of contexts. Hyposumoylation enhances pluripotency reprogramming in vitro and in vivo, increases lineage transdifferentiation, and facilitates leukemic cell differentiation. Suppressing sumoylation in embryonic stem cells (ESCs) promotes their conversion into 2-cell-embryo-like (2C-like) cells. During reprogramming to pluripotency, SUMO functions on fibroblastic enhancers to retain somatic transcription factors together with Oct4, Sox2, and Klf4, thus impeding somatic enhancer inactivation. In contrast, in ESCs, SUMO functions on heterochromatin to silence the 2C program, maintaining both proper H3K9me3 levels genome-wide and repression of the Dux locus by triggering recruitment of the sumoylated PRC1.6 and Kap/Setdb1 repressive complexes. Together, these studies show that SUMO acts on chromatin as a glue to stabilize key determinants of somatic and pluripotent states.</p>',
			'date' => '2018-10-25',
			'pmid' => 'http://www.pubmed.gov/30401455',
			'doi' => '10.1016/j.stem.2018.10.001',
			'modified' => '2019-07-22 09:18:55',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 99 => array(
			'id' => '3636',
			'name' => 'Caenorhabditis elegans sperm carry a histone-based epigenetic memory of both spermatogenesis and oogenesis.',
			'authors' => 'Tabuchi TM, Rechtsteiner A, Jeffers TE, Egelhofer TA, Murphy CT, Strome S',
			'description' => '<p>Paternal contributions to epigenetic inheritance are not well understood. Paternal contributions via marked nucleosomes are particularly understudied, in part because sperm in some organisms replace the majority of nucleosome packaging with protamine packaging. Here we report that in Caenorhabditis elegans sperm, the genome is packaged in nucleosomes and carries a histone-based epigenetic memory of genes expressed during spermatogenesis, which unexpectedly include genes well known for their expression during oogenesis. In sperm, genes with spermatogenesis-restricted expression are uniquely marked with both active and repressive marks, which may reflect a sperm-specific chromatin signature. We further demonstrate that epigenetic information provided by sperm is important and in fact sufficient to guide proper germ cell development in offspring. This study establishes one mode of paternal epigenetic inheritance and offers a potential mechanism for how the life experiences of fathers may impact the development and health of their descendants.</p>',
			'date' => '2018-10-17',
			'pmid' => 'http://www.pubmed.gov/30333496',
			'doi' => '10.1038/s41467-018-06236-8',
			'modified' => '2019-06-07 10:26:54',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 100 => array(
			'id' => '3556',
			'name' => 'PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex.',
			'authors' => 'Link S, Spitzer RMM, Sana M, Torrado M, Völker-Albert MC, Keilhauer EC, Burgold T, Pünzeler S, Low JKK, Lindström I, Nist A, Regnard C, Stiewe T, Hendrich B, Imhof A, Mann M, Mackay JP, Bartkuhn M, Hake SB',
			'description' => '<p>Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and cranial-facial development. Here, using in vitro assays, we show that distinct domains of PWWP2A mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly binds H3K36me3-containing gene bodies. Further, PWWP2A binds to an MTA1-specific subcomplex of the NuRD complex (M1HR), which consists solely of MTA1, HDAC1, and RBBP4/7, and excludes CHD, GATAD2 and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as a complex chromatin-binding protein that serves to direct the deacetylase complex M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels.</p>',
			'date' => '2018-10-16',
			'pmid' => 'http://www.pubmed.gov/30327463',
			'doi' => '10.1038/s41467-018-06665-5',
			'modified' => '2019-07-22 09:17:39',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 101 => array(
			'id' => '3498',
			'name' => 'Convergent evolution of complex genomic rearrangements in two fungal meiotic drive elements.',
			'authors' => 'Svedberg J, Hosseini S, Chen J, Vogan AA, Mozgova I, Hennig L, Manitchotpisit P, Abusharekh A, Hammond TM, Lascoux M, Johannesson H',
			'description' => '<p>Meiotic drive is widespread in nature. The conflict it generates is expected to be an important motor for evolutionary change and innovation. In this study, we investigated the genomic consequences of two large multi-gene meiotic drive elements, Sk-2 and Sk-3, found in the filamentous ascomycete Neurospora intermedia. Using long-read sequencing, we generated the first complete and well-annotated genome assemblies of large, highly diverged, non-recombining regions associated with meiotic drive elements. Phylogenetic analysis shows that, even though Sk-2 and Sk-3 are located in the same chromosomal region, they do not form sister clades, suggesting independent origins or at least a long evolutionary separation. We conclude that they have in a convergent manner accumulated similar patterns of tandem inversions and dense repeat clusters, presumably in response to similar needs to create linkage between genes causing drive and resistance.</p>',
			'date' => '2018-10-12',
			'pmid' => 'http://www.pubmed.gov/30315196',
			'doi' => '10.1038/s41467-018-06562-x',
			'modified' => '2019-07-22 09:20:24',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 102 => array(
			'id' => '3507',
			'name' => 'Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclones.',
			'authors' => 'de Boer B, Prick J, Pruis MG, Keane P, Imperato MR, Jaques J, Brouwers-Vos AZ, Hogeling SM, Woolthuis CM, Nijk MT, Diepstra A, Wandinger S, Versele M, Attar RM, Cockerill PN, Huls G, Vellenga E, Mulder AB, Bonifer C, Schuringa JJ',
			'description' => '<p>Intra-tumor heterogeneity caused by clonal evolution is a major problem in cancer treatment. To address this problem, we performed label-free quantitative proteomics on primary acute myeloid leukemia (AML) samples. We identified 50 leukemia-enriched plasma membrane proteins enabling the prospective isolation of genetically distinct subclones from individual AML patients. Subclones differed in their regulatory phenotype, drug sensitivity, growth, and engraftment behavior, as determined by RNA sequencing, DNase I hypersensitive site mapping, transcription factor occupancy analysis, in&nbsp;vitro culture, and xenograft transplantation. Finally, we show that these markers can be used to identify and longitudinally track distinct leukemic clones in patients in routine diagnostics. Our study describes a strategy for a major improvement in stratifying cancer diagnosis and treatment.</p>',
			'date' => '2018-10-08',
			'pmid' => 'http://www.pubmed.gov/30245083',
			'doi' => '10.1016/j.ccell.2018.08.014',
			'modified' => '2019-02-27 16:26:01',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 103 => array(
			'id' => '3505',
			'name' => 'Genomic Location of PRMT6-Dependent H3R2 Methylation Is Linked to the Transcriptional Outcome of Associated Genes.',
			'authors' => 'Bouchard C, Sahu P, Meixner M, Nötzold RR, Rust MB, Kremmer E, Feederle R, Hart-Smith G, Finkernagel F, Bartkuhn M, Savai Pullamsetti S, Nist A, Stiewe T, Philipsen S, Bauer UM',
			'description' => '<p>Protein arginine methyltransferase 6 (PRMT6) catalyzes asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a). This mark has been reported to associate with silent genes. Here, we use a cell model&nbsp;of neural differentiation, which upon PRMT6 knockout exhibits proliferation and differentiation defects. Strikingly, we detect PRMT6-dependent H3R2me2a at active genes, both at promoter and enhancer sites. Loss of H3R2me2a from promoter sites leads to enhanced KMT2A binding and H3K4me3 deposition together with increased target gene transcription, supporting a repressive nature of H3R2me2a. At enhancers, H3R2me2a peaks co-localize with the active enhancer marks H3K4me1 and H3K27ac. Here, loss of H3R2me2a results in reduced KMT2D binding and H3K4me1/H3K27ac deposition together with decreased transcription of associated genes, indicating that H3R2me2a also exerts activation functions. Our work suggests that PRMT6 via H3R2me2a interferes with the deposition of adjacent histone marks and modulates the activity of important differentiation-associated genes by opposing transcriptional effects.</p>',
			'date' => '2018-09-18',
			'pmid' => 'http://www.pubmed.gov/30232013',
			'doi' => '10.1016/j.celrep.2018.08.052',
			'modified' => '2019-02-28 10:05:16',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 104 => array(
			'id' => '3599',
			'name' => 'Enhancer-driven transcriptional regulation is a potential key determinant for human visceral and subcutaneous adipocytes.',
			'authors' => 'Liefke R, Bokelmann K, Ghadimi BM, Dango S',
			'description' => '<p>Obesity is characterized by the excess of body fat leading to impaired health. Abdominal fat is particularly harmful and is associated with cardiovascular and metabolic diseases and cancer. In contrast, subcutaneous fat is generally considered less detrimental. The mechanisms that establish the cellular characteristics of these distinct fat types in humans are not fully understood. Here, we explored whether differences of their gene regulatory mechanisms can be investigated in vitro. For this purpose, we in vitro differentiated human visceral and subcutaneous pre-adipocytes into mature adipocytes and obtained their gene expression profiles and genome-wide H3K4me3, H3K9me3 and H3K27ac patterns. Subsequently, we compared those data with public gene expression data from visceral and subcutaneous fat tissues. We found that the in vitro differentiated adipocytes show significant differences in their transcriptional landscapes, which correlate with biological pathways that are characteristic for visceral and subcutaneous fat tissues, respectively. Unexpectedly, visceral adipocyte enhancers are rich on motifs for transcription factors involved in the Hippo-YAP pathway, cell growth and inflammation, which are not typically associated with adipocyte function. In contrast, enhancers of subcutaneous adipocytes show enrichment of motifs for common adipogenic transcription factors, such as C/EBP, NFI and PPAR&gamma;, implicating substantially disparate gene regulatory networks in visceral and subcutaneous adipocytes. Consistent with the role in obesity, predominantly the histone modification pattern of visceral adipocytes is linked to obesity-associated diseases. Thus, this work suggests that the properties of visceral and subcutaneous fat tissues can be studied in vitro and provides preliminary insights into their gene regulatory processes.</p>',
			'date' => '2018-06-30',
			'pmid' => 'http://www.pubmed.gov/29966764',
			'doi' => '10.1016/j.bbagrm.2018.06.007',
			'modified' => '2019-04-17 15:05:35',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 105 => array(
			'id' => '3621',
			'name' => 'Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx.',
			'authors' => 'Hensel KO, Cantner F, Bangert F, Wirth S, Postberg J',
			'description' => '<p>BACKGROUND: In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of cccDNA and HBx remains unexplored. RESULTS: To identify virus-host genome interactions and the underlying nuclear landscape for the first time, we combined circular chromosome conformation capture (4C) with RNA-seq and ChIP-seq. Moreover, we studied HBx-binding to HBV episomes. In HBV-positive HepaRG hepatocytes, we observed preferential association of HBV episomes and HBx with actively transcribed nuclear domains on the host genome correlating in size with constrained topological units of chromatin. Interestingly, HBx alone occupied transcribed chromatin domains. Silencing of native HBx caused reduced episomal HBV stability. CONCLUSIONS: As part of the HBV episome, HBx might stabilize HBV episomal nuclear localization. Our observations may contribute to the understanding of long-term episomal stability and the facilitation of viral persistence. The exact mechanism by which HBx contributes to HBV nuclear persistence warrants further investigations.</p>',
			'date' => '2018-06-22',
			'pmid' => 'http://www.pubmed.gov/29933745',
			'doi' => '10.1186/s13072-018-0204-2',
			'modified' => '2019-05-16 11:23:59',
			'created' => '2019-04-25 11:11:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 106 => array(
			'id' => '3503',
			'name' => 'Genome-wide rules of nucleosome phasing',
			'authors' => 'Sandro Baldi, Dhawal S. Jain1, Lisa Harpprecht1, Angelika Zabel1, Marion Scheibe, Falk Butter, Tobias Straub and Peter B. Becker',
			'description' => '<p>Regular successions of positioned nucleosomes &ndash; phased nucleosome arrays (PNAs) &ndash; are predominantly known from transcriptional start sites (TSS). It is unclear whether PNAs occur elsewhere in the genome. To generate a comprehensive inventory of PNAs for Drosophila, we applied spectral analysis to nucleosome maps and identified thousands of PNAs throughout the genome. About half of them are not near TSS and strongly enriched for a novel sequence motif. Through genome-wide reconstitution of physiological chromatin in Drosophila embryo extracts we uncovered the molecular basis of PNA formation. We identified Phaser, an unstudied zinc finger protein that positions nucleosomes flanking the new motif. It also revealed how the global activity of the chromatin remodeler CHRAC/ACF, together with local barrier elements, generates islands of regular phasing throughout the genome. Our work demonstrates the potential of chromatin assembly by embryo extracts as a powerful tool to reconstitute chromatin features on a global scale in vitro.</p>',
			'date' => '2018-06-13',
			'pmid' => 'https://doi.org/10.1101/093666',
			'doi' => '10.1101/093666.',
			'modified' => '2019-02-28 10:28:59',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 107 => array(
			'id' => '3562',
			'name' => 'Insulin promoter in human pancreatic β cells contacts diabetes susceptibility loci and regulates genes affecting insulin metabolism.',
			'authors' => 'Jian X, Felsenfeld G',
			'description' => '<p>Both type 1 and type 2 diabetes involve a complex interplay between genetic, epigenetic, and environmental factors. Our laboratory has been interested in the physical interactions, in nuclei of human pancreatic &beta; cells, between the insulin ( gene and other genes that are involved in insulin metabolism. We have identified, using Circularized Chromosome Conformation Capture (4C), many physical contacts in a human pancreatic &beta; cell line between the promoter on chromosome 11 and sites on most other chromosomes. Many of these contacts are associated with type 1 or type 2 diabetes susceptibility loci. To determine whether physical contact is correlated with an ability of the locus to affect expression of these genes, we knock down expression by targeting the promoter; 259 genes are either up or down-regulated. Of these, 46 make physical contact with We analyze a subset of the contacted genes and show that all are associated with acetylation of histone H3 lysine 27, a marker of actively expressed genes. To demonstrate the usefulness of this approach in revealing regulatory pathways, we identify from among the contacted sites the previously uncharacterized gene and show that it plays an important role in controlling the effect of somatostatin-28 on insulin secretion. These results are consistent with models in which clustering of genes supports transcriptional activity. This may be a particularly important mechanism in pancreatic &beta; cells and in other cells where a small subset of genes is expressed at high levels.</p>',
			'date' => '2018-05-15',
			'pmid' => 'http://www.pubmed.gov/29712868',
			'doi' => '10.1073/pnas.1803146115',
			'modified' => '2019-03-25 11:27:48',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 108 => array(
			'id' => '3578',
			'name' => 'Modulation of gene transcription and epigenetics of colon carcinoma cells by bacterial membrane vesicles.',
			'authors' => 'Vdovikova S, Gilfillan S, Wang S, Dongre M, Wai SN, Hurtado A',
			'description' => '<p>Interactions between bacteria and colon cancer cells influence the transcription of the host cell. Yet is it undetermined whether the bacteria itself or the communication between the host and bacteria is responsible for the genomic changes in the eukaryotic cell. Now, we have investigated the genomic and epigenetic consequences of co-culturing colorectal carcinoma cells with membrane vesicles from pathogenic bacteria Vibrio cholerae and non-pathogenic commensal bacteria Escherichia coli. Our study reveals that membrane vesicles from pathogenic and commensal bacteria have a global impact on the gene expression of colon-carcinoma cells. The changes in gene expression correlate positively with both epigenetic changes and chromatin accessibility of promoters at transcription start sites of genes induced by both types of membrane vesicles. Moreover, we have demonstrated that membrane vesicles obtained only from V. cholerae induced the expression of genes associated with epithelial cell differentiation. Altogether, our study suggests that the observed genomic changes in host cells might be due to specific components of membrane vesicles and do not require communication by direct contact with the bacteria.</p>',
			'date' => '2018-05-09',
			'pmid' => 'http://www.pubmed.gov/29743643',
			'doi' => '10.1038/s41598-018-25308-9',
			'modified' => '2019-04-17 15:56:24',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 109 => array(
			'id' => '3459',
			'name' => 'Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI as a co-repressor for RUNX1.',
			'authors' => 'Feld C, Sahu P, Frech M, Finkernagel F, Nist A, Stiewe T, Bauer UM, Neubauer A',
			'description' => '<p>SKI is a transcriptional co-regulator and overexpressed in various human tumors, for example in acute myeloid leukemia (AML). SKI contributes to the origin and maintenance of the leukemic phenotype. Here, we use ChIP-seq and RNA-seq analysis to identify the epigenetic alterations induced by SKI overexpression in AML cells. We show that approximately two thirds of differentially expressed genes are up-regulated upon SKI deletion, of which &gt;40% harbor SKI binding sites in their proximity, primarily in enhancer regions. Gene ontology analysis reveals that many of the differentially expressed genes are annotated to hematopoietic cell differentiation and inflammatory response, corroborating our finding that SKI contributes to a myeloid differentiation block in HL60 cells. We find that SKI peaks are enriched for RUNX1 consensus motifs, particularly in up-regulated SKI targets upon SKI deletion. RUNX1 ChIP-seq displays that nearly 70% of RUNX1 binding sites overlap with SKI peaks, mainly at enhancer regions. SKI and RUNX1 occupy the same genomic sites and cooperate in gene silencing. Our work demonstrates for the first time the predominant co-repressive function of SKI in AML cells on a genome-wide scale and uncovers the transcription factor RUNX1 as an important mediator of SKI-dependent transcriptional repression.</p>',
			'date' => '2018-04-20',
			'pmid' => 'http://www.pubmed.gov/29471413',
			'doi' => '10.1093/nar/gky119',
			'modified' => '2019-02-15 21:13:23',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 110 => array(
			'id' => '3539',
			'name' => 'A long range distal enhancer controls temporal fine-tuning of PAX6 expression in neuronal precursors.',
			'authors' => 'Lacomme M, Medevielle F, Bourbon HM, Thierion E, Kleinjan DJ, Roussat M, Pituello F, Bel-Vialar S',
			'description' => '<p>Proper embryonic development relies on a tight control of spatial and temporal gene expression profiles in a highly regulated manner. One good example is the ON/OFF switching of the transcription factor PAX6 that governs important steps of neurogenesis. In the neural tube PAX6 expression is initiated in neural progenitors through the positive action of retinoic acid signaling and downregulated in neuronal precursors by the bHLH transcription factor NEUROG2. How these two regulatory inputs are integrated at the molecular level to properly fine tune temporal PAX6 expression is not known. In this study we identified and characterized a 940-bp long distal cis-regulatory module (CRM), located far away from the PAX6 transcription unit and which conveys positive input from RA signaling pathway and indirect repressive signal(s) from NEUROG2. These opposing regulatory signals are integrated through HOMZ, a 94 bp core region within E940 which is evolutionarily conserved in distant organisms such as the zebrafish. We show that within HOMZ, NEUROG2 and RA exert their opposite temporal activities through a short 60 bp region containing a functional RA-responsive element (RARE). We propose a model in which retinoic acid receptors (RARs) and NEUROG2 repressive target(s) compete on the same DNA motif to fine tune temporal PAX6 expression during the course of spinal neurogenesis.</p>',
			'date' => '2018-04-15',
			'pmid' => 'http://www.pubmed.gov/29486153',
			'doi' => '10.1016/j.ydbio.2018.02.015',
			'modified' => '2019-02-28 10:42:57',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 111 => array(
			'id' => '3432',
			'name' => 'HDAC1 and HDAC2 Modulate TGF-β Signaling during Endothelial-to-Hematopoietic Transition.',
			'authors' => 'Thambyrajah R, Fadlullah MZH, Proffitt M, Patel R, Cowley SM, Kouskoff V, Lacaud G',
			'description' => '<p>The first hematopoietic stem and progenitor cells are generated during development from hemogenic endothelium (HE) through trans-differentiation. The molecular mechanisms underlying this endothelial-to-hematopoietic transition (EHT) remain poorly understood. Here, we explored the role of the epigenetic regulators HDAC1 and HDAC2 in the emergence of these first blood cells in&nbsp;vitro and in&nbsp;vivo. Loss of either of these epigenetic silencers through conditional genetic deletion reduced hematopoietic transition from HE, while combined deletion was incompatible with blood generation. We investigated the molecular basis of HDAC1 and HDAC2 requirement and identified TGF-&beta; signaling as one of the pathways controlled by HDAC1 and HDAC2. Accordingly, we experimentally demonstrated that activation of this pathway in HE cells reinforces hematopoietic development. Altogether, our results establish that HDAC1 and HDAC2 modulate TGF-&beta; signaling and suggest that stimulation of this pathway in HE cells would be beneficial for production of hematopoietic cells for regenerative therapies.</p>',
			'date' => '2018-04-10',
			'pmid' => 'http://www.pubmed.gov/29641990',
			'doi' => '10.1016/j.stemcr.2018.03.011',
			'modified' => '2018-12-31 11:55:16',
			'created' => '2018-12-04 09:51:07',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 112 => array(
			'id' => '3468',
			'name' => 'EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma.',
			'authors' => 'Gorthi A, Romero JC, Loranc E, Cao L, Lawrence LA, Goodale E, Iniguez AB, Bernard X, Masamsetti VP, Roston S, Lawlor ER, Toretsky JA, Stegmaier K, Lessnick SL, Chen Y, Bishop AJR',
			'description' => '<p>Ewing sarcoma is an aggressive paediatric cancer of the bone and soft tissue. It results from a chromosomal translocation, predominantly t(11;22)(q24:q12), that fuses the N-terminal transactivation domain of the constitutively expressed EWSR1 protein with the C-terminal DNA binding domain of the rarely expressed FLI1 protein. Ewing sarcoma is highly sensitive to genotoxic agents such as etoposide, but the underlying molecular basis of this sensitivity is unclear. Here we show that Ewing sarcoma cells display alterations in regulation of damage-induced transcription, accumulation of R-loops and increased replication stress. In addition, homologous recombination is impaired in Ewing sarcoma owing to an enriched interaction between BRCA1 and the elongating transcription machinery. Finally, we uncover a role for EWSR1 in the transcriptional response to damage, suppressing R-loops and promoting homologous recombination. Our findings improve the current understanding of EWSR1 function, elucidate the mechanistic basis of the sensitivity of Ewing sarcoma to chemotherapy (including PARP1 inhibitors) and highlight a class of BRCA-deficient-like tumours.</p>',
			'date' => '2018-03-15',
			'pmid' => 'http://www.pubmed.gov/29513652',
			'doi' => '10.1038/nature25748',
			'modified' => '2019-02-15 21:16:23',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 113 => array(
			'id' => '3533',
			'name' => 'A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.',
			'authors' => 'Zanghì G, Vembar SS, Baumgarten S, Ding S, Guizetti J, Bryant JM, Mattei D, Jensen ATR, Rénia L, Goh YS, Sauerwein R, Hermsen CC, Franetich JF, Bordessoulles M, Silvie O, Soulard V, Scatton O, Chen P, Mecheri S, Mazier D, Scherf A',
			'description' => '<p>Heterochromatin plays a central role in the process of immune evasion, pathogenesis, and transmission of the malaria parasite Plasmodium falciparum during blood stage infection. Here, we use ChIP sequencing to demonstrate that sporozoites from mosquito salivary glands expand heterochromatin at subtelomeric regions to silence blood-stage-specific&nbsp;genes. Our data also revealed that heterochromatin enrichment is predictive of the transcription status of clonally variant genes members that mediate cytoadhesion in blood stage parasites. A specific member (here called NF54var) of the var gene family remains euchromatic, and the resultant PfEMP1 (NF54_SpzPfEMP1) is expressed at the&nbsp;sporozoite surface. NF54_SpzPfEMP1-specific antibodies efficiently block hepatocyte infection in&nbsp;a strain-specific manner. Furthermore, human volunteers immunized with infective sporozoites developed antibodies against NF54_SpzPfEMP1. Overall, we show that the epigenetic signature of var genes is reset in mosquito stages. Moreover, the identification of a strain-specific sporozoite PfEMP1 is highly relevant for vaccine design based on sporozoites.</p>',
			'date' => '2018-03-13',
			'pmid' => 'http://www.pubmed.gov/29539423',
			'doi' => '10.1016/j.celrep.2018.02.075',
			'modified' => '2019-02-28 10:47:11',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 114 => array(
			'id' => '3444',
			'name' => 'Genome-wide analysis of PDX1 target genes in human pancreatic progenitors.',
			'authors' => 'Wang X, Sterr M, Burtscher I, Chen S, Hieronimus A, Machicao F, Staiger H, Häring HU, Lederer G, Meitinger T, Cernilogar FM, Schotta G, Irmler M, Beckers J, Hrabě de Angelis M, Ray M, Wright CVE, Bakhti M, Lickert H',
			'description' => '<p>OBJECTIVE: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing &beta;-cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Also, comparative studies of PDX1 binding patterns in pancreatic progenitors and adult &beta;-cells have not been conducted so far. Furthermore, many studies reported the association between single nucleotide polymorphisms (SNPs) and T2DM, and it has been shown that islet enhancers are enriched in T2DM-associated SNPs. Whether regions, harboring T2DM-associated SNPs are PDX1 bound and active at the pancreatic progenitor stage has not been reported so far. METHODS: In this study, we have generated a novel induced pluripotent stem cell (iPSC) line that efficiently differentiates into human pancreatic progenitors (PPs). Furthermore, PDX1 and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) was used to identify PDX1 transcriptional targets and active enhancer and promoter regions. To address potential differences in the function of PDX1 during development and adulthood, we compared PDX1 binding profiles from PPs and adult islets. Moreover, combining ChIP-seq and GWAS meta-analysis data we identified T2DM-associated SNPs in PDX1 binding sites and active chromatin regions. RESULTS: ChIP-seq for PDX1 revealed a total of 8088 PDX1-bound regions that map to 5664 genes in iPSC-derived PPs. The PDX1 target regions include important pancreatic TFs, such as PDX1 itself, RFX6, HNF1B, and MEIS1, which were activated during the differentiation process as revealed by the active chromatin mark H3K27ac and mRNA expression profiling, suggesting that auto-regulatory feedback regulation maintains PDX1 expression and initiates a pancreatic TF program. Remarkably, we identified several PDX1 target genes that have not been reported in the literature in human so far, including RFX3, required for ciliogenesis and endocrine differentiation in mouse, and the ligand of the Notch receptor DLL1, which is important for endocrine induction and tip-trunk patterning. The comparison of PDX1 profiles from PPs and adult human islets identified sets of stage-specific target genes, associated with early pancreas development and adult &beta;-cell function, respectively. Furthermore, we found an enrichment of T2DM-associated SNPs in active chromatin regions from iPSC-derived PPs. Two of these SNPs fall into PDX1 occupied sites that are located in the intronic regions of TCF7L2 and HNF1B. Both of these genes are key transcriptional regulators of endocrine induction and mutations in cis-regulatory regions predispose to diabetes. CONCLUSIONS: Our data provide stage-specific target genes of PDX1 during in&nbsp;vitro differentiation of stem cells into pancreatic progenitors that could be useful to identify pathways and molecular targets that predispose for diabetes. In addition, we show that T2DM-associated SNPs are enriched in active chromatin regions at the pancreatic progenitor stage, suggesting that the susceptibility to T2DM might originate from imperfect execution of a &beta;-cell developmental program.</p>',
			'date' => '2018-03-01',
			'pmid' => 'http://www.pubmed.gov/29396371',
			'doi' => '10.1016/j.molmet.2018.01.011',
			'modified' => '2019-02-15 21:27:03',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 115 => array(
			'id' => '3543',
			'name' => 'A multi-omics study of the grapevine-downy mildew (Plasmopara viticola) pathosystem unveils a complex protein coding- and noncoding-based arms race during infection.',
			'authors' => 'Brilli M, Asquini E, Moser M, Bianchedi PL, Perazzolli M, Si-Ammour A',
			'description' => '<p>Fungicides are applied intensively to prevent downy mildew infections of grapevines (Vitis vinifera) with high impact on the environment. In order to develop alternative strategies we sequenced the genome of the oomycete pathogen Plasmopara viticola causing this disease. We show that it derives from a Phytophthora-like ancestor that switched to obligate biotrophy by losing genes involved in nitrogen metabolism and &gamma;-Aminobutyric acid catabolism. By combining multiple omics approaches we characterized the pathosystem and identified a RxLR effector that trigger an immune response in the wild species V. riparia. This effector is an ideal marker to screen novel grape resistant varieties. Our study reveals an unprecedented bidirectional noncoding RNA-based mechanism that, in one direction might be fundamental for P. viticola to proficiently infect its host, and in the other might reduce the effects of the infection on the plant.</p>',
			'date' => '2018-01-15',
			'pmid' => 'http://www.pubmed.gov/29335535',
			'doi' => '10.1038/s41598-018-19158-8',
			'modified' => '2019-02-28 11:00:21',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 116 => array(
			'id' => '3445',
			'name' => 'BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis.',
			'authors' => 'Kaufmann E, Sanz J, Dunn JL, Khan N, Mendonça LE, Pacis A, Tzelepis F, Pernet E, Dumaine A, Grenier JC, Mailhot-Léonard F, Ahmed E, Belle J, Besla R, Mazer B, King IL, Nijnik A, Robbins CS, Barreiro LB, Divangahi M',
			'description' => '<p>The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and&nbsp;location for generating such innate memory responses in&nbsp;vivo remain unknown. Here, we show that access of Bacillus Calmette-Gu&eacute;rin (BCG) to the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), leading to local cell&nbsp;expansion and enhanced myelopoiesis at the&nbsp;expense of lymphopoiesis. Importantly, BCG-educated HSCs generate epigenetically modified macrophages that provide significantly better protection against virulent M.&nbsp;tuberculosis infection than na&iuml;ve macrophages. By using parabiotic and chimeric mice, as well as adoptive transfer approaches, we demonstrate that training of the monocyte/macrophage lineage via BCG-induced HSC reprogramming is sustainable in&nbsp;vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.</p>',
			'date' => '2018-01-11',
			'pmid' => 'http://www.pubmed.gov/29328912',
			'doi' => '10.1016/j.cell.2017.12.031',
			'modified' => '2019-02-15 21:32:25',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 117 => 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) 118 => array(
			'id' => '3355',
			'name' => 'Functional dissection of Drosophila melanogaster SUUR protein influence on H3K27me3 profile',
			'authors' => 'Posukh O. V. et al.',
			'description' => '<div id="__sec1" class="sec sec-first">
<h3>Background</h3>
<p id="Par1" class="p p-first-last">In eukaryotes, heterochromatin replicates late in S phase of the cell cycle and contains specific covalent modifications of histones. <em>SuUR</em> mutation found in Drosophila makes heterochromatin replicate earlier than in wild type and reduces the level of repressive histone modifications. SUUR protein was shown to be associated with moving replication forks, apparently through the interaction with PCNA. The biological process underlying the effects of SUUR on replication and composition of heterochromatin remains unknown.</p>
</div>
<div id="__sec2" class="sec">
<h3>Results</h3>
<p id="Par2" class="p p-first-last">Here we performed a functional dissection of SUUR protein effects on H3K27me3 level. Using hidden Markow model-based algorithm we revealed <em>SuUR</em>-sensitive chromosomal regions that demonstrated unusual characteristics: They do not contain Polycomb and require SUUR function to sustain H3K27me3 level. We tested the role of SUUR protein in the mechanisms that could affect H3K27me3 histone levels in these regions. We found that SUUR does not affect the initial H3K27me3 pattern formation in embryogenesis or Polycomb distribution in the chromosomes. We also ruled out the possible effect of SUUR on histone genes expression and its involvement in DSB repair.</p>
</div>
<div id="__sec3" class="sec">
<h3>Conclusions</h3>
<p id="Par3" class="p p-first-last">Obtained results support the idea that SUUR protein contributes to the heterochromatin maintenance during the chromosome replication. A model that explains major SUUR-associated phenotypes is proposed.</p>
</div>',
			'date' => '2017-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709859/',
			'doi' => '',
			'modified' => '2018-04-05 12:28:59',
			'created' => '2018-04-05 12:28:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 119 => array(
			'id' => '3305',
			'name' => 'An endosiRNA-Based Repression Mechanism Counteracts Transposon Activation during Global DNA Demethylation in Embryonic Stem Cells',
			'authors' => 'Berrens R.V. et al.',
			'description' => '<p>Erasure of DNA methylation and repressive chromatin marks in the mammalian germline leads to risk of transcriptional activation of transposable elements (TEs). Here, we used mouse embryonic stem cells (ESCs) to identify an endosiRNA-based mechanism involved in suppression of TE transcription. In ESCs with DNA demethylation induced by acute deletion of Dnmt1, we saw an increase in sense transcription at TEs, resulting in an abundance of sense/antisense transcripts leading to high levels of ARGONAUTE2 (AGO2)-bound small RNAs. Inhibition of Dicer or Ago2 expression revealed that small RNAs are involved in an immediate response to demethylation-induced transposon activation, while the deposition of repressive histone marks follows as a chronic response. In&nbsp;vivo, we also found TE-specific endosiRNAs present during primordial germ cell development. Our results suggest that antisense TE transcription is a "trap" that elicits an endosiRNA response to restrain acute transposon activity during epigenetic reprogramming in the mammalian germline.</p>',
			'date' => '2017-11-02',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29100015',
			'doi' => '',
			'modified' => '2018-01-03 10:17:40',
			'created' => '2018-01-03 10:17:40',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 120 => array(
			'id' => '3281',
			'name' => 'Epigenome profiling and editing of neocortical progenitor cells during development',
			'authors' => 'Albert M. et al.',
			'description' => '<p>The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resolution are required. Here, we present genomewide histone methylation maps for distinct neural cell populations in the developing mouse neocortex. Using different chromatin features, we identify potential novel regulators of cortical NPCs. Moreover, we identify extensive H3K27me3 changes between NPC subtypes coinciding with major developmental and cell biological transitions. Interestingly, we detect dynamic H3K27me3 changes on promoters of several crucial transcription factors, including the basal progenitor regulator <i>Eomes</i> We use catalytically inactive Cas9 fused with the histone methyltransferase Ezh2 to edit H3K27me3 at the <i>Eomes</i> locus <i>in&nbsp;vivo</i>, which results in reduced Tbr2 expression and lower basal progenitor abundance, underscoring the relevance of dynamic H3K27me3 changes during neocortex development. Taken together, we provide a rich resource of neocortical histone methylation data and outline an approach to investigate its contribution to the regulation of selected genes during neocortical development.</p>',
			'date' => '2017-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28765163',
			'doi' => '',
			'modified' => '2017-10-17 10:25:58',
			'created' => '2017-10-17 10:25:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 121 => array(
			'id' => '3250',
			'name' => 'Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles',
			'authors' => 'Marincevic-Zuniga Y. et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL). In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts.</abstracttext></p>
<h4>METHODS:</h4>
<p><abstracttext label="METHODS" nlmcategory="METHODS">We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">We identified 64 unique fusion events distributed among 80 individual patients, of which over 50% have not previously been reported in ALL. Although the majority of the fusion genes were found only in a single patient, we identified several recurrent fusion gene families defined by promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5, and ZNF384, or recurrent fusion genes, such as DUX4-IGH. Our data show that patients harboring these fusion genes displayed characteristic genome-wide DNA methylation and gene expression signatures in addition to distinct patterns in single nucleotide variants and recurrent copy number alterations.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">Our study delineates the fusion gene landscape in pediatric ALL, including both known and novel fusion genes, and highlights fusion gene families with shared molecular etiologies, which may provide additional information for prognosis and therapeutic options in the future.</abstracttext></p>
</div>',
			'date' => '2017-08-14',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28806978',
			'doi' => '',
			'modified' => '2017-09-26 09:49:39',
			'created' => '2017-09-26 09:49:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 122 => array(
			'id' => '3259',
			'name' => 'Dynamics of RNA Polymerase II Pausing and Bivalent Histone H3 Methylation during Neuronal Differentiation in Brain Development',
			'authors' => 'Liu J. et al.',
			'description' => '<p>During cellular differentiation, genes important for differentiation are expected to be silent in stem/progenitor cells yet can be readily activated. RNA polymerase II (Pol II) pausing and bivalent chromatin marks are two paradigms suited for establishing such a poised state of gene expression; however, their specific contributions in development are not well understood. Here we characterized Pol II pausing and H3K4me3/H3K27me3 marks in neural progenitor cells (NPCs) and their daughter neurons purified from the developing mouse cortex. We show that genes paused in NPCs or neurons are characteristic of respective cellular functions important for each cell type, although pausing and pause release were not correlated with gene activation. Bivalent chromatin marks poised the marked genes&nbsp;in NPCs for activation in neurons. Interestingly, we&nbsp;observed a positive correlation between H3K27me3 and paused Pol II. This study thus reveals cell type-specific Pol II pausing and gene activation-associated bivalency during mammalian neuronal differentiation.</p>',
			'date' => '2017-08-08',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28793256',
			'doi' => '',
			'modified' => '2017-10-05 11:17:11',
			'created' => '2017-10-05 11:17:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 123 => 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) 124 => array(
			'id' => '3282',
			'name' => 'Krox20 hindbrain regulation incorporates multiple modes of cooperation between cis-acting elements',
			'authors' => 'Thierion E. et al.',
			'description' => '<p>Developmental genes can harbour multiple transcriptional enhancers that act simultaneously or in succession to achieve robust and precise spatiotemporal expression. However, the mechanisms underlying cooperation between cis-acting elements are poorly documented, notably in vertebrates. The mouse gene Krox20 encodes a transcription factor required for the specification of two segments (rhombomeres) of the developing hindbrain. In rhombomere 3, Krox20 is subject to direct positive feedback governed by an autoregulatory enhancer, element A. In contrast, a second enhancer, element C, distant by 70 kb, is active from the initiation of transcription independent of the presence of the KROX20 protein. Here, using both enhancer knock-outs and investigations of chromatin organisation, we show that element C possesses a dual activity: besides its classical enhancer function, it is also permanently required in cis to potentiate the autoregulatory activity of element A, by increasing its chromatin accessibility. This work uncovers a novel, asymmetrical, long-range mode of cooperation between cis-acting elements that might be essential to avoid promiscuous activation of positive autoregulatory elements.</p>',
			'date' => '2017-07-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28749941',
			'doi' => '',
			'modified' => '2017-10-23 17:38:21',
			'created' => '2017-10-23 17:38:21',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 125 => array(
			'id' => '3261',
			'name' => 'Ectopic application of the repressive histone modification H3K9me2 establishes post-zygotic reproductive isolation in Arabidopsis thaliana',
			'authors' => 'Jiang H. et al.',
			'description' => '<p>Hybrid seed lethality as a consequence of interspecies or interploidy hybridizations is a major mechanism of reproductive isolation in plants. This mechanism is manifested in the endosperm, a dosage-sensitive tissue supporting embryo growth. Deregulated expression of imprinted genes such as <em>ADMETOS</em> (<em>ADM</em>) underpin the interploidy hybridization barrier in <em>Arabidopsis thaliana</em>; however, the mechanisms of their action remained unknown. In this study, we show that ADM interacts with the AT hook domain protein AHL10 and the SET domain-containing SU(VAR)3&ndash;9 homolog SUVH9 and ectopically recruits the heterochromatic mark H3K9me2 to AT-rich transposable elements (TEs), causing deregulated expression of neighboring genes. Several hybrid incompatibility genes identified in <em>Drosophila</em> encode for dosage-sensitive heterochromatin-interacting proteins, which has led to the suggestion that hybrid incompatibilities evolve as a consequence of interspecies divergence of selfish DNA elements and their regulation. Our data show that imbalance of dosage-sensitive chromatin regulators underpins the barrier to interploidy hybridization in <em>Arabidopsis</em>, suggesting that reproductive isolation as a consequence of epigenetic regulation of TEs is a conserved feature in animals and plants.</p>',
			'date' => '2017-07-25',
			'pmid' => 'http://genesdev.cshlp.org/content/early/2017/07/25/gad.299347.117',
			'doi' => '',
			'modified' => '2017-10-05 11:34:59',
			'created' => '2017-10-05 11:34:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 126 => array(
			'id' => '3267',
			'name' => '2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: Alterations in biosynthesis, enterohepatic circulation, and microbial metabolism.',
			'authors' => 'Fader K. et al.',
			'description' => '<p>2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant which elicits hepatotoxicity through activation of the aryl hydrocarbon receptor (AhR). Male C57BL/6 mice orally gavaged with TCDD (0.01-30&thinsp;&micro;g/kg) every 4 days for 28 days exhibited bile duct proliferation and pericholangitis. Mass spectrometry analysis detected a 4.6-fold increase in total hepatic bile acid levels, despite the coordinated repression of genes involved in cholesterol and primary bile acid biosynthesis including Cyp7a1. Specifically, TCDD elicited a &gt;200-fold increase in taurolithocholic acid (TLCA), a potent G protein-coupled bile acid receptor 1 (GPBAR1) agonist associated with bile duct proliferation. Increased levels of microbial bile acid metabolism loci (bsh, baiCD) are consistent with accumulation of TLCA and other secondary bile acids. Fecal bile acids decreased 2.8-fold, suggesting enhanced intestinal reabsorption due to induction of ileal transporters (Slc10a2, Slc51a) and increases in whole gut transit time and intestinal permeability. Moreover, serum bile acids were increased 45.4-fold, consistent with blood-to-hepatocyte transporter repression (Slco1a1, Slc10a1, Slco2b1, Slco1b2, Slco1a4) and hepatocyte-to-blood transporter induction (Abcc4, Abcc3). These results suggest that systemic alterations in enterohepatic circulation, as well as host and microbiota bile acid metabolism, favor bile acid accumulation that contributes to AhR-mediated hepatotoxicity.</p>',
			'date' => '2017-07-19',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28725001',
			'doi' => '',
			'modified' => '2017-10-09 16:22:36',
			'created' => '2017-10-09 16:22:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 127 => 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) 128 => array(
			'id' => '3258',
			'name' => 'CRISPR/Cas9 Genome Editing Reveals That the Intron Is Not Essential for var2csa Gene Activation or Silencing in Plasmodium falciparum',
			'authors' => 'Bryant J.M. et al.',
			'description' => '<p id="p-4"><em>Plasmodium falciparum</em> relies on monoallelic expression of 1 of 60 <em>var</em> virulence genes for antigenic variation and host immune evasion. Each <em>var</em> gene contains a conserved intron which has been implicated in previous studies in both activation and repression of transcription via several epigenetic mechanisms, including interaction with the <em>var</em> promoter, production of long noncoding RNAs (lncRNAs), and localization to repressive perinuclear sites. However, functional studies have relied primarily on artificial expression constructs. Using the recently developed <em>P.&nbsp;falciparum</em> clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, we directly deleted the <em>var2csa P.&nbsp;falciparum</em> 3D7_1200600 (Pf3D7_1200600) endogenous intron, resulting in an intronless <em>var</em> gene in a natural, marker-free chromosomal context. Deletion of the <em>var2csa</em> intron resulted in an upregulation of transcription of the <em>var2csa</em> gene in ring-stage parasites and subsequent expression of the PfEMP1 protein in late-stage parasites. Intron deletion did not affect the normal temporal regulation and subsequent transcriptional silencing of the <em>var</em> gene in trophozoites but did result in increased rates of <em>var</em> gene switching in some mutant clones. Transcriptional repression of the intronless <em>var2csa</em> gene could be achieved via long-term culture or panning with the CD36 receptor, after which reactivation was possible with chondroitin sulfate A (CSA) panning. These data suggest that the <em>var2csa</em> intron is not required for silencing or activation in ring-stage parasites but point to a subtle role in regulation of switching within the <em>var</em> gene family.</p>
<p id="p-5"><strong>IMPORTANCE</strong> <em>Plasmodium falciparum</em> is the most virulent species of malaria parasite, causing high rates of morbidity and mortality in those infected. Chronic infection depends on an immune evasion mechanism termed antigenic variation, which in turn relies on monoallelic expression of 1 of ~60 <em>var</em> genes. Understanding antigenic variation and the transcriptional regulation of monoallelic expression is important for developing drugs and/or vaccines. The <em>var</em> gene family encodes the antigenic surface proteins that decorate infected erythrocytes. Until recently, studying the underlying genetic elements that regulate monoallelic expression in <em>P.&nbsp;falciparum</em> was difficult, and most studies relied on artificial systems such as episomal reporter genes. Our study was the first to use CRISPR/Cas9 genome editing for the functional study of an important, conserved genetic element of <em>var</em> genes&mdash;the intron&mdash;in an endogenous, episome-free manner. Our findings shed light on the role of the <em>var</em> gene intron in transcriptional regulation of monoallelic expression.</p>',
			'date' => '2017-07-11',
			'pmid' => 'http://mbio.asm.org/content/8/4/e00729-17.abstract',
			'doi' => '',
			'modified' => '2017-10-05 11:12:18',
			'created' => '2017-10-05 11:12:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 129 => array(
			'id' => '3218',
			'name' => 'Genome-wide mapping and analysis of aryl hydrocarbon receptor (AHR)- and aryl hydrocarbon receptor repressor (AHRR)-binding sites in human breast cancer cells',
			'authors' => 'Sunny Y. Yang, Shaimaa Ahmed, Somisetty V. Satheesh, Jason Matthews',
			'description' => '<p><span>The aryl hydrocarbon receptor (AHR) mediates the toxic actions of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-</span><em class="EmphasisTypeItalic ">&rho;</em><span>-dioxin (TCDD), and also plays roles in vascular development, the immune response, and cell cycle regulation. The AHR repressor (AHRR) is an AHR-regulated gene and a negative regulator of AHR; however, the mechanisms of AHRR-dependent repression of AHR are unclear. In this study, we compared the genome-wide binding profiles of AHR and AHRR in MCF-7 human breast cancer cells treated for 24&nbsp;h with TCDD using chromatin immunoprecipitation followed by next-generation sequencing (ChIP-Seq). We identified 3915 AHR- and 2811 AHRR-bound regions, of which 974 (35%) were common to both datasets. When these 24-h datasets were also compared with AHR-bound regions identified after 45&nbsp;min of TCDD treatment, 67% (1884) of AHRR-bound regions overlapped with those of AHR. This analysis identified 994 unique AHRR-bound regions. AHRR-bound regions mapped closer to promoter regions when compared with AHR-bound regions. The AHRE was identified and overrepresented in AHR:AHRR-co-bound regions, AHR-only regions, and AHRR-only regions. Candidate unique AHR- and AHRR-bound regions were validated by ChIP&ndash;qPCR and their ability to regulate gene expression was confirmed by luciferase reporter gene assays. Overall, this study reveals that AHR and AHRR exhibit similar but also distinct genome-wide binding profiles, supporting the notion that AHRR is a context- and gene-specific repressor of AHR activity.</span></p>',
			'date' => '2017-07-05',
			'pmid' => 'https://link.springer.com/article/10.1007/s00204-017-2022-x',
			'doi' => '10.1007/s00204-017-2022-x',
			'modified' => '2017-07-29 08:23:22',
			'created' => '2017-07-29 08:23:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 130 => 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) 131 => array(
			'id' => '3358',
			'name' => 'Characterization of the Polycomb-Group Mark H3K27me3 in Unicellular Algae',
			'authors' => 'Mikulski P. et al.',
			'description' => '<p>Polycomb Group (PcG) proteins mediate chromatin repression in plants and animals by catalyzing H3K27 methylation and H2AK118/119 mono-ubiquitination through the activity of the Polycomb repressive complex 2 (PRC2) and PRC1, respectively. PcG proteins were extensively studied in higher plants, but their function and target genes in unicellular branches of the green lineage remain largely unknown. To shed light on PcG function and <i>modus operandi</i> in a broad evolutionary context, we demonstrate phylogenetic relationship of core PRC1 and PRC2 proteins and H3K27me3 biochemical presence in several unicellular algae of different phylogenetic subclades. We focus then on one of the species, the model red alga <i>Cyanidioschizon merolae</i>, and show that H3K27me3 occupies both, genes and repetitive elements, and mediates the strength of repression depending on the differential occupancy over gene bodies. Furthermore, we report that H3K27me3 in <i>C. merolae</i> is enriched in telomeric and subtelomeric regions of the chromosomes and has unique preferential binding toward intein-containing genes involved in protein splicing. Thus, our study gives important insight for Polycomb-mediated repression in lower eukaryotes, uncovering a previously unknown link between H3K27me3 targets and protein splicing.</p>',
			'date' => '2017-04-26',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28491069',
			'doi' => '',
			'modified' => '2018-04-05 13:09:46',
			'created' => '2018-04-05 13:09:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 132 => 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) 133 => array(
			'id' => '3176',
			'name' => 'First landscape of binding to chromosomes for a domesticated mariner transposase in the human genome: diversity of genomic targets of SETMAR isoforms in two colorectal cell lines',
			'authors' => 'Antoine-Lorquin A. et al.',
			'description' => '<p>Setmar is a 3-exons gene coding a SET domain fused to a Hsmar1 transposase. Its different transcripts theoretically encode 8 isoforms with SET moieties differently spliced. In vitro, the largest isoform binds specifically to Hsmar1 DNA ends and with no specificity to DNA when it is associated with hPso4. In colon cell lines, we found they bind specifically to two chromosomal targets depending probably on the isoform, Hsmar1 ends and sites with no conserved motifs. We also discovered that the isoforms profile was different between cell lines and patient tissues, suggesting the isoforms encoded by this gene in healthy cells and their functions are currently not investigated.</p>',
			'date' => '2017-03-09',
			'pmid' => 'http://biorxiv.org/content/early/2017/03/09/115030',
			'doi' => '',
			'modified' => '2017-05-15 10:24:16',
			'created' => '2017-05-15 10:24:16',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 134 => array(
			'id' => '3156',
			'name' => 'Crebbp loss cooperates with Bcl2 over-expression to promote lymphoma in mice',
			'authors' => 'Idoia García-Ramírez, Saber Tadros, Inés González-Herrero, Alberto Martín-Lorenzo, Guillermo Rodríguez-Hernández, Dalia Moore, Lucía Ruiz-Roca, Oscar Blanco, Diego Alonso-López, Javier De Las Rivas, Keenan Hartert, Romain Duval, David Klinkebiel, Martin B',
			'description' => '<p><span>CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits in B-cell development and can cooperate with Bcl2 over-expression to promote B-cell lymphoma. Through transcriptional and epigenetic profiling of these B-cells we found that Crebbp inactivation was associated with broad transcriptional alterations, but no changes in the patterns of histone acetylation at the proximal regulatory regions of these genes. However, B-cells with Crebbp inactivation showed high expression of Myc and patterns of altered histone acetylation that were localized to intragenic regions, enriched for Myc DNA binding motifs, and showed Myc binding. Through the analysis of CREBBP mutations from a large cohort of primary human FL and DLBCL, we show a significant difference in the spectrum of CREBBP mutations in these two diseases, with higher frequencies of nonsense/frameshift mutations in DLBCL compared to FL. Together our data therefore provide important links between Crebbp inactivation and Bcl2 dependence, and show a role for Crebbp inactivation in the induction of Myc expression. We suggest this may parallel the role of CREBBP frameshift/nonsense mutations in DLBCL that result in loss of the protein, but may contrast the role of missense mutations in the lysine acetyltransferase domain that are more frequently observed in FL and yield an inactive protein.</span></p>',
			'date' => '2017-03-05',
			'pmid' => 'http://www.bloodjournal.org/content/early/2017/03/13/blood-2016-08-733469?sso-checked=true',
			'doi' => 'https://doi.org/10.1182/blood-2016-08-733469',
			'modified' => '2017-05-11 11:17:42',
			'created' => '2017-04-10 07:56:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 135 => array(
			'id' => '3151',
			'name' => 'Aorta macrophage inflammatory and epigenetic changes in a murine model of obstructive sleep apnea: Potential role of CD36.',
			'authors' => 'Cortese R. et al.',
			'description' => '<p>Obstructive sleep apnea (OSA) affects 8-10% of the population, is characterized by chronic intermittent hypoxia (CIH), and causally associates with cardiovascular morbidities. In CIH-exposed mice, closely mimicking the chronicity of human OSA, increased accumulation and proliferation of pro-inflammatory metabolic M1-like macrophages highly expressing CD36, emerged in aorta. Transcriptomic and MeDIP-seq approaches identified activation of pro-atherogenic pathways involving a complex interplay of histone modifications in functionally-relevant biological pathways, such as inflammation and oxidative stress in aorta macrophages. Discontinuation of CIH did not elicit significant improvements in aorta wall macrophage phenotype. However, CIH-induced aorta changes were absent in CD36 knockout mice, Our results provide mechanistic insights showing that CIH exposures during sleep in absence of concurrent pro-atherogenic settings (i.e., genetic propensity or dietary manipulation) lead to the recruitment of CD36(+)<sup>high</sup> macrophages to the aortic wall and trigger atherogenesis. Furthermore, long-term CIH-induced changes may not be reversible with usual OSA treatment.</p>',
			'date' => '2017-02-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28240319',
			'doi' => '',
			'modified' => '2017-03-28 09:16:02',
			'created' => '2017-03-28 09:16:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 136 => array(
			'id' => '3138',
			'name' => 'Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia',
			'authors' => 'Chen S. et al.',
			'description' => '<p>Severe neonatal hyperbilirubinemia (SNH) and the onset of bilirubin encephalopathy and kernicterus result in part from delayed expression of UDP-glucuronosyltransferase 1A1 (UGT1A1) and the inability to metabolize bilirubin. Although there is a good understanding of the early events after birth that lead to the rapid increase in serum bilirubin, the events that control delayed expression of UGT1A1 during development remain a mystery. Humanized <em>UGT1</em> (<em>hUGT1</em>) mice develop SNH spontaneously, which is linked to repression of both liver and intestinal UGT1A1. In this study, we report that deletion of intestinal nuclear receptor corepressor 1 (NCoR1) completely diminishes hyperbilirubinemia in <em>hUGT1</em> neonates because of intestinal <em>UGT1A1</em> gene derepression. Transcriptomic studies and immunohistochemistry analysis demonstrate that NCoR1 plays a major role in repressing developmental maturation of the intestines. Derepression is marked by accelerated metabolic and oxidative phosphorylation, drug metabolism, fatty acid metabolism, and intestinal maturation, events that are controlled predominantly by H3K27 acetylation. The control of NCoR1 function and derepression is linked to IKK&beta; function, as validated in <em>hUGT1</em> mice with targeted deletion of intestinal IKK&beta;. Physiological events during neonatal development that target activation of an IKK&beta;/NCoR1 loop in intestinal epithelial cells lead to derepression of genes involved in intestinal maturation and bilirubin detoxification. These findings provide a mechanism of NCoR1 in intestinal homeostasis during development and provide a key link to those events that control developmental repression of UGT1A1 and hyperbilirubinemia.</p>',
			'date' => '2017-02-21',
			'pmid' => 'http://www.pnas.org/content/114/8/E1432.abstract',
			'doi' => '',
			'modified' => '2017-03-21 17:48:23',
			'created' => '2017-03-21 17:48:23',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 137 => array(
			'id' => '3166',
			'name' => 'The Drosophila speciation factor HMR localizes to genomic insulator sites',
			'authors' => 'Gerland T.A. et al.',
			'description' => '<p>Hybrid incompatibility between Drosophila melanogaster and D. simulans is caused by a lethal interaction of the proteins encoded by the Hmr and Lhr genes. In D. melanogaster the loss of HMR results in mitotic defects, an increase in transcription of transposable elements and a deregulation of heterochromatic genes. To better understand the molecular mechanisms that mediate HMR's function, we measured genome-wide localization of HMR in D. melanogaster tissue culture cells by chromatin immunoprecipitation. Interestingly, we find HMR localizing to genomic insulator sites that can be classified into two groups. One group belongs to gypsy insulators and another one borders HP1a bound regions at active genes. The transcription of the latter group genes is strongly affected in larvae and ovaries of Hmr mutant flies. Our data suggest a novel link between HMR and insulator proteins, a finding that implicates a potential role for genome organization in the formation of species.</p>',
			'date' => '2017-02-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28207793',
			'doi' => '',
			'modified' => '2017-05-09 10:05:49',
			'created' => '2017-05-09 10:05:49',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 138 => array(
			'id' => '3357',
			'name' => 'Applying the INTACT method to purify endosperm nuclei and to generate parental-specific epigenome profiles.',
			'authors' => 'Moreno-Romero J. et al.',
			'description' => '<p>The early endosperm tissue of dicot species is very difficult to isolate by manual dissection. This protocol details how to apply the INTACT (isolation of nuclei tagged in specific cell types) system for isolating early endosperm nuclei of Arabidopsis at high purity and how to generate parental-specific epigenome profiles. As a Protocol Extension, this article describes an adaptation of an existing Nature Protocol that details the use of the INTACT method for purification of root nuclei. We address how to obtain the INTACT lines, generate the starting material and purify the nuclei. We describe a method that allows purity assessment, which has not been previously addressed. The purified nuclei can be used for ChIP and DNA bisulfite treatment followed by next-generation sequencing (seq) to study histone modifications and DNA methylation profiles, respectively. By using two different Arabidopsis accessions as parents that differ by a large number of single-nucleotide polymorphisms (SNPs), we were able to distinguish the parental origin of epigenetic modifications. Our protocol describes the only working method to our knowledge for generating parental-specific epigenome profiles of the early Arabidopsis endosperm. The complete protocol, from silique collection to finished libraries, can be completed in 2 d for bisulfite-seq (BS-seq) and 3 to 4 d for ChIP-seq experiments.This protocol is an extension to: Nat. Protoc. 6, 56-68 (2011); doi:10.1038/nprot.2010.175; published online 16 December 2010.</p>',
			'date' => '2017-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28055034',
			'doi' => '',
			'modified' => '2018-04-05 12:52:20',
			'created' => '2018-04-05 12:52:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 139 => array(
			'id' => '3042',
			'name' => 'BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire',
			'authors' => 'Najafova Z. et al.',
			'description' => '<p>Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4.</p>',
			'date' => '2016-09-19',
			'pmid' => 'http://nar.oxfordjournals.org/content/early/2016/09/19/nar.gkw826.abstract',
			'doi' => '',
			'modified' => '2016-10-10 09:58:41',
			'created' => '2016-10-10 09:49:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 140 => array(
			'id' => '3043',
			'name' => 'CTCF modulates Estrogen Receptor function through specific chromatin and nuclear matrix interactions',
			'authors' => 'Fiorito E. et al.',
			'description' => '<p>Enhancer regions and transcription start sites of estrogen-target regulated genes are connected by means of Estrogen Receptor long-range chromatin interactions. Yet, the complete molecular mechanisms controlling the transcriptional output of engaged enhancers and subsequent activation of coding genes remain elusive. Here, we report that CTCF binding to enhancer RNAs is enriched when breast cancer cells are stimulated with estrogen. CTCF binding to enhancer regions results in modulation of estrogen-induced gene transcription by preventing Estrogen Receptor chromatin binding and by hindering the formation of additional enhancer-promoter ER looping. Furthermore, the depletion of CTCF facilitates the expression of target genes associated with cell division and increases the rate of breast cancer cell proliferation. We have also uncovered a genomic network connecting loci enriched in cell cycle regulator genes to nuclear lamina that mediates the CTCF function. The nuclear lamina and chromatin interactions are regulated by estrogen-ER. We have observed that the chromatin loops formed when cells are treated with estrogen establish contacts with the nuclear lamina. Once there, the portion of CTCF associated with the nuclear lamina interacts with enhancer regions, limiting the formation of ER loops and the induction of genes present in the loop. Collectively, our results reveal an important, unanticipated interplay between CTCF and nuclear lamina to control the transcription of ER target genes, which has great implications in the rate of growth of breast cancer cells.</p>',
			'date' => '2016-09-15',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27638884',
			'doi' => '',
			'modified' => '2016-10-10 10:12:33',
			'created' => '2016-10-10 10:12:33',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 141 => array(
			'id' => '3052',
			'name' => 'PionX sites mark the X chromosome for dosage compensation',
			'authors' => 'Villa R et al.',
			'description' => '<p>The rules defining which small fraction of related DNA sequences can be selectively bound by a transcription factor are poorly understood. One of the most challenging tasks in DNA recognition is posed by dosage compensation systems that require the distinction between sex chromosomes and autosomes. In <i>Drosophila melanogaster</i>, the male-specific lethal dosage compensation complex (MSL-DCC) doubles the level of transcription from the single male X chromosome, but the nature of this selectivity is not known<sup><a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref1" title="Lucchesi, J. C. &amp; Kuroda, M. I. Dosage compensation in Drosophila. Cold Spring Harb. Perspect. Biol. 7, a019398 (2015)" id="ref-link-7">1</a></sup>. Previous efforts to identify X-chromosome-specific target sequences were unsuccessful as the identified MSL recognition elements lacked discriminative power<sup><a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref2" title="Alekseyenko, A. A. et al. A sequence motif within chromatin entry sites directs MSL establishment on the Drosophila X chromosome. Cell. 134, 599&ndash;609 (2008)" id="ref-link-8">2</a>, <a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref3" title="Straub, T., Grimaud, C., Gilfillan, G. D., Mitterweger, A. &amp; Becker, P. B. The chromosomal high-affinity binding sites for the Drosophila dosage compensation complex. PLoS Genet. 4, e1000302 (2008)" id="ref-link-9">3</a></sup>. Therefore, additional determinants such as co-factors, chromatin features, RNA and chromosome conformation have been proposed to refine targeting further<sup><a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref4" title="McElroy, K. A., Kang, H. &amp; Kuroda, M. I. Are we there yet? Initial targeting of the Male-Specific Lethal and Polycomb group chromatin complexes in Drosophila. Open Biol. 4, 140006 (2014)" id="ref-link-10">4</a></sup>. Here, using an <i>in vitro</i> genome-wide DNA binding assay, we show that recognition of the X chromosome is an intrinsic feature of the MSL-DCC. MSL2, the male-specific organizer of the complex, uses two distinct DNA interaction surfaces&mdash;the CXC and proline/basic-residue-rich domains&mdash;to identify complex DNA elements on the X chromosome. Specificity is provided by the CXC domain, which binds a novel motif defined by DNA sequence and shape. This motif characterizes a subclass of MSL2-binding sites, which we name PionX (pioneering sites on the X) as they appeared early during the recent evolution of an X chromosome in <i>D. miranda</i> and are the first chromosomal sites to be bound during <i>de novo</i> MSL-DCC assembly. Our data provide the first, to our knowledge, documented molecular mechanism through which the dosage compensation machinery distinguishes the X chromosome from an autosome. They highlight fundamental principles in the recognition of complex DNA elements by protein that will have a strong impact on many aspects of chromosome biology.</p>',
			'date' => '2016-08-31',
			'pmid' => 'http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html',
			'doi' => '',
			'modified' => '2016-10-24 14:23:31',
			'created' => '2016-10-24 14:23:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 142 => 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) 143 => array(
			'id' => '2976',
			'name' => 'Deletion of Polycomb Repressive Complex 2 From Mouse Intestine Causes Loss of Stem Cells',
			'authors' => 'Koppens MA et al.',
			'description' => '<h4>BACKGROUND &amp; AIMS:</h4>
<p><abstracttext label="BACKGROUND &amp; AIMS" nlmcategory="OBJECTIVE">The polycomb repressive complex 2 (PRC2) regulates differentiation by contributing to repression of gene expression and thereby stabilizing the fate of stem cells and their progeny. PRC2 helps to maintain adult stem cell populations, but little is known about its functions in intestinal stem cells. We studied phenotypes of mice with intestine-specific deletion of the PRC2 proteins EED (a subunit required for PRC2 function) and EZH2 (a histone methyltransferase).</abstracttext></p>
<h4>METHODS:</h4>
<p><abstracttext label="METHODS" nlmcategory="METHODS">We performed studies of AhCre;EedLoxP/LoxP (EED knockout) mice and AhCre;Ezh2LoxP/LoxP (EZH2 knockout) mice, which have intestine-specific disruption in EED and EZH2, respectively. Small intestinal crypts were isolated and subsequently cultured to grow organoids. Intestines and organoids were analyzed by immunohistochemical, in situ hybridization, RNA sequence, and chromatin immunoprecipitation methods.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Intestines of EED knockout mice had massive crypt degeneration and lower numbers of proliferating cells, compared with wildtype control mice; Cdkn2a became derepressed and we detected increased levels of P21. We did not observe any differences between EZH2 knockout and control mice. Intestinal crypts from EED knockout mice had signs of aberrant differentiation of uncommitted crypt cells-these differentiated toward the secretory cell lineage. Furthermore, crypts from EED-knockout mice had impaired Wnt signaling and concomitant loss of intestinal stem cells; this phenotype was not reversed upon ectopic stimulation of Wnt and Notch signaling in organoids. Analysis of gene expression patterns from intestinal tissues of EED knockout mice revealed dysregulation of several genes involved in Wnt signaling. Wnt signaling was directly regulated by PRC2.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">In intestinal tissues of mice, PRC2 maintains small intestinal stem cells by promoting proliferation and preventing differentiation in the intestinal stem cell compartment. PRC2 controls expression of genes in multiple signaling pathways that regulate intestinal homeostasis.</abstracttext></p>',
			'date' => '2016-06-21',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27342214',
			'doi' => ' 10.1053/j.gastro.2016.06.020',
			'modified' => '2016-07-07 10:04:31',
			'created' => '2016-07-07 10:04:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 144 => array(
			'id' => '2949',
			'name' => 'Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells',
			'authors' => 'von Meyenn F et al.',
			'description' => '<p>Global demethylation is part of a conserved program of epigenetic reprogramming to naive pluripotency. The transition from primed hypermethylated embryonic stem cells (ESCs) to naive hypomethylated ones (serum-to-2i) is a valuable model system for epigenetic reprogramming. We present a mathematical model, which accurately predicts global DNA demethylation kinetics. Experimentally, we show that the main drivers of global demethylation are neither active mechanisms (Aicda, Tdg, and Tet1-3) nor the&nbsp;reduction of de novo methylation. UHRF1 protein, the essential targeting factor for DNMT1, is reduced upon transition to 2i, and so is recruitment of the maintenance methylation machinery to replication foci. Concurrently, there is global loss of H3K9me2, which is needed for chromatin binding of UHRF1. These mechanisms synergistically enforce global DNA hypomethylation in a replication-coupled fashion. Our observations establish the molecular mechanism for global demethylation in naive ESCs, which has key parallels with those operating in primordial germ cells and early embryos.</p>',
			'date' => '2016-05-25',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27237052',
			'doi' => '10.1016/j.molcel.2016.04.025',
			'modified' => '2016-06-10 15:23:36',
			'created' => '2016-06-10 15:23:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 145 => array(
			'id' => '2918',
			'name' => 'Parental epigenetic asymmetry of PRC2-mediated histone modifications in the Arabidopsis endosperm',
			'authors' => 'Moreno-Romero J et al.',
			'description' => '<p>Parental genomes in the endosperm are marked by differential DNA methylation and are therefore epigenetically distinct. This epigenetic asymmetry is established in the gametes and maintained after fertilization by unknown mechanisms. In this manuscript, we have addressed the key question whether parentally inherited differential DNA methylation affects <em>de novo</em> targeting of chromatin modifiers in the early endosperm. Our data reveal that polycomb-mediated H3 lysine 27 trimethylation (H3K27me3) is preferentially localized to regions that are targeted by the DNA glycosylase DEMETER (DME), mechanistically linking DNA hypomethylation to imprinted gene expression. Our data furthermore suggest an absence of <em>de novo </em>DNA methylation in the early endosperm, providing an explanation how DME-mediated hypomethylation of the maternal genome is maintained after fertilization. Lastly, we show that paternal-specific H3K27me3-marked regions are located at pericentromeric regions, suggesting that H3K27me3 and DNA methylation are not necessarily exclusive marks at pericentromeric regions in the endosperm.</p>',
			'date' => '2016-04-25',
			'pmid' => 'http://onlinelibrary.wiley.com/doi/10.15252/embj.201593534/abstract',
			'doi' => '10.15252/embj.201593534',
			'modified' => '2016-05-14 00:49:53',
			'created' => '2016-05-13 11:30:16',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		)
	),
	'Testimonial' => array(
		(int) 0 => array(
			'id' => '68',
			'name' => 'Universidad de Chile',
			'description' => '<p>We sheared the DNA on the Diagenode One and used the MicroPlex Library Preparation v2 Kit to create DNA libraries for whole genome sequencing of four plant species for which there is no reference genome available. Previous attempts with a commercial Tn5-transposase based method gave unsatisfactory results. However, the Diagenode MicroPlex kit was quicker, easier, and gave the expected profile of fragment sizes. In just 30 seconds of sonication, we obtained a fragment distribution centered at 270 bp. The library construction took only 2 hours with this kit. The library was sequenced in a NexSeq 550 in High-Output mode, giving 85% based with&gt;Q30.</p>',
			'author' => 'PhD. Ricardo Verdugo, Assistant Professor, University of Chile',
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			'slug' => 'universidad-de-chile',
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			'modified' => '2018-05-14 14:50:37',
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		),
		(int) 1 => 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',
			'featured' => false,
			'slug' => 'kamila-kwasniewska',
			'meta_keywords' => '',
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			'modified' => '2016-02-01 10:45:40',
			'created' => '2016-02-01 09:56:38',
			'ProductsTestimonial' => array(
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		),
		(int) 2 => array(
			'id' => '45',
			'name' => 'Imperial College London - iDeal ChIP-seq kit for TF + MicroPlex v2',
			'description' => '<p>There are so many ChIP-related products on the market, but I feel so lucky that I have been using the ones from Diagenode since I started my CHIP-seq project. I have used their <a href="../p/ideal-chip-seq-kit-for-transcription-factors-x100-100-rxns">iDeal CHIP-seq Kit for Transcription Factors</a> and <a href="../p/microplex-library-preparation-kit-v2-x48-12-indices-48-rxns">MicroPlex Library Prep Kit v2</a>. Both of them are fantastic and very reproducible. With the very-well written protocols, you will just be home and dry. Particularly, I want to thank the technical support, who is very patient, knowledgeable and extremely helpful. I would definitely recommend my colleagues to use the CHIP products from Diagenode.</p>',
			'author' => 'Dr Kaiyu Lei, Faculty of Medicine, Department of Surgery & Cancer, Imperial College London',
			'featured' => false,
			'slug' => 'testimonial-kaiyu',
			'meta_keywords' => '',
			'meta_description' => '',
			'modified' => '2016-03-09 16:00:31',
			'created' => '2015-12-18 15:40:02',
			'ProductsTestimonial' => array(
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			)
		),
		(int) 3 => array(
			'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',
			'featured' => false,
			'slug' => 'microchip-andrea',
			'meta_keywords' => '',
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			'modified' => '2016-03-09 16:00:08',
			'created' => '2015-12-07 13:04:58',
			'ProductsTestimonial' => array(
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			)
		),
		(int) 4 => array(
			'id' => '35',
			'name' => 'Microplex v2 - Katia Basso',
			'description' => '<p>We used the MicroPlex version 2 kit to generate libraries using ChIP DNA for several transcription factors and compared the results to a standard library generation protocol starting from 5ng of ChIP DNA. Even when we reduced the starting amount of DNA by 10-fold, the MicroPlex Kit produced the same high yields and quality of the libraries. As expected, the number of duplicate reads increased but 15 to 20 million unique reads were sufficient to achieve excellent enrichment data. We found that no information was lost, and the MicroPlex Kit helped produce data that was consistent with the standard protocol despite the lower input. On top of this, the MicroPlex Kit was extremely user-friendly and saved us time. The MicroPlex version 2 kit will make challenging ChIP-seq experiments that rely on very limited amount of starting material much easier with robust results.</p>',
			'author' => 'Katia Basso, PhD, Assistant Professor, Columbia University, New York',
			'featured' => true,
			'slug' => 'microplex-v2-katia-basso',
			'meta_keywords' => '',
			'meta_description' => '',
			'modified' => '2016-03-22 11:32:30',
			'created' => '2015-08-25 10:01:00',
			'ProductsTestimonial' => array(
				[maximum depth reached]
			)
		),
		(int) 5 => array(
			'id' => '30',
			'name' => 'MicroPlex Kit - Sammons',
			'description' => '<p>The Diagenode MicroPlex kit is the quickest and most efficient way to make sequencing libraries, especially from samples with very low inputs. We regularly start with picogram amounts of ChIP material and produce excellent quality libraries that would be impossible to make using normal methods. Sequencing libraries made from the MicroPlex kit give us excellent results even in large genomes. The kit performs very well, and we will use the kit in the future for studies with low cell numbers or starting material.</p>',
			'author' => 'Dr. Morgan Sammons, Lab of Dr. Shelley Berger, University of Pennsylvania',
			'featured' => false,
			'slug' => '',
			'meta_keywords' => '',
			'meta_description' => '',
			'modified' => '2015-08-18 16:27:04',
			'created' => '2015-07-29 10:43:24',
			'ProductsTestimonial' => array(
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		)
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			'countries' => 'GB',
			'modified' => '2021-10-12 14:54:08',
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<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><span>The MicroPlex v2 kit (Cat. No. C05010013) 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>.</span></p>',
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$testimonials = '<blockquote><p>We sheared the DNA on the Diagenode One and used the MicroPlex Library Preparation v2 Kit to create DNA libraries for whole genome sequencing of four plant species for which there is no reference genome available. Previous attempts with a commercial Tn5-transposase based method gave unsatisfactory results. However, the Diagenode MicroPlex kit was quicker, easier, and gave the expected profile of fragment sizes. In just 30 seconds of sonication, we obtained a fragment distribution centered at 270 bp. The library construction took only 2 hours with this kit. The library was sequenced in a NexSeq 550 in High-Output mode, giving 85% based with&gt;Q30.</p><cite>PhD. Ricardo Verdugo, Assistant Professor, University of Chile</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>There are so many ChIP-related products on the market, but I feel so lucky that I have been using the ones from Diagenode since I started my CHIP-seq project. I have used their <a href="../p/ideal-chip-seq-kit-for-transcription-factors-x100-100-rxns">iDeal CHIP-seq Kit for Transcription Factors</a> and <a href="../p/microplex-library-preparation-kit-v2-x48-12-indices-48-rxns">MicroPlex Library Prep Kit v2</a>. Both of them are fantastic and very reproducible. With the very-well written protocols, you will just be home and dry. Particularly, I want to thank the technical support, who is very patient, knowledgeable and extremely helpful. I would definitely recommend my colleagues to use the CHIP products from Diagenode.</p><cite>Dr Kaiyu Lei, Faculty of Medicine, Department of Surgery & Cancer, Imperial College London</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>
<blockquote><p>The Diagenode MicroPlex kit is the quickest and most efficient way to make sequencing libraries, especially from samples with very low inputs. We regularly start with picogram amounts of ChIP material and produce excellent quality libraries that would be impossible to make using normal methods. Sequencing libraries made from the MicroPlex kit give us excellent results even in large genomes. The kit performs very well, and we will use the kit in the future for studies with low cell numbers or starting material.</p><cite>Dr. Morgan Sammons, Lab of Dr. Shelley Berger, University of Pennsylvania</cite></blockquote>
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$featured_testimonials = '<blockquote><span class="label-green" style="margin-bottom:16px;margin-left:-22px">TESTIMONIAL</span><p>We used the MicroPlex version 2 kit to generate libraries using ChIP DNA for several transcription factors and compared the results to a standard library generation protocol starting from 5ng of ChIP DNA. Even when we reduced the starting amount of DNA by 10-fold, the MicroPlex Kit produced the same high yields and quality of the libraries. As expected, the number of duplicate reads increased but 15 to 20 million unique reads were sufficient to achieve excellent enrichment data. We found that no information was lost, and the MicroPlex Kit helped produce data that was consistent with the standard protocol despite the lower input. On top of this, the MicroPlex Kit was extremely user-friendly and saved us time. The MicroPlex version 2 kit will make challenging ChIP-seq experiments that rely on very limited amount of starting material much easier with robust results.</p><cite>Katia Basso, PhD, Assistant Professor, Columbia University, New York</cite></blockquote>
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        <p><strong><input name="data[Cart][quantity]" placeholder="1" value="1" min="1" style="width:60px;display:inline" type="number" id="CartQuantity" required="required"/></strong>iDeal ChIP-seq kit for Transcription Factors個カートに追加。</p>

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<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>
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<td style="width: 144px;"></td>
<td style="width: 267px; text-align: center;"><span style="font-weight: 400;">Amount per IP</span></td>
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<td style="width: 144px;">Cells</td>
<td style="width: 267px; text-align: center;"><strong>4,000,000</strong></td>
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<td style="width: 267px; text-align: center;"><strong>30 mg</strong></td>
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<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>
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<li><span style="font-weight: 400;"><strong>Highly optimized protocol</strong> for ChIP-seq from cells and tissues</span></li>
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<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>
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<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>',
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			'name' => 'MicroPlex Library Preparation Kit v2 (12 indices)',
			'description' => '<p><strong>ChIP-seq</strong><strong>専用に最適化</strong></p>
<p>MicroPlex Library Preparation&trade;kit は、ChIP-seq専用に検証されていて、ピコグラム単位の入力だけで索引付きライブラリー調製できる唯一のキットです。 <span><a href="http://www.diagenode.com/en/catalog/chromatin-function-74/chromatin-immunoprecipitation-75/manual-chip-kits-77/product/true-microchip-kit-x16-2532">True MicroChIP kit</a></span>と組み合わせることで、わずか10,000細胞でChIP-seqを行えます。細胞入力数、手順数、用品数が減少するだけでなく、結果までの時間も短縮できます！</p>',
			'label1' => '特徴',
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<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>
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<p>MicroPlex Library Preparation&trade;kit は、ChIP-seq専用に検証されていて、ピコグラム単位の入力だけで索引付きライブラリー調製できる唯一のキットです。 <span><a href="http://www.diagenode.com/en/catalog/chromatin-function-74/chromatin-immunoprecipitation-75/manual-chip-kits-77/product/true-microchip-kit-x16-2532">True MicroChIP kit</a></span>と組み合わせることで、わずか10,000細胞でChIP-seqを行えます。細胞入力数、手順数、用品数が減少するだけでなく、結果までの時間も短縮できます！</p>',
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<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>
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<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>
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<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>',
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<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>',
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<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>',
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<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>
<p>
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</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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			'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',
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			'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',
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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]
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			'Image' => array(
				[maximum depth reached]
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		)
	),
	'Application' => array(
		(int) 0 => array(
			'id' => '14',
			'position' => '10',
			'parent_id' => '3',
			'name' => 'DNA/RNA library preparation',
			'description' => '<div class="row">
<div class="small-12 medium-12 large-12 columns">
<p><span style="font-weight: 400;">Most of the major next-generation sequencing platforms require ligation of specific adaptor oligos to </span><a href="../applications/dna-rna-shearing"><span style="font-weight: 400;">fragmented DNA or RNA</span></a><span style="font-weight: 400;"> prior to sequencing</span></p>
<p><span style="font-weight: 400;">After input DNA has been fragmented, it is end-repaired and blunt-ended</span><span style="font-weight: 400;">. The next step is a A-tailing in which dAMP is added to the 3&acute; end of the blunt phosphorylated DNA fragments to prevent concatemerization and to allow the ligation of adaptors with complementary dT overhangs. In addition, barcoded adapters can be incorporated to facilitate multiplexing prior to or during amplification.</span></p>
<center><img src="https://www.diagenode.com/img/categories/library-prep/flux.png" /></center>
<p><span style="font-weight: 400;">Diagenode offers a comprehensive product portfolio for library preparation:<br /></span></p>
<strong><a href="https://www.diagenode.com/en/categories/Library-preparation-for-RNA-seq">D-Plex&nbsp;RNA-seq Library Preparation Kits</a></strong><br />
<p><span style="font-weight: 400;">Diagenode&rsquo;s new RNA-sequencing solutions utilize the innovative c</span><span style="font-weight: 400;">apture and a</span><span style="font-weight: 400;">mplification by t</span><span style="font-weight: 400;">ailing and s</span><span style="font-weight: 400;">witching&rdquo;</span><span style="font-weight: 400;">, a ligation-free method to produce DNA libraries for next generation sequencing from low input amounts of RNA. </span><span style="font-weight: 400;"></span><a href="../categories/Library-preparation-for-RNA-seq">Learn more</a></p>
<strong><a href="../categories/library-preparation-for-ChIP-seq">ChIP-seq and DNA sequencing library preparation solutions</a></strong><br />
<p><span style="font-weight: 400;">Our kits have been optimized for DNA library preparation used for next generation sequencing for a wide range of inputs. Using a simple three-step protocols, our</span><a href="http://www.diagenode.com/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns"><span style="font-weight: 400;"> </span></a><span style="font-weight: 400;">kits are an optimal choice for library preparation from DNA inputs down to 50 pg.&nbsp;</span><a href="../categories/library-preparation-for-ChIP-seq">Learn more</a></p>
<a href="../p/bioruptor-pico-sonication-device"><span style="font-weight: 400;"></span><strong>Bioruptor Pico - short fragments</strong></a><a href="../categories/library-preparation-for-ChIP-seq-and-DNA-sequencing"><span style="font-weight: 400;"></span></a><br />
<p><span style="font-weight: 400;"></span><span style="font-weight: 400;">Our well-cited Bioruptor Pico is the shearing device of choice for chromatin and DNA fragmentation. Obtain uniform and tight fragment distributions &nbsp;between 150bp -2kb. </span><a href="../p/bioruptor-pico-sonication-device">Learn more</a></p>
<strong><a href="../p/megaruptor2-1-unit"><span href="../p/bioruptor-pico-sonication-device">Megaruptor</span>&reg; - long fragments</a></strong><a href="../p/bioruptor-pico-sonication-device"><span style="font-weight: 400;"></span></a><a href="../categories/library-preparation-for-ChIP-seq-and-DNA-sequencing"><span style="font-weight: 400;"></span></a><br />
<p><span style="font-weight: 400;"></span><span style="font-weight: 400;">The Megaruptor is designed to shear DNA from 3kb-75kb for long-read sequencing.&nbsp; <a href="../p/megaruptor2-1-unit">Learn more</a></span></p>
<span href="../p/bioruptor-pico-sonication-device"></span><span style="font-weight: 400;"></span></div>
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			'meta_title' => 'Library preparation for Next Generation Sequencing (NGS) | Diagenode',
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			'name' => '次世代シーケンシング',
			'description' => '<div class="row">
<div class="small-12 medium-12 large-12 columns">
<h2 style="font-size: 22px;">DNA断片化、ライブラリー調製、自動化：NGSのワンストップショップ</h2>
<table class="small-12 medium-12 large-12 columns">
<tbody>
<tr>
<th class="small-12 medium-12 large-12 columns">
<h4>1. 断片化装置を選択してください：150 bp〜75 kbの範囲でDNAを断片化します。</h4>
</th>
</tr>
<tr style="background-color: #ffffff;">
<td class="small-12 medium-12 large-12 columns"></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns"><a href="../p/bioruptor-pico-sonication-device"><img src="https://www.diagenode.com/img/product/shearing_technologies/bioruptor_pico.jpg" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/megaruptor2-1-unit"><img src="https://www.diagenode.com/img/product/shearing_technologies/B06010001_megaruptor2.jpg" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/bioruptor-one-sonication-device"><img src="https://www.diagenode.com/img/product/shearing_technologies/br-one-profil.png" /></a></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns">5&mu;lまで断片化：150 bp〜2 kb<br />NGS DNAライブラリー調製およびFFPE核酸抽出に最適で、</td>
<td class="small-4 medium-4 large-4 columns">2 kb〜75 kbの範囲をできます。<br />メイトペアライブラリー調製および長いフラグメントDNAシーケンシングに最適で、この軽量デスクトップデバイスで</td>
<td class="small-4 medium-4 large-4 columns">20または50&mu;lの断片化が可能です。</td>
</tr>
</tbody>
</table>
<table class="small-12 medium-12 large-12 columns">
<tbody>
<tr>
<th class="small-8 medium-8 large-8 columns">
<h4>2. 最適化されたライブラリー調整キットを選択してください。</h4>
</th>
<th class="small-4 medium-4 large-4 columns">
<h4>3. ライブラリー前処理自動化を選択して、比類のないデータ再現性を実感</h4>
</th>
</tr>
<tr style="background-color: #ffffff;">
<td class="small-12 medium-12 large-12 columns"></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns"><a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns"><img src="https://www.diagenode.com/img/product/kits/microPlex_library_preparation.png" style="display: block; margin-left: auto; margin-right: auto;" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns"><img src="https://www.diagenode.com/img/product/kits/box_kit.jpg" style="display: block; margin-left: auto; margin-right: auto;" height="173" width="250" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/sx-8g-ip-star-compact-automated-system-1-unit"><img src="https://www.diagenode.com/img/product/automation/B03000002%20_ipstar_compact.png" style="display: block; margin-left: auto; margin-right: auto;" /></a></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns" style="text-align: center;">50pgの低入力：MicroPlex Library Preparation Kit</td>
<td class="small-4 medium-4 large-4 columns" style="text-align: center;">5ng以上：iDeal&nbsp;Library Preparation Kit</td>
<td class="small-4 medium-4 large-4 columns" style="text-align: center;">Achieve great NGS data easily</td>
</tr>
</tbody>
</table>
</div>
</div>
<blockquote>
<div class="row">
<div class="small-12 medium-12 large-12 columns"><span class="label" style="margin-bottom: 16px; margin-left: -22px; font-size: 15px;">DiagenodeがNGS研究にぴったりなプロバイダーである理由</span>
<p>Diagenodeは15年以上もエピジェネティクス研究に専念、専門としています。 ChIP研究クロマチン用のユニークな断片化システムの開発から始まり、 専門知識を活かし、5&mu;lのせん断体積まで可能で、NGS DNAライブラリーの調製に最適な最先端DNA断片化装置の開発にたどり着きました。 我々は以来、ChIP-seq、Methyl-seq、NGSライブラリー調製用キットを研究開発し、業界をリードする免疫沈降研究と同様に、ライブラリー調製を自動化および完結させる独自の自動化システムを開発にも成功しました。</p>
<ul>
<li>信頼されるせん断装置</li>
<li>様々なインプットからのライブラリ作成キット</li>
<li>独自の自動化デバイス</li>
</ul>
</div>
</div>
</blockquote>
<div class="row">
<div class="small-12 columns">
<ul class="accordion" data-accordion="">
<li class="accordion-navigation"><a href="#panel1a">次世代シーケンシングへの理解とその専門知識</a>
<div id="panel1a" class="content">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<p><strong>次世代シーケンシング (NGS)</strong> ）は、著しいスケールとハイスループットでシーケンシングを行い、1日に数十億もの塩基生成を可能にします。 NGSのハイスループットは迅速でありながら正確で、再現性のあるデータセットを実現し、さらにシーケンシング費用を削減します。 NGSは、ゲノムシーケンシング、ゲノム再シーケンシング、デノボシーケンシング、トランスクリプトームシーケンシング、その他にDNA-タンパク質相互作用の検出やエピゲノムなどを示します。 指数関数的に増加するシーケンシングデータの需要は、計算分析の障害や解釈、データストレージなどの課題を解決します。</p>
<p>アプリケーションおよび出発物質に応じて、数百万から数十億の鋳型DNA分子を大規模に並行してシーケンシングすることが可能です。その為に、異なる化学物質を使用するいくつかの市販のNGSプラットフォームを利用することができます。 NGSプラットフォームの種類によっては、事前準備とライブラリー作成が必要です。</p>
<p>NGSにとっても、特にデータ処理と分析に関した大きな課題はあります。第3世代技術はゲノミクス研究にさらに革命を起こすであろうと大きく期待されています。</p>
</div>
</div>
<div class="row">
<div class="small-6 medium-6 large-6 columns">
<p><strong>NGS アプリケーション</strong></p>
<ul>
<li>全ゲノム配列決定</li>
<li>デノボシーケンシング</li>
<li>標的配列</li>
<li>Exomeシーケンシング</li>
<li>トランスクリプトーム配列決定</li>
<li>ゲノム配列決定</li>
<li>ミトコンドリア配列決定</li>
<li>DNA-タンパク質相互作用（ChIP-seq</li>
<li>バリアント検出</li>
<li>ゲノム仕上げ</li>
</ul>
</div>
<div class="small-6 medium-6 large-6 columns">
<p><strong>研究分野におけるNGS:</strong></p>
<ul>
<li>腫瘍学</li>
<li>リプロダクティブ・ヘルス</li>
<li>法医学ゲノミクス</li>
<li>アグリゲノミックス</li>
<li>複雑な病気</li>
<li>微生物ゲノミクス</li>
<li>食品・環境ゲノミクス</li>
<li>創薬ゲノミクス - パーソナライズド・メディカル</li>
</ul>
</div>
<div class="small-12 medium-12 large-12 columns">
<p><strong>NGSの用語</strong></p>
<dl>
<dt>リード（読み取り）</dt>
<dd>この装置から得られた連続した単一のストレッチ</dd>
<dt>断片リード</dt>
<dd>フラグメントライブラリからの読み込み。 シーケンシングプラットフォームに応じて、読み取りは通常約100〜300bp。</dd>
<dt>断片ペアエンドリード</dt>
<dd>断片ライブラリーからDNA断片の各末端2つの読み取り。</dd>
<dt>メイトペアリード</dt>
<dd>大きなDNA断片（通常は予め定義されたサイズ範囲）の各末端から2つの読み取り。</dd>
<dt>カバレッジ（例）</dt>
<dd>30&times;適用範囲とは、参照ゲノム中の各塩基対が平均30回の読み取りを示す。</dd>
</dl>
</div>
</div>
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<h2>NGSプラットフォーム</h2>
<h3><a href="http://www.illumina.com" target="_blank">イルミナ</a></h3>
<p>イルミナは、クローン的に増幅された鋳型DNA（クラスター）上に位置する、蛍光標識された可逆的鎖ターミネーターヌクレオチドを用いた配列別合成技術を使用。 DNAクラスターは、ガラスフローセルの表面上に固定化され、 ワークフローは、4つのヌクレオチド（それぞれ異なる蛍光色素で標識された）の組み込み、4色イメージング、色素や末端基の切断、取り込み、イメージングなどを繰り返します。フローセルは大規模な並列配列決定を受ける。 この方法により、単一蛍光標識されたヌクレオチドの制御添加によるモノヌクレオチドのエラーを回避する可能性があります。 読み取りの長さは、通常約100〜150 bpです。</p>
<h3><a href="http://www.lifetechnologies.com" target="_blank">イオン トレント</a></h3>
<p>イオントレントは、半導体技術チップを用いて、合成中にヌクレオチドを取り込む際に放出されたプロトンを検出します。 これは、イオン球粒子と呼ばれるビーズの表面にエマルションPCR（emPCR）を使用し、リンクされた特定のアダプターを用いてDNA断片を増幅します。 各ビーズは1種類のDNA断片で覆われていて、異なるDNA断片を有するビーズは次いで、チップの陽子感知ウェル内に配置されます。 チップには一度に4つのヌクレオチドのうちの1つが浸水し、このプロセスは異なるヌクレオチドで15秒ごとに繰り返されます。 配列決定の間に4つの塩基の各々が1つずつ導入されます、組み込みの場合はプロトンが放出され、電圧信号が取り込みに比例して検出されます。.</p>
<h3><a href="http://www.pacificbiosciences.com" target="_blank">パシフィック バイオサイエンス</a></h3>
<p>パシフィックバイオサイエンスでは、20kbを超える塩基対の読み取りも、単一分子リアルタイム（SMRT）シーケンシングによる構造および細胞タイプの変化を観察することができます。 このプラットフォームでは、超長鎖二本鎖DNA（dsDNA）断片が、Megaruptor（登録商標）のようなDiagenode装置を用いたランダムシアリングまたは目的の標的領域の増幅によって生成されます。 SMRTbellライブラリーは、ユニバーサルヘアピンアダプターをDNA断片の各末端に連結することによって生成します。 サイズ選択条件による洗浄ステップの後、配列決定プライマーをSMRTbellテンプレートにアニーリングし、鋳型DNAに結合したDNAポリメラーゼを含む配列決定を、蛍光標識ヌクレオチドの存在下で開始。 各塩基が取り込まれると、異なる蛍光のパルスをリアルタイムで検出します。</p>
<h3><a href="https://nanoporetech.com" target="_blank">オックスフォード ナノポア</a></h3>
<p>Oxford Nanoporeは、単一のDNA分子配列決定に基づく技術を開発します。その技術により生物学的分子、すなわちDNAが一群の電気抵抗性高分子膜として位置するナノスケールの孔（ナノ細孔）またはその近くを通過し、イオン電流が変化します。 この変化に関する情報は、例えば4つのヌクレオチド（AまたはG r CまたはT）ならびに修飾されたヌクレオチドすべてを区別することによって分子情報に訳されます。 シーケンシングミニオンデバイスのフローセルは、数百個のナノポアチャネルのセンサアレイを含みます。 DNAサンプルは、Diagenode社のMegaruptor（登録商標）を用いてランダムシアリングによって生成され得る超長鎖DNAフラグメントが必要です。</p>
<h3><a href="http://www.lifetechnologies.com/be/en/home/life-science/sequencing/next-generation-sequencing/solid-next-generation-sequencing.html" target="_blank">SOLiD</a></h3>
<p>SOLiDは、ユニークな化学作用により、何千という個々のDNA分子の同時配列決定を可能にします。 それは、アダプター対ライブラリーのフラグメントが適切で、せん断されたゲノムDNAへのアダプターのライゲーションによるライブラリー作製から始まります。 次のステップでは、エマルジョンPCR（emPCR）を実施して、ビーズの表面上の個々の鋳型DNA分子をクローン的に増幅。 emPCRでは、個々の鋳型DNAをPCR試薬と混合し、水中油型エマルジョン内の疎水性シェルで囲まれた水性液滴内のプライマーコートビーズを、配列決定のためにロードするスライドガラスの表面にランダムに付着。 この技術は、シークエンシングプライマーへのライゲーションで競合する4つの蛍光標識されたジ塩基プローブのセットを使用します。</p>
<h3><a href="http://454.com/products/technology.asp" target="_blank">454</a></h3>
<p>454は、大規模並列パイロシーケンシングを利用しています。 始めに全ゲノムDNAまたは標的遺伝子断片の300〜800bp断片のライブラリー調製します。 次に、DNAフラグメントへのアダプターの付着および単一のDNA鎖の分離。 その後アダプターに連結されたDNAフラグメントをエマルジョンベースのクローン増幅（emPCR）で処理し、DNAライブラリーフラグメントをミクロンサイズのビーズ上に配置します。 各DNA結合ビーズを光ファイバーチップ上のウェルに入れ、器具に挿入します。 4つのDNAヌクレオチドは、配列決定操作中に固定された順序で連続して加えられ、並行して配列決定されます。</p>
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</div>
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			'meta_description' => 'Diagenode offers kits and DNA/RNA shearing technology prior to next-generation sequencing, many Next-generation sequencing platforms require preparation of the DNA.',
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			'description' => '<div class="row">
<div class="large-12 columns text-justify">
<p>Library preparation following ChIP can be challenging due to the limited amount of DNA recovered after ChIP. Diagenode has developed the optimal solutions for ChIP-seq using two different approaches: the ligation-based library preparation on purified DNA or the tagmentation-based ChIPmentation.</p>
</div>
</div>
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<li><a href="#panel1" class="tips portal button">Ligation-based library prep</a></li>
<li><a href="#panel2" class="tips portal button">ChIPmentation</a></li>
<li><a href="#panel3" class="tips portal button">Kit choice guide</a></li>
<li><a href="#panel4" class="tips portal button">Resources</a></li>
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<li class="accordion-navigation"><a href="#v5" style="color: #13b29c;"><i class="fa fa-caret-right"></i> Standard input library prep</a>
<div id="v5" class="content">
<div class="small-12 medium-12 large-12 columns">
<p>The <strong>iDeal Library Preparation Kit</strong> reliably converts DNA into indexed libraries for next-generation sequencing, with input amounts down to <strong>5 ng</strong>. Our kit offers a simple and fast workflow, high yields, and ready-to-sequence DNA on the Illumina platform.</p>
<div class="extra-spaced">
<h2>Features</h2>
<ul class="nobullet">
<li><i class="fa fa-arrow-circle-right"></i> <strong>Sample</strong>: Fragmented dsDNA</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Input</strong>: 5 ng &ndash; 1 &micro;g</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Fast protocol</strong>: 3 hours</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Easy processing</strong>: 3 steps</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Indexing</strong>: single indexes for multiplexing up to 24 samples</li>
<li><i class="fa fa-arrow-circle-right"></i> Manual and automated protocols available</li>
<li><i class="fa fa-arrow-circle-right"></i> Sequencing technology: Illumina</li>
</ul>
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<div class="extra-spaced">
<h2>Applications</h2>
<ul class="square">
<li>MeDIP-seq library prep</li>
<li>Genomic DNA sequencing</li>
<li>High input ChIP-seq</li>
</ul>
</div>
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<tr>
<td class="catalog_number"><span class="success label">C05010020</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns" style="color: #b21329;" target="_blank">iDeal Library Preparation Kit x24 (incl. Index Primer Set 1)</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010021</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/ideal-library-index-primer-set-2-24-rxns" style="color: #b21329;" target="_blank">Index Primer Set 2 (iDeal Lib. Prep Kit x24)</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/ideal-library-index-primer-set-2-24-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
</tbody>
</table>
</div>
</div>
</div>
</li>
</ul>
<ul class="accordion" data-accordion="">
<li class="accordion-navigation"><a href="#v4" style="color: #13b29c;"><i class="fa fa-caret-right"></i> Low input library prep</a>
<div id="v4" class="content active"><center><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" target="_blank"><img src="https://www.diagenode.com/img/banners/banner-microplex-v3-580.jpg" class="extra-spaced" /></a></center>
<div align="center"><a href="https://www.diagenode.com/pages/form-microplex3" class="center alert radius button extra-spaced"><i class="fa fa-info"></i> Contact us</a></div>
<div class="extra-spaced">
<p>Diagenode&rsquo;s <strong>MicroPlex Library Preparation kits</strong> have been extensively validated for ChIP-seq samples. Generated libraries are compatible with single-end or paired-end sequencing. MicroPlex chemistry (using stem-loop adapters ) is specifically developed and optimized to generate DNA libraries with high molecular complexity from the lowest input amounts. Only <strong>50 pg to 50 ng</strong> of fragmented double-stranded DNA is required for library preparation. The entire <strong>three-step workflow</strong> takes place in a <strong>single tube</strong> or well in about <strong>2 hours</strong>. No intermediate purification steps and no sample transfers are necessary to prevent handling errors and loss of valuable samples.</p>
</div>
<div class="extra-spaced">
<h2>Features</h2>
<ul class="nobullet">
<li><i class="fa fa-arrow-circle-right"></i> <strong>Sample</strong>: Fragmented dsDNA</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Low input</strong>: 50 pg &ndash; 50 ng</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Fast protocol</strong>: 2 hours</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Easy processing</strong>: 3 steps in 1 tube</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>No intermediate purification</strong></li>
<li><i class="fa fa-arrow-circle-right"></i> Sequencing technology: Illumina</li>
<li><i class="fa fa-arrow-circle-right"></i> Manual and automated protocols available</li>
</ul>
</div>
<div class="extra-spaced">
<h2>Applications</h2>
<ul class="square">
<li>ChIP-seq library prep from ChIP-derived DNA</li>
<li>Low input DNA sequencing</li>
</ul>
</div>
<h2>Two versions are available:</h2>
<ul class="accordion" data-accordion="">
<li class="accordion-navigation"><a href="#v2" style="color: #13b29c;"><i class="fa fa-caret-right"></i> MicroPlex Library Preparation Kit v2 with single indexes</a>
<div id="v2" class="content">
<p>The MicroPlex Library Preparation Kit v2 contains all necessary reagents including single indexes for multiplexing up to 48 samples using single barcoding.</p>
<h4>KITS</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C05010012</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns" style="color: #b21329;" target="_blank">MicroPlex Library Preparation Kit v2 (12 indexes)</a></td>
<td class="format">12 rxns</td>
<td><a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
</tbody>
</table>
</div>
</li>
<li class="accordion-navigation"><a href="#v3" style="color: #13b29c;"><i class="fa fa-caret-right"></i> MicroPlex Library Preparation Kit v3 with dual indexes &nbsp;&nbsp;<strong><span class="diacol">NEW!</span></strong></a>
<div id="v3" class="content active">
<p>In this version the library preparation reagents and the dual indexes are available separately allowing for the flexibility choosing the number of indexes. MicroPlex v3 has multiplexing capacities up to 384 samples.</p>
<h4>KITS</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C05010001</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" style="color: #b21329;" target="_blank">MicroPlex Library Preparation Kit v3 /48 rxns</a></td>
<td class="format">48 rxns</td>
<td><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010002</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-96-rxns" style="color: #b21329;" target="_blank">MicroPlex Library Preparation Kit v3 /96 rxns</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-96-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
</tbody>
</table>
<h4>DUAL INDEXES</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C05010003</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/24-dual-indexes-for-microplex-kit-v3-48-rxns" style="color: #b21329;" target="_blank">24 Dual indexes for MicroPlex Kit v3</a></td>
<td class="format">48 rxns</td>
<td><a href="https://www.diagenode.com/en/p/24-dual-indexes-for-microplex-kit-v3-48-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010004</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-1" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set I</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-1" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010005</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-2" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set II</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-2" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010006</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-3" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set III</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-3" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010007</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-4" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set IV</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-4" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
</tbody>
</table>
</div>
</li>
</ul>
</div>
</li>
</ul>
</div>
</div>
</div>
<div class="content active" id="panel2">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<div class="extra-spaced">
<p>The TAG Kit for ChIPmentation offers an optimized ChIP-seq library preparation solution based on tagmentation. This kit includes reagents for tagmentation-based library preparation integrated in the IP and is compatible with any ChIP protocol based on magnetic beads. The primer indexes for multiplexing&nbsp;must be purchased separately and are available as a reference: <a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" target="_blank">24 SI for ChIPmentation</a>, Cat. No. C01011031. Alternatively, for histone marks, Diagenode proposes the complete solution (including all buffers for ChIP, tagmentation and multiplexing): <a href="https://www.diagenode.com/en/p/manual-chipmentation-kit-for-histones-24-rxns" target="_blank">ChIPmentation for Histones</a>.</p>
</div>
<div class="extra-spaced">
<h2>Features</h2>
<ul class="nobullet">
<li><i class="fa fa-arrow-circle-right"></i> Sample: chromatin-antibody-magnetic beads complexes</li>
<li><i class="fa fa-arrow-circle-right"></i> Input: chromatin from 5 K &ndash; 4 M cells</li>
<li><i class="fa fa-arrow-circle-right"></i> Easy and fast protocol</li>
<li><i class="fa fa-arrow-circle-right"></i> Compatible with any ChIP protocol based on magnetic beads</li>
<li><i class="fa fa-arrow-circle-right"></i> No adapter dimers</li>
<li><i class="fa fa-arrow-circle-right"></i> Sequencing technology: Illumina</li>
</ul>
</div>
<div class="extra-spaced">
<h2>Applications</h2>
<p class="lead"><em><strong>TAG kit for ChIPmentation</strong></em></p>
<ul class="square">
<li>ChIPmentation library preparation</li>
</ul>
<p class="lead"><em><strong>24 SI for for ChIPmentation</strong></em></p>
<ul class="square">
<li>ChIPmentation library preparation</li>
<li>Tagmentation-based library preparation methods like ATAC-seq, CUT&amp;Tag</li>
</ul>
</div>
<h4>KITS</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C01011030</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/tag-kit-for-chipmentation-24" style="color: #b21329;" target="_blank">TAG Kit for ChIPmentation</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/tag-kit-for-chipmentation-24" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C01011031</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" style="color: #b21329;" target="_blank">24 SI for ChIPmentation</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
</tbody>
</table>
</div>
</div>
</div>
<div class="content" id="panel3">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<div class="extra-spaced">
<h3 class="text-center diacol"><em>How to choose your library preparation kit?</em></h3>
</div>
<table class="noborder">
<tbody>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Sample</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Chromatin-antibody-beads complex</p>
</td>
<td colspan="2">
<p class="text-center" style="font-size: 15px;">Purified DNA</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Purified DNA</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td colspan="2"><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Application</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">ChIPmentation</p>
</td>
<td colspan="2">
<p class="text-center" style="font-size: 15px;">ChIP-seq library prep<br /> Low input DNA sequencing</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">MeDIP-seq library prep<br /> Genomic DNA sequencing<br /> High input ChIP-seq</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td colspan="2"><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Input</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Chromatin: 5 K to 4 M cells</p>
</td>
<td colspan="2&quot;">
<p class="text-center" style="font-size: 15px;">DNA: 50 pg &ndash; 50 ng</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">DNA: 5 ng &ndash; 1 &micro;g</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow-45-left.png" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow-45-right.png" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Multiplexing</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 24 samples</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 384 samples</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 48 samples</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 24 samples</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Indexes</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Single indexes (SI)</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Dual indexes (DI)</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Single indexes (SI)</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Single indexes (SI)</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Kit</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>TAG Kit for ChIPmentation</strong><br /> (indexes not included in the kit)</p>
<p class="text-center"><strong>Kit</strong><br /> <a href="https://www.diagenode.com/en/p/tag-kit-for-chipmentation-24" target="_blank">C01011030 &ndash; 24 rxns</a></p>
<p class="text-center"><strong>Single indexes</strong><br /> <a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" target="_blank">C01011031 &ndash; 24 SI/24 rxns</a></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>MicroPlex Library Preparation Kit v3</strong><br />(dual indexes not included in the kit)</p>
<p class="text-center"><strong>Kit</strong><br /> <a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" target="_blank">C05010001 - 48 rxns</a><br /> <a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-96-rxns" target="_blank">C05010002 - 96 rxns</a></p>
<br />
<p class="text-center"><strong>Unique dual indexes</strong><br /> <a href="https://www.diagenode.com/en/p/24-unique-dual-indexes-for-microplex-kit-v3-set1" target="_blank">C05010008 - Set I 24 UDI / 24 rxns</a><br /> <a href="https://www.diagenode.com/en/p/24-unique-dual-indexes-for-microplex-kit-v3-set2" target="_blank">C05010009 - Set II 24 UDI/ 24 rxns</a></p>
<p class="text-center"><strong>Dual indexes</strong><br /> <a href="https://www.diagenode.com/en/p/24-dual-indexes-for-microplex-kit-v3-48-rxns" target="_blank">C05010003 - 24 DI/ 48 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-1" target="_blank">C05010004 - Set I 96 DI/ 96 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-2" target="_blank">C05010005 - Set II 96 DI/ 96 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-3" target="_blank">C05010006 - Set III 96 DI/ 96 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-4" target="_blank">C05010007 - Set IV 96 DI/ 96 rxns</a></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>MicroPlex Library Preparation Kit v2</strong><br />(single indexes included in the kit)</p>
<p class="text-center"><a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns" target="_blank">C05010012 - 12 SI/ 12 rxns</a><br /> <a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x48-12-indices-48-rxns" target="_blank">C05010013 - 12 SI/ 48 rxns</a></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>iDeal Library Preparation Kit</strong><br />(Set 1 of indexes included in the kit)</p>
<p class="text-center"><a href="https://www.diagenode.com/en/p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns" target="_blank">C05010020 - 12 SI/ 24 rxns</a></p>
<p class="text-center" style="font-size: 15px;"><strong>Index Primer Set 2</strong></p>
<p class="text-center"><a href="https://www.diagenode.com/en/p/ideal-library-index-primer-set-2-24-rxns" target="_blank">C05010021 - 12 SI/ 24 rxns</a></p>
</td>
</tr>
</tbody>
</table>
</div>
</div>
</div>
<div class="content" id="panel4">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<p>Combined chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) has become the gold standard to investigate genome-wide epigenetic profiles. However, ChIP from a limited amount of cells has been a challenge. Here we provide a complete and robust workflow solution for successful ChIP-seq from small numbers of cells using the True MicroChIP kit and MicroPlex Library Preparation kit.</p>
<blockquote><span class="label-green" style="margin-bottom: 16px; margin-left: -22px;">APPLICATION NOTE</span>
<div class="row">
<div class="small-12 medium-6 large-6 columns"><center><img src="https://www.diagenode.com/img/categories/microplex/chip-efficiency-on-10000-cells.jpg" /></center>
<p><small><em>ChIP efficiency on 10,000 cells</em></small></p>
</div>
<div class="small-12 medium-6 large-6 columns">
<p><strong>From minuscule amounts to magnificent results:</strong><br /> reliable ChIP-seq data from 10,000 cells with the True MicroChIP&trade; and the MicroPlex Library Preparation&trade; kits.</p>
<a href="https://www.diagenode.com/files/application_notes/True_MicroChIP_and_MicroPlex_kits_Application_Note.pdf" class="details small button" target="_blank">DOWNLOAD</a></div>
</div>
</blockquote>
<blockquote><span class="label-green" style="margin-bottom: 16px; margin-left: -22px;">APPLICATION NOTE</span>
<div class="row">
<div class="small-12 medium-6 large-6 columns"><center><img src="https://www.diagenode.com/img/categories/microplex/quality-control-check.jpg" /></center>
<p class="text-left"><small><em>Quality control check of a ChIP-seq library on the Fragment Analyzer. High Efficiency ChIP performed on 10,000 cells</em></small></p>
</div>
<div class="small-12 medium-6 large-6 columns">
<p class="text-left"><strong>Best Workflow Practices for ChIP-seq Analysis with Small Samples</strong></p>
<a href="https://www.diagenode.com/files/application_notes/Diagenode_AATI_Joint.pdf" class="details small button" target="_blank">DOWNLOAD</a></div>
</div>
</blockquote>
</div>
</div>
</div>
<div class="content" id="panel5">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<div class="extra-spaced">
<h2>TAG Kit for ChIPmentation</h2>
<ol>
<li><strong>What is the difference between tagmentation and ChIPmentation?</strong><br />Tagmentation is a reaction where an enzyme (a transposase) cleaves DNA and incorporates sequencing adaptors at the ends of the fragments in one step. In our ChIPmentation technology we combine chromatin immunoprecipitation and tagmentation in one streamlined workflow where the tagmentation step occurs directly on chromatin.<br /><br /></li>
<li><strong>What is the expected concentration of ChIPmentation libraries?</strong><br />The concentration of libraries that you need to reach will depend on the sensitivity of the machine and kits that you will use to perform the quality control and the sequencing of your libraries. Usually a concentration of 4-8 ng/&mu;l is enough for a quality control using the Qubit High Sensitivity assay (ThermoFischer Scientific) and the High Sensitivity chip for BioAnalyzer (Agilent) and for sequencing on Illumina HiSeq3000/4000.<br /><br /></li>
<li><strong>Does the ChIPmentation approach work on plants?</strong><br />Our ChIPmentation solution has been validated on human cells and we do not have any data on plants. It should be compatible. We would recommend using our Universal Plant ChIP Kit in combination with the TAG Kit for ChIPmentation and the 24 SI for ChIPmentation.<br /><br /></li>
<li><strong>What is the size of the fragments after the tagmentation?</strong><br />The size of the fragments at the end of the ChIPmentation protocol can vary depending on many parameters like the shearing efficiency, the antibody used or the tagmentation time. However, with our standard protocol we usually obtain a library peak which is around 200-300 bp (see example of results at the end of the manual). If many fragments larger than 500 bp are present , the best would be to contact your sequencing provider to ask what their requirements are, because it can vary depending on the sequencer. If you want to remove the large fragments you can use the size selection protocol described in the manual.<br /><br /></li>
<li><strong>What is the size of the adapters?</strong><br />The sum of the adapters is 128 bp.</li>
</ol>
</div>
<div class="extra-spaced">
<h2>MicroPlex Library Preparation Kit</h2>
<ol>
<li><strong>Can I use the available Illumina primers and validate them with the MicroPlex Kit v2?</strong><br /> Although the final flanking sequences of MicroPlex are the same as those used by Illumina, the PCR primers are not identical and part of them is supplied with the buffer. For this reason Illumina primers will not work as substitute.<br /><br /></li>
<li><strong>The BioAnalyzer profile of purified library shows the presence of low molecular weight peaks (primers/adaptors) in the samples. Should I re- purify the samples or they can be used directly to the sequencing? If the second purification is recommended, which ratio sample/AMPure beads should I use?</strong><br /> You can do a second round of purification using 1:1 ratio of AMPure beads to sample and this should get rid of the majority of the dimers.<br /><br /></li>
<li><strong>I am going to use the MicroPlex Library Preparation Kit v2 on ChIP samples . Our thermocycler has ramp rate 1.5&deg;/s max while the protocol recommends using a ramp rate 3 to 5&deg;/s. How would this affect the library prep?</strong><br /> We have not used a thermocycler with a ramp rate of 1.5 &deg;C, which seems faster than most of thermocyclers. Too fast of a ramp rate may affect the primer annealing and ligation steps.<br /><br /></li>
<li><strong>What is the function of the replication stop site in the adapter loops?</strong><br /> The replication stop site in the adaptor loops function to stop the polymerase from continuing to copy the rest of the stem loop.<br /><br /></li>
<li><strong>I want to do ChIP-seq. Which ChIP-seq kit can I use for sample preparation prior to Microplex Library Preparation Kit v2?</strong><br /> In our portfolio there are several ChIP-seq kits compatible with Microplex Library Preparation Kit v2. Depending on your sample type and target studied you can use the following kits: iDeal ChIP-seq Kit for Transcription Factors (Cat. No. C01010055), iDeal ChIP-seq Kit for Histones (Cat. No. C01010051), True MicroChIP kit (Cat. No. C01010130), Universal Plant ChIP-seq Kit (Cat. No. C01010152). All these kits exist in manual and automated versions.<br /><br /></li>
<li><strong>Is Microplex Library Preparation Kit v2 compatible with exome enrichment methods?</strong><br /> Microplex Library Preparation Kit v2 is compatible with major exome and target enrichment products, including Agilent SureSelect<sup>&reg;</sup>, Roche NimbleGen<sup>&reg;</sup> SeqCap<sup>&reg;</sup> EZ and custom panels.<br /><br /></li>
<li><strong>What is the nick that is mentioned in the kit method overview?</strong><br /> The nick is simply a gap between a stem adaptor and 3&rsquo; DNA end, as shown on the schema in the kit method overview.<br /><br /></li>
<li><strong>Are the indexes of the MicroPlex library preparation kit v2 located at i5 or i7?</strong><br /> The libraries generated with the MicroPlex kit v2 contain indices located at i7.<br /><br /></li>
<li><strong>Is there a need to use custom index read primers for the sequencing to read the 8nt iPCRtags?</strong><br /> There is no need for using custom Sequencing primer to sequence MicroPlex libraires. MicroPlex libraries can be sequenced using standard Illumina Sequencing kits and protocols.<br /><br /></li>
<li><strong>What is the advantage of using stem-loop adapter in the MicroPlex kit?</strong><br /> There are several advantages of using stem-loop adaptors. First of all, stem-loop adaptors prevent from self-ligation thus increases the ligation efficiency between the adapter and DNA fragment. Moreover, the background is reduced using ds adaptors with no single-stranded tails. Finally, adaptor-adaptor ligation is reduced using blocked 5&rsquo; ends.<br /><br /></li>
</ol>
</div>
<div class="extra-spaced">
<h2>IDeal Library Preparation Kit</h2>
<ol>
<li><strong>Are the index from the iDeal library Prep kit compatible with the MicroPlex library prep kit?</strong><br /> No, it is important to use only the indexes provided in the MicroPlex kit to ensure proper library preparation with this kit</li>
</ol>
</div>
</div>
</div>
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<p><span>MicroPlex v2 builds on the innovative MicroPlex chemistry to generate DNA libraries with expanded multiplexing capability and with even greater diversity. Kits contain up to 48 Illumina</span><span>&reg; </span><span>-compatible indexes. MicroPlex v2 can be used in DNA- seq, RNA-seq, or ChIP-seq and offers robust target enrichment performance with all of the leading platforms. </span></p>
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			'name' => 'True MicroChIP and MicroPlex kits',
			'description' => '<p><span>From minuscule amounts to magnificent results: reliable ChIP-seq data from 10,000 cells with the True MicroChIP</span>&trade; <span>and the MicroPlex Library Preparation</span>&trade; <span>kits. </span></p>',
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			'id' => '16',
			'name' => 'ChIP kit results with True MicroChIP kit',
			'description' => '<p style="text-align: justify;"><span>Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become the gold standard for whole-genome mapping of protein-DNA interactions. However, conventional ChIP protocols require abundant amounts of starting material (at least hundreds of thousands of cells per immunoprecipitation) limiting the application for the ChIP technology to few cell samples. </span></p>',
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			'id' => '4843',
			'name' => 'Differentiation block in acute myeloid leukemia regulated by intronicsequences of FTO',
			'authors' => 'Camera  F. et al.',
			'description' => '<p>Iroquois transcription factor gene IRX3 is highly expressed in 20&acirc;&euro;&ldquo;30\% of acute myeloid leukemia (AML) and contributes to the pathognomonic differentiation block. Intron 8 FTO sequences &acirc;&circ;&frac14;220kB downstream of IRX3 exhibit histone acetylation, DNA methylation, and contacts with the IRX3 promoter, which correlate with IRX3 expression. Deletion of these intronic elements confirms a role in positively regulating IRX3. RNAseq revealed long non-coding (lnc) transcripts arising from this locus. FTO-lncAML knockdown (KD) induced differentiation of AML cells, loss of clonogenic activity, and reduced FTO intron 8:IRX3 promoter contacts. While both FTO-lncAML KD and IRX3 KD induced differentiation, FTO-lncAML but not IRX3 KD led to HOXA downregulation suggesting transcript activity in trans. FTO-lncAMLhigh AML samples expressed higher levels of HOXA and lower levels of differentiation genes. Thus, a regulatory module in FTO intron 8 consisting of clustered enhancer elements and a long non-coding RNA is active in human AML, impeding myeloid differentiation.</p>',
			'date' => '2023-08-01',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S2589004223013962',
			'doi' => '10.1016/j.isci.2023.107319',
			'modified' => '2023-08-01 14:14:01',
			'created' => '2023-08-01 15:59:38',
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		(int) 1 => array(
			'id' => '4851',
			'name' => 'Supraphysiological Androgens Promote the Tumor Suppressive Activity of the Androgen Receptor Through cMYC Repression and Recruitment of the DREAM Complex',
			'authors' => 'Nyquist  M. et al.',
			'description' => '<p>The androgen receptor (AR) pathway regulates key cell survival programs in prostate epithelium. The AR represents a near-universal driver and therapeutic vulnerability in metastatic prostate cancer, and targeting AR has a remarkable therapeutic index. Though most approaches directed toward AR focus on inhibiting AR signaling, laboratory and now clinical data have shown that high dose, supraphysiological androgen treatment (SPA) results in growth repression and improved outcomes in subsets of prostate cancer patients. A better understanding of the mechanisms contributing to SPA response and resistance could help guide patient selection and combination therapies to improve efficacy. To characterize SPA signaling, we integrated metrics of gene expression changes induced by SPA together with cistrome data and protein-interactomes. These analyses indicated that the Dimerization partner, RB-like, E2F and Multi-vulval class B (DREAM) complex mediates growth repression and downregulation of E2F targets in response to SPA. Notably, prostate cancers with complete genomic loss of RB1 responded to SPA treatment whereas loss of DREAM complex components such as RBL1/2 promoted resistance. Overexpression of MYC resulted in complete resistance to SPA and attenuated the SPA/AR-mediated repression of E2F target genes. These findings support a model of SPA-mediated growth repression that relies on the negative regulation of MYC by AR leading to repression of E2F1 signaling via the DREAM complex. The integrity of MYC signaling and DREAM complex assembly may consequently serve as determinants of SPA responses and as pathways mediating SPA resistance.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/37352376/',
			'doi' => '10.1158/0008-5472.CAN-22-2613',
			'modified' => '2023-08-01 18:09:31',
			'created' => '2023-08-01 15:59:38',
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		(int) 2 => array(
			'id' => '4852',
			'name' => 'In skeletal muscle and neural crest cells, SMCHD1 regulates biologicalpathways relevant for Bosma syndrome and facioscapulohumeral dystrophyphenotype.',
			'authors' => 'Laberthonnière  C. et al.',
			'description' => '<p>Many genetic syndromes are linked to mutations in genes encoding factors that guide chromatin organization. Among them, several distinct rare genetic diseases are linked to mutations in SMCHD1 that encodes the structural maintenance of chromosomes flexible hinge domain containing 1 chromatin-associated factor. In humans, its function as well as the impact of its mutations remains poorly defined. To fill this gap, we determined the episignature associated with heterozygous SMCHD1 variants in primary cells and cell lineages derived from induced pluripotent stem cells for Bosma arhinia and microphthalmia syndrome (BAMS) and type 2 facioscapulohumeral dystrophy (FSHD2). In human tissues, SMCHD1 regulates the distribution of methylated CpGs, H3K27 trimethylation and CTCF at repressed chromatin but also at euchromatin. Based on the exploration of tissues affected either in FSHD or in BAMS, i.e. skeletal muscle fibers and neural crest stem cells, respectively, our results emphasize multiple functions for SMCHD1, in chromatin compaction, chromatin insulation and gene regulation with variable targets or phenotypical outcomes. We concluded that in rare genetic diseases, SMCHD1 variants impact gene expression in two ways: (i) by changing the chromatin context at a number of euchromatin loci or (ii) by directly regulating some loci encoding master transcription factors required for cell fate determination and tissue differentiation.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37334829',
			'doi' => '10.1093/nar/gkad523',
			'modified' => '2023-08-01 14:35:38',
			'created' => '2023-08-01 15:59:38',
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		),
		(int) 3 => array(
			'id' => '4861',
			'name' => 'Hypomethylation and overexpression of Th17-associated genes is ahallmark of intestinal CD4+ lymphocytes in Crohn's disease.',
			'authors' => 'Sun  Z. et al.',
			'description' => '<p>BACKGROUND: The development of Crohn's disease (CD) involves immune cell signaling pathways regulated by epigenetic modifications. Aberrant DNA methylation has been identified in peripheral blood and bulk intestinal tissue from CD patients. However, the DNA methylome of disease-associated intestinal CD4 + lymphocytes has not been evaluated. MATERIALS AND METHODS: Genome-wide DNA methylation sequencing was performed from terminal ileum CD4 + cells from 21 CD patients and 12 age and sex matched controls. Data was analyzed for differentially methylated CpGs (DMCs) and methylated regions (DMRs). Integration was performed with RNA-sequencing data to evaluate the functional impact of DNA methylation changes on gene expression. DMRs were overlapped with regions of differentially open chromatin (by ATAC-seq) and CCCTC-binding factor (CTCF) binding sites (by ChIP-seq) between peripherally-derived Th17 and Treg cells. RESULTS: CD4+ cells in CD patients had significantly increased DNA methylation compared to those from the controls. A total of 119,051 DMCs and 8,113 DMRs were detected. While hyper-methylated genes were mostly related to cell metabolism and homeostasis, hypomethylated genes were significantly enriched within the Th17 signaling pathway. The differentially enriched ATAC regions in Th17 cells (compared to Tregs) were hypomethylated in CD patients, suggesting heightened Th17 activity. There was significant overlap between hypomethylated DNA regions and CTCF-associated binding sites. CONCLUSIONS: The methylome of CD patients demonstrate an overall dominant hypermethylation yet hypomethylation is more concentrated in proinflammatory pathways, including Th17 differentiation. Hypomethylation of Th17-related genes associated with areas of open chromatin and CTCF binding sites constitutes a hallmark of CD-associated intestinal CD4 + cells.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37280154',
			'doi' => '10.1093/ecco-jcc/jjad093',
			'modified' => '2023-08-01 14:52:39',
			'created' => '2023-08-01 15:59:38',
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		(int) 4 => 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',
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			'id' => '4782',
			'name' => 'Transient suppression of SUMOylation in embryonic stem cells generatesembryo-like structures.',
			'authors' => 'Cossec  J-C. et al.',
			'description' => '<p>Recent advances in synthetic embryology have opened new avenues for understanding the complex events controlling mammalian peri-implantation development. Here, we show that mouse embryonic stem cells (ESCs) solely exposed to chemical inhibition of SUMOylation generate embryo-like structures comprising anterior neural and trunk-associated regions. HypoSUMOylation-instructed ESCs give rise to spheroids that self-organize into gastrulating structures containing cell types spatially and functionally related to embryonic and extraembryonic compartments. Alternatively, spheroids cultured in a droplet microfluidic device form elongated structures that undergo axial organization reminiscent of natural embryo morphogenesis. Single-cell transcriptomics reveals various cellular lineages, including properly positioned anterior neuronal cell types and paraxial mesoderm segmented into somite-like structures. Transient SUMOylation suppression gradually increases DNA methylation genome wide and repressive mark deposition at Nanog. Interestingly, cell-to-cell variations in SUMOylation levels occur during early embryogenesis. Our approach provides a proof of principle for potentially powerful strategies to explore early embryogenesis by targeting chromatin roadblocks of cell fate change.</p>',
			'date' => '2023-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37061916',
			'doi' => '10.1016/j.celrep.2023.112380',
			'modified' => '2023-06-13 09:20:06',
			'created' => '2023-05-05 12:34:24',
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		(int) 6 => array(
			'id' => '4693',
			'name' => 'ZEB1 controls a lineage-specific transcriptional program essential formelanoma cell state transitions',
			'authors' => 'Tang  Y. et al.',
			'description' => '<p>Cell plasticity sustains intra-tumor heterogeneity and treatment resistance in melanoma. Deciphering the transcriptional mechanisms governing reversible phenotypic transitions between proliferative/differentiated and invasive/stem-like states is required in order to design novel therapeutic strategies. EMT-inducing transcription factors, extensively known for their role in metastasis in carcinoma, display cell-type specific functions in melanoma, with a decreased ZEB2/ZEB1 expression ratio fostering adaptive resistance to targeted therapies. While ZEB1 direct target genes have been well characterized in carcinoma models, they remain unknown in melanoma. Here, we performed a genome-wide characterization of ZEB1 transcriptional targets, by combining ChIP-sequencing and RNA-sequencing, upon phenotype switching in melanoma models. We identified and validated ZEB1 binding peaks in the promoter of key lineage-specific genes related to melanoma cell identity. Comparative analyses with breast carcinoma cells demonstrated melanoma-specific ZEB1 binding, further supporting lineage specificity. Gain- or loss-of-function of ZEB1, combined with functional analyses, further demonstrated that ZEB1 negatively regulates proliferative/melanocytic programs and positively regulates both invasive and stem-like programs. We then developed single-cell spatial multiplexed analyses to characterize melanoma cell states with respect to ZEB1/ZEB2 expression in human melanoma samples. We characterized the intra-tumoral heterogeneity of ZEB1 and ZEB2 and further validated ZEB1 increased expression in invasive cells, but also in stem-like cells, highlighting its relevance in vivo in both populations. Overall, our results define ZEB1 as a major transcriptional regulator of cell states transitions and provide a better understanding of lineage-specific transcriptional programs sustaining intra-tumor heterogeneity in melanoma.</p>',
			'date' => '2023-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2023.02.10.526467',
			'doi' => '10.1101/2023.02.10.526467',
			'modified' => '2023-04-14 09:11:23',
			'created' => '2023-02-28 12:19:11',
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		),
		(int) 7 => 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',
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		(int) 8 => array(
			'id' => '4710',
			'name' => 'Mechanisms and function of de novo DNA methylation in placentaldevelopment reveals an essential role for DNMT3B.',
			'authors' => 'Andrews  S. et al.',
			'description' => '<p>DNA methylation is a repressive epigenetic modification that is essential for development, exemplified by the embryonic and perinatal lethality observed in mice lacking de novo DNA methyltransferases (DNMTs). Here we characterise the role for DNMT3A, 3B and 3L in gene regulation and development of the mouse placenta. We find that each DNMT establishes unique aspects of the placental methylome through targeting to distinct chromatin features. Loss of Dnmt3b results in de-repression of germline genes in trophoblast lineages and impaired formation of the maternal-foetal interface in the placental labyrinth. Using Sox2-Cre to delete Dnmt3b in the embryo, leaving expression intact in placental cells, the placental phenotype was rescued and, consequently, the embryonic lethality, as Dnmt3b null embryos could now survive to birth. We conclude that de novo DNA methylation by DNMT3B during embryogenesis is principally required to regulate placental development and function, which in turn is critical for embryo survival.</p>',
			'date' => '2023-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36690623',
			'doi' => '10.1038/s41467-023-36019-9',
			'modified' => '2023-04-05 08:38:12',
			'created' => '2023-02-28 12:19:11',
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		),
		(int) 9 => array(
			'id' => '4651',
			'name' => 'TCDD induces multigenerational alterations in the expression ofmicroRNA in the thymus through epigenetic modifications',
			'authors' => 'Singh  Narendra P et al.',
			'description' => '<p>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, is an environmental contaminant that is known for mediating toxicity across generations. However, whether TCDD can induce multigenerational changes in the expression of miRNAs (miRs) has not been previously studied. In the current study, we investigated the effect of administration of TCDD in pregnant mice (F0) on gestational day 14, on the expression of miRs in the thymus of F0 and subsequent generations (F1 and F2). Of the 3200 miRs screened, 160 miRs were dysregulated similarly in F0, F1, and F2 generations while 46 miRs were differentially altered in F0-F2 generations. Pathway analysis revealed that the changes in miR signature profile mediated by TCDD affected the genes that regulate cell signaling, apoptosis, thymic atrophy, cancer, immunosuppression, and other physiological pathways. A significant number of miRs that showed altered expression exhibited dioxin response elements (DRE) on their promoters. Focusing on one such miR, namely miR-203 that expressed DREs and was induced across F0-F2 by TCDD, promoter analysis showed that one of the DREs expressed by miR-203 was functional to TCDD-mediated upregulation. Also, the histone methylation status of H3K4me3 in the miR-203 promoter was significantly increased near the transcriptional start site (TSS) in TCDD-treated thymocytes across F0-F2 generations. Genome-wide ChIP-seq study suggested that TCDD may cause alterations in histone methylation in certain genes across the three generations. Together, the current study demonstrates that gestational exposure to TCDD can alter the expression of miRs in F0 through direct activation of DREs as well as across F0, F1, and F2 generations through epigenetic pathways.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://academic.oup.com/pnasnexus/advance-article/doi/10.1093/pnasnexus/pgac290/6886578',
			'doi' => 'https://doi.org/10.1093/pnasnexus/pgac290',
			'modified' => '2023-03-13 10:55:36',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 10 => array(
			'id' => '4632',
			'name' => 'The histone acetyltransferase KAT6A is recruited to unmethylatedCpG islands via a DNA binding winged helix domain.',
			'authors' => 'Weber  L.M. et al.',
			'description' => '<p>The lysine acetyltransferase KAT6A (MOZ, MYST3) belongs to the MYST family of chromatin regulators, facilitating histone acetylation. Dysregulation of KAT6A has been implicated in developmental syndromes and the onset of acute myeloid leukemia (AML). Previous work suggests that KAT6A is recruited to its genomic targets by a combinatorial function of histone binding PHD fingers, transcription factors and chromatin binding interaction partners. Here, we demonstrate that a winged helix (WH) domain at the very N-terminus of KAT6A specifically interacts with unmethylated CpG motifs. This DNA binding function leads to the association of KAT6A with unmethylated CpG islands (CGIs) genome-wide. Mutation of the essential amino acids for DNA binding completely abrogates the enrichment of KAT6A at CGIs. In contrast, deletion of a second WH domain or the histone tail binding PHD fingers only subtly influences the binding of KAT6A to CGIs. Overexpression of a KAT6A WH1 mutant has a dominant negative effect on H3K9 histone acetylation, which is comparable to the effects upon overexpression of a KAT6A HAT domain mutant. Taken together, our work revealed a previously unrecognized chromatin recruitment mechanism of KAT6A, offering a new perspective on the role of KAT6A in gene regulation and human diseases.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36537216',
			'doi' => '10.1093/nar/gkac1188',
			'modified' => '2023-03-28 09:01:38',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 11 => array(
			'id' => '4629',
			'name' => 'Polyglutamine-expanded ATXN7 alters a specific epigenetic signatureunderlying photoreceptor identity gene expression in SCA7 mouseretinopathy.',
			'authors' => 'Niewiadomska-Cimicka  A.et al.',
			'description' => '<p>BACKGROUND: Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder that primarily affects the cerebellum and retina. SCA7 is caused by a polyglutamine expansion in the ATXN7 protein, a subunit of the transcriptional coactivator SAGA that acetylates histone H3 to deposit narrow H3K9ac mark at DNA regulatory elements of active genes. Defective histone acetylation has been presented as a possible cause for gene deregulation in SCA7 mouse models. However, the topography of acetylation defects at the whole genome level and its relationship to changes in gene expression remain to be determined. METHODS: We performed deep RNA-sequencing and chromatin immunoprecipitation coupled to high-throughput sequencing to examine the genome-wide correlation between gene deregulation and alteration of the active transcription marks, e.g. SAGA-related H3K9ac, CBP-related H3K27ac and RNA polymerase II (RNAPII), in a SCA7 mouse retinopathy model. RESULTS: Our analyses revealed that active transcription marks are reduced at most gene promoters in SCA7 retina, while a limited number of genes show changes in expression. We found that SCA7 retinopathy is caused by preferential downregulation of hundreds of highly expressed genes that define morphological and physiological identities of mature photoreceptors. We further uncovered that these photoreceptor genes harbor unusually broad H3K9ac profiles spanning the entire gene bodies and have a low RNAPII pausing. This broad H3K9ac signature co-occurs with other features that delineate superenhancers, including broad H3K27ac, binding sites for photoreceptor specific transcription factors and expression of enhancer-related non-coding RNAs (eRNAs). In SCA7 retina, downregulated photoreceptor genes show decreased H3K9 and H3K27 acetylation and eRNA expression as well as increased RNAPII pausing, suggesting that superenhancer-related features are altered. CONCLUSIONS: Our study thus provides evidence that distinctive epigenetic configurations underlying high expression of cell-type specific genes are preferentially impaired in SCA7, resulting in a defect in the maintenance of identity features of mature photoreceptors. Our results also suggest that continuous SAGA-driven acetylation plays a role in preserving post-mitotic neuronal identity.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36539812',
			'doi' => '10.1186/s12929-022-00892-1',
			'modified' => '2023-03-28 09:07:19',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 12 => array(
			'id' => '4575',
			'name' => 'Intranasal administration of Acinetobacter lwoffii in a murine model ofasthma induces IL-6-mediated protection associated with cecal microbiotachanges.',
			'authors' => 'Alashkar A. B. et al.',
			'description' => '<p>BACKGROUND: Early-life exposure to certain environmental bacteria including Acinetobacter lwoffii (AL) has been implicated in protection from chronic inflammatory diseases including asthma later in life. However, the underlying mechanisms at the immune-microbe interface remain largely unknown. METHODS: The effects of repeated intranasal AL exposure on local and systemic innate immune responses were investigated in wild-type and Il6 , Il10 , and Il17 mice exposed to ovalbumin-induced allergic airway inflammation. Those investigations were expanded by microbiome analyses. To assess for AL-associated changes in gene expression, the picture arising from animal data was supplemented by in vitro experiments of macrophage and T-cell responses, yielding expression and epigenetic data. RESULTS: The asthma preventive effect of AL was confirmed in the lung. Repeated intranasal AL administration triggered a proinflammatory immune response particularly characterized by elevated levels of IL-6, and consequently, IL-6 induced IL-10 production in CD4 T-cells. Both IL-6 and IL-10, but not IL-17, were required for asthma protection. AL had a profound impact on the gene regulatory landscape of CD4 T-cells which could be largely recapitulated by recombinant IL-6. AL administration also induced marked changes in the gastrointestinal microbiome but not in the lung microbiome. By comparing the effects on the microbiota according to mouse genotype and AL-treatment status, we have identified microbial taxa that were associated with either disease protection or activity. CONCLUSION: These experiments provide a novel mechanism of Acinetobacter lwoffii-induced asthma protection operating through IL-6-mediated epigenetic activation of IL-10 production and with associated effects on the intestinal microbiome.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36458896',
			'doi' => '10.1111/all.15606',
			'modified' => '2023-04-11 10:23:07',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 13 => array(
			'id' => '4535',
			'name' => 'Identification of genomic binding sites and direct target genes for thetranscription factor DDIT3/CHOP.',
			'authors' => 'Osman  A. et al.',
			'description' => '<p>DDIT3 is a tightly regulated basic leucine zipper (bZIP) transcription factor and key regulator in cellular stress responses. It is involved in a variety of pathological conditions and may cause cell cycle block and apoptosis. It is also implicated in differentiation of some specialized cell types and as an oncogene in several types of cancer. DDIT3 is believed to act as a dominant-negative inhibitor by forming heterodimers with other bZIP transcription factors, preventing their DNA binding and transactivating functions. DDIT3 has, however, been reported to bind DNA and regulate target genes. Here, we employed ChIP sequencing combined with microarray-based expression analysis to identify direct binding motifs and target genes of DDIT3. The results reveal DDIT3 binding to motifs similar to other bZIP transcription factors, known to form heterodimers with DDIT3. Binding to a class III satellite DNA repeat sequence was also detected. DDIT3 acted as a DNA-binding transcription factor and bound mainly to the promotor region of regulated genes. ChIP sequencing analysis of histone H3K27 methylation and acetylation showed a strong overlap between H3K27-acetylated marks and DDIT3 binding. These results support a role for DDIT3 as a transcriptional regulator of H3K27ac-marked genes in transcriptionally active chromatin.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36402425',
			'doi' => '10.1016/j.yexcr.2022.113418',
			'modified' => '2022-11-25 08:47:49',
			'created' => '2022-11-24 08:49:52',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 14 => array(
			'id' => '4494',
			'name' => 'Cryptococcal Hsf3 controls intramitochondrial ROS homeostasis byregulating the respiratory process.',
			'authors' => 'Gao  X.et al.',
			'description' => '<p>Mitochondrial quality control prevents accumulation of intramitochondrial-derived reactive oxygen species (mtROS), thereby protecting cells against DNA damage, genome instability, and programmed cell death. However, underlying mechanisms are incompletely understood, particularly in fungal species. Here, we show that Cryptococcus neoformans heat shock factor 3 (CnHsf3) exhibits an atypical function in regulating mtROS independent of the unfolded protein response. CnHsf3 acts in nuclei and mitochondria, and nuclear- and mitochondrial-targeting signals are required for its organelle-specific functions. It represses the expression of genes involved in the tricarboxylic acid cycle while promoting expression of genes involved in electron transfer chain. In addition, CnHsf3 responds to multiple intramitochondrial stresses; this response is mediated by oxidation of the cysteine residue on its DNA binding domain, which enhances DNA binding. Our results reveal a function of HSF proteins in regulating mtROS homeostasis that is independent of the unfolded protein response.</p>',
			'date' => '2022-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36109512',
			'doi' => '10.1038/s41467-022-33168-1',
			'modified' => '2022-11-18 12:43:17',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 15 => array(
			'id' => '4496',
			'name' => 'Dominant role of DNA methylation over H3K9me3 for IAP silencingin endoderm.',
			'authors' => 'Wang  Z. et al.',
			'description' => '<p>Silencing of endogenous retroviruses (ERVs) is largely mediated by repressive chromatin modifications H3K9me3 and DNA methylation. On ERVs, these modifications are mainly deposited by the histone methyltransferase Setdb1 and by the maintenance DNA methyltransferase Dnmt1. Knock-out of either Setdb1 or Dnmt1 leads to ERV de-repression in various cell types. However, it is currently not known if H3K9me3 and DNA methylation depend on each other for ERV silencing. Here we show that conditional knock-out of Setdb1 in mouse embryonic endoderm results in ERV de-repression in visceral endoderm (VE) descendants and does not occur in definitive endoderm (DE). Deletion of Setdb1 in VE progenitors results in loss of H3K9me3 and reduced DNA methylation of Intracisternal A-particle (IAP) elements, consistent with up-regulation of this ERV family. In DE, loss of Setdb1 does not affect H3K9me3 nor DNA methylation, suggesting Setdb1-independent pathways for maintaining these modifications. Importantly, Dnmt1 knock-out results in IAP de-repression in both visceral and definitive endoderm cells, while H3K9me3 is unaltered. Thus, our data suggest a dominant role of DNA methylation over H3K9me3 for IAP silencing in endoderm cells. Our findings suggest that Setdb1-meditated H3K9me3 is not sufficient for IAP silencing, but rather critical for maintaining high DNA methylation.</p>',
			'date' => '2022-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36123357',
			'doi' => '10.1038/s41467-022-32978-7',
			'modified' => '2022-11-21 10:26:30',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 16 => array(
			'id' => '4415',
			'name' => 'HDAC1 and PRC2 mediate combinatorial control in SPI1/PU.1-dependentgene repression in murine erythroleukaemia.',
			'authors' => 'Gregoricchio  S. et al.',
			'description' => '<p>Although originally described as transcriptional activator, SPI1/PU.1, a major player in haematopoiesis whose alterations are associated with haematological malignancies, has the ability to repress transcription. Here, we investigated the mechanisms underlying gene repression in the erythroid lineage, in which SPI1 exerts an oncogenic function by blocking differentiation. We show that SPI1 represses genes by binding active enhancers that are located in intergenic or gene body regions. HDAC1 acts as a cooperative mediator of SPI1-induced transcriptional repression by deacetylating SPI1-bound enhancers in a subset of genes, including those involved in erythroid differentiation. Enhancer deacetylation impacts on promoter acetylation, chromatin accessibility and RNA pol II occupancy. In addition to the activities of HDAC1, polycomb repressive complex 2 (PRC2) reinforces gene repression by depositing H3K27me3 at promoter sequences when SPI1 is located at enhancer sequences. Moreover, our study identified a synergistic relationship between PRC2 and HDAC1 complexes in mediating the transcriptional repression activity of SPI1, ultimately inducing synergistic adverse effects on leukaemic cell survival. Our results highlight the importance of the mechanism underlying transcriptional repression in leukemic cells, involving complex functional connections between SPI1 and the epigenetic regulators PRC2 and HDAC1.</p>',
			'date' => '2022-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35871293',
			'doi' => '10.1093/nar/gkac613',
			'modified' => '2022-09-15 08:59:26',
			'created' => '2022-09-08 16:32:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 17 => array(
			'id' => '4516',
			'name' => 'Dual role of histone variant H3.3B in spermatogenesis: positiveregulation of piRNA transcription and implication in X-chromosomeinactivation.',
			'authors' => 'Fontaine  E. et al.',
			'description' => '<p>The histone variant H3.3 is encoded by two distinct genes, H3f3a and H3f3b, exhibiting identical amino-acid sequence. H3.3 is required for spermatogenesis, but the molecular mechanism of its spermatogenic function remains obscure. Here, we have studied the role of each one of H3.3A and H3.3B proteins in spermatogenesis. We have generated transgenic conditional knock-out/knock-in (cKO/KI) epitope-tagged FLAG-FLAG-HA-H3.3B (H3.3BHA) and FLAG-FLAG-HA-H3.3A (H3.3AHA) mouse lines. We show that H3.3B, but not H3.3A, is required for spermatogenesis and male fertility. Analysis of the molecular mechanism unveils that the absence of H3.3B led to alterations in the meiotic/post-meiotic transition. Genome-wide RNA-seq reveals that the depletion of H3.3B in meiotic cells is associated with increased expression of the whole sex X and Y chromosomes as well as of both RLTR10B and RLTR10B2 retrotransposons. In contrast, the absence of H3.3B resulted in down-regulation of the expression of piRNA clusters. ChIP-seq experiments uncover that RLTR10B and RLTR10B2 retrotransposons, the whole sex chromosomes and the piRNA clusters are markedly enriched of H3.3. Taken together, our data dissect the molecular mechanism of H3.3B functions during spermatogenesis and demonstrate that H3.3B, depending on its chromatin localization, is involved in either up-regulation or down-regulation of expression of defined large chromatin regions.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35766398',
			'doi' => '10.1093/nar/gkac541',
			'modified' => '2022-11-24 08:51:34',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 18 => array(
			'id' => '4393',
			'name' => 'TBX2 acts as a potent transcriptional silencer of tumour suppressor genesthrough interaction with the CoREST complex to sustain theproliferation of breast cancers.',
			'authors' => 'McIntyre  A.J. et al.',
			'description' => '<p>Chromosome 17q23 amplification occurs in 20\% of primary breast tumours and is associated with poor outcome. The TBX2 gene is located on 17q23 and is often over-expressed in this breast tumour subset. TBX2 is an anti-senescence gene, promoting cell growth and survival through repression of Tumour Suppressor Genes (TSGs), such as NDRG1 and CST6. Previously we found that TBX2 cooperates with the PRC2 complex to repress several TSGs, and that PRC2 inhibition restored NDRG1 expression to impede cellular proliferation. Here, we now identify CoREST proteins, LSD1 and ZNF217, as novel interactors of TBX2. Genetic or pharmacological targeting of CoREST emulated TBX2 loss, inducing NDRG1 expression and abolishing breast cancer growth in vitro and in vivo. Furthermore, we uncover that TBX2/CoREST targeting of NDRG1 is achieved by recruitment of TBX2 to the NDRG1 promoter by Sp1, the abolishment of which resulted in NDRG1 upregulation and diminished cancer cell proliferation. Through ChIP-seq we reveal that 30\% of TBX2-bound promoters are shared with ZNF217 and identify novel targets repressed by TBX2/CoREST; of these targets a lncRNA, LINC00111, behaves as a negative regulator of cell proliferation. Overall, these data indicate that inhibition of CoREST proteins represents a promising therapeutic intervention for TBX2-addicted breast tumours.</p>',
			'date' => '2022-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35687133',
			'doi' => '10.1093/nar/gkac494',
			'modified' => '2022-08-11 14:23:06',
			'created' => '2022-08-11 12:14:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 19 => array(
			'id' => '4836',
			'name' => 'Caffeine intake exerts dual genome-wide effects on hippocampal metabolismand learning-dependent transcription.',
			'authors' => 'Paiva  I. et al.',
			'description' => '<p>Caffeine is the most widely consumed psychoactive substance in the world. Strikingly, the molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal omics techniques. Our results revealed that chronic caffeine exerts concerted pleiotropic effects in the hippocampus at the epigenomic, proteomic, and metabolomic levels. Caffeine lowered metabolism-related processes (e.g., at the level of metabolomics and gene expression) in bulk tissue, while it induced neuron-specific epigenetic changes at synaptic transmission/plasticity-related genes and increased experience-driven transcriptional activity. Altogether, these findings suggest that regular caffeine intake improves the signal-to-noise ratio during information encoding, in part through fine-tuning of metabolic genes, while boosting the salience of information processing during learning in neuronal circuits.</p>',
			'date' => '2022-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35536645',
			'doi' => '10.1172/JCI149371',
			'modified' => '2023-08-01 13:52:29',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 20 => 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) 21 => 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) 22 => 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) 23 => array(
			'id' => '4217',
			'name' => 'CREBBP/EP300 acetyltransferase inhibition disrupts FOXA1-bound enhancers to inhibit the proliferation of ER+ breast cancer cells.',
			'authors' => 'Bommi-Reddy A. et al.',
			'description' => '<p><span>Therapeutic targeting of the estrogen receptor (ER) is a clinically validated approach for estrogen receptor positive breast cancer (ER+ BC), but sustained response is limited by acquired resistance. Targeting the transcriptional coactivators required for estrogen receptor activity represents an alternative approach that is not subject to the same limitations as targeting estrogen receptor itself. In this report we demonstrate that the acetyltransferase activity of coactivator paralogs CREBBP/EP300 represents a promising therapeutic target in ER+ BC. Using the potent and selective inhibitor CPI-1612, we show that CREBBP/EP300 acetyltransferase inhibition potently suppresses in vitro and in vivo growth of breast cancer cell line models and acts in a manner orthogonal to directly targeting ER. CREBBP/EP300 acetyltransferase inhibition suppresses ER-dependent transcription by targeting lineage-specific enhancers defined by the pioneer transcription factor FOXA1. These results validate CREBBP/EP300 acetyltransferase activity as a viable target for clinical development in ER+ breast cancer.</span></p>',
			'date' => '2022-03-30',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/35353838/',
			'doi' => '10.1371/journal.pone.0262378',
			'modified' => '2022-04-12 10:56:54',
			'created' => '2022-04-12 10:56:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 24 => array(
			'id' => '4235',
			'name' => 'NuA4 and H2A.Z control environmental responses and autotrophicgrowth in Arabidopsis',
			'authors' => 'Bieluszewski T. et al.',
			'description' => '<p>Nucleosomal acetyltransferase of H4 (NuA4) is an essential transcriptional coactivator in eukaryotes, but remains poorly characterized in plants. Here, we describe Arabidopsis homologs of the NuA4 scaffold proteins Enhancer of Polycomb-Like 1 (AtEPL1) and Esa1-Associated Factor 1 (AtEAF1). Loss of AtEAF1 results in inhibition of growth and chloroplast development. These effects are stronger in the Atepl1 mutant and are further enhanced by loss of Golden2-Like (GLK) transcription factors, suggesting that NuA4 activates nuclear plastid genes alongside GLK. We demonstrate that AtEPL1 is necessary for nucleosomal acetylation of histones H4 and H2A.Z by NuA4 in vitro. These chromatin marks are diminished genome-wide in Atepl1, while another active chromatin mark, H3K9 acetylation (H3K9ac), is locally enhanced. Expression of many chloroplast-related genes depends on NuA4, as they are downregulated with loss of H4ac and H2A.Zac. Finally, we demonstrate that NuA4 promotes H2A.Z deposition and by doing so prevents spurious activation of stress response genes.</p>',
			'date' => '2022-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35022409',
			'doi' => '10.1038/s41467-021-27882-5',
			'modified' => '2022-05-19 17:02:00',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 25 => array(
			'id' => '4772',
			'name' => 'Three classes of epigenomic regulators converge to hyperactivate theessential maternal gene deadhead within a heterochromatin mini-domain.',
			'authors' => 'Torres-Campana  D. et al.',
			'description' => '<p>The formation of a diploid zygote is a highly complex cellular process that is entirely controlled by maternal gene products stored in the egg cytoplasm. This highly specialized transcriptional program is tightly controlled at the chromatin level in the female germline. As an extreme case in point, the massive and specific ovarian expression of the essential thioredoxin Deadhead (DHD) is critically regulated in Drosophila by the histone demethylase Lid and its partner, the histone deacetylase complex Sin3A/Rpd3, via yet unknown mechanisms. Here, we identified Snr1 and Mod(mdg4) as essential for dhd expression and investigated how these epigenomic effectors act with Lid and Sin3A to hyperactivate dhd. Using Cut\&amp;Run chromatin profiling with a dedicated data analysis procedure, we found that dhd is intriguingly embedded in an H3K27me3/H3K9me3-enriched mini-domain flanked by DNA regulatory elements, including a dhd promoter-proximal element essential for its expression. Surprisingly, Lid, Sin3a, Snr1 and Mod(mdg4) impact H3K27me3 and this regulatory element in distinct manners. However, we show that these effectors activate dhd independently of H3K27me3/H3K9me3, and that dhd remains silent in the absence of these marks. Together, our study demonstrates an atypical and critical role for chromatin regulators Lid, Sin3A, Snr1 and Mod(mdg4) to trigger tissue-specific hyperactivation within a unique heterochromatin mini-domain.</p>',
			'date' => '2022-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759638/',
			'doi' => '10.1371/journal.pgen.1009615',
			'modified' => '2023-04-17 09:46:00',
			'created' => '2023-04-14 13:41:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 26 => 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) 27 => array(
			'id' => '4245',
			'name' => 'Decreased PRC2 activity supports the survival of basal-like breastcancer cells to cytotoxic treatments',
			'authors' => 'Mieczkowska IK et al.',
			'description' => '<p>Breast cancer (BC) is the most common cancer occurring in women but also rarely develops in men. Recent advances in early diagnosis and development of targeted therapies have greatly improved the survival rate of BC patients. However, the basal-like BC subtype (BLBC), largely overlapping with the triple-negative BC subtype (TNBC), lacks such drug targets and conventional cytotoxic chemotherapies often remain the only treatment option. Thus, the development of resistance to cytotoxic therapies has fatal consequences. To assess the involvement of epigenetic mechanisms and their therapeutic potential increasing cytotoxic drug efficiency, we combined high-throughput RNA- and ChIP-sequencing analyses in BLBC cells. Tumor cells surviving chemotherapy upregulated transcriptional programs of epithelial-to-mesenchymal transition (EMT) and stemness. To our surprise, the same cells showed a pronounced reduction of polycomb repressive complex 2 (PRC2) activity via downregulation of its subunits Ezh2, Suz12, Rbbp7 and Mtf2. Mechanistically, loss of PRC2 activity leads to the de-repression of a set of genes through an epigenetic switch from repressive H3K27me3 to activating H3K27ac mark at regulatory regions. We identified Nfatc1 as an upregulated gene upon loss of PRC2 activity and directly implicated in the transcriptional changes happening upon survival to chemotherapy. Blocking NFATc1 activation reduced epithelial-to-mesenchymal transition, aggressiveness, and therapy resistance of BLBC cells. Our data demonstrate a previously unknown function of PRC2 maintaining low Nfatc1 expression levels and thereby repressing aggressiveness and therapy resistance in BLBC.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34845197',
			'doi' => '10.1038/s41419-021-04407-y',
			'modified' => '2022-05-20 09:21:56',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 28 => array(
			'id' => '4276',
			'name' => 'Ago1 controls myogenic differentiation by regulating eRNA-mediatedCBP-guided epigenome reprogramming.',
			'authors' => 'Fallatah Bodor et al.',
			'description' => '<p>The role of chromatin-associated RNAi components in the nucleus of mammalian cells and in particular in the context of developmental programs remains to be elucidated. Here, we investigate the function of nuclear Argonaute 1 (Ago1) in gene expression regulation during skeletal muscle differentiation. We show that Ago1 is required for activation of the myogenic program by supporting chromatin modification mediated by developmental enhancer activation. Mechanistically, we demonstrate that Ago1 directly controls global H3K27 acetylation (H3K27ac) by regulating enhancer RNA (eRNA)-CREB-binding protein (CBP) acetyltransferase interaction, a key step in enhancer-driven gene activation. In particular, we show that Ago1 is specifically required for myogenic differentiation 1 (MyoD) and downstream myogenic gene activation, whereas its depletion leads to failure of CBP acetyltransferase activation and blocking of the myogenic program. Our work establishes a role of the mammalian enhancer-associated RNAi component Ago1 in epigenome regulation and activation of developmental programs.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.celrep.2021.110066',
			'doi' => '10.1016/j.celrep.2021.110066',
			'modified' => '2022-05-23 09:53:14',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 29 => array(
			'id' => '4833',
			'name' => 'Extensive NEUROG3 occupancy in the human pancreatic endocrine generegulatory network.',
			'authors' => 'Schreiber  V. et al.',
			'description' => '<p>OBJECTIVE: Mice lacking the bHLH transcription factor (TF) Neurog3 do not form pancreatic islet cells, including insulin-secreting beta cells, the absence of which leads to diabetes. In humans, homozygous mutations of NEUROG3 manifest with neonatal or childhood diabetes. Despite this critical role in islet cell development, the precise function of and downstream genetic programs regulated directly by NEUROG3 remain elusive. Therefore, we mapped genome-wide NEUROG3 occupancy in human induced pluripotent stem cell (hiPSC)-derived endocrine progenitors and determined NEUROG3 dependency of associated genes to uncover direct targets. METHODS: We generated a novel hiPSC line (NEUROG3-HA-P2A-Venus) where NEUROG3 is HA-tagged and fused to a self-cleaving fluorescent VENUS reporter. We used the CUT\&amp;RUN technique to map NEUROG3 occupancy and epigenetic marks in pancreatic endocrine progenitors (PEP) that were differentiated from this hiPSC line. We integrated NEUROG3 occupancy data with chromatin status and gene expression in PEPs as well as their NEUROG3-dependence. In addition, we investigated whether NEUROG3 binds type 2 diabetes mellitus (T2DM)-associated variants at the PEP stage. RESULTS: CUT\&amp;RUN revealed a total of 863 NEUROG3 binding sites assigned to 1263 unique genes. NEUROG3 occupancy was found at promoters as well as at distant cis-regulatory elements that frequently overlapped within PEP active enhancers. De novo motif analyses defined a NEUROG3 consensus binding motif and suggested potential co-regulation of NEUROG3 target genes by FOXA or RFX transcription factors. We found that 22\% of the genes downregulated in NEUROG3 PEPs, and 10\% of genes enriched in NEUROG3-Venus positive endocrine cells were bound by NEUROG3 and thus likely to be directly regulated. NEUROG3 binds to 138 transcription factor genes, some with important roles in islet cell development or function, such as NEUROD1, PAX4, NKX2-2, SOX4, MLXIPL, LMX1B, RFX3, and NEUROG3 itself, and many others with unknown islet function. Unexpectedly, we uncovered that NEUROG3 targets genes critical for insulin secretion in beta cells (e.g., GCK, ABCC8/KCNJ11, CACNA1A, CHGA, SCG2, SLC30A8, and PCSK1). Thus, analysis of NEUROG3 occupancy suggests that the transient expression of NEUROG3 not only promotes islet destiny in uncommitted pancreatic progenitors, but could also initiate endocrine programs essential for beta cell function. Lastly, we identified eight T2DM risk SNPs within NEUROG3-bound regions. CONCLUSION: Mapping NEUROG3 genome occupancy in PEPs uncovered unexpectedly broad, direct control of the endocrine genes, raising novel hypotheses on how this master regulator controls islet and beta cell differentiation.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.04.14.439685',
			'doi' => '10.1016/j.molmet.2021.101313',
			'modified' => '2023-08-01 13:46:35',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 30 => array(
			'id' => '4285',
			'name' => 'Alveolar macrophages from persons living with HIV show impairedepigenetic response to Mycobacterium tuberculosis.',
			'authors' => 'Correa-Macedo Wilian et al.',
			'description' => '<p>Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV and antiretroviral therapy (ART) impact on the anti-mycobacterial response of AM is not known. To investigate the impact of HIV and ART on the transcriptomic and epigenetic response of AM to Mtb, we obtained AM by bronchoalveolar lavage from 20 PLWH receiving ART, 16 control subjects who were HIV-free (HC), and 14 subjects who received ART as pre-exposure prophylaxis (PrEP) to prevent HIV infection. Following in-vitro challenge with Mtb, AM from each group displayed overlapping but distinct profiles of significantly up- and down-regulated genes in response to Mtb. Comparatively, AM isolated from both PLWH and PrEP subjects presented a substantially weaker transcriptional response. In addition, AM from HC subjects challenged with Mtb responded with pronounced chromatin accessibility changes while AM obtained from PLWH and PrEP subjects displayed no significant changes in their chromatin state. Collectively, these results revealed a stronger adverse effect of ART than HIV on the epigenetic landscape and transcriptional responsiveness of AM.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/34473646/',
			'doi' => '10.1172/JCI148013',
			'modified' => '2022-05-24 09:08:39',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 31 => 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) 32 => array(
			'id' => '4304',
			'name' => 'The related coactivator complexes SAGA and ATAC control embryonicstem cell self-renewal through acetyltransferase-independent mechanisms',
			'authors' => 'Fischer Veronique et al.',
			'description' => '<p>SUMMARY SAGA (Spt-Ada-Gcn5 acetyltransferase) and ATAC (Ada-two-A-containing) are two related coactivator complexes, sharing the same histone acetyltransferase (HAT) subunit. The HAT activities of SAGA and ATAC are required for metazoan development, but the role of these complexes in RNA polymerase II transcription is less understood. To determine whether SAGA and ATAC have redundant or specific functions, we compare the effects of HAT inactivation in each complex with that of inactivation of either SAGA or ATAC core subunits in mouse embryonic stem cells (ESCs). We show that core subunits of SAGA or ATAC are required for complex assembly and mouse ESC growth and self-renewal. Surprisingly, depletion of HAT module subunits causes a global decrease in histone H3K9 acetylation, but does not result in significant phenotypic or transcriptional defects. Thus, our results indicate that SAGA and ATAC are differentially required for self-renewal of mouse ESCs by regulating transcription through different pathways in a HAT-independent manner.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34433046',
			'doi' => '10.1016/j.celrep.2021.109598',
			'modified' => '2022-05-30 09:57:39',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 33 => array(
			'id' => '4345',
			'name' => 'Altered Chromatin States Drive Cryptic Transcription in AgingMammalian Stem Cells.',
			'authors' => 'McCauley Brenna S et al.',
			'description' => '<p>A repressive chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation suppresses cryptic transcription in embryonic stem cells. Cryptic transcription is elevated with age in yeast and nematodes, and reducing it extends yeast lifespan, though whether this occurs in mammals is unknown. We show that cryptic transcription is elevated in aged mammalian stem cells, including murine hematopoietic stem cells (mHSCs) and neural stem cells (NSCs) and human mesenchymal stem cells (hMSCs). Precise mapping allowed quantification of age-associated cryptic transcription in hMSCs aged . Regions with significant age-associated cryptic transcription have a unique chromatin signature: decreased H3K36me3 and increased H3K4me1, H3K4me3, and H3K27ac with age. Genomic regions undergoing such changes resemble known promoter sequences and are bound by TBP even in young cells. Hence, the more permissive chromatin state at intragenic cryptic promoters likely underlies increased cryptic transcription in aged mammalian stem cells.</p>',
			'date' => '2021-08-01',
			'pmid' => 'https://doi.org/10.1038%2Fs43587-021-00091-x',
			'doi' => '10.1038/s43587-021-00091-x',
			'modified' => '2022-06-22 12:30:19',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 34 => array(
			'id' => '4333',
			'name' => 'Metabolically controlled histone H4K5 acylation/acetylation ratiodrives BRD4 genomic distribution.',
			'authors' => 'Gao M. et al.',
			'description' => '<p>In addition to acetylation, histones are modified by a series of competing longer-chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions hinder our understanding of histone acylations' specific roles. Here, by using an acute lymphoblastic leukemia (ALL) cell model and blasts from individuals with B-precusor ALL (B-ALL), we demonstrate a role of mitochondrial activity in controlling the histone acylation/acetylation ratio, especially at histone H4 lysine 5 (H4K5). An increase in the ratio of non-acetyl acylations (crotonylation or butyrylation) over acetylation on H4K5 weakens bromodomain containing protein 4 (BRD4) bromodomain-dependent chromatin interaction and enhances BRD4 nuclear mobility and availability for binding transcription start site regions of active genes. Our data suggest that the metabolism-driven control of the histone acetylation/longer-chain acylation(s) ratio could be a common mechanism regulating the bromodomain factors' functional genomic distribution.</p>',
			'date' => '2021-07-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.celrep.2021.109460',
			'doi' => '10.1016/j.celrep.2021.109460',
			'modified' => '2022-08-03 16:14:09',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 35 => array(
			'id' => '4341',
			'name' => 'Heterogeneity of neurons reprogrammed from spinal cord astrocytes by theproneural factors Ascl1 and Neurogenin2',
			'authors' => 'Kempf J. et al. ',
			'description' => '<p>Summary Astrocytes are a viable source for generating new neurons via direct conversion. However, little is known about the neurogenic cascades triggered in astrocytes from different regions of the CNS. Here, we examine the transcriptome induced by the proneural factors Ascl1 and Neurog2 in spinal cord-derived astrocytes in vitro. Each factor initially elicits different neurogenic programs that later converge to a V2 interneuron-like state. Intriguingly, patch sequencing (patch-seq) shows no overall correlation between functional properties and the transcriptome of the heterogenous induced neurons, except for K-channels. For example, some neurons with fully mature electrophysiological properties still express astrocyte genes, thus calling for careful molecular and functional analysis. Comparing the transcriptomes of spinal cord- and cerebral-cortex-derived astrocytes reveals profound differences, including developmental patterning cues maintained in vitro. These relate to the distinct neuronal identity elicited by Ascl1 and Neurog2 reflecting their developmental functions in subtype specification of the respective CNS region.</p>',
			'date' => '2021-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34289357',
			'doi' => '10.1016/j.celrep.2021.109409',
			'modified' => '2022-08-03 16:29:33',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 36 => 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) 37 => 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) 38 => array(
			'id' => '4147',
			'name' => 'Waves of sumoylation support transcription dynamics during adipocytedifferentiation',
			'authors' => 'Zhao, X. et al.',
			'description' => '<p>Tight control of gene expression networks required for adipose tissue formation and plasticity is essential for adaptation to energy needs and environmental cues. However, little is known about the mechanisms that orchestrate the dramatic transcriptional changes leading to adipocyte differentiation. We investigated the regulation of nascent transcription by the sumoylation pathway during adipocyte differentiation using SLAMseq and ChIPseq. We discovered that the sumoylation pathway has a dual function in differentiation; it supports the initial downregulation of pre-adipocyte-specific genes, while it promotes the establishment of the mature adipocyte transcriptional program. By characterizing sumoylome dynamics in differentiating adipocytes by mass spectrometry, we found that sumoylation of specific transcription factors like Ppar&gamma;/RXR and their co-factors is associated with the transcription of adipogenic genes. Our data demonstrate that the sumoylation pathway coordinates the rewiring of transcriptional networks required for formation of functional adipocytes. This study also provides an in-depth resource of gene transcription dynamics, SUMO-regulated genes and sumoylation sites during adipogenesis.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.02.20.432084',
			'doi' => '10.1101/2021.02.20.432084',
			'modified' => '2021-12-14 09:23:28',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 39 => array(
			'id' => '4192',
			'name' => 'Polycomb Repressive Complex 2 and KRYPTONITE regulate pathogen-inducedprogrammed cell death in Arabidopsis.',
			'authors' => 'Dvořák Tomaštíková E. et al.',
			'description' => '<p>The Polycomb Repressive Complex 2 (PRC2) is well-known for its role in controlling developmental transitions by suppressing the premature expression of key developmental regulators. Previous work revealed that PRC2 also controls the onset of senescence, a form of developmental programmed cell death (PCD) in plants. Whether the induction of PCD in response to stress is similarly suppressed by the PRC2 remained largely unknown. In this study, we explored whether PCD triggered in response to immunity- and disease-promoting pathogen effectors is associated with changes in the distribution of the PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) modification in Arabidopsis thaliana. We furthermore tested the distribution of the heterochromatic histone mark H3K9me2, which is established, to a large extent, by the H3K9 methyltransferase KRYPTONITE, and occupies chromatin regions generally not targeted by PRC2. We report that effector-induced PCD caused major changes in the distribution of both repressive epigenetic modifications and that both modifications have a regulatory role and impact on the onset of PCD during pathogen infection. Our work highlights that the transition to pathogen-induced PCD is epigenetically controlled, revealing striking similarities to developmental PCD.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33566101',
			'doi' => '10.1093/plphys/kiab035',
			'modified' => '2022-01-06 14:12:23',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 40 => array(
			'id' => '4273',
			'name' => 'An integrated multi-omics analysis identifies prognostic molecularsubtypes of non-muscle-invasive bladder cancer',
			'authors' => 'Lindskrog Sia Viborg et al.',
			'description' => '<p>The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n&thinsp;=&thinsp;834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33863885',
			'doi' => '10.1038/s41467-021-22465-w',
			'modified' => '2022-05-23 09:49:43',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 41 => 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) 42 => array(
			'id' => '4109',
			'name' => 'VPRBP functions downstream of the androgen receptor and OGT to restrict p53 activation in prostate cancer ',
			'authors' => 'Poulose N. et al. ',
			'description' => '<p>Androgen receptor (AR) is a major driver of prostate cancer (PCa) initiation and progression. O-GlcNAc transferase (OGT), the enzyme that catalyses the covalent addition of UDP-N-acetylglucosamine (UDP-GlcNAc) to serine and threonine residues of proteins, is often up-regulated in PCa with its expression correlated with high Gleason score. In this study we have identified an AR and OGT co-regulated factor, VPRBP/DCAF1. We show that VPRBP is regulated by the AR at the transcript level, and by OGT at the protein level. In human tissue samples, VPRBP protein expression correlated with AR amplification, OGT overexpression and poor prognosis. VPRBP knockdown in prostate cancer cells led to a significant decrease in cell proliferation, p53 stabilization, nucleolar fragmentation and increased p53 recruitment to the chromatin. In conclusion, we have shown that VPRBP/DCAF1 promotes prostate cancer cell proliferation by restraining p53 activation under the influence of the AR and OGT.</p>',
			'date' => '2021-02-21',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/2021.02.28.433236v1',
			'doi' => '',
			'modified' => '2021-07-07 11:59:15',
			'created' => '2021-07-07 11:59:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 43 => array(
			'id' => '4124',
			'name' => 'JAZF1, A Novel p400/TIP60/NuA4 Complex Member, Regulates H2A.ZAcetylation at Regulatory Regions.',
			'authors' => 'Procida, Tara and Friedrich, Tobias and Jack, Antonia P M and Peritore,Martina and Bönisch, Clemens and Eberl, H Christian and Daus, Nadine andKletenkov, Konstantin and Nist, Andrea and Stiewe, Thorsten and Borggrefe,Tilman and Mann, Matthias and Bartk',
			'description' => '<p>Histone variants differ in amino acid sequence, expression timing and genomic localization sites from canonical histones and convey unique functions to eukaryotic cells. Their tightly controlled spatial and temporal deposition into specific chromatin regions is accomplished by dedicated chaperone and/or remodeling complexes. While quantitatively identifying the chaperone complexes of many human H2A variants by using mass spectrometry, we also found additional members of the known H2A.Z chaperone complexes p400/TIP60/NuA4 and SRCAP. We discovered JAZF1, a nuclear/nucleolar protein, as a member of a p400 sub-complex containing MBTD1 but excluding ANP32E. Depletion of JAZF1 results in transcriptome changes that affect, among other pathways, ribosome biogenesis. To identify the underlying molecular mechanism contributing to JAZF1's function in gene regulation, we performed genome-wide ChIP-seq analyses. Interestingly, depletion of JAZF1 leads to reduced H2A.Z acetylation levels at &gt; 1000 regulatory sites without affecting H2A.Z nucleosome positioning. Since JAZF1 associates with the histone acetyltransferase TIP60, whose depletion causes a correlated H2A.Z deacetylation of several JAZF1-targeted enhancer regions, we speculate that JAZF1 acts as chromatin modulator by recruiting TIP60's enzymatic activity. Altogether, this study uncovers JAZF1 as a member of a TIP60-containing p400 chaperone complex orchestrating H2A.Z acetylation at regulatory regions controlling the expression of genes, many of which are involved in ribosome biogenesis.</p>',
			'date' => '2021-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33445503',
			'doi' => '10.3390/ijms22020678',
			'modified' => '2021-12-07 10:00:44',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 44 => array(
			'id' => '4153',
			'name' => 'Epigenetic impairment and blunted transcriptional response to Mycobacteriumtuberculosis of alveolar macrophages from persons living with HIV',
			'authors' => 'Correa-Macedo, W. et al.',
			'description' => '<p>Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV and antiretroviral therapy (ART) impact on the anti-mycobacterial response of AM is not known. To investigate the impact of HIV and ART on the transcriptomic and epigenetic response of AM to Mtb, we obtained AM by bronchoalveolar lavage from 20 PLWH receiving ART, 16 control subjects who were HIV-free (HC), and 14 subjects who received ART as pre-exposure prophylaxis (PrEP) to prevent HIV infection. Following in-vitro challenge with Mtb, AM from each group displayed overlapping but distinct profiles of significantly up- and down-regulated genes in response to Mtb. Compared to HC subjects, AM isolated from PLWH and PrEP subjects presented a substantially weaker transcriptional response. Further investigation of chromatin structure revealed that AM from control subjects challenged with Mtb responded with pronounced accessibility changes in over ten thousand regions. In stark contrast, AM obtained from PLWH and PrEP subjects displayed no significant changes in their chromatin state in response to Mtb. Collectively, these results revealed a previously unknown adverse effect of ART on the epigenetic landscape and transcriptional responsiveness of AM.</p>',
			'date' => '2021-01-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.01.26.21250318',
			'doi' => '10.1101/2021.01.26.21250318',
			'modified' => '2021-12-16 10:35:21',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 45 => array(
			'id' => '4179',
			'name' => 'Histone demethylase JMJD2B/KDM4B regulates transcriptional program viadistinctive epigenetic targets and protein interactors for the maintenanceof trophoblast stem cells.',
			'authors' => 'Mak, Kylie Hin-Man et al.',
			'description' => '<p>Trophoblast stem cell (TSC) is crucial to the formation of placenta in mammals. Histone demethylase JMJD2 (also known as KDM4) family proteins have been previously shown to support self-renewal and differentiation of stem cells. However, their roles in the context of the trophoblast lineage remain unclear. Here, we find that knockdown of Jmjd2b resulted in differentiation of TSCs, suggesting an indispensable role of JMJD2B/KDM4B in maintaining the stemness. Through the integration of transcriptome and ChIP-seq profiling data, we show that JMJD2B is associated with a loss of H3K36me3 in a subset of embryonic lineage genes which are marked by H3K9me3 for stable repression. By characterizing the JMJD2B binding motifs and other transcription factor binding datasets, we discover that JMJD2B forms a protein complex with AP-2 family transcription factor TFAP2C and histone demethylase LSD1. The JMJD2B-TFAP2C-LSD1 complex predominantly occupies active gene promoters, whereas the TFAP2C-LSD1 complex is located at putative enhancers, suggesting that these proteins mediate enhancer-promoter interaction for gene regulation. We conclude that JMJD2B is vital to the TSC transcriptional program and safeguards the trophoblast cell fate via distinctive protein interactors and epigenetic targets.</p>',
			'date' => '2021-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33441614',
			'doi' => '10.1038/s41598-020-79601-7',
			'modified' => '2021-12-21 16:43:16',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 46 => array(
			'id' => '4038',
			'name' => 'Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture.',
			'authors' => 'Yusufova, Nevin and Kloetgen, Andreas and Teater, Matt and Osunsade,Adewola and Camarillo, Jeannie M and Chin, Christopher R and Doane, AshleyS and Venters, Bryan J and Portillo-Ledesma, Stephanie and Conway, Josephand Phillip, Jude M and Elemento, Oli',
			'description' => '<p>Linker histone H1 proteins bind to nucleosomes and facilitate chromatin compaction, although their biological functions are poorly understood. Mutations in the genes that encode H1 isoforms B-E (H1B, H1C, H1D and H1E; also known as H1-5, H1-2, H1-3 and H1-4, respectively) are highly recurrent in B&nbsp;cell lymphomas, but the pathogenic relevance of these mutations to cancer and the mechanisms that are involved are unknown. Here we show that lymphoma-associated H1 alleles are genetic driver mutations in lymphomas. Disruption of H1 function results in a profound architectural remodelling of the genome, which is characterized by large-scale yet focal shifts of chromatin from a compacted to a relaxed state. This decompaction drives distinct changes in epigenetic states, primarily owing to a gain of histone H3 dimethylation at lysine 36 (H3K36me2) and/or loss of repressive H3 trimethylation at lysine 27 (H3K27me3). These changes unlock the expression of stem cell genes that are normally silenced during early development. In mice, loss of H1c and H1e (also known as H1f2 and H1f4, respectively) conferred germinal centre B&nbsp;cells with enhanced fitness and self-renewal properties, ultimately leading to aggressive lymphomas with an increased repopulating potential. Collectively, our data indicate that H1 proteins are normally required to sequester early developmental genes into architecturally inaccessible genomic compartments. We also establish H1 as a bona fide tumour suppressor and show that mutations in H1 drive malignant transformation primarily through three-dimensional genome reorganization, which leads to epigenetic reprogramming and derepression of developmentally silenced genes.</p>',
			'date' => '2020-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33299181',
			'doi' => '10.1038/s41586-020-3017-y',
			'modified' => '2021-02-18 17:15:52',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 47 => array(
			'id' => '4056',
			'name' => 'Multi-omic comparison of Alzheimer's variants in human ESC-derivedmicroglia reveals convergence at APOE.',
			'authors' => 'Liu, Tongfei and Zhu, Bing and Liu, Yan and Zhang, Xiaoming and Yin, Junand Li, Xiaoguang and Jiang, LuLin and Hodges, Andrew P and Rosenthal, SaraBrin and Zhou, Lisa and Yancey, Joel and McQuade, Amanda and Blurton-Jones,Mathew and Tanzi, Rudolph E an',
			'description' => '<p>Variations in many genes linked to sporadic Alzheimer's disease (AD) show abundant expression in microglia, but relationships among these genes remain largely elusive. Here, we establish isogenic human ESC-derived microglia-like cell lines (hMGLs) harboring AD variants in CD33, INPP5D, SORL1, and TREM2 loci and curate a comprehensive atlas comprising ATAC-seq, ChIP-seq, RNA-seq, and proteomics datasets. AD-like expression signatures are observed in AD mutant SORL1 and TREM2 hMGLs, while integrative multi-omic analysis of combined epigenetic and expression datasets indicates up-regulation of APOE as a convergent pathogenic node. We also observe cross-regulatory relationships between SORL1 and TREM2, in which SORL1R744X hMGLs induce TREM2 expression to enhance APOE expression. AD-associated SORL1 and TREM2 mutations also impaired hMGL A&beta; uptake in an APOE-dependent manner in vitro and attenuated A&beta; uptake/clearance in mouse AD brain xenotransplants. Using this modeling and analysis platform for human microglia, we provide new insight into epistatic interactions in AD genes and demonstrate convergence of microglial AD genes at the APOE locus.</p>',
			'date' => '2020-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32941599',
			'doi' => '10.1084/jem.20200474',
			'modified' => '2021-02-19 17:18:23',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 48 => array(
			'id' => '4060',
			'name' => 'A genetic variant controls interferon-β gene expression in human myeloidcells by preventing C/EBP-β binding on a conserved enhancer.',
			'authors' => 'Assouvie, Anaïs and Rotival, Maxime and Hamroune, Juliette and Busso,Didier and Romeo, Paul-Henri and Quintana-Murci, Lluis and Rousselet,Germain',
			'description' => '<p>Interferon &beta; (IFN-&beta;) is a cytokine that induces a global antiviral proteome, and regulates the adaptive immune response to infections and tumors. Its effects strongly depend on its level and timing of expression. Therefore, the transcription of its coding gene IFNB1 is strictly controlled. We have previously shown that in mice, the TRIM33 protein restrains Ifnb1 transcription in activated myeloid cells through an upstream inhibitory sequence called ICE. Here, we show that the deregulation of Ifnb1 expression observed in murine Trim33-/- macrophages correlates with abnormal looping of both ICE and the Ifnb1 gene to a 100 kb downstream region overlapping the Ptplad2/Hacd4 gene. This region is a predicted myeloid super-enhancer in which we could characterize 3 myeloid-specific active enhancers, one of which (E5) increases the response of the Ifnb1 promoter to activation. In humans, the orthologous region contains several single nucleotide polymorphisms (SNPs) known to be associated with decreased expression of IFNB1 in activated monocytes, and loops to the IFNB1 gene. The strongest association is found for the rs12553564 SNP, located in the E5 orthologous region. The minor allele of rs12553564 disrupts a conserved C/EBP-&beta; binding motif, prevents binding of C/EBP-&beta;, and abolishes the activation-induced enhancer activity of E5. Altogether, these results establish a link between a genetic variant preventing binding of a transcription factor and a higher order phenotype, and suggest that the frequent minor allele (around 30\% worldwide) might be associated with phenotypes regulated by IFN-&beta; expression in myeloid cells.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33147208',
			'doi' => '10.1371/journal.pgen.1009090',
			'modified' => '2021-02-19 17:29:34',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 49 => 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) 50 => array(
			'id' => '4210',
			'name' => 'Trans- and cis-acting effects of Firre on epigenetic features of theinactive X chromosome.',
			'authors' => 'Fang, He and Bonora, Giancarlo and Lewandowski, Jordan P and Thakur,Jitendra and Filippova, Galina N and Henikoff, Steven and Shendure, Jay andDuan, Zhijun and Rinn, John L and Deng, Xinxian and Noble, William S andDisteche, Christine M',
			'description' => '<p>Firre encodes a lncRNA involved in nuclear organization. Here, we show that Firre RNA expressed from the active X chromosome maintains histone H3K27me3 enrichment on the inactive X chromosome (Xi) in somatic cells. This trans-acting effect involves SUZ12, reflecting interactions between Firre RNA and components of the Polycomb repressive complexes. Without Firre RNA, H3K27me3 decreases on the Xi and the&nbsp;Xi-perinucleolar location is disrupted, possibly due to decreased CTCF binding on the Xi. We also observe widespread gene dysregulation, but not on the Xi. These effects are measurably rescued by ectopic expression of mouse or human Firre/FIRRE transgenes, supporting conserved trans-acting roles. We also find that the compact 3D structure of the Xi partly depends on the Firre locus and its RNA. In common lymphoid progenitors and T-cells Firre exerts a cis-acting effect on maintenance of H3K27me3 in a 26&thinsp;Mb region around the locus, demonstrating cell type-specific trans- and cis-acting roles of this lncRNA.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33247132',
			'doi' => '10.1038/s41467-020-19879-3',
			'modified' => '2022-01-13 15:03:45',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 51 => array(
			'id' => '4048',
			'name' => 'The histone H2B ubiquitin ligase RNF40 is required for HER2-drivenmammary tumorigenesis.',
			'authors' => 'Wegwitz, Florian and Prokakis, Evangelos and Pejkovska, Anastasija andKosinsky, Robyn Laura and Glatzel, Markus and Pantel, Klaus and Wikman,Harriet and Johnsen, Steven A',
			'description' => '<p>The HER2-positive breast cancer subtype (HER2-BC) displays a particularly aggressive behavior. Anti-HER2 therapies have significantly improved the survival of patients with HER2-BC. However, a large number of patients become refractory to current targeted therapies, necessitating the development of new treatment strategies. Epigenetic regulators are commonly misregulated in cancer and represent attractive molecular therapeutic targets. Monoubiquitination of histone 2B (H2Bub1) by the heterodimeric ubiquitin ligase complex RNF20/RNF40 has been described to have tumor suppressor functions and loss of H2Bub1 has been associated with cancer progression. In this study, we utilized human tumor samples, cell culture models, and a mammary carcinoma mouse model with tissue-specific Rnf40 deletion and identified an unexpected tumor-supportive role of RNF40 in HER2-BC. We demonstrate that RNF40-driven H2B monoubiquitination is essential for transcriptional activation of RHO/ROCK/LIMK pathway components and proper actin-cytoskeleton dynamics through a trans-histone crosstalk with histone 3 lysine 4 trimethylation (H3K4me3). Collectively, this work demonstrates a previously unknown essential role of RNF40 in HER2-BC, revealing the H2B monoubiquitination axis as a possible tumor context-dependent therapeutic target in breast cancer.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33070155',
			'doi' => '10.1038/s41419-020-03081-w',
			'modified' => '2021-02-19 14:03:18',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 52 => array(
			'id' => '4065',
			'name' => 'Polycomb Repressive Complex 2-mediated histone modification H3K27me3 isassociated with embryogenic potential in Norway spruce.',
			'authors' => 'Nakamura, Miyuki and Batista, Rita A and Köhler, Claudia and Hennig, Lars',
			'description' => '<p>Epigenetic reprogramming during germ cell formation is essential to gain pluripotency and thus embryogenic potential. The histone modification H3K27me3, which is catalysed by the Polycomb repressive complex 2 (PRC2), regulates important developmental processes in both plants and animals, and defects in PRC2 components cause pleiotropic developmental abnormalities. Nevertheless, the role of H3K27me3 in determining embryogenic potential in gymnosperms is still elusive. To address this, we generated H3K27me3 profiles of Norway spruce (Picea abies) embryonic callus and non-embryogenic callus using CUT\&amp;RUN, which is a powerful method for chromatin profiling. Here, we show that H3K27me3 mainly accumulated in genic regions in the Norway spruce genome, similarly to what is observed in other plant species. Interestingly, H3K27me3 levels in embryonic callus were much lower than those in the other examined tissues, but markedly increased upon embryo induction. These results show that H3K27me3 levels are associated with the embryogenic potential of a given tissue, and that the early phase of somatic embryogenesis is accompanied by changes in H3K27me3 levels. Thus, our study provides novel insights into the role of this epigenetic mark in spruce embryogenesis and reinforces the importance of PRC2 as a key regulator of cell fate determination across different plant species.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32894759',
			'doi' => '10.1093/jxb/eraa365',
			'modified' => '2021-02-19 17:45:29',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 53 => array(
			'id' => '4384',
			'name' => 'Age-associated cryptic transcription in mammalian stem cells is linked topermissive chromatin at cryptic promoters',
			'authors' => 'McCauley  B. S. et al.',
			'description' => '<p>Suppressing spurious cryptic transcription by a repressive intragenic chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation is critical for maintaining self-renewal capacity in mouse embryonic stem cells. In yeast and nematodes, such cryptic transcription is elevated with age, and reducing the levels of age-associated cryptic transcription extends yeast lifespan. Whether cryptic transcription is also increased during mammalian aging is unknown. We show for the first time an age-associated elevation in cryptic transcription in several stem cell populations, including murine hematopoietic stem cells (mHSCs) and neural stem cells (NSCs) and human mesenchymal stem cells (hMSCs). Using DECAP-seq, we mapped and quantified age-associated cryptic transcription in hMSCs aged in vitro. Regions with significant age-associated cryptic transcription have a unique chromatin signature: decreased H3K36me3 and increased H3K4me1, H3K4me3, and H3K27ac with age. Furthermore, genomic regions undergoing such age-dependent chromatin changes resemble known promoter sequences and are bound by the promoter-associated protein TBP even in young cells. Hence, the more permissive chromatin state at intragenic cryptic promoters likely underlies the increase of cryptic transcription in aged mammalian stem cells.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://europepmc.org/article/ppr/ppr221829',
			'doi' => '10.21203/rs.3.rs-82156/v1',
			'modified' => '2022-08-04 16:24:46',
			'created' => '2022-08-04 14:55:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 54 => array(
			'id' => '4076',
			'name' => 'RNF40 exerts stage-dependent functions in differentiating osteoblasts andis essential for bone cell crosstalk.',
			'authors' => 'Najafova, Zeynab and Liu, Peng and Wegwitz, Florian and Ahmad, Mubashir andTamon, Liezel and Kosinsky, Robyn Laura and Xie, Wanhua and Johnsen, StevenA and Tuckermann, Jan',
			'description' => '<p>The role of histone ubiquitination in directing cell lineage specification is only poorly understood. Our previous work indicated a role of the histone 2B ubiquitin ligase RNF40 in controlling osteoblast differentiation in vitro. Here, we demonstrate that RNF40 has a stage-dependent function in controlling osteoblast differentiation in vivo. RNF40 expression is essential for early stages of lineage specification, but is dispensable in mature osteoblasts. Paradoxically, while osteoblast-specific RNF40 deletion led to impaired bone formation, it also resulted in increased bone mass due to impaired bone cell crosstalk. Loss of RNF40 resulted in decreased osteoclast number and function through modulation of&nbsp;RANKL expression in OBs. Mechanistically, we demonstrate that&nbsp;Tnfsf11 (encoding RANKL)&nbsp;is an important target gene of H2B monoubiquitination. These data reveal an important role of RNF40-mediated H2B monoubiquitination in bone formation and remodeling and provide a basis for exploring this pathway for the treatment of conditions such as osteoporosis or cancer-associated osteolysis.</p>',
			'date' => '2020-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32901120',
			'doi' => '10.1038/s41418-020-00614-w',
			'modified' => '2021-02-19 18:10:55',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 55 => 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) 56 => array(
			'id' => '4010',
			'name' => 'Combined treatment with CBP and BET inhibitors reverses inadvertentactivation of detrimental super enhancer programs in DIPG cells.',
			'authors' => 'Wiese, M and Hamdan, FH and Kubiak, K and Diederichs, C and Gielen, GHand Nussbaumer, G and Carcaboso, AM and Hulleman, E and Johnsen, SA andKramm, CM',
			'description' => '<p>Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation. Hyperacetylation in DIPG favors the action of the Bromodomain and Extra-Terminal (BET) protein BRD4, and leads to the reprogramming of the enhancer landscape contributing to the activation of DIPG super enhancer-driven oncogenes. The activity of the acetyltransferase CREB-binding protein (CBP) is enhanced by BRD4 and associated with acetylation of nucleosomes at super enhancers (SE). In addition, CBP contributes to transcriptional activation through its function as a scaffold and protein bridge. Monotherapy with either a CBP (ICG-001) or BET inhibitor (JQ1) led to the reduction of tumor-related characteristics. Interestingly, combined treatment induced strong cytotoxic effects in H3.3K27M-mutated DIPG cell lines. RNA sequencing and chromatin immunoprecipitation revealed that these effects were caused by the inactivation of DIPG SE-controlled tumor-related genes. However, single treatment with ICG-001 or JQ1, respectively, led to activation of a subgroup of detrimental super enhancers. Combinatorial treatment reversed the inadvertent activation of these super enhancers and rescued the effect of ICG-001 and JQ1 single treatment on enhancer-driven oncogenes in H3K27M-mutated DIPG, but not in H3 wild-type pedHGG cells. In conclusion, combinatorial treatment with CBP and BET inhibitors is highly efficient in H3K27M-mutant DIPG due to reversal of inadvertent activation of detrimental SE programs in comparison with monotherapy.</p>',
			'date' => '2020-08-21',
			'pmid' => 'http://www.pubmed.gov/32826850',
			'doi' => '10.1038/s41419-020-02800-7',
			'modified' => '2020-12-18 13:25:09',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 57 => array(
			'id' => '4011',
			'name' => 'Exploring the virulence gene interactome with CRISPR/dCas9 in the humanmalaria parasite.',
			'authors' => 'Bryant, JM and Baumgarten, S and Dingli, F and Loew, D and Sinha, A andClaës, A and Preiser, PR and Dedon, PC and Scherf, A',
			'description' => '<p>Mutually exclusive expression of the var multigene family is key to immune evasion and pathogenesis in Plasmodium falciparum, but few factors have been shown to play a direct role. We adapted a CRISPR-based proteomics approach to identify novel factors associated with var genes in their natural chromatin context. Catalytically inactive Cas9 ("dCas9") was targeted to var gene regulatory elements, immunoprecipitated, and analyzed with mass spectrometry. Known and novel factors were enriched including structural proteins, DNA helicases, and chromatin remodelers. Functional characterization of PfISWI, an evolutionarily divergent putative chromatin remodeler enriched at the var gene promoter, revealed a role in transcriptional activation. Proteomics of PfISWI identified several proteins enriched at the var gene promoter such as acetyl-CoA synthetase, a putative MORC protein, and an ApiAP2 transcription factor. These findings validate the CRISPR/dCas9 proteomics method and define a new var gene-associated chromatin complex. This study establishes a tool for targeted chromatin purification of unaltered genomic loci and identifies novel chromatin-associated factors potentially involved in transcriptional control and/or chromatin organization of virulence genes in the human malaria parasite.</p>',
			'date' => '2020-08-02',
			'pmid' => 'http://www.pubmed.gov/32816370',
			'doi' => 'https://dx.doi.org/10.15252%2Fmsb.20209569',
			'modified' => '2020-12-18 13:26:33',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 58 => array(
			'id' => '4024',
			'name' => 'Tissue-Specific In Vivo Biotin Chromatin Immunoprecipitation withSequencing in Zebrafish and Chicken',
			'authors' => 'Lukoseviciute, Martyna and Ling, Irving T.C. and Senanayake, Upeka andCandido-Ferreira, Ivan and Taylor, Gunes and Williams, Ruth M. andSauka-Spengler, Tatjana',
			'description' => '<p>Chromatin immunoprecipitation with sequencing (ChIP-seq) has been instrumental in understanding transcription factor (TF) binding during gene regulation. ChIP-seq requires specific antibodies against desired TFs, which are not available for numerous species. Here, we describe a tissue-specific biotin ChIP-seq protocol for zebrafish and chicken embryos which utilizes AVI tagging of TFs, permitting their biotinylation by a co-expressed nuclear biotin ligase. Subsequently, biotinylated factors can be precipitated with streptavidin beads, enabling the user to construct TF genome-wide binding landscapes like conventional ChIP-seq methods.</p>',
			'date' => '2020-07-31',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S2666166720300538',
			'doi' => '10.1016/j.xpro.2020.100066',
			'modified' => '2020-12-16 17:50:09',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 59 => array(
			'id' => '4026',
			'name' => 'The gut microbiome switches mutant p53 from tumour-suppressive tooncogenic.',
			'authors' => 'Kadosh, E and Snir-Alkalay, I and Venkatachalam, A and May, S and Lasry, Aand Elyada, E and Zinger, A and Shaham, M and Vaalani, G and Mernberger, Mand Stiewe, T and Pikarsky, E and Oren, M and Ben-Neriah, Y',
			'description' => '<p>Somatic mutations in p53, which inactivate the tumour-suppressor function of p53 and often confer oncogenic gain-of-function properties, are very common in cancer. Here we studied the effects of hotspot gain-of-function mutations in Trp53 (the gene that encodes p53 in mice) in mouse models of WNT-driven intestinal cancer caused by Csnk1a1 deletion or Apc mutation. Cancer in these models is known to be facilitated by loss of p53. We found that mutant versions of p53 had contrasting effects in different segments of the gut: in the distal gut, mutant p53 had the expected oncogenic effect; however, in the proximal gut and in tumour organoids it had a pronounced tumour-suppressive effect. In the tumour-suppressive mode, mutant p53 eliminated dysplasia and tumorigenesis in Csnk1a1-deficient and Apc mice, and promoted normal growth and differentiation of tumour organoids derived from these mice. In these settings, mutant p53 was more effective than wild-type p53 at inhibiting tumour formation. Mechanistically, the tumour-suppressive effects of mutant p53 were driven by disruption of the WNT pathway, through preventing the binding of TCF4 to chromatin. Notably, this tumour-suppressive effect was completely abolished by the gut microbiome. Moreover, a single metabolite derived from the gut microbiota-gallic acid-could reproduce the entire effect of the microbiome. Supplementing gut-sterilized p53-mutant mice and p53-mutant organoids with gallic acid reinstated the TCF4-chromatin interaction and the hyperactivation of WNT, thus conferring a malignant phenotype to the organoids and throughout the gut. Our study demonstrates the substantial plasticity of a cancer mutation and highlights the role of the microenvironment in determining its functional outcome.</p>',
			'date' => '2020-07-29',
			'pmid' => 'http://www.pubmed.gov/32728212',
			'doi' => '10.1038/s41586-020-2541-0',
			'modified' => '2020-12-16 17:52:28',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 60 => array(
			'id' => '3992',
			'name' => 'Egr2-guided histone H2B monoubiquitination is required for peripheral nervous system myelination.',
			'authors' => 'Wüst HM, Wegener A, Fröb F, Hartwig AC, Wegwitz F, Kari V, Schimmel M, Tamm ER, Johnsen SA, Wegner M, Sock E',
			'description' => '<p>Schwann cells are the nerve ensheathing cells of the peripheral nervous system. Absence, loss and malfunction of Schwann cells or their myelin sheaths lead to peripheral neuropathies such as Charcot-Marie-Tooth disease in humans. During Schwann cell development and myelination chromatin is dramatically modified. However, impact and functional relevance of these modifications are poorly understood. Here, we analyzed histone H2B monoubiquitination as one such chromatin modification by conditionally deleting the Rnf40 subunit of the responsible E3 ligase in mice. Rnf40-deficient Schwann cells were arrested immediately before myelination or generated abnormally thin, unstable myelin, resulting in a peripheral neuropathy characterized by hypomyelination and progressive axonal degeneration. By combining sequencing techniques with functional studies we show that H2B monoubiquitination does not influence global gene expression patterns, but instead ensures selective high expression of myelin and lipid biosynthesis genes and proper repression of immaturity genes. This requires the specific recruitment of the Rnf40-containing E3 ligase by Egr2, the central transcriptional regulator of peripheral myelination, to its target genes. Our study identifies histone ubiquitination as essential for Schwann cell myelination and unravels new disease-relevant links between chromatin modifications and transcription factors in the underlying regulatory network.</p>',
			'date' => '2020-07-16',
			'pmid' => 'http://www.pubmed.gov/32672815',
			'doi' => '10.1093/nar/gkaa606',
			'modified' => '2020-09-01 15:02:28',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 61 => array(
			'id' => '4031',
			'name' => 'Battle of the sex chromosomes: competition between X- and Y-chromosomeencoded proteins for partner interaction and chromatin occupancy drivesmulti-copy gene expression and evolution in muroid rodents.',
			'authors' => 'Moretti, C and Blanco, M and Ialy-Radio, C and Serrentino, ME and Gobé,C and Friedman, R and Battail, C and Leduc, M and Ward, MA and Vaiman, Dand Tores, F and Cocquet, J',
			'description' => '<p>Transmission distorters (TDs) are genetic elements that favor their own transmission to the detriments of others. Slx/Slxl1 (Sycp3-like-X-linked and Slx-like1) and Sly (Sycp3-like-Y-linked) are TDs which have been co-amplified on the X and Y chromosomes of Mus species. They are involved in an intragenomic conflict in which each favors its own transmission, resulting in sex ratio distortion of the progeny when Slx/Slxl1 vs. Sly copy number is unbalanced. They are specifically expressed in male postmeiotic gametes (spermatids) and have opposite effects on gene expression: Sly knockdown leads to the upregulation of hundreds of spermatid-expressed genes, while Slx/Slxl1-deficiency downregulates them. When both Slx/Slxl1 and Sly are knocked-down, sex ratio distortion and gene deregulation are corrected. Slx/Slxl1 and Sly are, therefore, in competition but the molecular mechanism remains unknown. By comparing their chromatin binding profiles and protein partners, we show that SLX/SLXL1 and SLY proteins compete for interaction with H3K4me3-reader SSTY1 (Spermiogenesis-specific-transcript-on-the-Y1) at the promoter of thousands of genes to drive their expression, and that the opposite effect they have on gene expression is mediated by different abilities to recruit SMRT/N-Cor transcriptional complex. Their target genes are predominantly spermatid-specific multicopy genes encoded by the sex chromosomes and the autosomal Speer/Takusan. Many of them have co-amplified with Slx/Slxl1/Sly but also Ssty during muroid rodent evolution. Overall, we identify Ssty as a key element of the X vs. Y intragenomic conflict, which may have influenced gene content and hybrid sterility beyond Mus lineage since Ssty amplification on the Y pre-dated that of Slx/Slxl1/Sly.</p>',
			'date' => '2020-07-13',
			'pmid' => 'http://www.pubmed.gov/32658962',
			'doi' => '10.1093/molbev/msaa175/5870835',
			'modified' => '2020-12-18 13:27:51',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 62 => array(
			'id' => '3948',
			'name' => '2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters hepatic polyunsaturated fatty acid metabolism and eicosanoid biosynthesis in female Sprague-Dawley rats.',
			'authors' => 'Doskey CM, Fader KA, Nault R, Lydic T, Matthews J, Potter D, Sharratt B, Williams K, Zacharewski T',
			'description' => '<p>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent aryl hydrocarbon receptor (AhR) agonist that elicits a broad spectrum of dose-dependent hepatic effects including lipid accumulation, inflammation, and fibrosis. To determine the role of inflammatory lipid mediators in TCDD-mediated hepatotoxicity, eicosanoid metabolism was investigated. Female Sprague-Dawley (SD) rats were orally gavaged with sesame oil vehicle or 0.01-10&nbsp;&mu;g/kg TCDD every 4&nbsp;days for 28&nbsp;days. Hepatic RNA-Seq data was integrated with untargeted metabolomics of liver, serum, and urine, revealing dose-dependent changes in linoleic acid (LA) and arachidonic acid (AA) metabolism. TCDD also elicited dose-dependent differential gene expression associated with the cyclooxygenase, lipoxygenase, and cytochrome P450 epoxidation/hydroxylation pathways with corresponding changes in &omega;-6 (e.g. AA and LA) and &omega;-3 polyunsaturated fatty acids (PUFAs), as well as associated eicosanoid metabolites. Overall, TCDD increased the ratio of &omega;-6 to &omega;-3 PUFAs. Phospholipase A2 (Pla2g12a) was induced consistent with increased AA metabolism, while AA utilization by induced lipoxygenases Alox5 and Alox15 increased leukotrienes (LTs). More specifically, TCDD increased pro-inflammatory eicosanoids including leukotriene LTB, and LTB, known to recruit neutrophils to damaged tissue. Dose-response modeling suggests the cytochrome P450 hydroxylase/epoxygenase and lipoxygenase pathways are more sensitive to TCDD than the cyclooxygenase pathway. Hepatic AhR ChIP-Seq analysis found little enrichment within the regulatory regions of differentially expressed genes (DEGs) involved in eicosanoid biosynthesis, suggesting TCDD-elicited dysregulation of eicosanoid metabolism is a downstream effect of AhR activation. Overall, these results suggest alterations in eicosanoid metabolism may play a key role in TCDD-elicited hepatotoxicity associated with the progression of steatosis to steatohepatitis.</p>',
			'date' => '2020-07-01',
			'pmid' => 'http://www.pubmed.gov/32387183',
			'doi' => '10.1016/j.taap.2020.115034',
			'modified' => '2020-08-17 10:04:38',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 63 => 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) 64 => array(
			'id' => '3981',
			'name' => 'Vulnerability of drug-resistant EML4-ALK rearranged lung cancer to transcriptional inhibition.',
			'authors' => 'Paliouras AR, Buzzetti M, Shi L, Donaldson IJ, Magee P, Sahoo S, Leong HS, Fassan M, Carter M, Di Leva G, Krebs MG, Blackhall F, Lovly CM, Garofalo M',
			'description' => '<p>A subset of lung adenocarcinomas is driven by the EML4-ALK translocation. Even though ALK inhibitors in the clinic lead to excellent initial responses, acquired resistance to these inhibitors due to on-target mutations or parallel pathway alterations is a major clinical challenge. Exploring these mechanisms of resistance, we found that EML4-ALK cells parental or resistant to crizotinib, ceritinib or alectinib are remarkably sensitive to inhibition of CDK7/12 with THZ1 and CDK9 with alvocidib or dinaciclib. These compounds robustly induce apoptosis through transcriptional inhibition and downregulation of anti-apoptotic genes. Importantly, alvocidib reduced tumour progression in xenograft mouse models. In summary, our study takes advantage of the transcriptional addiction hypothesis to propose a new treatment strategy for a subset of patients with acquired resistance to first-, second- and third-generation ALK inhibitors.</p>',
			'date' => '2020-06-17',
			'pmid' => 'http://www.pubmed.gov/32558295',
			'doi' => 'https://doi.org/10.15252/emmm.201911099',
			'modified' => '2020-09-01 15:20:40',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 65 => array(
			'id' => '3975',
			'name' => 'Removal of H2Aub1 by ubiquitin-specific proteases 12 and 13 is required for stable Polycomb-mediated gene repression in Arabidopsis.',
			'authors' => 'Kralemann LEM, Liu S, Trejo-Arellano MS, Muñoz-Viana R, Köhler C, Hennig L',
			'description' => '<p>BACKGROUND: Stable gene repression is essential for normal growth and development. Polycomb repressive complexes 1 and 2 (PRC1&amp;2) are involved in this process by establishing monoubiquitination of histone 2A (H2Aub1) and subsequent trimethylation of lysine 27 of histone 3 (H3K27me3). Previous work proposed that H2Aub1 removal by the ubiquitin-specific proteases 12 and 13 (UBP12 and UBP13) is part of the repressive PRC1&amp;2 system, but its functional role remains elusive. RESULTS: We show that UBP12 and UBP13 work together with PRC1, PRC2, and EMF1 to repress genes involved in stimulus response. We find that PRC1-mediated H2Aub1 is associated with gene responsiveness, and its repressive function requires PRC2 recruitment. We further show that the requirement of PRC1 for PRC2 recruitment depends on the initial expression status of genes. Lastly, we demonstrate that removal of H2Aub1 by UBP12/13 prevents loss of H3K27me3, consistent with our finding that the H3K27me3 demethylase REF6 is positively associated with H2Aub1. CONCLUSIONS: Our data allow us to propose a model in which deposition of H2Aub1 permits genes to switch between repression and activation by H3K27me3 deposition and removal. Removal of H2Aub1 by UBP12/13 is required to achieve stable PRC2-mediated repression.</p>',
			'date' => '2020-06-16',
			'pmid' => 'http://www.pubmed.gov/32546254',
			'doi' => '10.1186/s13059-020-02062-8',
			'modified' => '2020-08-12 09:23:32',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 66 => array(
			'id' => '3969',
			'name' => 'Delineating the early transcriptional specification of the mammalian trachea and esophagus.',
			'authors' => 'Kuwahara A, Lewis AE, Coombes C, Leung FS, Percharde M, Bush JO',
			'description' => '<p>The genome-scale transcriptional programs that specify the mammalian trachea and esophagus are unknown. Though NKX2-1 and SOX2 are hypothesized to be co-repressive master regulators of tracheoesophageal fates, this is untested at a whole transcriptomic scale and their downstream networks remain unidentified. By combining single-cell RNA-sequencing with bulk RNA-sequencing of mutants and NKX2-1 ChIP-sequencing in mouse embryos, we delineate the NKX2-1 transcriptional program in tracheoesophageal specification, and discover that the majority of the tracheal and esophageal transcriptome is NKX2-1 independent. To decouple the NKX2-1 transcriptional program from regulation by SOX2, we interrogate the expression of newly-identified tracheal and esophageal markers in / compound mutants. Finally, we discover that NKX2-1 binds directly to and and regulates their expression to control mesenchymal specification to cartilage and smooth muscle, coupling epithelial identity with mesenchymal specification. These findings create a new framework for understanding early tracheoesophageal fate specification at the genome-wide level.</p>',
			'date' => '2020-06-09',
			'pmid' => 'http://www.pubmed.gov/32515350',
			'doi' => '10.7554/eLife.55526',
			'modified' => '2020-08-12 09:32:02',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 67 => array(
			'id' => '3950',
			'name' => 'Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response.',
			'authors' => 'Béguelin W, Teater M, Meydan C, Hoehn KB, Phillip JM, Soshnev AA, Venturutti L, Rivas MA, Calvo-Fernández MT, Gutierrez J, Camarillo JM, Takata K, Tarte K, Kelleher NL, Steidl C, Mason CE, Elemento O, Allis CD, Kleinstein SH, Melnick AM',
			'description' => '<p>Follicular lymphomas (FLs) are slow-growing, indolent tumors containing extensive follicular dendritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations. Paradoxically, FLs originate from highly proliferative germinal center (GC) B cells with proliferation strictly dependent on interactions with T follicular helper cells. Herein, we show that EZH2 mutations initiate FL by attenuating GC B cell requirement for T&nbsp;cell help and driving slow expansion of GC centrocytes that become enmeshed with and dependent on FDCs. By impairing T&nbsp;cell help, mutant EZH2 prevents induction of proliferative MYC programs. Thus, EZH2 mutation fosters malignant transformation by epigenetically reprograming B cells to form an aberrant immunological niche that reflects characteristic features of human FLs, explaining how indolent tumors arise from GC B cells.</p>',
			'date' => '2020-05-11',
			'pmid' => 'http://www.pubmed.gov/32396861',
			'doi' => '10.1016/j.ccell.2020.04.004',
			'modified' => '2020-08-17 09:56:58',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 68 => array(
			'id' => '4206',
			'name' => 'H2A.Z is dispensable for both basal and activated transcription inpost-mitotic mouse muscles.',
			'authors' => 'Belotti E. et al.',
			'description' => '<p>While the histone variant H2A.Z is known to be required for mitosis, it is also enriched in nucleosomes surrounding the transcription start site of active promoters, implicating H2A.Z in transcription. However, evidence obtained so far mainly rely on correlational data generated in actively dividing cells. We have exploited a paradigm in which transcription is uncoupled from the cell cycle by developing an in vivo system to inactivate H2A.Z in terminally differentiated post-mitotic muscle cells. ChIP-seq, RNA-seq and ATAC-seq experiments performed on H2A.Z KO post-mitotic muscle cells show that this histone variant is neither required to maintain nor to activate transcription. Altogether, this study provides in vivo evidence that in the absence of mitosis H2A.Z is dispensable for transcription and that the enrichment of H2A.Z on active promoters is a marker but not an active driver of transcription.</p>',
			'date' => '2020-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32266374',
			'doi' => '10.1093/nar/gkaa157',
			'modified' => '2022-01-13 13:46:38',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 69 => array(
			'id' => '3922',
			'name' => 'Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes.',
			'authors' => 'Crespo M, Damont A, Blanco M, Lastrucci E, Kennani SE, Ialy-Radio C, Khattabi LE, Terrier S, Louwagie M, Kieffer-Jaquinod S, Hesse AM, Bruley C, Chantalat S, Govin J, Fenaille F, Battail C, Cocquet J, Pflieger D',
			'description' => '<p>Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and crotonylation on histones H3 and H4 during mouse spermatogenesis. Lysine crotonylation appeared to be of significant abundance compared to acetylation, particularly on Lys27 of histone H3 (H3K27cr) that accumulates in sperm in a cleaved form of H3. We identified the genomic localization of H3K27cr and studied its effects on transcription compared to the classical active mark H3K27ac at promoters and distal enhancers. The presence of both marks was strongly associated with highest gene expression. Assessment of their co-localization with transcription regulators (SLY, SOX30) and chromatin-binding proteins (BRD4, BRDT, BORIS and CTCF) indicated systematic highest binding when both active marks were present and different selective binding when present alone at chromatin. H3K27cr and H3K27ac finally mark the building of some sperm super-enhancers. This integrated analysis of omics data provides an unprecedented level of understanding of gene expression regulation by H3K27cr in comparison to H3K27ac, and reveals both synergistic and specific actions of each histone modification.</p>',
			'date' => '2020-03-17',
			'pmid' => 'http://www.pubmed.gov/32182340',
			'doi' => '10.1093/nar/gkaa163',
			'modified' => '2020-08-17 10:56:19',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 70 => array(
			'id' => '3917',
			'name' => 'Anti-adipogenic signals at the onset of obesity-related inflammation in white adipose tissue.',
			'authors' => 'Caputo T, Tran VDT, Bararpour N, Winkler C, Aguileta G, Trang KB, Giordano Attianese GMP, Wilson A, Thomas A, Pagni M, Guex N, Desvergne B, Gilardi F',
			'description' => '<p>Chronic inflammation that affects primarily metabolic organs, such as white adipose tissue (WAT), is considered as a major cause of human obesity-associated co-morbidities. However, the molecular mechanisms initiating this inflammation in WAT are poorly understood. By combining transcriptomics, ChIP-seq and modeling approaches, we studied the global early and late responses to a high-fat diet (HFD) in visceral (vWAT) and subcutaneous (scWAT) AT, the first being more prone to obesity-induced inflammation. HFD rapidly triggers proliferation of adipocyte precursors within vWAT. However, concomitant antiadipogenic signals limit vWAT hyperplastic expansion by interfering with the differentiation of proliferating adipocyte precursors. Conversely, in scWAT, residing beige adipocytes lose their oxidizing properties and allow storage of excessive fatty acids. This phase is followed by tissue hyperplastic growth and increased angiogenic signals, which further enable scWAT expansion without generating inflammation. Our data indicate that scWAT and vWAT differential ability to modulate adipocyte number and differentiation in response to obesogenic stimuli has a crucial impact on the different susceptibility to obesity-related inflammation of these adipose tissue depots.</p>',
			'date' => '2020-03-11',
			'pmid' => 'http://www.pubmed.gov/32157317',
			'doi' => '10.1007/s00018-020-03485-z',
			'modified' => '2020-08-17 11:01:57',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 71 => array(
			'id' => '3888',
			'name' => 'HDAC3 functions as a positive regulator in Notch signal transduction.',
			'authors' => 'Ferrante F, Giaimo BD, Bartkuhn M, Zimmermann T, Close V, Mertens D, Nist A, Stiewe T, Meier-Soelch J, Kracht M, Just S, Klöble P, Oswald F, Borggrefe T',
			'description' => '<p>Aberrant Notch signaling plays a pivotal role in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL). Amplitude and duration of the Notch response is controlled by ubiquitin-dependent proteasomal degradation of the Notch1 intracellular domain (NICD1), a hallmark of the leukemogenic process. Here, we show that HDAC3 controls NICD1 acetylation levels directly affecting NICD1 protein stability. Either genetic loss-of-function of HDAC3 or nanomolar concentrations of HDAC inhibitor apicidin lead to downregulation of Notch target genes accompanied by a local reduction of histone acetylation. Importantly, an HDAC3-insensitive NICD1 mutant is more stable but biologically less active. Collectively, these data show a new HDAC3- and acetylation-dependent mechanism that may be exploited to treat Notch1-dependent leukemias.</p>',
			'date' => '2020-02-28',
			'pmid' => 'http://www.pubmed.gov/32107550',
			'doi' => '10.1093/nar/gkaa088',
			'modified' => '2020-03-20 17:21:31',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 72 => array(
			'id' => '3860',
			'name' => 'Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon.',
			'authors' => 'Zambusi A, Pelin Burhan Ö, Di Giaimo R, Schmid B, Ninkovic J',
			'description' => '<p>Granulins (GRN) are secreted factors that promote neuronal survival and regulate inflammation in various pathological conditions. However, their roles in physiological conditions in the brain remain poorly understood. To address this knowledge gap, we analysed the telencephalon in Grn-deficient zebrafish and identified morphological and transcriptional changes in microglial cells, indicative of a pro-inflammatory phenotype in the absence of any insult. Unexpectedly, activated mutant microglia shared part of their transcriptional signature with aged human microglia. Furthermore, transcriptome profiles of the entire telencephali isolated from young Grn-deficient animals showed remarkable similarities with the profiles of the telencephali isolated from aged wildtype animals. Additionally, 50% of differentially regulated genes during aging were regulated in the telencephalon of young Grn-deficient animals compared to their wildtype littermates. Importantly, the telencephalon transcriptome in young Grn-deficent animals changed only mildly with aging, further suggesting premature aging of Grn-deficient brain. Indeed, Grn loss led to decreased neurogenesis and oligodendrogenesis, and to shortening of telomeres at young ages, to an extent comparable to that observed during aging. Altogether, our data demonstrate a role of Grn in regulating aging kinetics in the zebrafish telencephalon, thus providing a valuable tool for the development of new therapeutic approaches to treat age-associated pathologies.</p>',
			'date' => '2020-02-03',
			'pmid' => 'http://www.pubmed.gov/32028681',
			'doi' => '10.3390/cells9020350',
			'modified' => '2020-03-20 17:55:13',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 73 => array(
			'id' => '3872',
			'name' => 'An inferred fitness consequence map of the rice genome.',
			'authors' => 'Joly-Lopez Z, Platts AE, Gulko B, Choi JY, Groen SC, Zhong X, Siepel A, Purugganan MD',
			'description' => '<p>The extent to which sequence variation impacts plant fitness is poorly understood. High-resolution maps detailing the constraint acting on the genome, especially in regulatory sites, would be beneficial as functional annotation of noncoding sequences remains sparse. Here, we present a fitness consequence (fitCons) map for rice (Oryza sativa). We inferred fitCons scores (&rho;) for 246 inferred genome classes derived from nine functional genomic and epigenomic datasets, including chromatin accessibility, messenger RNA/small RNA transcription, DNA methylation, histone modifications and engaged RNA polymerase activity. These were integrated with genome-wide polymorphism and divergence data from 1,477 rice accessions and 11 reference genome sequences in the Oryzeae. We found &rho; to be multimodal, with ~9% of the rice genome falling into classes where more than half of the bases would probably have a fitness consequence if mutated. Around 2% of the rice genome showed evidence of weak negative selection, frequently at candidate regulatory sites, including a novel set of 1,000 potentially active enhancer elements. This fitCons map provides perspective on the evolutionary forces associated with genome diversity, aids in genome annotation and can guide crop breeding programs.</p>',
			'date' => '2020-02-02',
			'pmid' => 'http://www.pubmed.gov/32042156',
			'doi' => '10.1038/s41477-019-0589-3',
			'modified' => '2020-03-20 17:43:24',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 74 => array(
			'id' => '3850',
			'name' => 'Dual-initiation promoters with intertwined canonical and TCT/TOP transcription start sites diversify transcript processing.',
			'authors' => 'Nepal C, Hadzhiev Y, Balwierz P, Tarifeño-Saldivia E, Cardenas R, Wragg JW, Suzuki AM, Carninci P, Peers B, Lenhard B, Andersen JB, Müller F',
			'description' => '<p>Variations in transcription start site (TSS) selection reflect diversity of preinitiation complexes and can impact on post-transcriptional RNA fates. Most metazoan polymerase II-transcribed genes carry canonical initiation with pyrimidine/purine (YR) dinucleotide, while translation machinery-associated genes carry polypyrimidine initiator (5'-TOP or TCT). By addressing the developmental regulation of TSS selection in zebrafish we uncovered a class of dual-initiation promoters in thousands of genes, including snoRNA host genes. 5'-TOP/TCT initiation is intertwined with canonical initiation and used divergently in hundreds of dual-initiation promoters during maternal to zygotic transition. Dual-initiation in snoRNA host genes selectively generates host and snoRNA with often different spatio-temporal expression. Dual-initiation promoters are pervasive in human and fruit fly, reflecting evolutionary conservation. We propose that dual-initiation on shared promoters represents a composite promoter architecture, which can function both coordinately and divergently to diversify RNAs.</p>',
			'date' => '2020-01-10',
			'pmid' => 'http://www.pubmed.gov/31924754',
			'doi' => '10.1038/s41467-019-13687-0',
			'modified' => '2020-02-13 11:09:58',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 75 => 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) 76 => 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) 77 => array(
			'id' => '3845',
			'name' => 'Combinatorial action of NF-Y and TALE at embryonic enhancers defines distinct gene expression programs during zygotic genome activation in zebrafish.',
			'authors' => 'Stanney W, Ladam F, Donaldson IJ, Parsons TJ, Maehr R, Bobola N, Sagerström CG',
			'description' => '<p>Animal embryogenesis is initiated by maternal factors, but zygotic genome activation (ZGA) shifts regulatory control to the embryo during blastula stages. ZGA is thought to be mediated by maternally provided transcription factors (TFs), but few such TFs have been identified in vertebrates. Here we report that NF-Y and TALE TFs bind zebrafish genomic elements associated with developmental control genes already at ZGA. In particular, co-regulation by NF-Y and TALE is associated with broadly acting genes involved in transcriptional control, while regulation by either NF-Y or TALE defines genes in specific developmental processes, such that NF-Y controls a cilia gene expression program while TALE controls expression of hox genes. We also demonstrate that NF-Y and TALE-occupied genomic elements function as enhancers during embryogenesis. We conclude that combinatorial use of NF-Y and TALE at developmental enhancers permits the establishment of distinct gene expression programs at zebrafish ZGA.</p>',
			'date' => '2019-12-17',
			'pmid' => 'http://www.pubmed.gov/31862379',
			'doi' => '10.1016/j.ydbio.2019.12.003',
			'modified' => '2020-02-20 11:13:27',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 78 => array(
			'id' => '3819',
			'name' => 'Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites.',
			'authors' => 'Hammam E, Ananda G, Sinha A, Scheidig-Benatar C, Bohec M, Preiser PR, Dedon PC, Scherf A, Vembar SS',
			'description' => '<p>DNA cytosine modifications are key epigenetic regulators of cellular processes in mammalian cells, with their misregulation leading to varied disease states. In the human malaria parasite Plasmodium falciparum, a unicellular eukaryotic pathogen, little is known about the predominant cytosine modifications, cytosine methylation (5mC) and hydroxymethylation (5hmC). Here, we report the first identification of a hydroxymethylcytosine-like (5hmC-like) modification in P. falciparum asexual blood stages using a suite of biochemical methods. In contrast to mammalian cells, we report 5hmC-like levels in the P. falciparum genome of 0.2-0.4%, which are significantly higher than the methylated cytosine (mC) levels of 0.01-0.05%. Immunoprecipitation of hydroxymethylated DNA followed by next generation sequencing (hmeDIP-seq) revealed that 5hmC-like modifications are enriched in gene bodies with minimal dynamic changes during asexual development. Moreover, levels of the 5hmC-like base in gene bodies positively correlated to transcript levels, with more than 2000 genes stably marked with this modification throughout asexual development. Our work highlights the existence of a new predominant cytosine DNA modification pathway in P. falciparum and opens up exciting avenues for gene regulation research and the development of antimalarials.</p>',
			'date' => '2019-11-28',
			'pmid' => 'http://www.pubmed.gov/31777939',
			'doi' => '10.1093/nar/gkz1093.',
			'modified' => '2020-02-25 13:47:09',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 79 => array(
			'id' => '3820',
			'name' => 'A stress-responsive enhancer induces dynamic drug resistance in acute myeloid leukemia.',
			'authors' => 'Williams MS, Amaral FM, Simeoni F, Somervaille TC',
			'description' => '<p>The drug efflux pump ABCB1 is a key driver of chemoresistance, and high expression predicts for treatment failure in acute myeloid leukemia (AML). In this study, we identified and functionally validated the network of enhancers that controls expression of ABCB1. We show that exposure of leukemia cells to daunorubicin activated an integrated stress response-like transcriptional program to induce ABCB1 through remodeling and activation of an ATF4-bound, stress-responsive enhancer. Protracted stress primed enhancers for rapid increases in activity following re-exposure of cells to daunorubicin, providing an epigenetic memory of prior drug treatment. In primary human AML, exposure of fresh blast cells to daunorubicin activated the stress-responsive enhancer and led to dose-dependent induction of ABCB1. Dynamic induction of ABCB1 by diverse stressors, including chemotherapy, facilitated escape of leukemia cells from targeted third-generation ABCB1 inhibition, providing an explanation for the failure of ABCB1 inhibitors in clinical trials. Stress-induced up regulation of ABCB1 was mitigated by combined use of pharmacologic inhibitors U0126 and ISRIB, which inhibit stress signalling and have potential for use as adjuvants to enhance the activity of ABCB1 inhibitors.</p>',
			'date' => '2019-11-26',
			'pmid' => 'http://www.pubmed.gov/31770110',
			'doi' => '/',
			'modified' => '2020-02-25 13:46:19',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 80 => array(
			'id' => '3810',
			'name' => 'Distinct CoREST complexes act in a cell-type-specific manner.',
			'authors' => 'Mačinković I, Theofel I, Hundertmark T, Kovač K, Awe S, Lenz J, Forné I, Lamp B, Nist A, Imhof A, Stiewe T, Renkawitz-Pohl R, Rathke C, Brehm A',
			'description' => '<p>CoREST has been identified as a subunit of several protein complexes that generate transcriptionally repressive chromatin structures during development. However, a comprehensive analysis of the CoREST interactome has not been carried out. We use proteomic approaches to define the interactomes of two dCoREST isoforms, dCoREST-L and dCoREST-M, in Drosophila. We identify three distinct histone deacetylase complexes built around a common dCoREST/dRPD3 core: A dLSD1/dCoREST complex, the LINT complex and a dG9a/dCoREST complex. The latter two complexes can incorporate both dCoREST isoforms. By contrast, the dLSD1/dCoREST complex exclusively assembles with the dCoREST-L isoform. Genome-wide studies show that the three dCoREST complexes associate with chromatin predominantly at promoters. Transcriptome analyses in S2 cells and testes reveal that different cell lineages utilize distinct dCoREST complexes to maintain cell-type-specific gene expression programmes: In macrophage-like S2 cells, LINT represses germ line-related genes whereas other dCoREST complexes are largely dispensable. By contrast, in testes, the dLSD1/dCoREST complex prevents transcription of germ line-inappropriate genes and is essential for spermatogenesis and fertility, whereas depletion of other dCoREST complexes has no effect. Our study uncovers three distinct dCoREST complexes that function in a lineage-restricted fashion to repress specific sets of genes thereby maintaining cell-type-specific gene expression programmes.</p>',
			'date' => '2019-11-08',
			'pmid' => 'http://www.pubmed.gov/31701127',
			'doi' => '10.1093/nar/gkz1050',
			'modified' => '2019-12-05 11:02:22',
			'created' => '2019-12-02 15:25:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 81 => array(
			'id' => '3782',
			'name' => 'Residual apoptotic activity of a tumorigenic p53 mutant improves cancer therapy responses.',
			'authors' => 'Timofeev O, Klimovich B, Schneikert J, Wanzel M, Pavlakis E, Noll J, Mutlu S, Elmshäuser S, Nist A, Mernberger M, Lamp B, Wenig U, Brobeil A, Gattenlöhner S, Köhler K, Stiewe T',
			'description' => '<p>Engineered p53 mutant mice are valuable tools for delineating p53 functions in tumor suppression and cancer therapy. Here, we have introduced the R178E mutation into the Trp53 gene of mice to specifically ablate the cooperative nature of p53 DNA binding. Trp53 mice show no detectable target gene regulation and, at first sight, are largely indistinguishable from Trp53 mice. Surprisingly, stabilization of p53 in Mdm2 mice nevertheless triggers extensive apoptosis, indicative of residual wild-type activities. Although this apoptotic activity suffices to trigger lethality of Trp53 ;Mdm2 embryos, it proves insufficient for suppression of spontaneous and oncogene-driven tumorigenesis. Trp53 mice develop tumors indistinguishably from Trp53 mice and tumors retain and even stabilize the p53 protein, further attesting to the lack of significant tumor suppressor activity. However, Trp53 tumors exhibit remarkably better chemotherapy responses than Trp53 ones, resulting in enhanced eradication of p53-mutated tumor cells. Together, this provides genetic proof-of-principle evidence that a p53 mutant can be highly tumorigenic and yet retain apoptotic activity which provides a survival benefit in the context of cancer therapy.</p>',
			'date' => '2019-09-04',
			'pmid' => 'http://www.pubmed.gov/31483066',
			'doi' => '10.15252/embj.2019102096',
			'modified' => '2019-10-02 16:50:40',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 82 => array(
			'id' => '3759',
			'name' => 'EOMES interacts with RUNX3 and BRG1 to promote innate memory cell formation through epigenetic reprogramming.',
			'authors' => 'Istaces N, Splittgerber M, Lima Silva V, Nguyen M, Thomas S, Le A, Achouri Y, Calonne E, Defrance M, Fuks F, Goriely S, Azouz A',
			'description' => '<p>Memory CD8 T cells have the ability to provide lifelong immunity against pathogens. Although memory features generally arise after challenge with a foreign antigen, na&iuml;ve CD8 single positive (SP) thymocytes may acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associated with the induction of the T-box transcription factor Eomesodermin (EOMES). However, the underlying molecular mechanisms remain ill-defined. Using epigenomic profiling, we show that these innate memory CD8SP cells acquire only a portion of the active enhancer repertoire of conventional memory cells. This reprograming is secondary to EOMES recruitment, mostly to RUNX3-bound enhancers. Furthermore, EOMES is found within chromatin-associated complexes containing BRG1 and promotes the recruitment of this chromatin remodelling factor. Also, the in vivo acquisition of EOMES-dependent program is BRG1-dependent. In conclusion, our results support a strong epigenetic basis for the EOMES-driven establishment of CD8 T cell innate memory program.</p>',
			'date' => '2019-07-24',
			'pmid' => 'http://www.pubmed.gov/31341159',
			'doi' => '10.1038/s41467-019-11233-6',
			'modified' => '2019-10-03 10:06:15',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 83 => 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) 84 => array(
			'id' => '3743',
			'name' => 'ARID1A facilitates KRAS signaling-regulated enhancer activity in an AP1-dependent manner in colorectal cancer cells.',
			'authors' => 'Sen M, Wang X, Hamdan FH, Rapp J, Eggert J, Kosinsky RL, Wegwitz F, Kutschat AP, Younesi FS, Gaedcke J, Grade M, Hessmann E, Papantonis A, Strӧbel P, Johnsen SA',
			'description' => '<p>BACKGROUND: ARID1A (AT-rich interactive domain-containing protein 1A) is a subunit of the BAF chromatin remodeling complex and plays roles in transcriptional regulation and DNA damage response. Mutations in ARID1A that lead to inactivation or&nbsp;loss of expression are frequent and widespread across many cancer types including colorectal cancer (CRC). A tumor suppressor role of ARID1A has been established in a number of tumor types including CRC where the genetic inactivation of Arid1a alone led to the formation of invasive colorectal adenocarcinomas in mice. Mechanistically, ARID1A has been described to largely function through the regulation of enhancer activity. METHODS: To mimic ARID1A-deficient colorectal cancer, we used CRISPR/Cas9-mediated gene editing to inactivate the ARID1A gene in established colorectal cancer cell lines. We integrated gene expression analyses with genome-wide ARID1A occupancy and epigenomic mapping data to decipher ARID1A-dependent transcriptional regulatory mechanisms. RESULTS: Interestingly, we found that CRC cell lines harboring KRAS mutations are critically dependent on ARID1A function. In the absence of ARID1A, proliferation of these cell lines is severely impaired, suggesting an essential role for ARID1A in this context. Mechanistically, we showed that ARID1A acts as a co-factor at enhancers occupied by AP1 transcription factors acting downstream of the MEK/ERK pathway. Consistently, loss of ARID1A led to a disruption of KRAS/AP1-dependent enhancer activity, accompanied by a downregulation of expression of the associated target genes. CONCLUSIONS: We identify a previously unknown context-dependent tumor-supporting function of ARID1A in CRC downstream of KRAS signaling. Upon the loss of ARID1A in KRAS-mutated cells, enhancers that are co-occupied by ARID1A and the AP1 transcription factors become inactive, thereby leading to decreased target gene expression. Thus, targeting of the BAF complex in KRAS-mutated CRC may offer a unique, previously unknown, context-dependent therapeutic option in CRC.</p>',
			'date' => '2019-06-19',
			'pmid' => 'http://www.pubmed.gov/31217031',
			'doi' => '10.1186/s13148-019-0690-5',
			'modified' => '2019-08-06 16:37:28',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 85 => array(
			'id' => '3631',
			'name' => 'Guidelines for optimized gene knockout using CRISPR/Cas9',
			'authors' => 'Campenhout CV et al.',
			'description' => '<p>CRISPR/Cas9 technology has evolved as the most powerful approach to generate genetic models both for fundamental and preclinical research. Despite its apparent simplicity, the outcome of a genome-editing experiment can be substantially impacted by technical parameters and biological considerations. Here, we present guidelines and tools to optimize CRISPR/Cas9 genome-targeting efficiency and specificity. The nature of the target locus, the design of the single guide RNA and the choice of the delivery method should all be carefully considered prior to a genome-editing experiment. Different methods can also be used to detect off-target cleavages and decrease the risk of unwanted mutations. Together, these optimized tools and proper controls are essential to the assessment of CRISPR/Cas9 genome-editing experiments.</p>',
			'date' => '2019-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/31039627',
			'doi' => '10.2144/btn-2018-0187',
			'modified' => '2019-05-09 15:37:50',
			'created' => '2019-05-09 15:37:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 86 => array(
			'id' => '3710',
			'name' => 'BRCA1 mutations attenuate super-enhancer function and chromatin looping in haploinsufficient human breast epithelial cells.',
			'authors' => 'Zhang X, Wang Y, Chiang HC, Hsieh YP, Lu C, Park BH, Jatoi I, Jin VX, Hu Y, Li R',
			'description' => '<p>BACKGROUND: BRCA1-associated breast cancer originates from luminal progenitor cells. BRCA1 functions in multiple biological processes, including double-strand break repair, replication stress suppression, transcriptional regulation, and chromatin reorganization. While non-malignant cells carrying cancer-predisposing BRCA1 mutations exhibit increased genomic instability, it remains unclear whether BRCA1 haploinsufficiency affects transcription and chromatin dynamics in breast epithelial cells. METHODS: H3K27ac-associated super-enhancers were compared in primary breast epithelial cells from BRCA1 mutation carriers (BRCA1) and non-carriers (BRCA1). Non-tumorigenic MCF10A breast epithelial cells with engineered BRCA1 haploinsufficiency were used to confirm the H3K27ac changes. The impact of BRCA1 mutations on enhancer function and enhancer-promoter looping was assessed in MCF10A cells. RESULTS: Here, we show that primary mammary epithelial cells from women with BRCA1 mutations display significant loss of H3K27ac-associated super-enhancers. These BRCA1-dependent super-enhancers are enriched with binding motifs for the GATA family. Non-tumorigenic BRCA1 MCF10A cells recapitulate the H3K27ac loss. Attenuated histone mark and enhancer activity in these BRCA1 MCF10A cells can be partially restored with wild-type BRCA1. Furthermore, chromatin conformation analysis demonstrates impaired enhancer-promoter looping in BRCA1 MCF10A cells. CONCLUSIONS: H3K27ac-associated super-enhancer loss is a previously unappreciated functional deficiency in ostensibly normal BRCA1 mutation-carrying breast epithelium. Our findings offer new mechanistic insights into BRCA1 mutation-associated transcriptional and epigenetic abnormality in breast epithelial cells and tissue/cell lineage-specific tumorigenesis.</p>',
			'date' => '2019-04-17',
			'pmid' => 'http://www.pubmed.gov/30995943',
			'doi' => '10.1186/s13058-019-1132-1',
			'modified' => '2019-07-05 14:32:42',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 87 => array(
			'id' => '3613',
			'name' => 'Point mutations in the PDX1 transactivation domain impair human β-cell development and function.',
			'authors' => 'Wang X, Sterr M, Ansarullah , Burtscher I, Böttcher A, Beckenbauer J, Siehler J, Meitinger T, Häring HU, Staiger H, Cernilogar FM, Schotta G, Irmler M, Beckers J, Wright CVE, Bakhti M, Lickert H',
			'description' => '<p>OBJECTIVE: Hundreds of missense mutations in the coding region of PDX1 exist; however, if these mutations predispose to diabetes mellitus is unknown. METHODS: In this study, we screened a large cohort of subjects with increased risk for diabetes and identified two subjects with impaired glucose tolerance carrying common, heterozygous, missense mutations in the PDX1 coding region leading to single amino acid exchanges (P33T, C18R) in its transactivation domain. We generated iPSCs from patients with heterozygous PDX1, PDX1 mutations and engineered isogenic cell lines carrying homozygous PDX1, PDX1 mutations and a heterozygous PDX1 loss-of-function mutation (PDX1). RESULTS: Using an in&nbsp;vitro &beta;-cell differentiation protocol, we demonstrated that both, heterozygous PDX1, PDX1 and homozygous PDX1, PDX1 mutations impair &beta;-cell differentiation and function. Furthermore, PDX1 and PDX1 mutations reduced differentiation efficiency of pancreatic progenitors (PPs), due to downregulation of PDX1-bound genes, including transcription factors MNX1 and PDX1 as well as insulin resistance gene CES1. Additionally, both PDX1 and PDX1 mutations in PPs reduced the expression of PDX1-bound genes including the long-noncoding RNA, MEG3 and the imprinted gene NNAT, both involved in insulin synthesis and secretion. CONCLUSIONS: Our results reveal mechanistic details of how common coding mutations in PDX1 impair human pancreatic endocrine lineage formation and &beta;-cell function and contribute to the predisposition for diabetes.</p>',
			'date' => '2019-03-20',
			'pmid' => 'http://www.pubmed.gov/30930126',
			'doi' => '10.1016/j.molmet.2019.03.006',
			'modified' => '2019-04-17 14:43:53',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 88 => 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) 89 => array(
			'id' => '3727',
			'name' => 'Transcriptome-wide dynamics of extensive m6A mRNA methylation during Plasmodium falciparum blood-stage development',
			'authors' => 'Sebastian Baumgarten, Jessica M. Bryant, Ameya Sinha, Thibaud Reyser, Peter R. Preiser, Peter C. Dedon, Artur Scherf',
			'description' => '<p>Malaria pathogenesis results from the asexual replication of Plasmodium falciparum within human red blood cells, which relies on a precisely timed cascade of gene expression over a 48-hour life cycle. Although substantial post-transcriptional regulation of this hardwired program has been observed, it remains unclear how these processes are mediated on a transcriptome-wide level. To this end, we identified mRNA modifications in the P. falciparum transcriptome and performed a comprehensive characterization of N6-methyladenosine (m6A) over the course of blood stage development. Using mass spectrometry and m6A RNA sequencing, we demonstrate that m6A is highly developmentally regulated, exceeding m6A levels known in any other eukaryote. We identify an evolutionarily conserved m6A writer complex and show that knockdown of the putative m6A methyltransferase by CRISPR interference leads to increased levels of transcripts that normally contain m6A. In accordance, we find an inverse correlation between m6A status and mRNA stability or translational efficiency. Our data reveal the crucial role of extensive m6A mRNA methylation in dynamically fine-tuning the transcriptional program of a unicellular eukaryote as well as a new &lsquo;epitranscriptomic&rsquo; layer of gene regulation in malaria parasites.</p>',
			'date' => '2019-03-09',
			'pmid' => 'https://www.nature.com/articles/s41564-019-0521-7',
			'doi' => '10.1101/572891.',
			'modified' => '2022-05-18 19:27:33',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 90 => 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) 91 => array(
			'id' => '3662',
			'name' => 'NF-κB p65 dimerization and DNA-binding is important for inflammatory gene expression.',
			'authors' => 'Riedlinger T, Liefke R, Meier-Soelch J, Jurida L, Nist A, Stiewe T, Kracht M, Schmitz ML',
			'description' => '<p>Increasing evidence shows that many transcription factors execute important biologic functions independent from their DNA-binding capacity. The NF-&kappa;B p65 (RELA) subunit is a central regulator of innate immunity. Here, we investigated the relative functional contribution of p65 DNA-binding and dimerization in p65-deficient human and murine cells reconstituted with single amino acid mutants preventing either DNA-binding (p65 E/I) or dimerization (p65 FL/DD). DNA-binding of p65 was required for RelB-dependent stabilization of the NF-&kappa;B p100 protein. The antiapoptotic function of p65 and expression of the majority of TNF-&alpha;-induced genes were dependent on p65's ability to bind DNA and to dimerize. Chromatin immunoprecipitation with massively parallel DNA sequencing experiments revealed that impaired DNA-binding and dimerization strongly diminish the chromatin association of p65. However, there were also p65-independent TNF-&alpha;-inducible genes and a subgroup of p65 binding sites still allowed some residual chromatin association of the mutants. These sites were enriched in activator protein 1 (AP-1) binding motifs and showed increased chromatin accessibility and basal transcription. This suggests a mechanism of assisted p65 chromatin association that can be in part facilitated by chromatin priming and cooperativity with other transcription factors such as AP-1.-Riedlinger, T., Liefke, R., Meier-Soelch, J., Jurida, L., Nist, A., Stiewe, T., Kracht, M., Schmitz, M. L. NF-&kappa;B p65 dimerization and DNA-binding is important for inflammatory gene expression.</p>',
			'date' => '2019-03-01',
			'pmid' => 'http://www.pubmed.gov/30526044',
			'doi' => '10.1096/fj.201801638R',
			'modified' => '2019-07-01 11:42:50',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 92 => array(
			'id' => '3646',
			'name' => 'Differential regulation of RNA polymerase III genes during liver regeneration.',
			'authors' => 'Yeganeh M, Praz V, Carmeli C, Villeneuve D, Rib L, Guex N, Herr W, Delorenzi M, Hernandez N,  ',
			'description' => '<p>Mouse liver regeneration after partial hepatectomy involves cells in the remaining tissue synchronously entering the cell division cycle. We have used this system and H3K4me3, Pol II and Pol III profiling to characterize adaptations in Pol III transcription. Our results broadly define a class of genes close to H3K4me3 and Pol II peaks, whose Pol III occupancy is high and stable, and another class, distant from Pol II peaks, whose Pol III occupancy strongly increases after partial hepatectomy. Pol III regulation in the liver thus entails both highly expressed housekeeping genes and genes whose expression can adapt to increased demand.</p>',
			'date' => '2019-02-28',
			'pmid' => 'http://www.pubmed.gov/30597109',
			'doi' => '10.1093/nar/gky1282',
			'modified' => '2019-06-07 10:14:59',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 93 => array(
			'id' => '3678',
			'name' => 'CBX7 Induces Self-Renewal of Human Normal and Malignant Hematopoietic Stem and Progenitor Cells by Canonical and Non-canonical Interactions.',
			'authors' => 'Jung J, Buisman SC, Weersing E, Dethmers-Ausema A, Zwart E, Schepers H, Dekker MR, Lazare SS, Hammerl F, Skokova Y, Kooistra SM, Klauke K, Poot RA, Bystrykh LV, de Haan G',
			'description' => '<p>In this study, we demonstrate that, among all five CBX Polycomb proteins, only CBX7 possesses the ability to control self-renewal of human hematopoietic stem and progenitor cells (HSPCs). Xenotransplantation of CBX7-overexpressing HSPCs resulted in increased multi-lineage long-term engraftment and myelopoiesis.&nbsp;Gene expression and chromatin analyses revealed perturbations in genes involved in differentiation,&nbsp;DNA and chromatin maintenance, and cell cycle control. CBX7 is upregulated in acute myeloid leukemia (AML), and its genetic or pharmacological repression in AML cells inhibited proliferation and induced differentiation. Mass spectrometry analysis revealed several non-histone protein interactions between CBX7 and the H3K9 methyltransferases SETDB1, EHMT1, and EHMT2. These CBX7-binding proteins possess a trimethylated lysine peptide motif highly similar to the canonical CBX7 target H3K27me3. Depletion of SETDB1 in AML cells phenocopied repression of CBX7. We identify CBX7 as an important regulator of self-renewal and uncover non-canonical crosstalk between distinct pathways, revealing therapeutic opportunities for leukemia.</p>',
			'date' => '2019-02-12',
			'pmid' => 'http://www.pubmed.gov/30759399',
			'doi' => '10.1016/j.celrep.2019.01.050',
			'modified' => '2019-07-01 11:20:46',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 94 => array(
			'id' => '3659',
			'name' => 'Fluorescence-Activated Cell Sorting-Based Isolation and Characterization of Neural Stem Cells from the Adult Zebrafish Telencephalon.',
			'authors' => 'Di Giaimo R, Aschenbroich S, Ninkovic J',
			'description' => '<p>Adult mammalian brain, including humans, has rather limited addition of new neurons and poor regenerative capacity. In contrast, neural stem cells (NSC) with glial identity and neurogenesis are highly abundant throughout the adult zebrafish brain. Importantly, the activation of NSC and production of new neurons in response to injuries lead to the brain regeneration in zebrafish brain. Therefore, understanding of the molecular pathways regulating NSC behavior in response to injury is crucial in order to set the basis for experimental modification of these pathways in glial cells after injury in the mammalian brain and to elicit neuronal regeneration. Here, we describe the procedure that we successfully used to prospectively isolate NSCs from adult zebrafish telencephalon, extract RNA, and prepare cDNA libraries for next generation sequencing (NGS) and full transcriptome analysis as the first step toward understanding regulatory mechanisms leading to restorative neurogenesis in zebrafish. Moreover, we describe an alternative approach to analyze antigenic properties of NSC in the adult zebrafish brain using intracellular fluorescence activated cell sorting (FACS). We employ this method to analyze the number of proliferating NSCs positive for proliferating cell nuclear antigen (PCNA) in the prospectively isolated population of stem cells.</p>',
			'date' => '2019-01-09',
			'pmid' => 'http://www.pubmed.gov/30617972',
			'doi' => '10.1007/978-1-4939-9068-9_4,',
			'modified' => '2019-06-07 08:57:58',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 95 => array(
			'id' => '3651',
			'name' => 'DeltaNp63-dependent super enhancers define molecular identity in pancreatic cancer by an interconnected transcription factor network.',
			'authors' => 'Hamdan FH, Johnsen SA',
			'description' => '<p>Molecular subtyping of cancer offers tremendous promise for the optimization of a precision oncology approach to anticancer therapy. Recent advances in pancreatic cancer research uncovered various molecular subtypes with tumors expressing a squamous/basal-like gene expression signature displaying a worse prognosis. Through unbiased epigenome mapping, we identified deltaNp63 as a major driver of a gene signature in pancreatic cancer cell lines, which we report to faithfully represent the highly aggressive pancreatic squamous subtype observed in vivo, and display the specific epigenetic marking of genes associated with decreased survival. Importantly, depletion of deltaNp63 in these systems significantly decreased cell proliferation and gene expression patterns associated with a squamous subtype and transcriptionally mimicked a subtype switch. Using genomic localization data of deltaNp63 in pancreatic cancer cell lines coupled with epigenome mapping data from patient-derived xenografts, we uncovered that deltaNp63 mainly exerts its effects by activating subtype-specific super enhancers. Furthermore, we identified a group of 45 subtype-specific super enhancers that are associated with poorer prognosis and are highly dependent on deltaNp63. Genes associated with these enhancers included a network of transcription factors, including HIF1A, BHLHE40, and RXRA, which form a highly intertwined transcriptional regulatory network with deltaNp63 to further activate downstream genes associated with poor survival.</p>',
			'date' => '2018-12-26',
			'pmid' => 'http://www.pubmed.gov/30541891',
			'doi' => '10.1073/pnas.1812915116',
			'modified' => '2019-06-07 09:29:25',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 96 => array(
			'id' => '3610',
			'name' => 'The Aryl Hydrocarbon Receptor Pathway Defines the Time Frame for Restorative Neurogenesis.',
			'authors' => 'Di Giaimo R, Durovic T, Barquin P, Kociaj A, Lepko T, Aschenbroich S, Breunig CT, Irmler M, Cernilogar FM, Schotta G, Barbosa JS, Trümbach D, Baumgart EV, Neuner AM, Beckers J, Wurst W, Stricker SH, Ninkovic J',
			'description' => '<p>Zebrafish have a high capacity to replace lost neurons after brain injury. New neurons involved in repair are generated by a specific set of glial cells, known as ependymoglial cells. We analyze changes in the transcriptome of ependymoglial cells and their progeny after injury to infer the molecular pathways governing restorative neurogenesis. We identify the aryl hydrocarbon receptor (AhR) as a regulator of ependymoglia differentiation toward post-mitotic neurons. In&nbsp;vivo imaging shows that high AhR signaling promotes the direct conversion of a specific subset of ependymoglia into post-mitotic neurons, while low AhR signaling promotes ependymoglial proliferation. Interestingly, we observe the inactivation of AhR signaling shortly after injury followed by a return to the basal levels 7&nbsp;days post injury. Interference with timely AhR regulation after injury leads to aberrant restorative neurogenesis. Taken together, we identify AhR signaling as a crucial regulator of restorative neurogenesis timing in the zebrafish brain.</p>',
			'date' => '2018-12-18',
			'pmid' => 'http://www.pubmed.gov/30566853',
			'doi' => '10.1016/j.celrep.2018.11.055',
			'modified' => '2019-04-17 14:47:22',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 97 => array(
			'id' => '3649',
			'name' => 'Genome-wide identification of RETINOBLASTOMA RELATED 1 binding sites in Arabidopsis reveals novel DNA damage regulators.',
			'authors' => 'Bouyer D, Heese M, Chen P, Harashima H, Roudier F, Grüttner C, Schnittger A',
			'description' => '<p>Retinoblastoma (pRb) is a multifunctional regulator, which was likely present in the last common ancestor of all eukaryotes. The Arabidopsis pRb homolog RETINOBLASTOMA RELATED 1 (RBR1), similar to its animal counterparts, controls not only cell proliferation but is also implicated in developmental decisions, stress responses and maintenance of genome integrity. Although most functions of pRb-type proteins involve chromatin association, a genome-wide understanding of RBR1 binding sites in Arabidopsis is still missing. Here, we present a plant chromatin immunoprecipitation protocol optimized for genome-wide studies of indirectly DNA-bound proteins like RBR1. Our analysis revealed binding of Arabidopsis RBR1 to approximately 1000 genes and roughly 500 transposable elements, preferentially MITES. The RBR1-decorated genes broadly overlap with previously identified targets of two major transcription factors controlling the cell cycle, i.e. E2F and MYB3R3 and represent a robust inventory of RBR1-targets in dividing cells. Consistently, enriched motifs in the RBR1-marked domains include sequences related to the E2F consensus site and the MSA-core element bound by MYB3R transcription factors. Following up a key role of RBR1 in DNA damage response, we performed a meta-analysis combining the information about the RBR1-binding sites with genome-wide expression studies under DNA stress. As a result, we present the identification and mutant characterization of three novel genes required for growth upon genotoxic stress.</p>',
			'date' => '2018-11-01',
			'pmid' => 'http://www.pubmed.gov/30500810',
			'doi' => '10.1371/journal.',
			'modified' => '2019-06-07 10:12:16',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 98 => array(
			'id' => '3576',
			'name' => 'SUMO Safeguards Somatic and Pluripotent Cell Identities by Enforcing Distinct Chromatin States',
			'authors' => 'Cossec Jack-Christophe, Theurillat Ilan, Chica Claudia, Búa Aguín Sabela, Gaume Xavier, Andrieux Alexandra, Iturbide Ane, Jouvion Gregory, Li Han, Bossis Guillaume, Seeler Jacob-Sebastian, Torres-Padilla Maria-Elena, Dejean Anne',
			'description' => '<p>Understanding general principles that safeguard cellular identity should reveal critical insights into common mechanisms underlying specification of varied cell types. Here, we show that SUMO modification acts to stabilize cell fate in a variety of contexts. Hyposumoylation enhances pluripotency reprogramming in vitro and in vivo, increases lineage transdifferentiation, and facilitates leukemic cell differentiation. Suppressing sumoylation in embryonic stem cells (ESCs) promotes their conversion into 2-cell-embryo-like (2C-like) cells. During reprogramming to pluripotency, SUMO functions on fibroblastic enhancers to retain somatic transcription factors together with Oct4, Sox2, and Klf4, thus impeding somatic enhancer inactivation. In contrast, in ESCs, SUMO functions on heterochromatin to silence the 2C program, maintaining both proper H3K9me3 levels genome-wide and repression of the Dux locus by triggering recruitment of the sumoylated PRC1.6 and Kap/Setdb1 repressive complexes. Together, these studies show that SUMO acts on chromatin as a glue to stabilize key determinants of somatic and pluripotent states.</p>',
			'date' => '2018-10-25',
			'pmid' => 'http://www.pubmed.gov/30401455',
			'doi' => '10.1016/j.stem.2018.10.001',
			'modified' => '2019-07-22 09:18:55',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 99 => array(
			'id' => '3636',
			'name' => 'Caenorhabditis elegans sperm carry a histone-based epigenetic memory of both spermatogenesis and oogenesis.',
			'authors' => 'Tabuchi TM, Rechtsteiner A, Jeffers TE, Egelhofer TA, Murphy CT, Strome S',
			'description' => '<p>Paternal contributions to epigenetic inheritance are not well understood. Paternal contributions via marked nucleosomes are particularly understudied, in part because sperm in some organisms replace the majority of nucleosome packaging with protamine packaging. Here we report that in Caenorhabditis elegans sperm, the genome is packaged in nucleosomes and carries a histone-based epigenetic memory of genes expressed during spermatogenesis, which unexpectedly include genes well known for their expression during oogenesis. In sperm, genes with spermatogenesis-restricted expression are uniquely marked with both active and repressive marks, which may reflect a sperm-specific chromatin signature. We further demonstrate that epigenetic information provided by sperm is important and in fact sufficient to guide proper germ cell development in offspring. This study establishes one mode of paternal epigenetic inheritance and offers a potential mechanism for how the life experiences of fathers may impact the development and health of their descendants.</p>',
			'date' => '2018-10-17',
			'pmid' => 'http://www.pubmed.gov/30333496',
			'doi' => '10.1038/s41467-018-06236-8',
			'modified' => '2019-06-07 10:26:54',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 100 => array(
			'id' => '3556',
			'name' => 'PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex.',
			'authors' => 'Link S, Spitzer RMM, Sana M, Torrado M, Völker-Albert MC, Keilhauer EC, Burgold T, Pünzeler S, Low JKK, Lindström I, Nist A, Regnard C, Stiewe T, Hendrich B, Imhof A, Mann M, Mackay JP, Bartkuhn M, Hake SB',
			'description' => '<p>Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and cranial-facial development. Here, using in vitro assays, we show that distinct domains of PWWP2A mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly binds H3K36me3-containing gene bodies. Further, PWWP2A binds to an MTA1-specific subcomplex of the NuRD complex (M1HR), which consists solely of MTA1, HDAC1, and RBBP4/7, and excludes CHD, GATAD2 and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as a complex chromatin-binding protein that serves to direct the deacetylase complex M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels.</p>',
			'date' => '2018-10-16',
			'pmid' => 'http://www.pubmed.gov/30327463',
			'doi' => '10.1038/s41467-018-06665-5',
			'modified' => '2019-07-22 09:17:39',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 101 => array(
			'id' => '3498',
			'name' => 'Convergent evolution of complex genomic rearrangements in two fungal meiotic drive elements.',
			'authors' => 'Svedberg J, Hosseini S, Chen J, Vogan AA, Mozgova I, Hennig L, Manitchotpisit P, Abusharekh A, Hammond TM, Lascoux M, Johannesson H',
			'description' => '<p>Meiotic drive is widespread in nature. The conflict it generates is expected to be an important motor for evolutionary change and innovation. In this study, we investigated the genomic consequences of two large multi-gene meiotic drive elements, Sk-2 and Sk-3, found in the filamentous ascomycete Neurospora intermedia. Using long-read sequencing, we generated the first complete and well-annotated genome assemblies of large, highly diverged, non-recombining regions associated with meiotic drive elements. Phylogenetic analysis shows that, even though Sk-2 and Sk-3 are located in the same chromosomal region, they do not form sister clades, suggesting independent origins or at least a long evolutionary separation. We conclude that they have in a convergent manner accumulated similar patterns of tandem inversions and dense repeat clusters, presumably in response to similar needs to create linkage between genes causing drive and resistance.</p>',
			'date' => '2018-10-12',
			'pmid' => 'http://www.pubmed.gov/30315196',
			'doi' => '10.1038/s41467-018-06562-x',
			'modified' => '2019-07-22 09:20:24',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 102 => array(
			'id' => '3507',
			'name' => 'Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclones.',
			'authors' => 'de Boer B, Prick J, Pruis MG, Keane P, Imperato MR, Jaques J, Brouwers-Vos AZ, Hogeling SM, Woolthuis CM, Nijk MT, Diepstra A, Wandinger S, Versele M, Attar RM, Cockerill PN, Huls G, Vellenga E, Mulder AB, Bonifer C, Schuringa JJ',
			'description' => '<p>Intra-tumor heterogeneity caused by clonal evolution is a major problem in cancer treatment. To address this problem, we performed label-free quantitative proteomics on primary acute myeloid leukemia (AML) samples. We identified 50 leukemia-enriched plasma membrane proteins enabling the prospective isolation of genetically distinct subclones from individual AML patients. Subclones differed in their regulatory phenotype, drug sensitivity, growth, and engraftment behavior, as determined by RNA sequencing, DNase I hypersensitive site mapping, transcription factor occupancy analysis, in&nbsp;vitro culture, and xenograft transplantation. Finally, we show that these markers can be used to identify and longitudinally track distinct leukemic clones in patients in routine diagnostics. Our study describes a strategy for a major improvement in stratifying cancer diagnosis and treatment.</p>',
			'date' => '2018-10-08',
			'pmid' => 'http://www.pubmed.gov/30245083',
			'doi' => '10.1016/j.ccell.2018.08.014',
			'modified' => '2019-02-27 16:26:01',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 103 => array(
			'id' => '3505',
			'name' => 'Genomic Location of PRMT6-Dependent H3R2 Methylation Is Linked to the Transcriptional Outcome of Associated Genes.',
			'authors' => 'Bouchard C, Sahu P, Meixner M, Nötzold RR, Rust MB, Kremmer E, Feederle R, Hart-Smith G, Finkernagel F, Bartkuhn M, Savai Pullamsetti S, Nist A, Stiewe T, Philipsen S, Bauer UM',
			'description' => '<p>Protein arginine methyltransferase 6 (PRMT6) catalyzes asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a). This mark has been reported to associate with silent genes. Here, we use a cell model&nbsp;of neural differentiation, which upon PRMT6 knockout exhibits proliferation and differentiation defects. Strikingly, we detect PRMT6-dependent H3R2me2a at active genes, both at promoter and enhancer sites. Loss of H3R2me2a from promoter sites leads to enhanced KMT2A binding and H3K4me3 deposition together with increased target gene transcription, supporting a repressive nature of H3R2me2a. At enhancers, H3R2me2a peaks co-localize with the active enhancer marks H3K4me1 and H3K27ac. Here, loss of H3R2me2a results in reduced KMT2D binding and H3K4me1/H3K27ac deposition together with decreased transcription of associated genes, indicating that H3R2me2a also exerts activation functions. Our work suggests that PRMT6 via H3R2me2a interferes with the deposition of adjacent histone marks and modulates the activity of important differentiation-associated genes by opposing transcriptional effects.</p>',
			'date' => '2018-09-18',
			'pmid' => 'http://www.pubmed.gov/30232013',
			'doi' => '10.1016/j.celrep.2018.08.052',
			'modified' => '2019-02-28 10:05:16',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 104 => array(
			'id' => '3599',
			'name' => 'Enhancer-driven transcriptional regulation is a potential key determinant for human visceral and subcutaneous adipocytes.',
			'authors' => 'Liefke R, Bokelmann K, Ghadimi BM, Dango S',
			'description' => '<p>Obesity is characterized by the excess of body fat leading to impaired health. Abdominal fat is particularly harmful and is associated with cardiovascular and metabolic diseases and cancer. In contrast, subcutaneous fat is generally considered less detrimental. The mechanisms that establish the cellular characteristics of these distinct fat types in humans are not fully understood. Here, we explored whether differences of their gene regulatory mechanisms can be investigated in vitro. For this purpose, we in vitro differentiated human visceral and subcutaneous pre-adipocytes into mature adipocytes and obtained their gene expression profiles and genome-wide H3K4me3, H3K9me3 and H3K27ac patterns. Subsequently, we compared those data with public gene expression data from visceral and subcutaneous fat tissues. We found that the in vitro differentiated adipocytes show significant differences in their transcriptional landscapes, which correlate with biological pathways that are characteristic for visceral and subcutaneous fat tissues, respectively. Unexpectedly, visceral adipocyte enhancers are rich on motifs for transcription factors involved in the Hippo-YAP pathway, cell growth and inflammation, which are not typically associated with adipocyte function. In contrast, enhancers of subcutaneous adipocytes show enrichment of motifs for common adipogenic transcription factors, such as C/EBP, NFI and PPAR&gamma;, implicating substantially disparate gene regulatory networks in visceral and subcutaneous adipocytes. Consistent with the role in obesity, predominantly the histone modification pattern of visceral adipocytes is linked to obesity-associated diseases. Thus, this work suggests that the properties of visceral and subcutaneous fat tissues can be studied in vitro and provides preliminary insights into their gene regulatory processes.</p>',
			'date' => '2018-06-30',
			'pmid' => 'http://www.pubmed.gov/29966764',
			'doi' => '10.1016/j.bbagrm.2018.06.007',
			'modified' => '2019-04-17 15:05:35',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 105 => array(
			'id' => '3621',
			'name' => 'Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx.',
			'authors' => 'Hensel KO, Cantner F, Bangert F, Wirth S, Postberg J',
			'description' => '<p>BACKGROUND: In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of cccDNA and HBx remains unexplored. RESULTS: To identify virus-host genome interactions and the underlying nuclear landscape for the first time, we combined circular chromosome conformation capture (4C) with RNA-seq and ChIP-seq. Moreover, we studied HBx-binding to HBV episomes. In HBV-positive HepaRG hepatocytes, we observed preferential association of HBV episomes and HBx with actively transcribed nuclear domains on the host genome correlating in size with constrained topological units of chromatin. Interestingly, HBx alone occupied transcribed chromatin domains. Silencing of native HBx caused reduced episomal HBV stability. CONCLUSIONS: As part of the HBV episome, HBx might stabilize HBV episomal nuclear localization. Our observations may contribute to the understanding of long-term episomal stability and the facilitation of viral persistence. The exact mechanism by which HBx contributes to HBV nuclear persistence warrants further investigations.</p>',
			'date' => '2018-06-22',
			'pmid' => 'http://www.pubmed.gov/29933745',
			'doi' => '10.1186/s13072-018-0204-2',
			'modified' => '2019-05-16 11:23:59',
			'created' => '2019-04-25 11:11:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 106 => array(
			'id' => '3503',
			'name' => 'Genome-wide rules of nucleosome phasing',
			'authors' => 'Sandro Baldi, Dhawal S. Jain1, Lisa Harpprecht1, Angelika Zabel1, Marion Scheibe, Falk Butter, Tobias Straub and Peter B. Becker',
			'description' => '<p>Regular successions of positioned nucleosomes &ndash; phased nucleosome arrays (PNAs) &ndash; are predominantly known from transcriptional start sites (TSS). It is unclear whether PNAs occur elsewhere in the genome. To generate a comprehensive inventory of PNAs for Drosophila, we applied spectral analysis to nucleosome maps and identified thousands of PNAs throughout the genome. About half of them are not near TSS and strongly enriched for a novel sequence motif. Through genome-wide reconstitution of physiological chromatin in Drosophila embryo extracts we uncovered the molecular basis of PNA formation. We identified Phaser, an unstudied zinc finger protein that positions nucleosomes flanking the new motif. It also revealed how the global activity of the chromatin remodeler CHRAC/ACF, together with local barrier elements, generates islands of regular phasing throughout the genome. Our work demonstrates the potential of chromatin assembly by embryo extracts as a powerful tool to reconstitute chromatin features on a global scale in vitro.</p>',
			'date' => '2018-06-13',
			'pmid' => 'https://doi.org/10.1101/093666',
			'doi' => '10.1101/093666.',
			'modified' => '2019-02-28 10:28:59',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 107 => array(
			'id' => '3562',
			'name' => 'Insulin promoter in human pancreatic β cells contacts diabetes susceptibility loci and regulates genes affecting insulin metabolism.',
			'authors' => 'Jian X, Felsenfeld G',
			'description' => '<p>Both type 1 and type 2 diabetes involve a complex interplay between genetic, epigenetic, and environmental factors. Our laboratory has been interested in the physical interactions, in nuclei of human pancreatic &beta; cells, between the insulin ( gene and other genes that are involved in insulin metabolism. We have identified, using Circularized Chromosome Conformation Capture (4C), many physical contacts in a human pancreatic &beta; cell line between the promoter on chromosome 11 and sites on most other chromosomes. Many of these contacts are associated with type 1 or type 2 diabetes susceptibility loci. To determine whether physical contact is correlated with an ability of the locus to affect expression of these genes, we knock down expression by targeting the promoter; 259 genes are either up or down-regulated. Of these, 46 make physical contact with We analyze a subset of the contacted genes and show that all are associated with acetylation of histone H3 lysine 27, a marker of actively expressed genes. To demonstrate the usefulness of this approach in revealing regulatory pathways, we identify from among the contacted sites the previously uncharacterized gene and show that it plays an important role in controlling the effect of somatostatin-28 on insulin secretion. These results are consistent with models in which clustering of genes supports transcriptional activity. This may be a particularly important mechanism in pancreatic &beta; cells and in other cells where a small subset of genes is expressed at high levels.</p>',
			'date' => '2018-05-15',
			'pmid' => 'http://www.pubmed.gov/29712868',
			'doi' => '10.1073/pnas.1803146115',
			'modified' => '2019-03-25 11:27:48',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 108 => array(
			'id' => '3578',
			'name' => 'Modulation of gene transcription and epigenetics of colon carcinoma cells by bacterial membrane vesicles.',
			'authors' => 'Vdovikova S, Gilfillan S, Wang S, Dongre M, Wai SN, Hurtado A',
			'description' => '<p>Interactions between bacteria and colon cancer cells influence the transcription of the host cell. Yet is it undetermined whether the bacteria itself or the communication between the host and bacteria is responsible for the genomic changes in the eukaryotic cell. Now, we have investigated the genomic and epigenetic consequences of co-culturing colorectal carcinoma cells with membrane vesicles from pathogenic bacteria Vibrio cholerae and non-pathogenic commensal bacteria Escherichia coli. Our study reveals that membrane vesicles from pathogenic and commensal bacteria have a global impact on the gene expression of colon-carcinoma cells. The changes in gene expression correlate positively with both epigenetic changes and chromatin accessibility of promoters at transcription start sites of genes induced by both types of membrane vesicles. Moreover, we have demonstrated that membrane vesicles obtained only from V. cholerae induced the expression of genes associated with epithelial cell differentiation. Altogether, our study suggests that the observed genomic changes in host cells might be due to specific components of membrane vesicles and do not require communication by direct contact with the bacteria.</p>',
			'date' => '2018-05-09',
			'pmid' => 'http://www.pubmed.gov/29743643',
			'doi' => '10.1038/s41598-018-25308-9',
			'modified' => '2019-04-17 15:56:24',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 109 => array(
			'id' => '3459',
			'name' => 'Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI as a co-repressor for RUNX1.',
			'authors' => 'Feld C, Sahu P, Frech M, Finkernagel F, Nist A, Stiewe T, Bauer UM, Neubauer A',
			'description' => '<p>SKI is a transcriptional co-regulator and overexpressed in various human tumors, for example in acute myeloid leukemia (AML). SKI contributes to the origin and maintenance of the leukemic phenotype. Here, we use ChIP-seq and RNA-seq analysis to identify the epigenetic alterations induced by SKI overexpression in AML cells. We show that approximately two thirds of differentially expressed genes are up-regulated upon SKI deletion, of which &gt;40% harbor SKI binding sites in their proximity, primarily in enhancer regions. Gene ontology analysis reveals that many of the differentially expressed genes are annotated to hematopoietic cell differentiation and inflammatory response, corroborating our finding that SKI contributes to a myeloid differentiation block in HL60 cells. We find that SKI peaks are enriched for RUNX1 consensus motifs, particularly in up-regulated SKI targets upon SKI deletion. RUNX1 ChIP-seq displays that nearly 70% of RUNX1 binding sites overlap with SKI peaks, mainly at enhancer regions. SKI and RUNX1 occupy the same genomic sites and cooperate in gene silencing. Our work demonstrates for the first time the predominant co-repressive function of SKI in AML cells on a genome-wide scale and uncovers the transcription factor RUNX1 as an important mediator of SKI-dependent transcriptional repression.</p>',
			'date' => '2018-04-20',
			'pmid' => 'http://www.pubmed.gov/29471413',
			'doi' => '10.1093/nar/gky119',
			'modified' => '2019-02-15 21:13:23',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 110 => array(
			'id' => '3539',
			'name' => 'A long range distal enhancer controls temporal fine-tuning of PAX6 expression in neuronal precursors.',
			'authors' => 'Lacomme M, Medevielle F, Bourbon HM, Thierion E, Kleinjan DJ, Roussat M, Pituello F, Bel-Vialar S',
			'description' => '<p>Proper embryonic development relies on a tight control of spatial and temporal gene expression profiles in a highly regulated manner. One good example is the ON/OFF switching of the transcription factor PAX6 that governs important steps of neurogenesis. In the neural tube PAX6 expression is initiated in neural progenitors through the positive action of retinoic acid signaling and downregulated in neuronal precursors by the bHLH transcription factor NEUROG2. How these two regulatory inputs are integrated at the molecular level to properly fine tune temporal PAX6 expression is not known. In this study we identified and characterized a 940-bp long distal cis-regulatory module (CRM), located far away from the PAX6 transcription unit and which conveys positive input from RA signaling pathway and indirect repressive signal(s) from NEUROG2. These opposing regulatory signals are integrated through HOMZ, a 94 bp core region within E940 which is evolutionarily conserved in distant organisms such as the zebrafish. We show that within HOMZ, NEUROG2 and RA exert their opposite temporal activities through a short 60 bp region containing a functional RA-responsive element (RARE). We propose a model in which retinoic acid receptors (RARs) and NEUROG2 repressive target(s) compete on the same DNA motif to fine tune temporal PAX6 expression during the course of spinal neurogenesis.</p>',
			'date' => '2018-04-15',
			'pmid' => 'http://www.pubmed.gov/29486153',
			'doi' => '10.1016/j.ydbio.2018.02.015',
			'modified' => '2019-02-28 10:42:57',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 111 => array(
			'id' => '3432',
			'name' => 'HDAC1 and HDAC2 Modulate TGF-β Signaling during Endothelial-to-Hematopoietic Transition.',
			'authors' => 'Thambyrajah R, Fadlullah MZH, Proffitt M, Patel R, Cowley SM, Kouskoff V, Lacaud G',
			'description' => '<p>The first hematopoietic stem and progenitor cells are generated during development from hemogenic endothelium (HE) through trans-differentiation. The molecular mechanisms underlying this endothelial-to-hematopoietic transition (EHT) remain poorly understood. Here, we explored the role of the epigenetic regulators HDAC1 and HDAC2 in the emergence of these first blood cells in&nbsp;vitro and in&nbsp;vivo. Loss of either of these epigenetic silencers through conditional genetic deletion reduced hematopoietic transition from HE, while combined deletion was incompatible with blood generation. We investigated the molecular basis of HDAC1 and HDAC2 requirement and identified TGF-&beta; signaling as one of the pathways controlled by HDAC1 and HDAC2. Accordingly, we experimentally demonstrated that activation of this pathway in HE cells reinforces hematopoietic development. Altogether, our results establish that HDAC1 and HDAC2 modulate TGF-&beta; signaling and suggest that stimulation of this pathway in HE cells would be beneficial for production of hematopoietic cells for regenerative therapies.</p>',
			'date' => '2018-04-10',
			'pmid' => 'http://www.pubmed.gov/29641990',
			'doi' => '10.1016/j.stemcr.2018.03.011',
			'modified' => '2018-12-31 11:55:16',
			'created' => '2018-12-04 09:51:07',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 112 => array(
			'id' => '3468',
			'name' => 'EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma.',
			'authors' => 'Gorthi A, Romero JC, Loranc E, Cao L, Lawrence LA, Goodale E, Iniguez AB, Bernard X, Masamsetti VP, Roston S, Lawlor ER, Toretsky JA, Stegmaier K, Lessnick SL, Chen Y, Bishop AJR',
			'description' => '<p>Ewing sarcoma is an aggressive paediatric cancer of the bone and soft tissue. It results from a chromosomal translocation, predominantly t(11;22)(q24:q12), that fuses the N-terminal transactivation domain of the constitutively expressed EWSR1 protein with the C-terminal DNA binding domain of the rarely expressed FLI1 protein. Ewing sarcoma is highly sensitive to genotoxic agents such as etoposide, but the underlying molecular basis of this sensitivity is unclear. Here we show that Ewing sarcoma cells display alterations in regulation of damage-induced transcription, accumulation of R-loops and increased replication stress. In addition, homologous recombination is impaired in Ewing sarcoma owing to an enriched interaction between BRCA1 and the elongating transcription machinery. Finally, we uncover a role for EWSR1 in the transcriptional response to damage, suppressing R-loops and promoting homologous recombination. Our findings improve the current understanding of EWSR1 function, elucidate the mechanistic basis of the sensitivity of Ewing sarcoma to chemotherapy (including PARP1 inhibitors) and highlight a class of BRCA-deficient-like tumours.</p>',
			'date' => '2018-03-15',
			'pmid' => 'http://www.pubmed.gov/29513652',
			'doi' => '10.1038/nature25748',
			'modified' => '2019-02-15 21:16:23',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 113 => array(
			'id' => '3533',
			'name' => 'A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.',
			'authors' => 'Zanghì G, Vembar SS, Baumgarten S, Ding S, Guizetti J, Bryant JM, Mattei D, Jensen ATR, Rénia L, Goh YS, Sauerwein R, Hermsen CC, Franetich JF, Bordessoulles M, Silvie O, Soulard V, Scatton O, Chen P, Mecheri S, Mazier D, Scherf A',
			'description' => '<p>Heterochromatin plays a central role in the process of immune evasion, pathogenesis, and transmission of the malaria parasite Plasmodium falciparum during blood stage infection. Here, we use ChIP sequencing to demonstrate that sporozoites from mosquito salivary glands expand heterochromatin at subtelomeric regions to silence blood-stage-specific&nbsp;genes. Our data also revealed that heterochromatin enrichment is predictive of the transcription status of clonally variant genes members that mediate cytoadhesion in blood stage parasites. A specific member (here called NF54var) of the var gene family remains euchromatic, and the resultant PfEMP1 (NF54_SpzPfEMP1) is expressed at the&nbsp;sporozoite surface. NF54_SpzPfEMP1-specific antibodies efficiently block hepatocyte infection in&nbsp;a strain-specific manner. Furthermore, human volunteers immunized with infective sporozoites developed antibodies against NF54_SpzPfEMP1. Overall, we show that the epigenetic signature of var genes is reset in mosquito stages. Moreover, the identification of a strain-specific sporozoite PfEMP1 is highly relevant for vaccine design based on sporozoites.</p>',
			'date' => '2018-03-13',
			'pmid' => 'http://www.pubmed.gov/29539423',
			'doi' => '10.1016/j.celrep.2018.02.075',
			'modified' => '2019-02-28 10:47:11',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 114 => array(
			'id' => '3444',
			'name' => 'Genome-wide analysis of PDX1 target genes in human pancreatic progenitors.',
			'authors' => 'Wang X, Sterr M, Burtscher I, Chen S, Hieronimus A, Machicao F, Staiger H, Häring HU, Lederer G, Meitinger T, Cernilogar FM, Schotta G, Irmler M, Beckers J, Hrabě de Angelis M, Ray M, Wright CVE, Bakhti M, Lickert H',
			'description' => '<p>OBJECTIVE: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing &beta;-cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Also, comparative studies of PDX1 binding patterns in pancreatic progenitors and adult &beta;-cells have not been conducted so far. Furthermore, many studies reported the association between single nucleotide polymorphisms (SNPs) and T2DM, and it has been shown that islet enhancers are enriched in T2DM-associated SNPs. Whether regions, harboring T2DM-associated SNPs are PDX1 bound and active at the pancreatic progenitor stage has not been reported so far. METHODS: In this study, we have generated a novel induced pluripotent stem cell (iPSC) line that efficiently differentiates into human pancreatic progenitors (PPs). Furthermore, PDX1 and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) was used to identify PDX1 transcriptional targets and active enhancer and promoter regions. To address potential differences in the function of PDX1 during development and adulthood, we compared PDX1 binding profiles from PPs and adult islets. Moreover, combining ChIP-seq and GWAS meta-analysis data we identified T2DM-associated SNPs in PDX1 binding sites and active chromatin regions. RESULTS: ChIP-seq for PDX1 revealed a total of 8088 PDX1-bound regions that map to 5664 genes in iPSC-derived PPs. The PDX1 target regions include important pancreatic TFs, such as PDX1 itself, RFX6, HNF1B, and MEIS1, which were activated during the differentiation process as revealed by the active chromatin mark H3K27ac and mRNA expression profiling, suggesting that auto-regulatory feedback regulation maintains PDX1 expression and initiates a pancreatic TF program. Remarkably, we identified several PDX1 target genes that have not been reported in the literature in human so far, including RFX3, required for ciliogenesis and endocrine differentiation in mouse, and the ligand of the Notch receptor DLL1, which is important for endocrine induction and tip-trunk patterning. The comparison of PDX1 profiles from PPs and adult human islets identified sets of stage-specific target genes, associated with early pancreas development and adult &beta;-cell function, respectively. Furthermore, we found an enrichment of T2DM-associated SNPs in active chromatin regions from iPSC-derived PPs. Two of these SNPs fall into PDX1 occupied sites that are located in the intronic regions of TCF7L2 and HNF1B. Both of these genes are key transcriptional regulators of endocrine induction and mutations in cis-regulatory regions predispose to diabetes. CONCLUSIONS: Our data provide stage-specific target genes of PDX1 during in&nbsp;vitro differentiation of stem cells into pancreatic progenitors that could be useful to identify pathways and molecular targets that predispose for diabetes. In addition, we show that T2DM-associated SNPs are enriched in active chromatin regions at the pancreatic progenitor stage, suggesting that the susceptibility to T2DM might originate from imperfect execution of a &beta;-cell developmental program.</p>',
			'date' => '2018-03-01',
			'pmid' => 'http://www.pubmed.gov/29396371',
			'doi' => '10.1016/j.molmet.2018.01.011',
			'modified' => '2019-02-15 21:27:03',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 115 => array(
			'id' => '3543',
			'name' => 'A multi-omics study of the grapevine-downy mildew (Plasmopara viticola) pathosystem unveils a complex protein coding- and noncoding-based arms race during infection.',
			'authors' => 'Brilli M, Asquini E, Moser M, Bianchedi PL, Perazzolli M, Si-Ammour A',
			'description' => '<p>Fungicides are applied intensively to prevent downy mildew infections of grapevines (Vitis vinifera) with high impact on the environment. In order to develop alternative strategies we sequenced the genome of the oomycete pathogen Plasmopara viticola causing this disease. We show that it derives from a Phytophthora-like ancestor that switched to obligate biotrophy by losing genes involved in nitrogen metabolism and &gamma;-Aminobutyric acid catabolism. By combining multiple omics approaches we characterized the pathosystem and identified a RxLR effector that trigger an immune response in the wild species V. riparia. This effector is an ideal marker to screen novel grape resistant varieties. Our study reveals an unprecedented bidirectional noncoding RNA-based mechanism that, in one direction might be fundamental for P. viticola to proficiently infect its host, and in the other might reduce the effects of the infection on the plant.</p>',
			'date' => '2018-01-15',
			'pmid' => 'http://www.pubmed.gov/29335535',
			'doi' => '10.1038/s41598-018-19158-8',
			'modified' => '2019-02-28 11:00:21',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 116 => array(
			'id' => '3445',
			'name' => 'BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis.',
			'authors' => 'Kaufmann E, Sanz J, Dunn JL, Khan N, Mendonça LE, Pacis A, Tzelepis F, Pernet E, Dumaine A, Grenier JC, Mailhot-Léonard F, Ahmed E, Belle J, Besla R, Mazer B, King IL, Nijnik A, Robbins CS, Barreiro LB, Divangahi M',
			'description' => '<p>The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and&nbsp;location for generating such innate memory responses in&nbsp;vivo remain unknown. Here, we show that access of Bacillus Calmette-Gu&eacute;rin (BCG) to the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), leading to local cell&nbsp;expansion and enhanced myelopoiesis at the&nbsp;expense of lymphopoiesis. Importantly, BCG-educated HSCs generate epigenetically modified macrophages that provide significantly better protection against virulent M.&nbsp;tuberculosis infection than na&iuml;ve macrophages. By using parabiotic and chimeric mice, as well as adoptive transfer approaches, we demonstrate that training of the monocyte/macrophage lineage via BCG-induced HSC reprogramming is sustainable in&nbsp;vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.</p>',
			'date' => '2018-01-11',
			'pmid' => 'http://www.pubmed.gov/29328912',
			'doi' => '10.1016/j.cell.2017.12.031',
			'modified' => '2019-02-15 21:32:25',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 117 => 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) 118 => array(
			'id' => '3355',
			'name' => 'Functional dissection of Drosophila melanogaster SUUR protein influence on H3K27me3 profile',
			'authors' => 'Posukh O. V. et al.',
			'description' => '<div id="__sec1" class="sec sec-first">
<h3>Background</h3>
<p id="Par1" class="p p-first-last">In eukaryotes, heterochromatin replicates late in S phase of the cell cycle and contains specific covalent modifications of histones. <em>SuUR</em> mutation found in Drosophila makes heterochromatin replicate earlier than in wild type and reduces the level of repressive histone modifications. SUUR protein was shown to be associated with moving replication forks, apparently through the interaction with PCNA. The biological process underlying the effects of SUUR on replication and composition of heterochromatin remains unknown.</p>
</div>
<div id="__sec2" class="sec">
<h3>Results</h3>
<p id="Par2" class="p p-first-last">Here we performed a functional dissection of SUUR protein effects on H3K27me3 level. Using hidden Markow model-based algorithm we revealed <em>SuUR</em>-sensitive chromosomal regions that demonstrated unusual characteristics: They do not contain Polycomb and require SUUR function to sustain H3K27me3 level. We tested the role of SUUR protein in the mechanisms that could affect H3K27me3 histone levels in these regions. We found that SUUR does not affect the initial H3K27me3 pattern formation in embryogenesis or Polycomb distribution in the chromosomes. We also ruled out the possible effect of SUUR on histone genes expression and its involvement in DSB repair.</p>
</div>
<div id="__sec3" class="sec">
<h3>Conclusions</h3>
<p id="Par3" class="p p-first-last">Obtained results support the idea that SUUR protein contributes to the heterochromatin maintenance during the chromosome replication. A model that explains major SUUR-associated phenotypes is proposed.</p>
</div>',
			'date' => '2017-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709859/',
			'doi' => '',
			'modified' => '2018-04-05 12:28:59',
			'created' => '2018-04-05 12:28:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 119 => array(
			'id' => '3305',
			'name' => 'An endosiRNA-Based Repression Mechanism Counteracts Transposon Activation during Global DNA Demethylation in Embryonic Stem Cells',
			'authors' => 'Berrens R.V. et al.',
			'description' => '<p>Erasure of DNA methylation and repressive chromatin marks in the mammalian germline leads to risk of transcriptional activation of transposable elements (TEs). Here, we used mouse embryonic stem cells (ESCs) to identify an endosiRNA-based mechanism involved in suppression of TE transcription. In ESCs with DNA demethylation induced by acute deletion of Dnmt1, we saw an increase in sense transcription at TEs, resulting in an abundance of sense/antisense transcripts leading to high levels of ARGONAUTE2 (AGO2)-bound small RNAs. Inhibition of Dicer or Ago2 expression revealed that small RNAs are involved in an immediate response to demethylation-induced transposon activation, while the deposition of repressive histone marks follows as a chronic response. In&nbsp;vivo, we also found TE-specific endosiRNAs present during primordial germ cell development. Our results suggest that antisense TE transcription is a "trap" that elicits an endosiRNA response to restrain acute transposon activity during epigenetic reprogramming in the mammalian germline.</p>',
			'date' => '2017-11-02',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29100015',
			'doi' => '',
			'modified' => '2018-01-03 10:17:40',
			'created' => '2018-01-03 10:17:40',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 120 => array(
			'id' => '3281',
			'name' => 'Epigenome profiling and editing of neocortical progenitor cells during development',
			'authors' => 'Albert M. et al.',
			'description' => '<p>The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resolution are required. Here, we present genomewide histone methylation maps for distinct neural cell populations in the developing mouse neocortex. Using different chromatin features, we identify potential novel regulators of cortical NPCs. Moreover, we identify extensive H3K27me3 changes between NPC subtypes coinciding with major developmental and cell biological transitions. Interestingly, we detect dynamic H3K27me3 changes on promoters of several crucial transcription factors, including the basal progenitor regulator <i>Eomes</i> We use catalytically inactive Cas9 fused with the histone methyltransferase Ezh2 to edit H3K27me3 at the <i>Eomes</i> locus <i>in&nbsp;vivo</i>, which results in reduced Tbr2 expression and lower basal progenitor abundance, underscoring the relevance of dynamic H3K27me3 changes during neocortex development. Taken together, we provide a rich resource of neocortical histone methylation data and outline an approach to investigate its contribution to the regulation of selected genes during neocortical development.</p>',
			'date' => '2017-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28765163',
			'doi' => '',
			'modified' => '2017-10-17 10:25:58',
			'created' => '2017-10-17 10:25:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 121 => array(
			'id' => '3250',
			'name' => 'Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles',
			'authors' => 'Marincevic-Zuniga Y. et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL). In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts.</abstracttext></p>
<h4>METHODS:</h4>
<p><abstracttext label="METHODS" nlmcategory="METHODS">We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">We identified 64 unique fusion events distributed among 80 individual patients, of which over 50% have not previously been reported in ALL. Although the majority of the fusion genes were found only in a single patient, we identified several recurrent fusion gene families defined by promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5, and ZNF384, or recurrent fusion genes, such as DUX4-IGH. Our data show that patients harboring these fusion genes displayed characteristic genome-wide DNA methylation and gene expression signatures in addition to distinct patterns in single nucleotide variants and recurrent copy number alterations.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">Our study delineates the fusion gene landscape in pediatric ALL, including both known and novel fusion genes, and highlights fusion gene families with shared molecular etiologies, which may provide additional information for prognosis and therapeutic options in the future.</abstracttext></p>
</div>',
			'date' => '2017-08-14',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28806978',
			'doi' => '',
			'modified' => '2017-09-26 09:49:39',
			'created' => '2017-09-26 09:49:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 122 => array(
			'id' => '3259',
			'name' => 'Dynamics of RNA Polymerase II Pausing and Bivalent Histone H3 Methylation during Neuronal Differentiation in Brain Development',
			'authors' => 'Liu J. et al.',
			'description' => '<p>During cellular differentiation, genes important for differentiation are expected to be silent in stem/progenitor cells yet can be readily activated. RNA polymerase II (Pol II) pausing and bivalent chromatin marks are two paradigms suited for establishing such a poised state of gene expression; however, their specific contributions in development are not well understood. Here we characterized Pol II pausing and H3K4me3/H3K27me3 marks in neural progenitor cells (NPCs) and their daughter neurons purified from the developing mouse cortex. We show that genes paused in NPCs or neurons are characteristic of respective cellular functions important for each cell type, although pausing and pause release were not correlated with gene activation. Bivalent chromatin marks poised the marked genes&nbsp;in NPCs for activation in neurons. Interestingly, we&nbsp;observed a positive correlation between H3K27me3 and paused Pol II. This study thus reveals cell type-specific Pol II pausing and gene activation-associated bivalency during mammalian neuronal differentiation.</p>',
			'date' => '2017-08-08',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28793256',
			'doi' => '',
			'modified' => '2017-10-05 11:17:11',
			'created' => '2017-10-05 11:17:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 123 => 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) 124 => array(
			'id' => '3282',
			'name' => 'Krox20 hindbrain regulation incorporates multiple modes of cooperation between cis-acting elements',
			'authors' => 'Thierion E. et al.',
			'description' => '<p>Developmental genes can harbour multiple transcriptional enhancers that act simultaneously or in succession to achieve robust and precise spatiotemporal expression. However, the mechanisms underlying cooperation between cis-acting elements are poorly documented, notably in vertebrates. The mouse gene Krox20 encodes a transcription factor required for the specification of two segments (rhombomeres) of the developing hindbrain. In rhombomere 3, Krox20 is subject to direct positive feedback governed by an autoregulatory enhancer, element A. In contrast, a second enhancer, element C, distant by 70 kb, is active from the initiation of transcription independent of the presence of the KROX20 protein. Here, using both enhancer knock-outs and investigations of chromatin organisation, we show that element C possesses a dual activity: besides its classical enhancer function, it is also permanently required in cis to potentiate the autoregulatory activity of element A, by increasing its chromatin accessibility. This work uncovers a novel, asymmetrical, long-range mode of cooperation between cis-acting elements that might be essential to avoid promiscuous activation of positive autoregulatory elements.</p>',
			'date' => '2017-07-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28749941',
			'doi' => '',
			'modified' => '2017-10-23 17:38:21',
			'created' => '2017-10-23 17:38:21',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 125 => array(
			'id' => '3261',
			'name' => 'Ectopic application of the repressive histone modification H3K9me2 establishes post-zygotic reproductive isolation in Arabidopsis thaliana',
			'authors' => 'Jiang H. et al.',
			'description' => '<p>Hybrid seed lethality as a consequence of interspecies or interploidy hybridizations is a major mechanism of reproductive isolation in plants. This mechanism is manifested in the endosperm, a dosage-sensitive tissue supporting embryo growth. Deregulated expression of imprinted genes such as <em>ADMETOS</em> (<em>ADM</em>) underpin the interploidy hybridization barrier in <em>Arabidopsis thaliana</em>; however, the mechanisms of their action remained unknown. In this study, we show that ADM interacts with the AT hook domain protein AHL10 and the SET domain-containing SU(VAR)3&ndash;9 homolog SUVH9 and ectopically recruits the heterochromatic mark H3K9me2 to AT-rich transposable elements (TEs), causing deregulated expression of neighboring genes. Several hybrid incompatibility genes identified in <em>Drosophila</em> encode for dosage-sensitive heterochromatin-interacting proteins, which has led to the suggestion that hybrid incompatibilities evolve as a consequence of interspecies divergence of selfish DNA elements and their regulation. Our data show that imbalance of dosage-sensitive chromatin regulators underpins the barrier to interploidy hybridization in <em>Arabidopsis</em>, suggesting that reproductive isolation as a consequence of epigenetic regulation of TEs is a conserved feature in animals and plants.</p>',
			'date' => '2017-07-25',
			'pmid' => 'http://genesdev.cshlp.org/content/early/2017/07/25/gad.299347.117',
			'doi' => '',
			'modified' => '2017-10-05 11:34:59',
			'created' => '2017-10-05 11:34:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 126 => array(
			'id' => '3267',
			'name' => '2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: Alterations in biosynthesis, enterohepatic circulation, and microbial metabolism.',
			'authors' => 'Fader K. et al.',
			'description' => '<p>2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant which elicits hepatotoxicity through activation of the aryl hydrocarbon receptor (AhR). Male C57BL/6 mice orally gavaged with TCDD (0.01-30&thinsp;&micro;g/kg) every 4 days for 28 days exhibited bile duct proliferation and pericholangitis. Mass spectrometry analysis detected a 4.6-fold increase in total hepatic bile acid levels, despite the coordinated repression of genes involved in cholesterol and primary bile acid biosynthesis including Cyp7a1. Specifically, TCDD elicited a &gt;200-fold increase in taurolithocholic acid (TLCA), a potent G protein-coupled bile acid receptor 1 (GPBAR1) agonist associated with bile duct proliferation. Increased levels of microbial bile acid metabolism loci (bsh, baiCD) are consistent with accumulation of TLCA and other secondary bile acids. Fecal bile acids decreased 2.8-fold, suggesting enhanced intestinal reabsorption due to induction of ileal transporters (Slc10a2, Slc51a) and increases in whole gut transit time and intestinal permeability. Moreover, serum bile acids were increased 45.4-fold, consistent with blood-to-hepatocyte transporter repression (Slco1a1, Slc10a1, Slco2b1, Slco1b2, Slco1a4) and hepatocyte-to-blood transporter induction (Abcc4, Abcc3). These results suggest that systemic alterations in enterohepatic circulation, as well as host and microbiota bile acid metabolism, favor bile acid accumulation that contributes to AhR-mediated hepatotoxicity.</p>',
			'date' => '2017-07-19',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28725001',
			'doi' => '',
			'modified' => '2017-10-09 16:22:36',
			'created' => '2017-10-09 16:22:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 127 => 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) 128 => array(
			'id' => '3258',
			'name' => 'CRISPR/Cas9 Genome Editing Reveals That the Intron Is Not Essential for var2csa Gene Activation or Silencing in Plasmodium falciparum',
			'authors' => 'Bryant J.M. et al.',
			'description' => '<p id="p-4"><em>Plasmodium falciparum</em> relies on monoallelic expression of 1 of 60 <em>var</em> virulence genes for antigenic variation and host immune evasion. Each <em>var</em> gene contains a conserved intron which has been implicated in previous studies in both activation and repression of transcription via several epigenetic mechanisms, including interaction with the <em>var</em> promoter, production of long noncoding RNAs (lncRNAs), and localization to repressive perinuclear sites. However, functional studies have relied primarily on artificial expression constructs. Using the recently developed <em>P.&nbsp;falciparum</em> clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, we directly deleted the <em>var2csa P.&nbsp;falciparum</em> 3D7_1200600 (Pf3D7_1200600) endogenous intron, resulting in an intronless <em>var</em> gene in a natural, marker-free chromosomal context. Deletion of the <em>var2csa</em> intron resulted in an upregulation of transcription of the <em>var2csa</em> gene in ring-stage parasites and subsequent expression of the PfEMP1 protein in late-stage parasites. Intron deletion did not affect the normal temporal regulation and subsequent transcriptional silencing of the <em>var</em> gene in trophozoites but did result in increased rates of <em>var</em> gene switching in some mutant clones. Transcriptional repression of the intronless <em>var2csa</em> gene could be achieved via long-term culture or panning with the CD36 receptor, after which reactivation was possible with chondroitin sulfate A (CSA) panning. These data suggest that the <em>var2csa</em> intron is not required for silencing or activation in ring-stage parasites but point to a subtle role in regulation of switching within the <em>var</em> gene family.</p>
<p id="p-5"><strong>IMPORTANCE</strong> <em>Plasmodium falciparum</em> is the most virulent species of malaria parasite, causing high rates of morbidity and mortality in those infected. Chronic infection depends on an immune evasion mechanism termed antigenic variation, which in turn relies on monoallelic expression of 1 of ~60 <em>var</em> genes. Understanding antigenic variation and the transcriptional regulation of monoallelic expression is important for developing drugs and/or vaccines. The <em>var</em> gene family encodes the antigenic surface proteins that decorate infected erythrocytes. Until recently, studying the underlying genetic elements that regulate monoallelic expression in <em>P.&nbsp;falciparum</em> was difficult, and most studies relied on artificial systems such as episomal reporter genes. Our study was the first to use CRISPR/Cas9 genome editing for the functional study of an important, conserved genetic element of <em>var</em> genes&mdash;the intron&mdash;in an endogenous, episome-free manner. Our findings shed light on the role of the <em>var</em> gene intron in transcriptional regulation of monoallelic expression.</p>',
			'date' => '2017-07-11',
			'pmid' => 'http://mbio.asm.org/content/8/4/e00729-17.abstract',
			'doi' => '',
			'modified' => '2017-10-05 11:12:18',
			'created' => '2017-10-05 11:12:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 129 => array(
			'id' => '3218',
			'name' => 'Genome-wide mapping and analysis of aryl hydrocarbon receptor (AHR)- and aryl hydrocarbon receptor repressor (AHRR)-binding sites in human breast cancer cells',
			'authors' => 'Sunny Y. Yang, Shaimaa Ahmed, Somisetty V. Satheesh, Jason Matthews',
			'description' => '<p><span>The aryl hydrocarbon receptor (AHR) mediates the toxic actions of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-</span><em class="EmphasisTypeItalic ">&rho;</em><span>-dioxin (TCDD), and also plays roles in vascular development, the immune response, and cell cycle regulation. The AHR repressor (AHRR) is an AHR-regulated gene and a negative regulator of AHR; however, the mechanisms of AHRR-dependent repression of AHR are unclear. In this study, we compared the genome-wide binding profiles of AHR and AHRR in MCF-7 human breast cancer cells treated for 24&nbsp;h with TCDD using chromatin immunoprecipitation followed by next-generation sequencing (ChIP-Seq). We identified 3915 AHR- and 2811 AHRR-bound regions, of which 974 (35%) were common to both datasets. When these 24-h datasets were also compared with AHR-bound regions identified after 45&nbsp;min of TCDD treatment, 67% (1884) of AHRR-bound regions overlapped with those of AHR. This analysis identified 994 unique AHRR-bound regions. AHRR-bound regions mapped closer to promoter regions when compared with AHR-bound regions. The AHRE was identified and overrepresented in AHR:AHRR-co-bound regions, AHR-only regions, and AHRR-only regions. Candidate unique AHR- and AHRR-bound regions were validated by ChIP&ndash;qPCR and their ability to regulate gene expression was confirmed by luciferase reporter gene assays. Overall, this study reveals that AHR and AHRR exhibit similar but also distinct genome-wide binding profiles, supporting the notion that AHRR is a context- and gene-specific repressor of AHR activity.</span></p>',
			'date' => '2017-07-05',
			'pmid' => 'https://link.springer.com/article/10.1007/s00204-017-2022-x',
			'doi' => '10.1007/s00204-017-2022-x',
			'modified' => '2017-07-29 08:23:22',
			'created' => '2017-07-29 08:23:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 130 => 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) 131 => array(
			'id' => '3358',
			'name' => 'Characterization of the Polycomb-Group Mark H3K27me3 in Unicellular Algae',
			'authors' => 'Mikulski P. et al.',
			'description' => '<p>Polycomb Group (PcG) proteins mediate chromatin repression in plants and animals by catalyzing H3K27 methylation and H2AK118/119 mono-ubiquitination through the activity of the Polycomb repressive complex 2 (PRC2) and PRC1, respectively. PcG proteins were extensively studied in higher plants, but their function and target genes in unicellular branches of the green lineage remain largely unknown. To shed light on PcG function and <i>modus operandi</i> in a broad evolutionary context, we demonstrate phylogenetic relationship of core PRC1 and PRC2 proteins and H3K27me3 biochemical presence in several unicellular algae of different phylogenetic subclades. We focus then on one of the species, the model red alga <i>Cyanidioschizon merolae</i>, and show that H3K27me3 occupies both, genes and repetitive elements, and mediates the strength of repression depending on the differential occupancy over gene bodies. Furthermore, we report that H3K27me3 in <i>C. merolae</i> is enriched in telomeric and subtelomeric regions of the chromosomes and has unique preferential binding toward intein-containing genes involved in protein splicing. Thus, our study gives important insight for Polycomb-mediated repression in lower eukaryotes, uncovering a previously unknown link between H3K27me3 targets and protein splicing.</p>',
			'date' => '2017-04-26',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28491069',
			'doi' => '',
			'modified' => '2018-04-05 13:09:46',
			'created' => '2018-04-05 13:09:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 132 => 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) 133 => array(
			'id' => '3176',
			'name' => 'First landscape of binding to chromosomes for a domesticated mariner transposase in the human genome: diversity of genomic targets of SETMAR isoforms in two colorectal cell lines',
			'authors' => 'Antoine-Lorquin A. et al.',
			'description' => '<p>Setmar is a 3-exons gene coding a SET domain fused to a Hsmar1 transposase. Its different transcripts theoretically encode 8 isoforms with SET moieties differently spliced. In vitro, the largest isoform binds specifically to Hsmar1 DNA ends and with no specificity to DNA when it is associated with hPso4. In colon cell lines, we found they bind specifically to two chromosomal targets depending probably on the isoform, Hsmar1 ends and sites with no conserved motifs. We also discovered that the isoforms profile was different between cell lines and patient tissues, suggesting the isoforms encoded by this gene in healthy cells and their functions are currently not investigated.</p>',
			'date' => '2017-03-09',
			'pmid' => 'http://biorxiv.org/content/early/2017/03/09/115030',
			'doi' => '',
			'modified' => '2017-05-15 10:24:16',
			'created' => '2017-05-15 10:24:16',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 134 => array(
			'id' => '3156',
			'name' => 'Crebbp loss cooperates with Bcl2 over-expression to promote lymphoma in mice',
			'authors' => 'Idoia García-Ramírez, Saber Tadros, Inés González-Herrero, Alberto Martín-Lorenzo, Guillermo Rodríguez-Hernández, Dalia Moore, Lucía Ruiz-Roca, Oscar Blanco, Diego Alonso-López, Javier De Las Rivas, Keenan Hartert, Romain Duval, David Klinkebiel, Martin B',
			'description' => '<p><span>CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits in B-cell development and can cooperate with Bcl2 over-expression to promote B-cell lymphoma. Through transcriptional and epigenetic profiling of these B-cells we found that Crebbp inactivation was associated with broad transcriptional alterations, but no changes in the patterns of histone acetylation at the proximal regulatory regions of these genes. However, B-cells with Crebbp inactivation showed high expression of Myc and patterns of altered histone acetylation that were localized to intragenic regions, enriched for Myc DNA binding motifs, and showed Myc binding. Through the analysis of CREBBP mutations from a large cohort of primary human FL and DLBCL, we show a significant difference in the spectrum of CREBBP mutations in these two diseases, with higher frequencies of nonsense/frameshift mutations in DLBCL compared to FL. Together our data therefore provide important links between Crebbp inactivation and Bcl2 dependence, and show a role for Crebbp inactivation in the induction of Myc expression. We suggest this may parallel the role of CREBBP frameshift/nonsense mutations in DLBCL that result in loss of the protein, but may contrast the role of missense mutations in the lysine acetyltransferase domain that are more frequently observed in FL and yield an inactive protein.</span></p>',
			'date' => '2017-03-05',
			'pmid' => 'http://www.bloodjournal.org/content/early/2017/03/13/blood-2016-08-733469?sso-checked=true',
			'doi' => 'https://doi.org/10.1182/blood-2016-08-733469',
			'modified' => '2017-05-11 11:17:42',
			'created' => '2017-04-10 07:56:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 135 => array(
			'id' => '3151',
			'name' => 'Aorta macrophage inflammatory and epigenetic changes in a murine model of obstructive sleep apnea: Potential role of CD36.',
			'authors' => 'Cortese R. et al.',
			'description' => '<p>Obstructive sleep apnea (OSA) affects 8-10% of the population, is characterized by chronic intermittent hypoxia (CIH), and causally associates with cardiovascular morbidities. In CIH-exposed mice, closely mimicking the chronicity of human OSA, increased accumulation and proliferation of pro-inflammatory metabolic M1-like macrophages highly expressing CD36, emerged in aorta. Transcriptomic and MeDIP-seq approaches identified activation of pro-atherogenic pathways involving a complex interplay of histone modifications in functionally-relevant biological pathways, such as inflammation and oxidative stress in aorta macrophages. Discontinuation of CIH did not elicit significant improvements in aorta wall macrophage phenotype. However, CIH-induced aorta changes were absent in CD36 knockout mice, Our results provide mechanistic insights showing that CIH exposures during sleep in absence of concurrent pro-atherogenic settings (i.e., genetic propensity or dietary manipulation) lead to the recruitment of CD36(+)<sup>high</sup> macrophages to the aortic wall and trigger atherogenesis. Furthermore, long-term CIH-induced changes may not be reversible with usual OSA treatment.</p>',
			'date' => '2017-02-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28240319',
			'doi' => '',
			'modified' => '2017-03-28 09:16:02',
			'created' => '2017-03-28 09:16:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 136 => array(
			'id' => '3138',
			'name' => 'Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia',
			'authors' => 'Chen S. et al.',
			'description' => '<p>Severe neonatal hyperbilirubinemia (SNH) and the onset of bilirubin encephalopathy and kernicterus result in part from delayed expression of UDP-glucuronosyltransferase 1A1 (UGT1A1) and the inability to metabolize bilirubin. Although there is a good understanding of the early events after birth that lead to the rapid increase in serum bilirubin, the events that control delayed expression of UGT1A1 during development remain a mystery. Humanized <em>UGT1</em> (<em>hUGT1</em>) mice develop SNH spontaneously, which is linked to repression of both liver and intestinal UGT1A1. In this study, we report that deletion of intestinal nuclear receptor corepressor 1 (NCoR1) completely diminishes hyperbilirubinemia in <em>hUGT1</em> neonates because of intestinal <em>UGT1A1</em> gene derepression. Transcriptomic studies and immunohistochemistry analysis demonstrate that NCoR1 plays a major role in repressing developmental maturation of the intestines. Derepression is marked by accelerated metabolic and oxidative phosphorylation, drug metabolism, fatty acid metabolism, and intestinal maturation, events that are controlled predominantly by H3K27 acetylation. The control of NCoR1 function and derepression is linked to IKK&beta; function, as validated in <em>hUGT1</em> mice with targeted deletion of intestinal IKK&beta;. Physiological events during neonatal development that target activation of an IKK&beta;/NCoR1 loop in intestinal epithelial cells lead to derepression of genes involved in intestinal maturation and bilirubin detoxification. These findings provide a mechanism of NCoR1 in intestinal homeostasis during development and provide a key link to those events that control developmental repression of UGT1A1 and hyperbilirubinemia.</p>',
			'date' => '2017-02-21',
			'pmid' => 'http://www.pnas.org/content/114/8/E1432.abstract',
			'doi' => '',
			'modified' => '2017-03-21 17:48:23',
			'created' => '2017-03-21 17:48:23',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 137 => array(
			'id' => '3166',
			'name' => 'The Drosophila speciation factor HMR localizes to genomic insulator sites',
			'authors' => 'Gerland T.A. et al.',
			'description' => '<p>Hybrid incompatibility between Drosophila melanogaster and D. simulans is caused by a lethal interaction of the proteins encoded by the Hmr and Lhr genes. In D. melanogaster the loss of HMR results in mitotic defects, an increase in transcription of transposable elements and a deregulation of heterochromatic genes. To better understand the molecular mechanisms that mediate HMR's function, we measured genome-wide localization of HMR in D. melanogaster tissue culture cells by chromatin immunoprecipitation. Interestingly, we find HMR localizing to genomic insulator sites that can be classified into two groups. One group belongs to gypsy insulators and another one borders HP1a bound regions at active genes. The transcription of the latter group genes is strongly affected in larvae and ovaries of Hmr mutant flies. Our data suggest a novel link between HMR and insulator proteins, a finding that implicates a potential role for genome organization in the formation of species.</p>',
			'date' => '2017-02-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28207793',
			'doi' => '',
			'modified' => '2017-05-09 10:05:49',
			'created' => '2017-05-09 10:05:49',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 138 => array(
			'id' => '3357',
			'name' => 'Applying the INTACT method to purify endosperm nuclei and to generate parental-specific epigenome profiles.',
			'authors' => 'Moreno-Romero J. et al.',
			'description' => '<p>The early endosperm tissue of dicot species is very difficult to isolate by manual dissection. This protocol details how to apply the INTACT (isolation of nuclei tagged in specific cell types) system for isolating early endosperm nuclei of Arabidopsis at high purity and how to generate parental-specific epigenome profiles. As a Protocol Extension, this article describes an adaptation of an existing Nature Protocol that details the use of the INTACT method for purification of root nuclei. We address how to obtain the INTACT lines, generate the starting material and purify the nuclei. We describe a method that allows purity assessment, which has not been previously addressed. The purified nuclei can be used for ChIP and DNA bisulfite treatment followed by next-generation sequencing (seq) to study histone modifications and DNA methylation profiles, respectively. By using two different Arabidopsis accessions as parents that differ by a large number of single-nucleotide polymorphisms (SNPs), we were able to distinguish the parental origin of epigenetic modifications. Our protocol describes the only working method to our knowledge for generating parental-specific epigenome profiles of the early Arabidopsis endosperm. The complete protocol, from silique collection to finished libraries, can be completed in 2 d for bisulfite-seq (BS-seq) and 3 to 4 d for ChIP-seq experiments.This protocol is an extension to: Nat. Protoc. 6, 56-68 (2011); doi:10.1038/nprot.2010.175; published online 16 December 2010.</p>',
			'date' => '2017-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28055034',
			'doi' => '',
			'modified' => '2018-04-05 12:52:20',
			'created' => '2018-04-05 12:52:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 139 => array(
			'id' => '3042',
			'name' => 'BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire',
			'authors' => 'Najafova Z. et al.',
			'description' => '<p>Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4.</p>',
			'date' => '2016-09-19',
			'pmid' => 'http://nar.oxfordjournals.org/content/early/2016/09/19/nar.gkw826.abstract',
			'doi' => '',
			'modified' => '2016-10-10 09:58:41',
			'created' => '2016-10-10 09:49:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 140 => array(
			'id' => '3043',
			'name' => 'CTCF modulates Estrogen Receptor function through specific chromatin and nuclear matrix interactions',
			'authors' => 'Fiorito E. et al.',
			'description' => '<p>Enhancer regions and transcription start sites of estrogen-target regulated genes are connected by means of Estrogen Receptor long-range chromatin interactions. Yet, the complete molecular mechanisms controlling the transcriptional output of engaged enhancers and subsequent activation of coding genes remain elusive. Here, we report that CTCF binding to enhancer RNAs is enriched when breast cancer cells are stimulated with estrogen. CTCF binding to enhancer regions results in modulation of estrogen-induced gene transcription by preventing Estrogen Receptor chromatin binding and by hindering the formation of additional enhancer-promoter ER looping. Furthermore, the depletion of CTCF facilitates the expression of target genes associated with cell division and increases the rate of breast cancer cell proliferation. We have also uncovered a genomic network connecting loci enriched in cell cycle regulator genes to nuclear lamina that mediates the CTCF function. The nuclear lamina and chromatin interactions are regulated by estrogen-ER. We have observed that the chromatin loops formed when cells are treated with estrogen establish contacts with the nuclear lamina. Once there, the portion of CTCF associated with the nuclear lamina interacts with enhancer regions, limiting the formation of ER loops and the induction of genes present in the loop. Collectively, our results reveal an important, unanticipated interplay between CTCF and nuclear lamina to control the transcription of ER target genes, which has great implications in the rate of growth of breast cancer cells.</p>',
			'date' => '2016-09-15',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27638884',
			'doi' => '',
			'modified' => '2016-10-10 10:12:33',
			'created' => '2016-10-10 10:12:33',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 141 => array(
			'id' => '3052',
			'name' => 'PionX sites mark the X chromosome for dosage compensation',
			'authors' => 'Villa R et al.',
			'description' => '<p>The rules defining which small fraction of related DNA sequences can be selectively bound by a transcription factor are poorly understood. One of the most challenging tasks in DNA recognition is posed by dosage compensation systems that require the distinction between sex chromosomes and autosomes. In <i>Drosophila melanogaster</i>, the male-specific lethal dosage compensation complex (MSL-DCC) doubles the level of transcription from the single male X chromosome, but the nature of this selectivity is not known<sup><a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref1" title="Lucchesi, J. C. &amp; Kuroda, M. I. Dosage compensation in Drosophila. Cold Spring Harb. Perspect. Biol. 7, a019398 (2015)" id="ref-link-7">1</a></sup>. Previous efforts to identify X-chromosome-specific target sequences were unsuccessful as the identified MSL recognition elements lacked discriminative power<sup><a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref2" title="Alekseyenko, A. A. et al. A sequence motif within chromatin entry sites directs MSL establishment on the Drosophila X chromosome. Cell. 134, 599&ndash;609 (2008)" id="ref-link-8">2</a>, <a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref3" title="Straub, T., Grimaud, C., Gilfillan, G. D., Mitterweger, A. &amp; Becker, P. B. The chromosomal high-affinity binding sites for the Drosophila dosage compensation complex. PLoS Genet. 4, e1000302 (2008)" id="ref-link-9">3</a></sup>. Therefore, additional determinants such as co-factors, chromatin features, RNA and chromosome conformation have been proposed to refine targeting further<sup><a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref4" title="McElroy, K. A., Kang, H. &amp; Kuroda, M. I. Are we there yet? Initial targeting of the Male-Specific Lethal and Polycomb group chromatin complexes in Drosophila. Open Biol. 4, 140006 (2014)" id="ref-link-10">4</a></sup>. Here, using an <i>in vitro</i> genome-wide DNA binding assay, we show that recognition of the X chromosome is an intrinsic feature of the MSL-DCC. MSL2, the male-specific organizer of the complex, uses two distinct DNA interaction surfaces&mdash;the CXC and proline/basic-residue-rich domains&mdash;to identify complex DNA elements on the X chromosome. Specificity is provided by the CXC domain, which binds a novel motif defined by DNA sequence and shape. This motif characterizes a subclass of MSL2-binding sites, which we name PionX (pioneering sites on the X) as they appeared early during the recent evolution of an X chromosome in <i>D. miranda</i> and are the first chromosomal sites to be bound during <i>de novo</i> MSL-DCC assembly. Our data provide the first, to our knowledge, documented molecular mechanism through which the dosage compensation machinery distinguishes the X chromosome from an autosome. They highlight fundamental principles in the recognition of complex DNA elements by protein that will have a strong impact on many aspects of chromosome biology.</p>',
			'date' => '2016-08-31',
			'pmid' => 'http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html',
			'doi' => '',
			'modified' => '2016-10-24 14:23:31',
			'created' => '2016-10-24 14:23:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 142 => 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',
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			'id' => '2976',
			'name' => 'Deletion of Polycomb Repressive Complex 2 From Mouse Intestine Causes Loss of Stem Cells',
			'authors' => 'Koppens MA et al.',
			'description' => '<h4>BACKGROUND &amp; AIMS:</h4>
<p><abstracttext label="BACKGROUND &amp; AIMS" nlmcategory="OBJECTIVE">The polycomb repressive complex 2 (PRC2) regulates differentiation by contributing to repression of gene expression and thereby stabilizing the fate of stem cells and their progeny. PRC2 helps to maintain adult stem cell populations, but little is known about its functions in intestinal stem cells. We studied phenotypes of mice with intestine-specific deletion of the PRC2 proteins EED (a subunit required for PRC2 function) and EZH2 (a histone methyltransferase).</abstracttext></p>
<h4>METHODS:</h4>
<p><abstracttext label="METHODS" nlmcategory="METHODS">We performed studies of AhCre;EedLoxP/LoxP (EED knockout) mice and AhCre;Ezh2LoxP/LoxP (EZH2 knockout) mice, which have intestine-specific disruption in EED and EZH2, respectively. Small intestinal crypts were isolated and subsequently cultured to grow organoids. Intestines and organoids were analyzed by immunohistochemical, in situ hybridization, RNA sequence, and chromatin immunoprecipitation methods.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Intestines of EED knockout mice had massive crypt degeneration and lower numbers of proliferating cells, compared with wildtype control mice; Cdkn2a became derepressed and we detected increased levels of P21. We did not observe any differences between EZH2 knockout and control mice. Intestinal crypts from EED knockout mice had signs of aberrant differentiation of uncommitted crypt cells-these differentiated toward the secretory cell lineage. Furthermore, crypts from EED-knockout mice had impaired Wnt signaling and concomitant loss of intestinal stem cells; this phenotype was not reversed upon ectopic stimulation of Wnt and Notch signaling in organoids. Analysis of gene expression patterns from intestinal tissues of EED knockout mice revealed dysregulation of several genes involved in Wnt signaling. Wnt signaling was directly regulated by PRC2.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">In intestinal tissues of mice, PRC2 maintains small intestinal stem cells by promoting proliferation and preventing differentiation in the intestinal stem cell compartment. PRC2 controls expression of genes in multiple signaling pathways that regulate intestinal homeostasis.</abstracttext></p>',
			'date' => '2016-06-21',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27342214',
			'doi' => ' 10.1053/j.gastro.2016.06.020',
			'modified' => '2016-07-07 10:04:31',
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			'name' => 'Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells',
			'authors' => 'von Meyenn F et al.',
			'description' => '<p>Global demethylation is part of a conserved program of epigenetic reprogramming to naive pluripotency. The transition from primed hypermethylated embryonic stem cells (ESCs) to naive hypomethylated ones (serum-to-2i) is a valuable model system for epigenetic reprogramming. We present a mathematical model, which accurately predicts global DNA demethylation kinetics. Experimentally, we show that the main drivers of global demethylation are neither active mechanisms (Aicda, Tdg, and Tet1-3) nor the&nbsp;reduction of de novo methylation. UHRF1 protein, the essential targeting factor for DNMT1, is reduced upon transition to 2i, and so is recruitment of the maintenance methylation machinery to replication foci. Concurrently, there is global loss of H3K9me2, which is needed for chromatin binding of UHRF1. These mechanisms synergistically enforce global DNA hypomethylation in a replication-coupled fashion. Our observations establish the molecular mechanism for global demethylation in naive ESCs, which has key parallels with those operating in primordial germ cells and early embryos.</p>',
			'date' => '2016-05-25',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27237052',
			'doi' => '10.1016/j.molcel.2016.04.025',
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			'authors' => 'Moreno-Romero J et al.',
			'description' => '<p>Parental genomes in the endosperm are marked by differential DNA methylation and are therefore epigenetically distinct. This epigenetic asymmetry is established in the gametes and maintained after fertilization by unknown mechanisms. In this manuscript, we have addressed the key question whether parentally inherited differential DNA methylation affects <em>de novo</em> targeting of chromatin modifiers in the early endosperm. Our data reveal that polycomb-mediated H3 lysine 27 trimethylation (H3K27me3) is preferentially localized to regions that are targeted by the DNA glycosylase DEMETER (DME), mechanistically linking DNA hypomethylation to imprinted gene expression. Our data furthermore suggest an absence of <em>de novo </em>DNA methylation in the early endosperm, providing an explanation how DME-mediated hypomethylation of the maternal genome is maintained after fertilization. Lastly, we show that paternal-specific H3K27me3-marked regions are located at pericentromeric regions, suggesting that H3K27me3 and DNA methylation are not necessarily exclusive marks at pericentromeric regions in the endosperm.</p>',
			'date' => '2016-04-25',
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			'description' => '<p>We sheared the DNA on the Diagenode One and used the MicroPlex Library Preparation v2 Kit to create DNA libraries for whole genome sequencing of four plant species for which there is no reference genome available. Previous attempts with a commercial Tn5-transposase based method gave unsatisfactory results. However, the Diagenode MicroPlex kit was quicker, easier, and gave the expected profile of fragment sizes. In just 30 seconds of sonication, we obtained a fragment distribution centered at 270 bp. The library construction took only 2 hours with this kit. The library was sequenced in a NexSeq 550 in High-Output mode, giving 85% based with&gt;Q30.</p>',
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<p>Thanks Diagenode for saving my PhD!</p>',
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			'description' => '<p>There are so many ChIP-related products on the market, but I feel so lucky that I have been using the ones from Diagenode since I started my CHIP-seq project. I have used their <a href="../p/ideal-chip-seq-kit-for-transcription-factors-x100-100-rxns">iDeal CHIP-seq Kit for Transcription Factors</a> and <a href="../p/microplex-library-preparation-kit-v2-x48-12-indices-48-rxns">MicroPlex Library Prep Kit v2</a>. Both of them are fantastic and very reproducible. With the very-well written protocols, you will just be home and dry. Particularly, I want to thank the technical support, who is very patient, knowledgeable and extremely helpful. I would definitely recommend my colleagues to use the CHIP products from Diagenode.</p>',
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<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>
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<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>There are so many ChIP-related products on the market, but I feel so lucky that I have been using the ones from Diagenode since I started my CHIP-seq project. I have used their <a href="../p/ideal-chip-seq-kit-for-transcription-factors-x100-100-rxns">iDeal CHIP-seq Kit for Transcription Factors</a> and <a href="../p/microplex-library-preparation-kit-v2-x48-12-indices-48-rxns">MicroPlex Library Prep Kit v2</a>. Both of them are fantastic and very reproducible. With the very-well written protocols, you will just be home and dry. Particularly, I want to thank the technical support, who is very patient, knowledgeable and extremely helpful. I would definitely recommend my colleagues to use the CHIP products from Diagenode.</p><cite>Dr Kaiyu Lei, Faculty of Medicine, Department of Surgery & Cancer, Imperial College London</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>
<blockquote><p>The Diagenode MicroPlex kit is the quickest and most efficient way to make sequencing libraries, especially from samples with very low inputs. We regularly start with picogram amounts of ChIP material and produce excellent quality libraries that would be impossible to make using normal methods. Sequencing libraries made from the MicroPlex kit give us excellent results even in large genomes. The kit performs very well, and we will use the kit in the future for studies with low cell numbers or starting material.</p><cite>Dr. Morgan Sammons, Lab of Dr. Shelley Berger, University of Pennsylvania</cite></blockquote>
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$featured_testimonials = '<blockquote><span class="label-green" style="margin-bottom:16px;margin-left:-22px">TESTIMONIAL</span><p>We used the MicroPlex version 2 kit to generate libraries using ChIP DNA for several transcription factors and compared the results to a standard library generation protocol starting from 5ng of ChIP DNA. Even when we reduced the starting amount of DNA by 10-fold, the MicroPlex Kit produced the same high yields and quality of the libraries. As expected, the number of duplicate reads increased but 15 to 20 million unique reads were sufficient to achieve excellent enrichment data. We found that no information was lost, and the MicroPlex Kit helped produce data that was consistent with the standard protocol despite the lower input. On top of this, the MicroPlex Kit was extremely user-friendly and saved us time. The MicroPlex version 2 kit will make challenging ChIP-seq experiments that rely on very limited amount of starting material much easier with robust results.</p><cite>Katia Basso, PhD, Assistant Professor, Columbia University, New York</cite></blockquote>
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        <p><strong><input name="data[Cart][quantity]" placeholder="1" value="1" min="1" style="width:60px;display:inline" type="number" id="CartQuantity" required="required"/></strong>iDeal ChIP-seq kit for Transcription Factors個カートに追加。</p>

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<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;">
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<td style="width: 144px;"></td>
<td style="width: 267px; text-align: center;"><span style="font-weight: 400;">Amount per IP</span></td>
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<td style="width: 144px;">Cells</td>
<td style="width: 267px; text-align: center;"><strong>4,000,000</strong></td>
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<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>',
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<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>
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<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>',
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	'description' => '<p>Parental genomes in the endosperm are marked by differential DNA methylation and are therefore epigenetically distinct. This epigenetic asymmetry is established in the gametes and maintained after fertilization by unknown mechanisms. In this manuscript, we have addressed the key question whether parentally inherited differential DNA methylation affects <em>de novo</em> targeting of chromatin modifiers in the early endosperm. Our data reveal that polycomb-mediated H3 lysine 27 trimethylation (H3K27me3) is preferentially localized to regions that are targeted by the DNA glycosylase DEMETER (DME), mechanistically linking DNA hypomethylation to imprinted gene expression. Our data furthermore suggest an absence of <em>de novo </em>DNA methylation in the early endosperm, providing an explanation how DME-mediated hypomethylation of the maternal genome is maintained after fertilization. Lastly, we show that paternal-specific H3K27me3-marked regions are located at pericentromeric regions, suggesting that H3K27me3 and DNA methylation are not necessarily exclusive marks at pericentromeric regions in the endosperm.</p>',
	'date' => '2016-04-25',
	'pmid' => 'http://onlinelibrary.wiley.com/doi/10.15252/embj.201593534/abstract',
	'doi' => '10.15252/embj.201593534',
	'modified' => '2016-05-14 00:49:53',
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$externalLink = ' <a href="http://onlinelibrary.wiley.com/doi/10.15252/embj.201593534/abstract" target="_blank"><i class="fa fa-external-link"></i></a>'
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			'name' => 'MicroPlex Library Preparation Kit v2 (12 indices)',
			'description' => '<p><strong>ChIP-seq</strong><strong>専用に最適化</strong></p>
<p>MicroPlex Library Preparation&trade;kit は、ChIP-seq専用に検証されていて、ピコグラム単位の入力だけで索引付きライブラリー調製できる唯一のキットです。 <span><a href="http://www.diagenode.com/en/catalog/chromatin-function-74/chromatin-immunoprecipitation-75/manual-chip-kits-77/product/true-microchip-kit-x16-2532">True MicroChIP kit</a></span>と組み合わせることで、わずか10,000細胞でChIP-seqを行えます。細胞入力数、手順数、用品数が減少するだけでなく、結果までの時間も短縮できます！</p>',
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<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>
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<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>
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<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>',
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		'name' => 'MicroPlex Library Preparation Kit v2 (12 indices)',
		'description' => '<p><strong>ChIP-seq</strong><strong>専用に最適化</strong></p>
<p>MicroPlex Library Preparation&trade;kit は、ChIP-seq専用に検証されていて、ピコグラム単位の入力だけで索引付きライブラリー調製できる唯一のキットです。 <span><a href="http://www.diagenode.com/en/catalog/chromatin-function-74/chromatin-immunoprecipitation-75/manual-chip-kits-77/product/true-microchip-kit-x16-2532">True MicroChIP kit</a></span>と組み合わせることで、わずか10,000細胞でChIP-seqを行えます。細胞入力数、手順数、用品数が減少するだけでなく、結果までの時間も短縮できます！</p>',
		'label1' => '特徴',
		'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>',
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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)',
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			'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>',
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			'format' => '12 rxns',
			'catalog_number' => 'C05010012',
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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)',
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		'Product' => array(
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	'Related' => array(
		(int) 0 => 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>
<p>
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<div class="extra-spaced" align="center"></div>
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<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>
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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>',
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			'meta_title' => 'True MicroChIP-seq Kit | Diagenode C01010132',
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			'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.',
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			'name' => 'iDeal ChIP-seq kit for Transcription Factors',
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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>',
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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',
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			'meta_description' => 'iDeal ChIP-seq kit for Transcription Factors x24',
			'modified' => '2023-06-20 18:27:37',
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			'name' => 'DNA/RNA library preparation',
			'description' => '<div class="row">
<div class="small-12 medium-12 large-12 columns">
<p><span style="font-weight: 400;">Most of the major next-generation sequencing platforms require ligation of specific adaptor oligos to </span><a href="../applications/dna-rna-shearing"><span style="font-weight: 400;">fragmented DNA or RNA</span></a><span style="font-weight: 400;"> prior to sequencing</span></p>
<p><span style="font-weight: 400;">After input DNA has been fragmented, it is end-repaired and blunt-ended</span><span style="font-weight: 400;">. The next step is a A-tailing in which dAMP is added to the 3&acute; end of the blunt phosphorylated DNA fragments to prevent concatemerization and to allow the ligation of adaptors with complementary dT overhangs. In addition, barcoded adapters can be incorporated to facilitate multiplexing prior to or during amplification.</span></p>
<center><img src="https://www.diagenode.com/img/categories/library-prep/flux.png" /></center>
<p><span style="font-weight: 400;">Diagenode offers a comprehensive product portfolio for library preparation:<br /></span></p>
<strong><a href="https://www.diagenode.com/en/categories/Library-preparation-for-RNA-seq">D-Plex&nbsp;RNA-seq Library Preparation Kits</a></strong><br />
<p><span style="font-weight: 400;">Diagenode&rsquo;s new RNA-sequencing solutions utilize the innovative c</span><span style="font-weight: 400;">apture and a</span><span style="font-weight: 400;">mplification by t</span><span style="font-weight: 400;">ailing and s</span><span style="font-weight: 400;">witching&rdquo;</span><span style="font-weight: 400;">, a ligation-free method to produce DNA libraries for next generation sequencing from low input amounts of RNA. </span><span style="font-weight: 400;"></span><a href="../categories/Library-preparation-for-RNA-seq">Learn more</a></p>
<strong><a href="../categories/library-preparation-for-ChIP-seq">ChIP-seq and DNA sequencing library preparation solutions</a></strong><br />
<p><span style="font-weight: 400;">Our kits have been optimized for DNA library preparation used for next generation sequencing for a wide range of inputs. Using a simple three-step protocols, our</span><a href="http://www.diagenode.com/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns"><span style="font-weight: 400;"> </span></a><span style="font-weight: 400;">kits are an optimal choice for library preparation from DNA inputs down to 50 pg.&nbsp;</span><a href="../categories/library-preparation-for-ChIP-seq">Learn more</a></p>
<a href="../p/bioruptor-pico-sonication-device"><span style="font-weight: 400;"></span><strong>Bioruptor Pico - short fragments</strong></a><a href="../categories/library-preparation-for-ChIP-seq-and-DNA-sequencing"><span style="font-weight: 400;"></span></a><br />
<p><span style="font-weight: 400;"></span><span style="font-weight: 400;">Our well-cited Bioruptor Pico is the shearing device of choice for chromatin and DNA fragmentation. Obtain uniform and tight fragment distributions &nbsp;between 150bp -2kb. </span><a href="../p/bioruptor-pico-sonication-device">Learn more</a></p>
<strong><a href="../p/megaruptor2-1-unit"><span href="../p/bioruptor-pico-sonication-device">Megaruptor</span>&reg; - long fragments</a></strong><a href="../p/bioruptor-pico-sonication-device"><span style="font-weight: 400;"></span></a><a href="../categories/library-preparation-for-ChIP-seq-and-DNA-sequencing"><span style="font-weight: 400;"></span></a><br />
<p><span style="font-weight: 400;"></span><span style="font-weight: 400;">The Megaruptor is designed to shear DNA from 3kb-75kb for long-read sequencing.&nbsp; <a href="../p/megaruptor2-1-unit">Learn more</a></span></p>
<span href="../p/bioruptor-pico-sonication-device"></span><span style="font-weight: 400;"></span></div>
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			'meta_description' => 'Diagenode offers a comprehensive product portfolio for library preparation such as CATS RNA-seq Library Preparation Kits,ChIP-seq and DNA sequencing library preparation solutions',
			'meta_title' => 'Library preparation for Next Generation Sequencing (NGS) | Diagenode',
			'modified' => '2021-03-10 03:27:16',
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			'name' => '次世代シーケンシング',
			'description' => '<div class="row">
<div class="small-12 medium-12 large-12 columns">
<h2 style="font-size: 22px;">DNA断片化、ライブラリー調製、自動化：NGSのワンストップショップ</h2>
<table class="small-12 medium-12 large-12 columns">
<tbody>
<tr>
<th class="small-12 medium-12 large-12 columns">
<h4>1. 断片化装置を選択してください：150 bp〜75 kbの範囲でDNAを断片化します。</h4>
</th>
</tr>
<tr style="background-color: #ffffff;">
<td class="small-12 medium-12 large-12 columns"></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns"><a href="../p/bioruptor-pico-sonication-device"><img src="https://www.diagenode.com/img/product/shearing_technologies/bioruptor_pico.jpg" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/megaruptor2-1-unit"><img src="https://www.diagenode.com/img/product/shearing_technologies/B06010001_megaruptor2.jpg" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/bioruptor-one-sonication-device"><img src="https://www.diagenode.com/img/product/shearing_technologies/br-one-profil.png" /></a></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns">5&mu;lまで断片化：150 bp〜2 kb<br />NGS DNAライブラリー調製およびFFPE核酸抽出に最適で、</td>
<td class="small-4 medium-4 large-4 columns">2 kb〜75 kbの範囲をできます。<br />メイトペアライブラリー調製および長いフラグメントDNAシーケンシングに最適で、この軽量デスクトップデバイスで</td>
<td class="small-4 medium-4 large-4 columns">20または50&mu;lの断片化が可能です。</td>
</tr>
</tbody>
</table>
<table class="small-12 medium-12 large-12 columns">
<tbody>
<tr>
<th class="small-8 medium-8 large-8 columns">
<h4>2. 最適化されたライブラリー調整キットを選択してください。</h4>
</th>
<th class="small-4 medium-4 large-4 columns">
<h4>3. ライブラリー前処理自動化を選択して、比類のないデータ再現性を実感</h4>
</th>
</tr>
<tr style="background-color: #ffffff;">
<td class="small-12 medium-12 large-12 columns"></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns"><a href="../p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns"><img src="https://www.diagenode.com/img/product/kits/microPlex_library_preparation.png" style="display: block; margin-left: auto; margin-right: auto;" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns"><img src="https://www.diagenode.com/img/product/kits/box_kit.jpg" style="display: block; margin-left: auto; margin-right: auto;" height="173" width="250" /></a></td>
<td class="small-4 medium-4 large-4 columns"><a href="../p/sx-8g-ip-star-compact-automated-system-1-unit"><img src="https://www.diagenode.com/img/product/automation/B03000002%20_ipstar_compact.png" style="display: block; margin-left: auto; margin-right: auto;" /></a></td>
</tr>
<tr>
<td class="small-4 medium-4 large-4 columns" style="text-align: center;">50pgの低入力：MicroPlex Library Preparation Kit</td>
<td class="small-4 medium-4 large-4 columns" style="text-align: center;">5ng以上：iDeal&nbsp;Library Preparation Kit</td>
<td class="small-4 medium-4 large-4 columns" style="text-align: center;">Achieve great NGS data easily</td>
</tr>
</tbody>
</table>
</div>
</div>
<blockquote>
<div class="row">
<div class="small-12 medium-12 large-12 columns"><span class="label" style="margin-bottom: 16px; margin-left: -22px; font-size: 15px;">DiagenodeがNGS研究にぴったりなプロバイダーである理由</span>
<p>Diagenodeは15年以上もエピジェネティクス研究に専念、専門としています。 ChIP研究クロマチン用のユニークな断片化システムの開発から始まり、 専門知識を活かし、5&mu;lのせん断体積まで可能で、NGS DNAライブラリーの調製に最適な最先端DNA断片化装置の開発にたどり着きました。 我々は以来、ChIP-seq、Methyl-seq、NGSライブラリー調製用キットを研究開発し、業界をリードする免疫沈降研究と同様に、ライブラリー調製を自動化および完結させる独自の自動化システムを開発にも成功しました。</p>
<ul>
<li>信頼されるせん断装置</li>
<li>様々なインプットからのライブラリ作成キット</li>
<li>独自の自動化デバイス</li>
</ul>
</div>
</div>
</blockquote>
<div class="row">
<div class="small-12 columns">
<ul class="accordion" data-accordion="">
<li class="accordion-navigation"><a href="#panel1a">次世代シーケンシングへの理解とその専門知識</a>
<div id="panel1a" class="content">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<p><strong>次世代シーケンシング (NGS)</strong> ）は、著しいスケールとハイスループットでシーケンシングを行い、1日に数十億もの塩基生成を可能にします。 NGSのハイスループットは迅速でありながら正確で、再現性のあるデータセットを実現し、さらにシーケンシング費用を削減します。 NGSは、ゲノムシーケンシング、ゲノム再シーケンシング、デノボシーケンシング、トランスクリプトームシーケンシング、その他にDNA-タンパク質相互作用の検出やエピゲノムなどを示します。 指数関数的に増加するシーケンシングデータの需要は、計算分析の障害や解釈、データストレージなどの課題を解決します。</p>
<p>アプリケーションおよび出発物質に応じて、数百万から数十億の鋳型DNA分子を大規模に並行してシーケンシングすることが可能です。その為に、異なる化学物質を使用するいくつかの市販のNGSプラットフォームを利用することができます。 NGSプラットフォームの種類によっては、事前準備とライブラリー作成が必要です。</p>
<p>NGSにとっても、特にデータ処理と分析に関した大きな課題はあります。第3世代技術はゲノミクス研究にさらに革命を起こすであろうと大きく期待されています。</p>
</div>
</div>
<div class="row">
<div class="small-6 medium-6 large-6 columns">
<p><strong>NGS アプリケーション</strong></p>
<ul>
<li>全ゲノム配列決定</li>
<li>デノボシーケンシング</li>
<li>標的配列</li>
<li>Exomeシーケンシング</li>
<li>トランスクリプトーム配列決定</li>
<li>ゲノム配列決定</li>
<li>ミトコンドリア配列決定</li>
<li>DNA-タンパク質相互作用（ChIP-seq</li>
<li>バリアント検出</li>
<li>ゲノム仕上げ</li>
</ul>
</div>
<div class="small-6 medium-6 large-6 columns">
<p><strong>研究分野におけるNGS:</strong></p>
<ul>
<li>腫瘍学</li>
<li>リプロダクティブ・ヘルス</li>
<li>法医学ゲノミクス</li>
<li>アグリゲノミックス</li>
<li>複雑な病気</li>
<li>微生物ゲノミクス</li>
<li>食品・環境ゲノミクス</li>
<li>創薬ゲノミクス - パーソナライズド・メディカル</li>
</ul>
</div>
<div class="small-12 medium-12 large-12 columns">
<p><strong>NGSの用語</strong></p>
<dl>
<dt>リード（読み取り）</dt>
<dd>この装置から得られた連続した単一のストレッチ</dd>
<dt>断片リード</dt>
<dd>フラグメントライブラリからの読み込み。 シーケンシングプラットフォームに応じて、読み取りは通常約100〜300bp。</dd>
<dt>断片ペアエンドリード</dt>
<dd>断片ライブラリーからDNA断片の各末端2つの読み取り。</dd>
<dt>メイトペアリード</dt>
<dd>大きなDNA断片（通常は予め定義されたサイズ範囲）の各末端から2つの読み取り。</dd>
<dt>カバレッジ（例）</dt>
<dd>30&times;適用範囲とは、参照ゲノム中の各塩基対が平均30回の読み取りを示す。</dd>
</dl>
</div>
</div>
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<h2>NGSプラットフォーム</h2>
<h3><a href="http://www.illumina.com" target="_blank">イルミナ</a></h3>
<p>イルミナは、クローン的に増幅された鋳型DNA（クラスター）上に位置する、蛍光標識された可逆的鎖ターミネーターヌクレオチドを用いた配列別合成技術を使用。 DNAクラスターは、ガラスフローセルの表面上に固定化され、 ワークフローは、4つのヌクレオチド（それぞれ異なる蛍光色素で標識された）の組み込み、4色イメージング、色素や末端基の切断、取り込み、イメージングなどを繰り返します。フローセルは大規模な並列配列決定を受ける。 この方法により、単一蛍光標識されたヌクレオチドの制御添加によるモノヌクレオチドのエラーを回避する可能性があります。 読み取りの長さは、通常約100〜150 bpです。</p>
<h3><a href="http://www.lifetechnologies.com" target="_blank">イオン トレント</a></h3>
<p>イオントレントは、半導体技術チップを用いて、合成中にヌクレオチドを取り込む際に放出されたプロトンを検出します。 これは、イオン球粒子と呼ばれるビーズの表面にエマルションPCR（emPCR）を使用し、リンクされた特定のアダプターを用いてDNA断片を増幅します。 各ビーズは1種類のDNA断片で覆われていて、異なるDNA断片を有するビーズは次いで、チップの陽子感知ウェル内に配置されます。 チップには一度に4つのヌクレオチドのうちの1つが浸水し、このプロセスは異なるヌクレオチドで15秒ごとに繰り返されます。 配列決定の間に4つの塩基の各々が1つずつ導入されます、組み込みの場合はプロトンが放出され、電圧信号が取り込みに比例して検出されます。.</p>
<h3><a href="http://www.pacificbiosciences.com" target="_blank">パシフィック バイオサイエンス</a></h3>
<p>パシフィックバイオサイエンスでは、20kbを超える塩基対の読み取りも、単一分子リアルタイム（SMRT）シーケンシングによる構造および細胞タイプの変化を観察することができます。 このプラットフォームでは、超長鎖二本鎖DNA（dsDNA）断片が、Megaruptor（登録商標）のようなDiagenode装置を用いたランダムシアリングまたは目的の標的領域の増幅によって生成されます。 SMRTbellライブラリーは、ユニバーサルヘアピンアダプターをDNA断片の各末端に連結することによって生成します。 サイズ選択条件による洗浄ステップの後、配列決定プライマーをSMRTbellテンプレートにアニーリングし、鋳型DNAに結合したDNAポリメラーゼを含む配列決定を、蛍光標識ヌクレオチドの存在下で開始。 各塩基が取り込まれると、異なる蛍光のパルスをリアルタイムで検出します。</p>
<h3><a href="https://nanoporetech.com" target="_blank">オックスフォード ナノポア</a></h3>
<p>Oxford Nanoporeは、単一のDNA分子配列決定に基づく技術を開発します。その技術により生物学的分子、すなわちDNAが一群の電気抵抗性高分子膜として位置するナノスケールの孔（ナノ細孔）またはその近くを通過し、イオン電流が変化します。 この変化に関する情報は、例えば4つのヌクレオチド（AまたはG r CまたはT）ならびに修飾されたヌクレオチドすべてを区別することによって分子情報に訳されます。 シーケンシングミニオンデバイスのフローセルは、数百個のナノポアチャネルのセンサアレイを含みます。 DNAサンプルは、Diagenode社のMegaruptor（登録商標）を用いてランダムシアリングによって生成され得る超長鎖DNAフラグメントが必要です。</p>
<h3><a href="http://www.lifetechnologies.com/be/en/home/life-science/sequencing/next-generation-sequencing/solid-next-generation-sequencing.html" target="_blank">SOLiD</a></h3>
<p>SOLiDは、ユニークな化学作用により、何千という個々のDNA分子の同時配列決定を可能にします。 それは、アダプター対ライブラリーのフラグメントが適切で、せん断されたゲノムDNAへのアダプターのライゲーションによるライブラリー作製から始まります。 次のステップでは、エマルジョンPCR（emPCR）を実施して、ビーズの表面上の個々の鋳型DNA分子をクローン的に増幅。 emPCRでは、個々の鋳型DNAをPCR試薬と混合し、水中油型エマルジョン内の疎水性シェルで囲まれた水性液滴内のプライマーコートビーズを、配列決定のためにロードするスライドガラスの表面にランダムに付着。 この技術は、シークエンシングプライマーへのライゲーションで競合する4つの蛍光標識されたジ塩基プローブのセットを使用します。</p>
<h3><a href="http://454.com/products/technology.asp" target="_blank">454</a></h3>
<p>454は、大規模並列パイロシーケンシングを利用しています。 始めに全ゲノムDNAまたは標的遺伝子断片の300〜800bp断片のライブラリー調製します。 次に、DNAフラグメントへのアダプターの付着および単一のDNA鎖の分離。 その後アダプターに連結されたDNAフラグメントをエマルジョンベースのクローン増幅（emPCR）で処理し、DNAライブラリーフラグメントをミクロンサイズのビーズ上に配置します。 各DNA結合ビーズを光ファイバーチップ上のウェルに入れ、器具に挿入します。 4つのDNAヌクレオチドは、配列決定操作中に固定された順序で連続して加えられ、並行して配列決定されます。</p>
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			'meta_description' => 'Diagenode offers kits and DNA/RNA shearing technology prior to next-generation sequencing, many Next-generation sequencing platforms require preparation of the DNA.',
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<div class="large-12 columns text-justify">
<p>Library preparation following ChIP can be challenging due to the limited amount of DNA recovered after ChIP. Diagenode has developed the optimal solutions for ChIP-seq using two different approaches: the ligation-based library preparation on purified DNA or the tagmentation-based ChIPmentation.</p>
</div>
</div>
<div class="row extra-spaced">
<div class="large-12 columns"><center><a href="https://www.diagenode.com/en/pages/form-microplex-promo" target="_blank"></a></center></div>
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<div id="portal" class="main-portal">
<div class="portal-inner"><nav class="portal-nav">
<ul data-tab="" class="tips-menu">
<li><a href="#panel1" class="tips portal button">Ligation-based library prep</a></li>
<li><a href="#panel2" class="tips portal button">ChIPmentation</a></li>
<li><a href="#panel3" class="tips portal button">Kit choice guide</a></li>
<li><a href="#panel4" class="tips portal button">Resources</a></li>
<li><a href="#panel5" class="tips portal button">FAQs</a></li>
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<li class="accordion-navigation"><a href="#v5" style="color: #13b29c;"><i class="fa fa-caret-right"></i> Standard input library prep</a>
<div id="v5" class="content">
<div class="small-12 medium-12 large-12 columns">
<p>The <strong>iDeal Library Preparation Kit</strong> reliably converts DNA into indexed libraries for next-generation sequencing, with input amounts down to <strong>5 ng</strong>. Our kit offers a simple and fast workflow, high yields, and ready-to-sequence DNA on the Illumina platform.</p>
<div class="extra-spaced">
<h2>Features</h2>
<ul class="nobullet">
<li><i class="fa fa-arrow-circle-right"></i> <strong>Sample</strong>: Fragmented dsDNA</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Input</strong>: 5 ng &ndash; 1 &micro;g</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Fast protocol</strong>: 3 hours</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Easy processing</strong>: 3 steps</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Indexing</strong>: single indexes for multiplexing up to 24 samples</li>
<li><i class="fa fa-arrow-circle-right"></i> Manual and automated protocols available</li>
<li><i class="fa fa-arrow-circle-right"></i> Sequencing technology: Illumina</li>
</ul>
</div>
<div class="extra-spaced">
<h2>Applications</h2>
<ul class="square">
<li>MeDIP-seq library prep</li>
<li>Genomic DNA sequencing</li>
<li>High input ChIP-seq</li>
</ul>
</div>
<div class="extra-spaced">
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
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</tr>
</thead>
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<tr>
<td class="catalog_number"><span class="success label">C05010020</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns" style="color: #b21329;" target="_blank">iDeal Library Preparation Kit x24 (incl. Index Primer Set 1)</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
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<td class="catalog_number"><span class="success label">C05010021</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/ideal-library-index-primer-set-2-24-rxns" style="color: #b21329;" target="_blank">Index Primer Set 2 (iDeal Lib. Prep Kit x24)</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/ideal-library-index-primer-set-2-24-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
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<li class="accordion-navigation"><a href="#v4" style="color: #13b29c;"><i class="fa fa-caret-right"></i> Low input library prep</a>
<div id="v4" class="content active"><center><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" target="_blank"><img src="https://www.diagenode.com/img/banners/banner-microplex-v3-580.jpg" class="extra-spaced" /></a></center>
<div align="center"><a href="https://www.diagenode.com/pages/form-microplex3" class="center alert radius button extra-spaced"><i class="fa fa-info"></i> Contact us</a></div>
<div class="extra-spaced">
<p>Diagenode&rsquo;s <strong>MicroPlex Library Preparation kits</strong> have been extensively validated for ChIP-seq samples. Generated libraries are compatible with single-end or paired-end sequencing. MicroPlex chemistry (using stem-loop adapters ) is specifically developed and optimized to generate DNA libraries with high molecular complexity from the lowest input amounts. Only <strong>50 pg to 50 ng</strong> of fragmented double-stranded DNA is required for library preparation. The entire <strong>three-step workflow</strong> takes place in a <strong>single tube</strong> or well in about <strong>2 hours</strong>. No intermediate purification steps and no sample transfers are necessary to prevent handling errors and loss of valuable samples.</p>
</div>
<div class="extra-spaced">
<h2>Features</h2>
<ul class="nobullet">
<li><i class="fa fa-arrow-circle-right"></i> <strong>Sample</strong>: Fragmented dsDNA</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Low input</strong>: 50 pg &ndash; 50 ng</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Fast protocol</strong>: 2 hours</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>Easy processing</strong>: 3 steps in 1 tube</li>
<li><i class="fa fa-arrow-circle-right"></i> <strong>No intermediate purification</strong></li>
<li><i class="fa fa-arrow-circle-right"></i> Sequencing technology: Illumina</li>
<li><i class="fa fa-arrow-circle-right"></i> Manual and automated protocols available</li>
</ul>
</div>
<div class="extra-spaced">
<h2>Applications</h2>
<ul class="square">
<li>ChIP-seq library prep from ChIP-derived DNA</li>
<li>Low input DNA sequencing</li>
</ul>
</div>
<h2>Two versions are available:</h2>
<ul class="accordion" data-accordion="">
<li class="accordion-navigation"><a href="#v2" style="color: #13b29c;"><i class="fa fa-caret-right"></i> MicroPlex Library Preparation Kit v2 with single indexes</a>
<div id="v2" class="content">
<p>The MicroPlex Library Preparation Kit v2 contains all necessary reagents including single indexes for multiplexing up to 48 samples using single barcoding.</p>
<h4>KITS</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C05010012</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns" style="color: #b21329;" target="_blank">MicroPlex Library Preparation Kit v2 (12 indexes)</a></td>
<td class="format">12 rxns</td>
<td><a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
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</tbody>
</table>
</div>
</li>
<li class="accordion-navigation"><a href="#v3" style="color: #13b29c;"><i class="fa fa-caret-right"></i> MicroPlex Library Preparation Kit v3 with dual indexes &nbsp;&nbsp;<strong><span class="diacol">NEW!</span></strong></a>
<div id="v3" class="content active">
<p>In this version the library preparation reagents and the dual indexes are available separately allowing for the flexibility choosing the number of indexes. MicroPlex v3 has multiplexing capacities up to 384 samples.</p>
<h4>KITS</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C05010001</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" style="color: #b21329;" target="_blank">MicroPlex Library Preparation Kit v3 /48 rxns</a></td>
<td class="format">48 rxns</td>
<td><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010002</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-96-rxns" style="color: #b21329;" target="_blank">MicroPlex Library Preparation Kit v3 /96 rxns</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-96-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
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</tbody>
</table>
<h4>DUAL INDEXES</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C05010003</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/24-dual-indexes-for-microplex-kit-v3-48-rxns" style="color: #b21329;" target="_blank">24 Dual indexes for MicroPlex Kit v3</a></td>
<td class="format">48 rxns</td>
<td><a href="https://www.diagenode.com/en/p/24-dual-indexes-for-microplex-kit-v3-48-rxns" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010004</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-1" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set I</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-1" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010005</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-2" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set II</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-2" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010006</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-3" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set III</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-3" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C05010007</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-4" style="color: #b21329;" target="_blank">96 Dual indexes for MicroPlex Kit v3 &ndash; Set IV</a></td>
<td class="format">96 rxns</td>
<td><a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-4" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
</tbody>
</table>
</div>
</li>
</ul>
</div>
</li>
</ul>
</div>
</div>
</div>
<div class="content active" id="panel2">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<div class="extra-spaced">
<p>The TAG Kit for ChIPmentation offers an optimized ChIP-seq library preparation solution based on tagmentation. This kit includes reagents for tagmentation-based library preparation integrated in the IP and is compatible with any ChIP protocol based on magnetic beads. The primer indexes for multiplexing&nbsp;must be purchased separately and are available as a reference: <a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" target="_blank">24 SI for ChIPmentation</a>, Cat. No. C01011031. Alternatively, for histone marks, Diagenode proposes the complete solution (including all buffers for ChIP, tagmentation and multiplexing): <a href="https://www.diagenode.com/en/p/manual-chipmentation-kit-for-histones-24-rxns" target="_blank">ChIPmentation for Histones</a>.</p>
</div>
<div class="extra-spaced">
<h2>Features</h2>
<ul class="nobullet">
<li><i class="fa fa-arrow-circle-right"></i> Sample: chromatin-antibody-magnetic beads complexes</li>
<li><i class="fa fa-arrow-circle-right"></i> Input: chromatin from 5 K &ndash; 4 M cells</li>
<li><i class="fa fa-arrow-circle-right"></i> Easy and fast protocol</li>
<li><i class="fa fa-arrow-circle-right"></i> Compatible with any ChIP protocol based on magnetic beads</li>
<li><i class="fa fa-arrow-circle-right"></i> No adapter dimers</li>
<li><i class="fa fa-arrow-circle-right"></i> Sequencing technology: Illumina</li>
</ul>
</div>
<div class="extra-spaced">
<h2>Applications</h2>
<p class="lead"><em><strong>TAG kit for ChIPmentation</strong></em></p>
<ul class="square">
<li>ChIPmentation library preparation</li>
</ul>
<p class="lead"><em><strong>24 SI for for ChIPmentation</strong></em></p>
<ul class="square">
<li>ChIPmentation library preparation</li>
<li>Tagmentation-based library preparation methods like ATAC-seq, CUT&amp;Tag</li>
</ul>
</div>
<h4>KITS</h4>
<table>
<thead>
<tr>
<th>Cat. No.</th>
<th>Product</th>
<th>Format</th>
<th width="120"></th>
</tr>
</thead>
<tbody class="list">
<tr>
<td class="catalog_number"><span class="success label">C01011030</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/tag-kit-for-chipmentation-24" style="color: #b21329;" target="_blank">TAG Kit for ChIPmentation</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/tag-kit-for-chipmentation-24" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
<tr>
<td class="catalog_number"><span class="success label">C01011031</span></td>
<td class="name"><a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" style="color: #b21329;" target="_blank">24 SI for ChIPmentation</a></td>
<td class="format">24 rxns</td>
<td><a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" class="tiny details button radius" target="_blank"><i class="fa fa-eye"></i></a></td>
</tr>
</tbody>
</table>
</div>
</div>
</div>
<div class="content" id="panel3">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<div class="extra-spaced">
<h3 class="text-center diacol"><em>How to choose your library preparation kit?</em></h3>
</div>
<table class="noborder">
<tbody>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Sample</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Chromatin-antibody-beads complex</p>
</td>
<td colspan="2">
<p class="text-center" style="font-size: 15px;">Purified DNA</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Purified DNA</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td colspan="2"><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Application</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">ChIPmentation</p>
</td>
<td colspan="2">
<p class="text-center" style="font-size: 15px;">ChIP-seq library prep<br /> Low input DNA sequencing</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">MeDIP-seq library prep<br /> Genomic DNA sequencing<br /> High input ChIP-seq</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td colspan="2"><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Input</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Chromatin: 5 K to 4 M cells</p>
</td>
<td colspan="2&quot;">
<p class="text-center" style="font-size: 15px;">DNA: 50 pg &ndash; 50 ng</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">DNA: 5 ng &ndash; 1 &micro;g</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow-45-left.png" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow-45-right.png" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Multiplexing</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 24 samples</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 384 samples</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 48 samples</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Up to 24 samples</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Indexes</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Single indexes (SI)</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Dual indexes (DI)</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Single indexes (SI)</p>
</td>
<td>
<p class="text-center" style="font-size: 15px;">Single indexes (SI)</p>
</td>
</tr>
<tr style="background-color: #fff;">
<td></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
<td><center><img src="https://www.diagenode.com/img/long-arrow.gif" /></center></td>
</tr>
<tr valign="top">
<td class="text-right">
<p style="font-size: 15px;"><strong>Kit</strong></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>TAG Kit for ChIPmentation</strong><br /> (indexes not included in the kit)</p>
<p class="text-center"><strong>Kit</strong><br /> <a href="https://www.diagenode.com/en/p/tag-kit-for-chipmentation-24" target="_blank">C01011030 &ndash; 24 rxns</a></p>
<p class="text-center"><strong>Single indexes</strong><br /> <a href="https://www.diagenode.com/en/p/24-si-for-chipmentation" target="_blank">C01011031 &ndash; 24 SI/24 rxns</a></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>MicroPlex Library Preparation Kit v3</strong><br />(dual indexes not included in the kit)</p>
<p class="text-center"><strong>Kit</strong><br /> <a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-48-rxns" target="_blank">C05010001 - 48 rxns</a><br /> <a href="https://www.diagenode.com/en/p/microplex-lib-prep-kit-v3-96-rxns" target="_blank">C05010002 - 96 rxns</a></p>
<br />
<p class="text-center"><strong>Unique dual indexes</strong><br /> <a href="https://www.diagenode.com/en/p/24-unique-dual-indexes-for-microplex-kit-v3-set1" target="_blank">C05010008 - Set I 24 UDI / 24 rxns</a><br /> <a href="https://www.diagenode.com/en/p/24-unique-dual-indexes-for-microplex-kit-v3-set2" target="_blank">C05010009 - Set II 24 UDI/ 24 rxns</a></p>
<p class="text-center"><strong>Dual indexes</strong><br /> <a href="https://www.diagenode.com/en/p/24-dual-indexes-for-microplex-kit-v3-48-rxns" target="_blank">C05010003 - 24 DI/ 48 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-1" target="_blank">C05010004 - Set I 96 DI/ 96 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-2" target="_blank">C05010005 - Set II 96 DI/ 96 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-3" target="_blank">C05010006 - Set III 96 DI/ 96 rxns</a><br /> <a href="https://www.diagenode.com/en/p/96-dual-indexes-for-microplex-kit-v3-set-4" target="_blank">C05010007 - Set IV 96 DI/ 96 rxns</a></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>MicroPlex Library Preparation Kit v2</strong><br />(single indexes included in the kit)</p>
<p class="text-center"><a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x12-12-indices-12-rxns" target="_blank">C05010012 - 12 SI/ 12 rxns</a><br /> <a href="https://www.diagenode.com/en/p/microplex-library-preparation-kit-v2-x48-12-indices-48-rxns" target="_blank">C05010013 - 12 SI/ 48 rxns</a></p>
</td>
<td>
<p class="text-center" style="font-size: 15px;"><strong>iDeal Library Preparation Kit</strong><br />(Set 1 of indexes included in the kit)</p>
<p class="text-center"><a href="https://www.diagenode.com/en/p/ideal-library-preparation-kit-x24-incl-index-primer-set-1-24-rxns" target="_blank">C05010020 - 12 SI/ 24 rxns</a></p>
<p class="text-center" style="font-size: 15px;"><strong>Index Primer Set 2</strong></p>
<p class="text-center"><a href="https://www.diagenode.com/en/p/ideal-library-index-primer-set-2-24-rxns" target="_blank">C05010021 - 12 SI/ 24 rxns</a></p>
</td>
</tr>
</tbody>
</table>
</div>
</div>
</div>
<div class="content" id="panel4">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<p>Combined chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) has become the gold standard to investigate genome-wide epigenetic profiles. However, ChIP from a limited amount of cells has been a challenge. Here we provide a complete and robust workflow solution for successful ChIP-seq from small numbers of cells using the True MicroChIP kit and MicroPlex Library Preparation kit.</p>
<blockquote><span class="label-green" style="margin-bottom: 16px; margin-left: -22px;">APPLICATION NOTE</span>
<div class="row">
<div class="small-12 medium-6 large-6 columns"><center><img src="https://www.diagenode.com/img/categories/microplex/chip-efficiency-on-10000-cells.jpg" /></center>
<p><small><em>ChIP efficiency on 10,000 cells</em></small></p>
</div>
<div class="small-12 medium-6 large-6 columns">
<p><strong>From minuscule amounts to magnificent results:</strong><br /> reliable ChIP-seq data from 10,000 cells with the True MicroChIP&trade; and the MicroPlex Library Preparation&trade; kits.</p>
<a href="https://www.diagenode.com/files/application_notes/True_MicroChIP_and_MicroPlex_kits_Application_Note.pdf" class="details small button" target="_blank">DOWNLOAD</a></div>
</div>
</blockquote>
<blockquote><span class="label-green" style="margin-bottom: 16px; margin-left: -22px;">APPLICATION NOTE</span>
<div class="row">
<div class="small-12 medium-6 large-6 columns"><center><img src="https://www.diagenode.com/img/categories/microplex/quality-control-check.jpg" /></center>
<p class="text-left"><small><em>Quality control check of a ChIP-seq library on the Fragment Analyzer. High Efficiency ChIP performed on 10,000 cells</em></small></p>
</div>
<div class="small-12 medium-6 large-6 columns">
<p class="text-left"><strong>Best Workflow Practices for ChIP-seq Analysis with Small Samples</strong></p>
<a href="https://www.diagenode.com/files/application_notes/Diagenode_AATI_Joint.pdf" class="details small button" target="_blank">DOWNLOAD</a></div>
</div>
</blockquote>
</div>
</div>
</div>
<div class="content" id="panel5">
<div class="row">
<div class="small-12 medium-12 large-12 columns">
<div class="extra-spaced">
<h2>TAG Kit for ChIPmentation</h2>
<ol>
<li><strong>What is the difference between tagmentation and ChIPmentation?</strong><br />Tagmentation is a reaction where an enzyme (a transposase) cleaves DNA and incorporates sequencing adaptors at the ends of the fragments in one step. In our ChIPmentation technology we combine chromatin immunoprecipitation and tagmentation in one streamlined workflow where the tagmentation step occurs directly on chromatin.<br /><br /></li>
<li><strong>What is the expected concentration of ChIPmentation libraries?</strong><br />The concentration of libraries that you need to reach will depend on the sensitivity of the machine and kits that you will use to perform the quality control and the sequencing of your libraries. Usually a concentration of 4-8 ng/&mu;l is enough for a quality control using the Qubit High Sensitivity assay (ThermoFischer Scientific) and the High Sensitivity chip for BioAnalyzer (Agilent) and for sequencing on Illumina HiSeq3000/4000.<br /><br /></li>
<li><strong>Does the ChIPmentation approach work on plants?</strong><br />Our ChIPmentation solution has been validated on human cells and we do not have any data on plants. It should be compatible. We would recommend using our Universal Plant ChIP Kit in combination with the TAG Kit for ChIPmentation and the 24 SI for ChIPmentation.<br /><br /></li>
<li><strong>What is the size of the fragments after the tagmentation?</strong><br />The size of the fragments at the end of the ChIPmentation protocol can vary depending on many parameters like the shearing efficiency, the antibody used or the tagmentation time. However, with our standard protocol we usually obtain a library peak which is around 200-300 bp (see example of results at the end of the manual). If many fragments larger than 500 bp are present , the best would be to contact your sequencing provider to ask what their requirements are, because it can vary depending on the sequencer. If you want to remove the large fragments you can use the size selection protocol described in the manual.<br /><br /></li>
<li><strong>What is the size of the adapters?</strong><br />The sum of the adapters is 128 bp.</li>
</ol>
</div>
<div class="extra-spaced">
<h2>MicroPlex Library Preparation Kit</h2>
<ol>
<li><strong>Can I use the available Illumina primers and validate them with the MicroPlex Kit v2?</strong><br /> Although the final flanking sequences of MicroPlex are the same as those used by Illumina, the PCR primers are not identical and part of them is supplied with the buffer. For this reason Illumina primers will not work as substitute.<br /><br /></li>
<li><strong>The BioAnalyzer profile of purified library shows the presence of low molecular weight peaks (primers/adaptors) in the samples. Should I re- purify the samples or they can be used directly to the sequencing? If the second purification is recommended, which ratio sample/AMPure beads should I use?</strong><br /> You can do a second round of purification using 1:1 ratio of AMPure beads to sample and this should get rid of the majority of the dimers.<br /><br /></li>
<li><strong>I am going to use the MicroPlex Library Preparation Kit v2 on ChIP samples . Our thermocycler has ramp rate 1.5&deg;/s max while the protocol recommends using a ramp rate 3 to 5&deg;/s. How would this affect the library prep?</strong><br /> We have not used a thermocycler with a ramp rate of 1.5 &deg;C, which seems faster than most of thermocyclers. Too fast of a ramp rate may affect the primer annealing and ligation steps.<br /><br /></li>
<li><strong>What is the function of the replication stop site in the adapter loops?</strong><br /> The replication stop site in the adaptor loops function to stop the polymerase from continuing to copy the rest of the stem loop.<br /><br /></li>
<li><strong>I want to do ChIP-seq. Which ChIP-seq kit can I use for sample preparation prior to Microplex Library Preparation Kit v2?</strong><br /> In our portfolio there are several ChIP-seq kits compatible with Microplex Library Preparation Kit v2. Depending on your sample type and target studied you can use the following kits: iDeal ChIP-seq Kit for Transcription Factors (Cat. No. C01010055), iDeal ChIP-seq Kit for Histones (Cat. No. C01010051), True MicroChIP kit (Cat. No. C01010130), Universal Plant ChIP-seq Kit (Cat. No. C01010152). All these kits exist in manual and automated versions.<br /><br /></li>
<li><strong>Is Microplex Library Preparation Kit v2 compatible with exome enrichment methods?</strong><br /> Microplex Library Preparation Kit v2 is compatible with major exome and target enrichment products, including Agilent SureSelect<sup>&reg;</sup>, Roche NimbleGen<sup>&reg;</sup> SeqCap<sup>&reg;</sup> EZ and custom panels.<br /><br /></li>
<li><strong>What is the nick that is mentioned in the kit method overview?</strong><br /> The nick is simply a gap between a stem adaptor and 3&rsquo; DNA end, as shown on the schema in the kit method overview.<br /><br /></li>
<li><strong>Are the indexes of the MicroPlex library preparation kit v2 located at i5 or i7?</strong><br /> The libraries generated with the MicroPlex kit v2 contain indices located at i7.<br /><br /></li>
<li><strong>Is there a need to use custom index read primers for the sequencing to read the 8nt iPCRtags?</strong><br /> There is no need for using custom Sequencing primer to sequence MicroPlex libraires. MicroPlex libraries can be sequenced using standard Illumina Sequencing kits and protocols.<br /><br /></li>
<li><strong>What is the advantage of using stem-loop adapter in the MicroPlex kit?</strong><br /> There are several advantages of using stem-loop adaptors. First of all, stem-loop adaptors prevent from self-ligation thus increases the ligation efficiency between the adapter and DNA fragment. Moreover, the background is reduced using ds adaptors with no single-stranded tails. Finally, adaptor-adaptor ligation is reduced using blocked 5&rsquo; ends.<br /><br /></li>
</ol>
</div>
<div class="extra-spaced">
<h2>IDeal Library Preparation Kit</h2>
<ol>
<li><strong>Are the index from the iDeal library Prep kit compatible with the MicroPlex library prep kit?</strong><br /> No, it is important to use only the indexes provided in the MicroPlex kit to ensure proper library preparation with this kit</li>
</ol>
</div>
</div>
</div>
</div>
</div>
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<p><span>MicroPlex v2 builds on the innovative MicroPlex chemistry to generate DNA libraries with expanded multiplexing capability and with even greater diversity. Kits contain up to 48 Illumina</span><span>&reg; </span><span>-compatible indexes. MicroPlex v2 can be used in DNA- seq, RNA-seq, or ChIP-seq and offers robust target enrichment performance with all of the leading platforms. </span></p>
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			'description' => '<p style="text-align: justify;"><span>Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become the gold standard for whole-genome mapping of protein-DNA interactions. However, conventional ChIP protocols require abundant amounts of starting material (at least hundreds of thousands of cells per immunoprecipitation) limiting the application for the ChIP technology to few cell samples. </span></p>',
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			'modified' => '2018-04-17 11:52:29',
			'created' => '2018-03-15 15:50:34',
			'ProductsImage' => array(
				[maximum depth reached]
			)
		)
	),
	'Promotion' => array(),
	'Protocol' => array(),
	'Publication' => array(
		(int) 0 => array(
			'id' => '4843',
			'name' => 'Differentiation block in acute myeloid leukemia regulated by intronicsequences of FTO',
			'authors' => 'Camera  F. et al.',
			'description' => '<p>Iroquois transcription factor gene IRX3 is highly expressed in 20&acirc;&euro;&ldquo;30\% of acute myeloid leukemia (AML) and contributes to the pathognomonic differentiation block. Intron 8 FTO sequences &acirc;&circ;&frac14;220kB downstream of IRX3 exhibit histone acetylation, DNA methylation, and contacts with the IRX3 promoter, which correlate with IRX3 expression. Deletion of these intronic elements confirms a role in positively regulating IRX3. RNAseq revealed long non-coding (lnc) transcripts arising from this locus. FTO-lncAML knockdown (KD) induced differentiation of AML cells, loss of clonogenic activity, and reduced FTO intron 8:IRX3 promoter contacts. While both FTO-lncAML KD and IRX3 KD induced differentiation, FTO-lncAML but not IRX3 KD led to HOXA downregulation suggesting transcript activity in trans. FTO-lncAMLhigh AML samples expressed higher levels of HOXA and lower levels of differentiation genes. Thus, a regulatory module in FTO intron 8 consisting of clustered enhancer elements and a long non-coding RNA is active in human AML, impeding myeloid differentiation.</p>',
			'date' => '2023-08-01',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S2589004223013962',
			'doi' => '10.1016/j.isci.2023.107319',
			'modified' => '2023-08-01 14:14:01',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 1 => array(
			'id' => '4851',
			'name' => 'Supraphysiological Androgens Promote the Tumor Suppressive Activity of the Androgen Receptor Through cMYC Repression and Recruitment of the DREAM Complex',
			'authors' => 'Nyquist  M. et al.',
			'description' => '<p>The androgen receptor (AR) pathway regulates key cell survival programs in prostate epithelium. The AR represents a near-universal driver and therapeutic vulnerability in metastatic prostate cancer, and targeting AR has a remarkable therapeutic index. Though most approaches directed toward AR focus on inhibiting AR signaling, laboratory and now clinical data have shown that high dose, supraphysiological androgen treatment (SPA) results in growth repression and improved outcomes in subsets of prostate cancer patients. A better understanding of the mechanisms contributing to SPA response and resistance could help guide patient selection and combination therapies to improve efficacy. To characterize SPA signaling, we integrated metrics of gene expression changes induced by SPA together with cistrome data and protein-interactomes. These analyses indicated that the Dimerization partner, RB-like, E2F and Multi-vulval class B (DREAM) complex mediates growth repression and downregulation of E2F targets in response to SPA. Notably, prostate cancers with complete genomic loss of RB1 responded to SPA treatment whereas loss of DREAM complex components such as RBL1/2 promoted resistance. Overexpression of MYC resulted in complete resistance to SPA and attenuated the SPA/AR-mediated repression of E2F target genes. These findings support a model of SPA-mediated growth repression that relies on the negative regulation of MYC by AR leading to repression of E2F1 signaling via the DREAM complex. The integrity of MYC signaling and DREAM complex assembly may consequently serve as determinants of SPA responses and as pathways mediating SPA resistance.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/37352376/',
			'doi' => '10.1158/0008-5472.CAN-22-2613',
			'modified' => '2023-08-01 18:09:31',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 2 => array(
			'id' => '4852',
			'name' => 'In skeletal muscle and neural crest cells, SMCHD1 regulates biologicalpathways relevant for Bosma syndrome and facioscapulohumeral dystrophyphenotype.',
			'authors' => 'Laberthonnière  C. et al.',
			'description' => '<p>Many genetic syndromes are linked to mutations in genes encoding factors that guide chromatin organization. Among them, several distinct rare genetic diseases are linked to mutations in SMCHD1 that encodes the structural maintenance of chromosomes flexible hinge domain containing 1 chromatin-associated factor. In humans, its function as well as the impact of its mutations remains poorly defined. To fill this gap, we determined the episignature associated with heterozygous SMCHD1 variants in primary cells and cell lineages derived from induced pluripotent stem cells for Bosma arhinia and microphthalmia syndrome (BAMS) and type 2 facioscapulohumeral dystrophy (FSHD2). In human tissues, SMCHD1 regulates the distribution of methylated CpGs, H3K27 trimethylation and CTCF at repressed chromatin but also at euchromatin. Based on the exploration of tissues affected either in FSHD or in BAMS, i.e. skeletal muscle fibers and neural crest stem cells, respectively, our results emphasize multiple functions for SMCHD1, in chromatin compaction, chromatin insulation and gene regulation with variable targets or phenotypical outcomes. We concluded that in rare genetic diseases, SMCHD1 variants impact gene expression in two ways: (i) by changing the chromatin context at a number of euchromatin loci or (ii) by directly regulating some loci encoding master transcription factors required for cell fate determination and tissue differentiation.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37334829',
			'doi' => '10.1093/nar/gkad523',
			'modified' => '2023-08-01 14:35:38',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 3 => array(
			'id' => '4861',
			'name' => 'Hypomethylation and overexpression of Th17-associated genes is ahallmark of intestinal CD4+ lymphocytes in Crohn's disease.',
			'authors' => 'Sun  Z. et al.',
			'description' => '<p>BACKGROUND: The development of Crohn's disease (CD) involves immune cell signaling pathways regulated by epigenetic modifications. Aberrant DNA methylation has been identified in peripheral blood and bulk intestinal tissue from CD patients. However, the DNA methylome of disease-associated intestinal CD4 + lymphocytes has not been evaluated. MATERIALS AND METHODS: Genome-wide DNA methylation sequencing was performed from terminal ileum CD4 + cells from 21 CD patients and 12 age and sex matched controls. Data was analyzed for differentially methylated CpGs (DMCs) and methylated regions (DMRs). Integration was performed with RNA-sequencing data to evaluate the functional impact of DNA methylation changes on gene expression. DMRs were overlapped with regions of differentially open chromatin (by ATAC-seq) and CCCTC-binding factor (CTCF) binding sites (by ChIP-seq) between peripherally-derived Th17 and Treg cells. RESULTS: CD4+ cells in CD patients had significantly increased DNA methylation compared to those from the controls. A total of 119,051 DMCs and 8,113 DMRs were detected. While hyper-methylated genes were mostly related to cell metabolism and homeostasis, hypomethylated genes were significantly enriched within the Th17 signaling pathway. The differentially enriched ATAC regions in Th17 cells (compared to Tregs) were hypomethylated in CD patients, suggesting heightened Th17 activity. There was significant overlap between hypomethylated DNA regions and CTCF-associated binding sites. CONCLUSIONS: The methylome of CD patients demonstrate an overall dominant hypermethylation yet hypomethylation is more concentrated in proinflammatory pathways, including Th17 differentiation. Hypomethylation of Th17-related genes associated with areas of open chromatin and CTCF binding sites constitutes a hallmark of CD-associated intestinal CD4 + cells.</p>',
			'date' => '2023-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37280154',
			'doi' => '10.1093/ecco-jcc/jjad093',
			'modified' => '2023-08-01 14:52:39',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 4 => 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) 5 => array(
			'id' => '4782',
			'name' => 'Transient suppression of SUMOylation in embryonic stem cells generatesembryo-like structures.',
			'authors' => 'Cossec  J-C. et al.',
			'description' => '<p>Recent advances in synthetic embryology have opened new avenues for understanding the complex events controlling mammalian peri-implantation development. Here, we show that mouse embryonic stem cells (ESCs) solely exposed to chemical inhibition of SUMOylation generate embryo-like structures comprising anterior neural and trunk-associated regions. HypoSUMOylation-instructed ESCs give rise to spheroids that self-organize into gastrulating structures containing cell types spatially and functionally related to embryonic and extraembryonic compartments. Alternatively, spheroids cultured in a droplet microfluidic device form elongated structures that undergo axial organization reminiscent of natural embryo morphogenesis. Single-cell transcriptomics reveals various cellular lineages, including properly positioned anterior neuronal cell types and paraxial mesoderm segmented into somite-like structures. Transient SUMOylation suppression gradually increases DNA methylation genome wide and repressive mark deposition at Nanog. Interestingly, cell-to-cell variations in SUMOylation levels occur during early embryogenesis. Our approach provides a proof of principle for potentially powerful strategies to explore early embryogenesis by targeting chromatin roadblocks of cell fate change.</p>',
			'date' => '2023-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37061916',
			'doi' => '10.1016/j.celrep.2023.112380',
			'modified' => '2023-06-13 09:20:06',
			'created' => '2023-05-05 12:34:24',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 6 => array(
			'id' => '4693',
			'name' => 'ZEB1 controls a lineage-specific transcriptional program essential formelanoma cell state transitions',
			'authors' => 'Tang  Y. et al.',
			'description' => '<p>Cell plasticity sustains intra-tumor heterogeneity and treatment resistance in melanoma. Deciphering the transcriptional mechanisms governing reversible phenotypic transitions between proliferative/differentiated and invasive/stem-like states is required in order to design novel therapeutic strategies. EMT-inducing transcription factors, extensively known for their role in metastasis in carcinoma, display cell-type specific functions in melanoma, with a decreased ZEB2/ZEB1 expression ratio fostering adaptive resistance to targeted therapies. While ZEB1 direct target genes have been well characterized in carcinoma models, they remain unknown in melanoma. Here, we performed a genome-wide characterization of ZEB1 transcriptional targets, by combining ChIP-sequencing and RNA-sequencing, upon phenotype switching in melanoma models. We identified and validated ZEB1 binding peaks in the promoter of key lineage-specific genes related to melanoma cell identity. Comparative analyses with breast carcinoma cells demonstrated melanoma-specific ZEB1 binding, further supporting lineage specificity. Gain- or loss-of-function of ZEB1, combined with functional analyses, further demonstrated that ZEB1 negatively regulates proliferative/melanocytic programs and positively regulates both invasive and stem-like programs. We then developed single-cell spatial multiplexed analyses to characterize melanoma cell states with respect to ZEB1/ZEB2 expression in human melanoma samples. We characterized the intra-tumoral heterogeneity of ZEB1 and ZEB2 and further validated ZEB1 increased expression in invasive cells, but also in stem-like cells, highlighting its relevance in vivo in both populations. Overall, our results define ZEB1 as a major transcriptional regulator of cell states transitions and provide a better understanding of lineage-specific transcriptional programs sustaining intra-tumor heterogeneity in melanoma.</p>',
			'date' => '2023-02-01',
			'pmid' => 'https://doi.org/10.1101%2F2023.02.10.526467',
			'doi' => '10.1101/2023.02.10.526467',
			'modified' => '2023-04-14 09:11:23',
			'created' => '2023-02-28 12:19:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 7 => 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) 8 => array(
			'id' => '4710',
			'name' => 'Mechanisms and function of de novo DNA methylation in placentaldevelopment reveals an essential role for DNMT3B.',
			'authors' => 'Andrews  S. et al.',
			'description' => '<p>DNA methylation is a repressive epigenetic modification that is essential for development, exemplified by the embryonic and perinatal lethality observed in mice lacking de novo DNA methyltransferases (DNMTs). Here we characterise the role for DNMT3A, 3B and 3L in gene regulation and development of the mouse placenta. We find that each DNMT establishes unique aspects of the placental methylome through targeting to distinct chromatin features. Loss of Dnmt3b results in de-repression of germline genes in trophoblast lineages and impaired formation of the maternal-foetal interface in the placental labyrinth. Using Sox2-Cre to delete Dnmt3b in the embryo, leaving expression intact in placental cells, the placental phenotype was rescued and, consequently, the embryonic lethality, as Dnmt3b null embryos could now survive to birth. We conclude that de novo DNA methylation by DNMT3B during embryogenesis is principally required to regulate placental development and function, which in turn is critical for embryo survival.</p>',
			'date' => '2023-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36690623',
			'doi' => '10.1038/s41467-023-36019-9',
			'modified' => '2023-04-05 08:38:12',
			'created' => '2023-02-28 12:19:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 9 => array(
			'id' => '4651',
			'name' => 'TCDD induces multigenerational alterations in the expression ofmicroRNA in the thymus through epigenetic modifications',
			'authors' => 'Singh  Narendra P et al.',
			'description' => '<p>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, is an environmental contaminant that is known for mediating toxicity across generations. However, whether TCDD can induce multigenerational changes in the expression of miRNAs (miRs) has not been previously studied. In the current study, we investigated the effect of administration of TCDD in pregnant mice (F0) on gestational day 14, on the expression of miRs in the thymus of F0 and subsequent generations (F1 and F2). Of the 3200 miRs screened, 160 miRs were dysregulated similarly in F0, F1, and F2 generations while 46 miRs were differentially altered in F0-F2 generations. Pathway analysis revealed that the changes in miR signature profile mediated by TCDD affected the genes that regulate cell signaling, apoptosis, thymic atrophy, cancer, immunosuppression, and other physiological pathways. A significant number of miRs that showed altered expression exhibited dioxin response elements (DRE) on their promoters. Focusing on one such miR, namely miR-203 that expressed DREs and was induced across F0-F2 by TCDD, promoter analysis showed that one of the DREs expressed by miR-203 was functional to TCDD-mediated upregulation. Also, the histone methylation status of H3K4me3 in the miR-203 promoter was significantly increased near the transcriptional start site (TSS) in TCDD-treated thymocytes across F0-F2 generations. Genome-wide ChIP-seq study suggested that TCDD may cause alterations in histone methylation in certain genes across the three generations. Together, the current study demonstrates that gestational exposure to TCDD can alter the expression of miRs in F0 through direct activation of DREs as well as across F0, F1, and F2 generations through epigenetic pathways.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://academic.oup.com/pnasnexus/advance-article/doi/10.1093/pnasnexus/pgac290/6886578',
			'doi' => 'https://doi.org/10.1093/pnasnexus/pgac290',
			'modified' => '2023-03-13 10:55:36',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 10 => array(
			'id' => '4632',
			'name' => 'The histone acetyltransferase KAT6A is recruited to unmethylatedCpG islands via a DNA binding winged helix domain.',
			'authors' => 'Weber  L.M. et al.',
			'description' => '<p>The lysine acetyltransferase KAT6A (MOZ, MYST3) belongs to the MYST family of chromatin regulators, facilitating histone acetylation. Dysregulation of KAT6A has been implicated in developmental syndromes and the onset of acute myeloid leukemia (AML). Previous work suggests that KAT6A is recruited to its genomic targets by a combinatorial function of histone binding PHD fingers, transcription factors and chromatin binding interaction partners. Here, we demonstrate that a winged helix (WH) domain at the very N-terminus of KAT6A specifically interacts with unmethylated CpG motifs. This DNA binding function leads to the association of KAT6A with unmethylated CpG islands (CGIs) genome-wide. Mutation of the essential amino acids for DNA binding completely abrogates the enrichment of KAT6A at CGIs. In contrast, deletion of a second WH domain or the histone tail binding PHD fingers only subtly influences the binding of KAT6A to CGIs. Overexpression of a KAT6A WH1 mutant has a dominant negative effect on H3K9 histone acetylation, which is comparable to the effects upon overexpression of a KAT6A HAT domain mutant. Taken together, our work revealed a previously unrecognized chromatin recruitment mechanism of KAT6A, offering a new perspective on the role of KAT6A in gene regulation and human diseases.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36537216',
			'doi' => '10.1093/nar/gkac1188',
			'modified' => '2023-03-28 09:01:38',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 11 => array(
			'id' => '4629',
			'name' => 'Polyglutamine-expanded ATXN7 alters a specific epigenetic signatureunderlying photoreceptor identity gene expression in SCA7 mouseretinopathy.',
			'authors' => 'Niewiadomska-Cimicka  A.et al.',
			'description' => '<p>BACKGROUND: Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder that primarily affects the cerebellum and retina. SCA7 is caused by a polyglutamine expansion in the ATXN7 protein, a subunit of the transcriptional coactivator SAGA that acetylates histone H3 to deposit narrow H3K9ac mark at DNA regulatory elements of active genes. Defective histone acetylation has been presented as a possible cause for gene deregulation in SCA7 mouse models. However, the topography of acetylation defects at the whole genome level and its relationship to changes in gene expression remain to be determined. METHODS: We performed deep RNA-sequencing and chromatin immunoprecipitation coupled to high-throughput sequencing to examine the genome-wide correlation between gene deregulation and alteration of the active transcription marks, e.g. SAGA-related H3K9ac, CBP-related H3K27ac and RNA polymerase II (RNAPII), in a SCA7 mouse retinopathy model. RESULTS: Our analyses revealed that active transcription marks are reduced at most gene promoters in SCA7 retina, while a limited number of genes show changes in expression. We found that SCA7 retinopathy is caused by preferential downregulation of hundreds of highly expressed genes that define morphological and physiological identities of mature photoreceptors. We further uncovered that these photoreceptor genes harbor unusually broad H3K9ac profiles spanning the entire gene bodies and have a low RNAPII pausing. This broad H3K9ac signature co-occurs with other features that delineate superenhancers, including broad H3K27ac, binding sites for photoreceptor specific transcription factors and expression of enhancer-related non-coding RNAs (eRNAs). In SCA7 retina, downregulated photoreceptor genes show decreased H3K9 and H3K27 acetylation and eRNA expression as well as increased RNAPII pausing, suggesting that superenhancer-related features are altered. CONCLUSIONS: Our study thus provides evidence that distinctive epigenetic configurations underlying high expression of cell-type specific genes are preferentially impaired in SCA7, resulting in a defect in the maintenance of identity features of mature photoreceptors. Our results also suggest that continuous SAGA-driven acetylation plays a role in preserving post-mitotic neuronal identity.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36539812',
			'doi' => '10.1186/s12929-022-00892-1',
			'modified' => '2023-03-28 09:07:19',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 12 => array(
			'id' => '4575',
			'name' => 'Intranasal administration of Acinetobacter lwoffii in a murine model ofasthma induces IL-6-mediated protection associated with cecal microbiotachanges.',
			'authors' => 'Alashkar A. B. et al.',
			'description' => '<p>BACKGROUND: Early-life exposure to certain environmental bacteria including Acinetobacter lwoffii (AL) has been implicated in protection from chronic inflammatory diseases including asthma later in life. However, the underlying mechanisms at the immune-microbe interface remain largely unknown. METHODS: The effects of repeated intranasal AL exposure on local and systemic innate immune responses were investigated in wild-type and Il6 , Il10 , and Il17 mice exposed to ovalbumin-induced allergic airway inflammation. Those investigations were expanded by microbiome analyses. To assess for AL-associated changes in gene expression, the picture arising from animal data was supplemented by in vitro experiments of macrophage and T-cell responses, yielding expression and epigenetic data. RESULTS: The asthma preventive effect of AL was confirmed in the lung. Repeated intranasal AL administration triggered a proinflammatory immune response particularly characterized by elevated levels of IL-6, and consequently, IL-6 induced IL-10 production in CD4 T-cells. Both IL-6 and IL-10, but not IL-17, were required for asthma protection. AL had a profound impact on the gene regulatory landscape of CD4 T-cells which could be largely recapitulated by recombinant IL-6. AL administration also induced marked changes in the gastrointestinal microbiome but not in the lung microbiome. By comparing the effects on the microbiota according to mouse genotype and AL-treatment status, we have identified microbial taxa that were associated with either disease protection or activity. CONCLUSION: These experiments provide a novel mechanism of Acinetobacter lwoffii-induced asthma protection operating through IL-6-mediated epigenetic activation of IL-10 production and with associated effects on the intestinal microbiome.</p>',
			'date' => '2022-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36458896',
			'doi' => '10.1111/all.15606',
			'modified' => '2023-04-11 10:23:07',
			'created' => '2023-02-21 09:59:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 13 => array(
			'id' => '4535',
			'name' => 'Identification of genomic binding sites and direct target genes for thetranscription factor DDIT3/CHOP.',
			'authors' => 'Osman  A. et al.',
			'description' => '<p>DDIT3 is a tightly regulated basic leucine zipper (bZIP) transcription factor and key regulator in cellular stress responses. It is involved in a variety of pathological conditions and may cause cell cycle block and apoptosis. It is also implicated in differentiation of some specialized cell types and as an oncogene in several types of cancer. DDIT3 is believed to act as a dominant-negative inhibitor by forming heterodimers with other bZIP transcription factors, preventing their DNA binding and transactivating functions. DDIT3 has, however, been reported to bind DNA and regulate target genes. Here, we employed ChIP sequencing combined with microarray-based expression analysis to identify direct binding motifs and target genes of DDIT3. The results reveal DDIT3 binding to motifs similar to other bZIP transcription factors, known to form heterodimers with DDIT3. Binding to a class III satellite DNA repeat sequence was also detected. DDIT3 acted as a DNA-binding transcription factor and bound mainly to the promotor region of regulated genes. ChIP sequencing analysis of histone H3K27 methylation and acetylation showed a strong overlap between H3K27-acetylated marks and DDIT3 binding. These results support a role for DDIT3 as a transcriptional regulator of H3K27ac-marked genes in transcriptionally active chromatin.</p>',
			'date' => '2022-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36402425',
			'doi' => '10.1016/j.yexcr.2022.113418',
			'modified' => '2022-11-25 08:47:49',
			'created' => '2022-11-24 08:49:52',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 14 => array(
			'id' => '4494',
			'name' => 'Cryptococcal Hsf3 controls intramitochondrial ROS homeostasis byregulating the respiratory process.',
			'authors' => 'Gao  X.et al.',
			'description' => '<p>Mitochondrial quality control prevents accumulation of intramitochondrial-derived reactive oxygen species (mtROS), thereby protecting cells against DNA damage, genome instability, and programmed cell death. However, underlying mechanisms are incompletely understood, particularly in fungal species. Here, we show that Cryptococcus neoformans heat shock factor 3 (CnHsf3) exhibits an atypical function in regulating mtROS independent of the unfolded protein response. CnHsf3 acts in nuclei and mitochondria, and nuclear- and mitochondrial-targeting signals are required for its organelle-specific functions. It represses the expression of genes involved in the tricarboxylic acid cycle while promoting expression of genes involved in electron transfer chain. In addition, CnHsf3 responds to multiple intramitochondrial stresses; this response is mediated by oxidation of the cysteine residue on its DNA binding domain, which enhances DNA binding. Our results reveal a function of HSF proteins in regulating mtROS homeostasis that is independent of the unfolded protein response.</p>',
			'date' => '2022-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36109512',
			'doi' => '10.1038/s41467-022-33168-1',
			'modified' => '2022-11-18 12:43:17',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 15 => array(
			'id' => '4496',
			'name' => 'Dominant role of DNA methylation over H3K9me3 for IAP silencingin endoderm.',
			'authors' => 'Wang  Z. et al.',
			'description' => '<p>Silencing of endogenous retroviruses (ERVs) is largely mediated by repressive chromatin modifications H3K9me3 and DNA methylation. On ERVs, these modifications are mainly deposited by the histone methyltransferase Setdb1 and by the maintenance DNA methyltransferase Dnmt1. Knock-out of either Setdb1 or Dnmt1 leads to ERV de-repression in various cell types. However, it is currently not known if H3K9me3 and DNA methylation depend on each other for ERV silencing. Here we show that conditional knock-out of Setdb1 in mouse embryonic endoderm results in ERV de-repression in visceral endoderm (VE) descendants and does not occur in definitive endoderm (DE). Deletion of Setdb1 in VE progenitors results in loss of H3K9me3 and reduced DNA methylation of Intracisternal A-particle (IAP) elements, consistent with up-regulation of this ERV family. In DE, loss of Setdb1 does not affect H3K9me3 nor DNA methylation, suggesting Setdb1-independent pathways for maintaining these modifications. Importantly, Dnmt1 knock-out results in IAP de-repression in both visceral and definitive endoderm cells, while H3K9me3 is unaltered. Thus, our data suggest a dominant role of DNA methylation over H3K9me3 for IAP silencing in endoderm cells. Our findings suggest that Setdb1-meditated H3K9me3 is not sufficient for IAP silencing, but rather critical for maintaining high DNA methylation.</p>',
			'date' => '2022-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/36123357',
			'doi' => '10.1038/s41467-022-32978-7',
			'modified' => '2022-11-21 10:26:30',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 16 => array(
			'id' => '4415',
			'name' => 'HDAC1 and PRC2 mediate combinatorial control in SPI1/PU.1-dependentgene repression in murine erythroleukaemia.',
			'authors' => 'Gregoricchio  S. et al.',
			'description' => '<p>Although originally described as transcriptional activator, SPI1/PU.1, a major player in haematopoiesis whose alterations are associated with haematological malignancies, has the ability to repress transcription. Here, we investigated the mechanisms underlying gene repression in the erythroid lineage, in which SPI1 exerts an oncogenic function by blocking differentiation. We show that SPI1 represses genes by binding active enhancers that are located in intergenic or gene body regions. HDAC1 acts as a cooperative mediator of SPI1-induced transcriptional repression by deacetylating SPI1-bound enhancers in a subset of genes, including those involved in erythroid differentiation. Enhancer deacetylation impacts on promoter acetylation, chromatin accessibility and RNA pol II occupancy. In addition to the activities of HDAC1, polycomb repressive complex 2 (PRC2) reinforces gene repression by depositing H3K27me3 at promoter sequences when SPI1 is located at enhancer sequences. Moreover, our study identified a synergistic relationship between PRC2 and HDAC1 complexes in mediating the transcriptional repression activity of SPI1, ultimately inducing synergistic adverse effects on leukaemic cell survival. Our results highlight the importance of the mechanism underlying transcriptional repression in leukemic cells, involving complex functional connections between SPI1 and the epigenetic regulators PRC2 and HDAC1.</p>',
			'date' => '2022-08-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35871293',
			'doi' => '10.1093/nar/gkac613',
			'modified' => '2022-09-15 08:59:26',
			'created' => '2022-09-08 16:32:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 17 => array(
			'id' => '4516',
			'name' => 'Dual role of histone variant H3.3B in spermatogenesis: positiveregulation of piRNA transcription and implication in X-chromosomeinactivation.',
			'authors' => 'Fontaine  E. et al.',
			'description' => '<p>The histone variant H3.3 is encoded by two distinct genes, H3f3a and H3f3b, exhibiting identical amino-acid sequence. H3.3 is required for spermatogenesis, but the molecular mechanism of its spermatogenic function remains obscure. Here, we have studied the role of each one of H3.3A and H3.3B proteins in spermatogenesis. We have generated transgenic conditional knock-out/knock-in (cKO/KI) epitope-tagged FLAG-FLAG-HA-H3.3B (H3.3BHA) and FLAG-FLAG-HA-H3.3A (H3.3AHA) mouse lines. We show that H3.3B, but not H3.3A, is required for spermatogenesis and male fertility. Analysis of the molecular mechanism unveils that the absence of H3.3B led to alterations in the meiotic/post-meiotic transition. Genome-wide RNA-seq reveals that the depletion of H3.3B in meiotic cells is associated with increased expression of the whole sex X and Y chromosomes as well as of both RLTR10B and RLTR10B2 retrotransposons. In contrast, the absence of H3.3B resulted in down-regulation of the expression of piRNA clusters. ChIP-seq experiments uncover that RLTR10B and RLTR10B2 retrotransposons, the whole sex chromosomes and the piRNA clusters are markedly enriched of H3.3. Taken together, our data dissect the molecular mechanism of H3.3B functions during spermatogenesis and demonstrate that H3.3B, depending on its chromatin localization, is involved in either up-regulation or down-regulation of expression of defined large chromatin regions.</p>',
			'date' => '2022-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35766398',
			'doi' => '10.1093/nar/gkac541',
			'modified' => '2022-11-24 08:51:34',
			'created' => '2022-11-15 09:26:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 18 => array(
			'id' => '4393',
			'name' => 'TBX2 acts as a potent transcriptional silencer of tumour suppressor genesthrough interaction with the CoREST complex to sustain theproliferation of breast cancers.',
			'authors' => 'McIntyre  A.J. et al.',
			'description' => '<p>Chromosome 17q23 amplification occurs in 20\% of primary breast tumours and is associated with poor outcome. The TBX2 gene is located on 17q23 and is often over-expressed in this breast tumour subset. TBX2 is an anti-senescence gene, promoting cell growth and survival through repression of Tumour Suppressor Genes (TSGs), such as NDRG1 and CST6. Previously we found that TBX2 cooperates with the PRC2 complex to repress several TSGs, and that PRC2 inhibition restored NDRG1 expression to impede cellular proliferation. Here, we now identify CoREST proteins, LSD1 and ZNF217, as novel interactors of TBX2. Genetic or pharmacological targeting of CoREST emulated TBX2 loss, inducing NDRG1 expression and abolishing breast cancer growth in vitro and in vivo. Furthermore, we uncover that TBX2/CoREST targeting of NDRG1 is achieved by recruitment of TBX2 to the NDRG1 promoter by Sp1, the abolishment of which resulted in NDRG1 upregulation and diminished cancer cell proliferation. Through ChIP-seq we reveal that 30\% of TBX2-bound promoters are shared with ZNF217 and identify novel targets repressed by TBX2/CoREST; of these targets a lncRNA, LINC00111, behaves as a negative regulator of cell proliferation. Overall, these data indicate that inhibition of CoREST proteins represents a promising therapeutic intervention for TBX2-addicted breast tumours.</p>',
			'date' => '2022-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35687133',
			'doi' => '10.1093/nar/gkac494',
			'modified' => '2022-08-11 14:23:06',
			'created' => '2022-08-11 12:14:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 19 => array(
			'id' => '4836',
			'name' => 'Caffeine intake exerts dual genome-wide effects on hippocampal metabolismand learning-dependent transcription.',
			'authors' => 'Paiva  I. et al.',
			'description' => '<p>Caffeine is the most widely consumed psychoactive substance in the world. Strikingly, the molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal omics techniques. Our results revealed that chronic caffeine exerts concerted pleiotropic effects in the hippocampus at the epigenomic, proteomic, and metabolomic levels. Caffeine lowered metabolism-related processes (e.g., at the level of metabolomics and gene expression) in bulk tissue, while it induced neuron-specific epigenetic changes at synaptic transmission/plasticity-related genes and increased experience-driven transcriptional activity. Altogether, these findings suggest that regular caffeine intake improves the signal-to-noise ratio during information encoding, in part through fine-tuning of metabolic genes, while boosting the salience of information processing during learning in neuronal circuits.</p>',
			'date' => '2022-06-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35536645',
			'doi' => '10.1172/JCI149371',
			'modified' => '2023-08-01 13:52:29',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 20 => 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) 21 => 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) 22 => 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) 23 => array(
			'id' => '4217',
			'name' => 'CREBBP/EP300 acetyltransferase inhibition disrupts FOXA1-bound enhancers to inhibit the proliferation of ER+ breast cancer cells.',
			'authors' => 'Bommi-Reddy A. et al.',
			'description' => '<p><span>Therapeutic targeting of the estrogen receptor (ER) is a clinically validated approach for estrogen receptor positive breast cancer (ER+ BC), but sustained response is limited by acquired resistance. Targeting the transcriptional coactivators required for estrogen receptor activity represents an alternative approach that is not subject to the same limitations as targeting estrogen receptor itself. In this report we demonstrate that the acetyltransferase activity of coactivator paralogs CREBBP/EP300 represents a promising therapeutic target in ER+ BC. Using the potent and selective inhibitor CPI-1612, we show that CREBBP/EP300 acetyltransferase inhibition potently suppresses in vitro and in vivo growth of breast cancer cell line models and acts in a manner orthogonal to directly targeting ER. CREBBP/EP300 acetyltransferase inhibition suppresses ER-dependent transcription by targeting lineage-specific enhancers defined by the pioneer transcription factor FOXA1. These results validate CREBBP/EP300 acetyltransferase activity as a viable target for clinical development in ER+ breast cancer.</span></p>',
			'date' => '2022-03-30',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/35353838/',
			'doi' => '10.1371/journal.pone.0262378',
			'modified' => '2022-04-12 10:56:54',
			'created' => '2022-04-12 10:56:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 24 => array(
			'id' => '4235',
			'name' => 'NuA4 and H2A.Z control environmental responses and autotrophicgrowth in Arabidopsis',
			'authors' => 'Bieluszewski T. et al.',
			'description' => '<p>Nucleosomal acetyltransferase of H4 (NuA4) is an essential transcriptional coactivator in eukaryotes, but remains poorly characterized in plants. Here, we describe Arabidopsis homologs of the NuA4 scaffold proteins Enhancer of Polycomb-Like 1 (AtEPL1) and Esa1-Associated Factor 1 (AtEAF1). Loss of AtEAF1 results in inhibition of growth and chloroplast development. These effects are stronger in the Atepl1 mutant and are further enhanced by loss of Golden2-Like (GLK) transcription factors, suggesting that NuA4 activates nuclear plastid genes alongside GLK. We demonstrate that AtEPL1 is necessary for nucleosomal acetylation of histones H4 and H2A.Z by NuA4 in vitro. These chromatin marks are diminished genome-wide in Atepl1, while another active chromatin mark, H3K9 acetylation (H3K9ac), is locally enhanced. Expression of many chloroplast-related genes depends on NuA4, as they are downregulated with loss of H4ac and H2A.Zac. Finally, we demonstrate that NuA4 promotes H2A.Z deposition and by doing so prevents spurious activation of stress response genes.</p>',
			'date' => '2022-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35022409',
			'doi' => '10.1038/s41467-021-27882-5',
			'modified' => '2022-05-19 17:02:00',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 25 => array(
			'id' => '4772',
			'name' => 'Three classes of epigenomic regulators converge to hyperactivate theessential maternal gene deadhead within a heterochromatin mini-domain.',
			'authors' => 'Torres-Campana  D. et al.',
			'description' => '<p>The formation of a diploid zygote is a highly complex cellular process that is entirely controlled by maternal gene products stored in the egg cytoplasm. This highly specialized transcriptional program is tightly controlled at the chromatin level in the female germline. As an extreme case in point, the massive and specific ovarian expression of the essential thioredoxin Deadhead (DHD) is critically regulated in Drosophila by the histone demethylase Lid and its partner, the histone deacetylase complex Sin3A/Rpd3, via yet unknown mechanisms. Here, we identified Snr1 and Mod(mdg4) as essential for dhd expression and investigated how these epigenomic effectors act with Lid and Sin3A to hyperactivate dhd. Using Cut\&amp;Run chromatin profiling with a dedicated data analysis procedure, we found that dhd is intriguingly embedded in an H3K27me3/H3K9me3-enriched mini-domain flanked by DNA regulatory elements, including a dhd promoter-proximal element essential for its expression. Surprisingly, Lid, Sin3a, Snr1 and Mod(mdg4) impact H3K27me3 and this regulatory element in distinct manners. However, we show that these effectors activate dhd independently of H3K27me3/H3K9me3, and that dhd remains silent in the absence of these marks. Together, our study demonstrates an atypical and critical role for chromatin regulators Lid, Sin3A, Snr1 and Mod(mdg4) to trigger tissue-specific hyperactivation within a unique heterochromatin mini-domain.</p>',
			'date' => '2022-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759638/',
			'doi' => '10.1371/journal.pgen.1009615',
			'modified' => '2023-04-17 09:46:00',
			'created' => '2023-04-14 13:41:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 26 => 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) 27 => array(
			'id' => '4245',
			'name' => 'Decreased PRC2 activity supports the survival of basal-like breastcancer cells to cytotoxic treatments',
			'authors' => 'Mieczkowska IK et al.',
			'description' => '<p>Breast cancer (BC) is the most common cancer occurring in women but also rarely develops in men. Recent advances in early diagnosis and development of targeted therapies have greatly improved the survival rate of BC patients. However, the basal-like BC subtype (BLBC), largely overlapping with the triple-negative BC subtype (TNBC), lacks such drug targets and conventional cytotoxic chemotherapies often remain the only treatment option. Thus, the development of resistance to cytotoxic therapies has fatal consequences. To assess the involvement of epigenetic mechanisms and their therapeutic potential increasing cytotoxic drug efficiency, we combined high-throughput RNA- and ChIP-sequencing analyses in BLBC cells. Tumor cells surviving chemotherapy upregulated transcriptional programs of epithelial-to-mesenchymal transition (EMT) and stemness. To our surprise, the same cells showed a pronounced reduction of polycomb repressive complex 2 (PRC2) activity via downregulation of its subunits Ezh2, Suz12, Rbbp7 and Mtf2. Mechanistically, loss of PRC2 activity leads to the de-repression of a set of genes through an epigenetic switch from repressive H3K27me3 to activating H3K27ac mark at regulatory regions. We identified Nfatc1 as an upregulated gene upon loss of PRC2 activity and directly implicated in the transcriptional changes happening upon survival to chemotherapy. Blocking NFATc1 activation reduced epithelial-to-mesenchymal transition, aggressiveness, and therapy resistance of BLBC cells. Our data demonstrate a previously unknown function of PRC2 maintaining low Nfatc1 expression levels and thereby repressing aggressiveness and therapy resistance in BLBC.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34845197',
			'doi' => '10.1038/s41419-021-04407-y',
			'modified' => '2022-05-20 09:21:56',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 28 => array(
			'id' => '4276',
			'name' => 'Ago1 controls myogenic differentiation by regulating eRNA-mediatedCBP-guided epigenome reprogramming.',
			'authors' => 'Fallatah Bodor et al.',
			'description' => '<p>The role of chromatin-associated RNAi components in the nucleus of mammalian cells and in particular in the context of developmental programs remains to be elucidated. Here, we investigate the function of nuclear Argonaute 1 (Ago1) in gene expression regulation during skeletal muscle differentiation. We show that Ago1 is required for activation of the myogenic program by supporting chromatin modification mediated by developmental enhancer activation. Mechanistically, we demonstrate that Ago1 directly controls global H3K27 acetylation (H3K27ac) by regulating enhancer RNA (eRNA)-CREB-binding protein (CBP) acetyltransferase interaction, a key step in enhancer-driven gene activation. In particular, we show that Ago1 is specifically required for myogenic differentiation 1 (MyoD) and downstream myogenic gene activation, whereas its depletion leads to failure of CBP acetyltransferase activation and blocking of the myogenic program. Our work establishes a role of the mammalian enhancer-associated RNAi component Ago1 in epigenome regulation and activation of developmental programs.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.celrep.2021.110066',
			'doi' => '10.1016/j.celrep.2021.110066',
			'modified' => '2022-05-23 09:53:14',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 29 => array(
			'id' => '4833',
			'name' => 'Extensive NEUROG3 occupancy in the human pancreatic endocrine generegulatory network.',
			'authors' => 'Schreiber  V. et al.',
			'description' => '<p>OBJECTIVE: Mice lacking the bHLH transcription factor (TF) Neurog3 do not form pancreatic islet cells, including insulin-secreting beta cells, the absence of which leads to diabetes. In humans, homozygous mutations of NEUROG3 manifest with neonatal or childhood diabetes. Despite this critical role in islet cell development, the precise function of and downstream genetic programs regulated directly by NEUROG3 remain elusive. Therefore, we mapped genome-wide NEUROG3 occupancy in human induced pluripotent stem cell (hiPSC)-derived endocrine progenitors and determined NEUROG3 dependency of associated genes to uncover direct targets. METHODS: We generated a novel hiPSC line (NEUROG3-HA-P2A-Venus) where NEUROG3 is HA-tagged and fused to a self-cleaving fluorescent VENUS reporter. We used the CUT\&amp;RUN technique to map NEUROG3 occupancy and epigenetic marks in pancreatic endocrine progenitors (PEP) that were differentiated from this hiPSC line. We integrated NEUROG3 occupancy data with chromatin status and gene expression in PEPs as well as their NEUROG3-dependence. In addition, we investigated whether NEUROG3 binds type 2 diabetes mellitus (T2DM)-associated variants at the PEP stage. RESULTS: CUT\&amp;RUN revealed a total of 863 NEUROG3 binding sites assigned to 1263 unique genes. NEUROG3 occupancy was found at promoters as well as at distant cis-regulatory elements that frequently overlapped within PEP active enhancers. De novo motif analyses defined a NEUROG3 consensus binding motif and suggested potential co-regulation of NEUROG3 target genes by FOXA or RFX transcription factors. We found that 22\% of the genes downregulated in NEUROG3 PEPs, and 10\% of genes enriched in NEUROG3-Venus positive endocrine cells were bound by NEUROG3 and thus likely to be directly regulated. NEUROG3 binds to 138 transcription factor genes, some with important roles in islet cell development or function, such as NEUROD1, PAX4, NKX2-2, SOX4, MLXIPL, LMX1B, RFX3, and NEUROG3 itself, and many others with unknown islet function. Unexpectedly, we uncovered that NEUROG3 targets genes critical for insulin secretion in beta cells (e.g., GCK, ABCC8/KCNJ11, CACNA1A, CHGA, SCG2, SLC30A8, and PCSK1). Thus, analysis of NEUROG3 occupancy suggests that the transient expression of NEUROG3 not only promotes islet destiny in uncommitted pancreatic progenitors, but could also initiate endocrine programs essential for beta cell function. Lastly, we identified eight T2DM risk SNPs within NEUROG3-bound regions. CONCLUSION: Mapping NEUROG3 genome occupancy in PEPs uncovered unexpectedly broad, direct control of the endocrine genes, raising novel hypotheses on how this master regulator controls islet and beta cell differentiation.</p>',
			'date' => '2021-11-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.04.14.439685',
			'doi' => '10.1016/j.molmet.2021.101313',
			'modified' => '2023-08-01 13:46:35',
			'created' => '2023-08-01 15:59:38',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 30 => array(
			'id' => '4285',
			'name' => 'Alveolar macrophages from persons living with HIV show impairedepigenetic response to Mycobacterium tuberculosis.',
			'authors' => 'Correa-Macedo Wilian et al.',
			'description' => '<p>Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV and antiretroviral therapy (ART) impact on the anti-mycobacterial response of AM is not known. To investigate the impact of HIV and ART on the transcriptomic and epigenetic response of AM to Mtb, we obtained AM by bronchoalveolar lavage from 20 PLWH receiving ART, 16 control subjects who were HIV-free (HC), and 14 subjects who received ART as pre-exposure prophylaxis (PrEP) to prevent HIV infection. Following in-vitro challenge with Mtb, AM from each group displayed overlapping but distinct profiles of significantly up- and down-regulated genes in response to Mtb. Comparatively, AM isolated from both PLWH and PrEP subjects presented a substantially weaker transcriptional response. In addition, AM from HC subjects challenged with Mtb responded with pronounced chromatin accessibility changes while AM obtained from PLWH and PrEP subjects displayed no significant changes in their chromatin state. Collectively, these results revealed a stronger adverse effect of ART than HIV on the epigenetic landscape and transcriptional responsiveness of AM.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/34473646/',
			'doi' => '10.1172/JCI148013',
			'modified' => '2022-05-24 09:08:39',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 31 => 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) 32 => array(
			'id' => '4304',
			'name' => 'The related coactivator complexes SAGA and ATAC control embryonicstem cell self-renewal through acetyltransferase-independent mechanisms',
			'authors' => 'Fischer Veronique et al.',
			'description' => '<p>SUMMARY SAGA (Spt-Ada-Gcn5 acetyltransferase) and ATAC (Ada-two-A-containing) are two related coactivator complexes, sharing the same histone acetyltransferase (HAT) subunit. The HAT activities of SAGA and ATAC are required for metazoan development, but the role of these complexes in RNA polymerase II transcription is less understood. To determine whether SAGA and ATAC have redundant or specific functions, we compare the effects of HAT inactivation in each complex with that of inactivation of either SAGA or ATAC core subunits in mouse embryonic stem cells (ESCs). We show that core subunits of SAGA or ATAC are required for complex assembly and mouse ESC growth and self-renewal. Surprisingly, depletion of HAT module subunits causes a global decrease in histone H3K9 acetylation, but does not result in significant phenotypic or transcriptional defects. Thus, our results indicate that SAGA and ATAC are differentially required for self-renewal of mouse ESCs by regulating transcription through different pathways in a HAT-independent manner.</p>',
			'date' => '2021-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34433046',
			'doi' => '10.1016/j.celrep.2021.109598',
			'modified' => '2022-05-30 09:57:39',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 33 => array(
			'id' => '4345',
			'name' => 'Altered Chromatin States Drive Cryptic Transcription in AgingMammalian Stem Cells.',
			'authors' => 'McCauley Brenna S et al.',
			'description' => '<p>A repressive chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation suppresses cryptic transcription in embryonic stem cells. Cryptic transcription is elevated with age in yeast and nematodes, and reducing it extends yeast lifespan, though whether this occurs in mammals is unknown. We show that cryptic transcription is elevated in aged mammalian stem cells, including murine hematopoietic stem cells (mHSCs) and neural stem cells (NSCs) and human mesenchymal stem cells (hMSCs). Precise mapping allowed quantification of age-associated cryptic transcription in hMSCs aged . Regions with significant age-associated cryptic transcription have a unique chromatin signature: decreased H3K36me3 and increased H3K4me1, H3K4me3, and H3K27ac with age. Genomic regions undergoing such changes resemble known promoter sequences and are bound by TBP even in young cells. Hence, the more permissive chromatin state at intragenic cryptic promoters likely underlies increased cryptic transcription in aged mammalian stem cells.</p>',
			'date' => '2021-08-01',
			'pmid' => 'https://doi.org/10.1038%2Fs43587-021-00091-x',
			'doi' => '10.1038/s43587-021-00091-x',
			'modified' => '2022-06-22 12:30:19',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 34 => array(
			'id' => '4333',
			'name' => 'Metabolically controlled histone H4K5 acylation/acetylation ratiodrives BRD4 genomic distribution.',
			'authors' => 'Gao M. et al.',
			'description' => '<p>In addition to acetylation, histones are modified by a series of competing longer-chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions hinder our understanding of histone acylations' specific roles. Here, by using an acute lymphoblastic leukemia (ALL) cell model and blasts from individuals with B-precusor ALL (B-ALL), we demonstrate a role of mitochondrial activity in controlling the histone acylation/acetylation ratio, especially at histone H4 lysine 5 (H4K5). An increase in the ratio of non-acetyl acylations (crotonylation or butyrylation) over acetylation on H4K5 weakens bromodomain containing protein 4 (BRD4) bromodomain-dependent chromatin interaction and enhances BRD4 nuclear mobility and availability for binding transcription start site regions of active genes. Our data suggest that the metabolism-driven control of the histone acetylation/longer-chain acylation(s) ratio could be a common mechanism regulating the bromodomain factors' functional genomic distribution.</p>',
			'date' => '2021-07-01',
			'pmid' => 'https://doi.org/10.1016%2Fj.celrep.2021.109460',
			'doi' => '10.1016/j.celrep.2021.109460',
			'modified' => '2022-08-03 16:14:09',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 35 => array(
			'id' => '4341',
			'name' => 'Heterogeneity of neurons reprogrammed from spinal cord astrocytes by theproneural factors Ascl1 and Neurogenin2',
			'authors' => 'Kempf J. et al. ',
			'description' => '<p>Summary Astrocytes are a viable source for generating new neurons via direct conversion. However, little is known about the neurogenic cascades triggered in astrocytes from different regions of the CNS. Here, we examine the transcriptome induced by the proneural factors Ascl1 and Neurog2 in spinal cord-derived astrocytes in vitro. Each factor initially elicits different neurogenic programs that later converge to a V2 interneuron-like state. Intriguingly, patch sequencing (patch-seq) shows no overall correlation between functional properties and the transcriptome of the heterogenous induced neurons, except for K-channels. For example, some neurons with fully mature electrophysiological properties still express astrocyte genes, thus calling for careful molecular and functional analysis. Comparing the transcriptomes of spinal cord- and cerebral-cortex-derived astrocytes reveals profound differences, including developmental patterning cues maintained in vitro. These relate to the distinct neuronal identity elicited by Ascl1 and Neurog2 reflecting their developmental functions in subtype specification of the respective CNS region.</p>',
			'date' => '2021-07-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34289357',
			'doi' => '10.1016/j.celrep.2021.109409',
			'modified' => '2022-08-03 16:29:33',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 36 => 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) 37 => 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) 38 => array(
			'id' => '4147',
			'name' => 'Waves of sumoylation support transcription dynamics during adipocytedifferentiation',
			'authors' => 'Zhao, X. et al.',
			'description' => '<p>Tight control of gene expression networks required for adipose tissue formation and plasticity is essential for adaptation to energy needs and environmental cues. However, little is known about the mechanisms that orchestrate the dramatic transcriptional changes leading to adipocyte differentiation. We investigated the regulation of nascent transcription by the sumoylation pathway during adipocyte differentiation using SLAMseq and ChIPseq. We discovered that the sumoylation pathway has a dual function in differentiation; it supports the initial downregulation of pre-adipocyte-specific genes, while it promotes the establishment of the mature adipocyte transcriptional program. By characterizing sumoylome dynamics in differentiating adipocytes by mass spectrometry, we found that sumoylation of specific transcription factors like Ppar&gamma;/RXR and their co-factors is associated with the transcription of adipogenic genes. Our data demonstrate that the sumoylation pathway coordinates the rewiring of transcriptional networks required for formation of functional adipocytes. This study also provides an in-depth resource of gene transcription dynamics, SUMO-regulated genes and sumoylation sites during adipogenesis.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.02.20.432084',
			'doi' => '10.1101/2021.02.20.432084',
			'modified' => '2021-12-14 09:23:28',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 39 => array(
			'id' => '4192',
			'name' => 'Polycomb Repressive Complex 2 and KRYPTONITE regulate pathogen-inducedprogrammed cell death in Arabidopsis.',
			'authors' => 'Dvořák Tomaštíková E. et al.',
			'description' => '<p>The Polycomb Repressive Complex 2 (PRC2) is well-known for its role in controlling developmental transitions by suppressing the premature expression of key developmental regulators. Previous work revealed that PRC2 also controls the onset of senescence, a form of developmental programmed cell death (PCD) in plants. Whether the induction of PCD in response to stress is similarly suppressed by the PRC2 remained largely unknown. In this study, we explored whether PCD triggered in response to immunity- and disease-promoting pathogen effectors is associated with changes in the distribution of the PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) modification in Arabidopsis thaliana. We furthermore tested the distribution of the heterochromatic histone mark H3K9me2, which is established, to a large extent, by the H3K9 methyltransferase KRYPTONITE, and occupies chromatin regions generally not targeted by PRC2. We report that effector-induced PCD caused major changes in the distribution of both repressive epigenetic modifications and that both modifications have a regulatory role and impact on the onset of PCD during pathogen infection. Our work highlights that the transition to pathogen-induced PCD is epigenetically controlled, revealing striking similarities to developmental PCD.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33566101',
			'doi' => '10.1093/plphys/kiab035',
			'modified' => '2022-01-06 14:12:23',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 40 => array(
			'id' => '4273',
			'name' => 'An integrated multi-omics analysis identifies prognostic molecularsubtypes of non-muscle-invasive bladder cancer',
			'authors' => 'Lindskrog Sia Viborg et al.',
			'description' => '<p>The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n&thinsp;=&thinsp;834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.</p>',
			'date' => '2021-04-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33863885',
			'doi' => '10.1038/s41467-021-22465-w',
			'modified' => '2022-05-23 09:49:43',
			'created' => '2022-05-19 10:41:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 41 => 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) 42 => array(
			'id' => '4109',
			'name' => 'VPRBP functions downstream of the androgen receptor and OGT to restrict p53 activation in prostate cancer ',
			'authors' => 'Poulose N. et al. ',
			'description' => '<p>Androgen receptor (AR) is a major driver of prostate cancer (PCa) initiation and progression. O-GlcNAc transferase (OGT), the enzyme that catalyses the covalent addition of UDP-N-acetylglucosamine (UDP-GlcNAc) to serine and threonine residues of proteins, is often up-regulated in PCa with its expression correlated with high Gleason score. In this study we have identified an AR and OGT co-regulated factor, VPRBP/DCAF1. We show that VPRBP is regulated by the AR at the transcript level, and by OGT at the protein level. In human tissue samples, VPRBP protein expression correlated with AR amplification, OGT overexpression and poor prognosis. VPRBP knockdown in prostate cancer cells led to a significant decrease in cell proliferation, p53 stabilization, nucleolar fragmentation and increased p53 recruitment to the chromatin. In conclusion, we have shown that VPRBP/DCAF1 promotes prostate cancer cell proliferation by restraining p53 activation under the influence of the AR and OGT.</p>',
			'date' => '2021-02-21',
			'pmid' => 'https://www.biorxiv.org/content/10.1101/2021.02.28.433236v1',
			'doi' => '',
			'modified' => '2021-07-07 11:59:15',
			'created' => '2021-07-07 11:59:15',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 43 => array(
			'id' => '4124',
			'name' => 'JAZF1, A Novel p400/TIP60/NuA4 Complex Member, Regulates H2A.ZAcetylation at Regulatory Regions.',
			'authors' => 'Procida, Tara and Friedrich, Tobias and Jack, Antonia P M and Peritore,Martina and Bönisch, Clemens and Eberl, H Christian and Daus, Nadine andKletenkov, Konstantin and Nist, Andrea and Stiewe, Thorsten and Borggrefe,Tilman and Mann, Matthias and Bartk',
			'description' => '<p>Histone variants differ in amino acid sequence, expression timing and genomic localization sites from canonical histones and convey unique functions to eukaryotic cells. Their tightly controlled spatial and temporal deposition into specific chromatin regions is accomplished by dedicated chaperone and/or remodeling complexes. While quantitatively identifying the chaperone complexes of many human H2A variants by using mass spectrometry, we also found additional members of the known H2A.Z chaperone complexes p400/TIP60/NuA4 and SRCAP. We discovered JAZF1, a nuclear/nucleolar protein, as a member of a p400 sub-complex containing MBTD1 but excluding ANP32E. Depletion of JAZF1 results in transcriptome changes that affect, among other pathways, ribosome biogenesis. To identify the underlying molecular mechanism contributing to JAZF1's function in gene regulation, we performed genome-wide ChIP-seq analyses. Interestingly, depletion of JAZF1 leads to reduced H2A.Z acetylation levels at &gt; 1000 regulatory sites without affecting H2A.Z nucleosome positioning. Since JAZF1 associates with the histone acetyltransferase TIP60, whose depletion causes a correlated H2A.Z deacetylation of several JAZF1-targeted enhancer regions, we speculate that JAZF1 acts as chromatin modulator by recruiting TIP60's enzymatic activity. Altogether, this study uncovers JAZF1 as a member of a TIP60-containing p400 chaperone complex orchestrating H2A.Z acetylation at regulatory regions controlling the expression of genes, many of which are involved in ribosome biogenesis.</p>',
			'date' => '2021-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33445503',
			'doi' => '10.3390/ijms22020678',
			'modified' => '2021-12-07 10:00:44',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 44 => array(
			'id' => '4153',
			'name' => 'Epigenetic impairment and blunted transcriptional response to Mycobacteriumtuberculosis of alveolar macrophages from persons living with HIV',
			'authors' => 'Correa-Macedo, W. et al.',
			'description' => '<p>Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV and antiretroviral therapy (ART) impact on the anti-mycobacterial response of AM is not known. To investigate the impact of HIV and ART on the transcriptomic and epigenetic response of AM to Mtb, we obtained AM by bronchoalveolar lavage from 20 PLWH receiving ART, 16 control subjects who were HIV-free (HC), and 14 subjects who received ART as pre-exposure prophylaxis (PrEP) to prevent HIV infection. Following in-vitro challenge with Mtb, AM from each group displayed overlapping but distinct profiles of significantly up- and down-regulated genes in response to Mtb. Compared to HC subjects, AM isolated from PLWH and PrEP subjects presented a substantially weaker transcriptional response. Further investigation of chromatin structure revealed that AM from control subjects challenged with Mtb responded with pronounced accessibility changes in over ten thousand regions. In stark contrast, AM obtained from PLWH and PrEP subjects displayed no significant changes in their chromatin state in response to Mtb. Collectively, these results revealed a previously unknown adverse effect of ART on the epigenetic landscape and transcriptional responsiveness of AM.</p>',
			'date' => '2021-01-01',
			'pmid' => 'https://doi.org/10.1101%2F2021.01.26.21250318',
			'doi' => '10.1101/2021.01.26.21250318',
			'modified' => '2021-12-16 10:35:21',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 45 => array(
			'id' => '4179',
			'name' => 'Histone demethylase JMJD2B/KDM4B regulates transcriptional program viadistinctive epigenetic targets and protein interactors for the maintenanceof trophoblast stem cells.',
			'authors' => 'Mak, Kylie Hin-Man et al.',
			'description' => '<p>Trophoblast stem cell (TSC) is crucial to the formation of placenta in mammals. Histone demethylase JMJD2 (also known as KDM4) family proteins have been previously shown to support self-renewal and differentiation of stem cells. However, their roles in the context of the trophoblast lineage remain unclear. Here, we find that knockdown of Jmjd2b resulted in differentiation of TSCs, suggesting an indispensable role of JMJD2B/KDM4B in maintaining the stemness. Through the integration of transcriptome and ChIP-seq profiling data, we show that JMJD2B is associated with a loss of H3K36me3 in a subset of embryonic lineage genes which are marked by H3K9me3 for stable repression. By characterizing the JMJD2B binding motifs and other transcription factor binding datasets, we discover that JMJD2B forms a protein complex with AP-2 family transcription factor TFAP2C and histone demethylase LSD1. The JMJD2B-TFAP2C-LSD1 complex predominantly occupies active gene promoters, whereas the TFAP2C-LSD1 complex is located at putative enhancers, suggesting that these proteins mediate enhancer-promoter interaction for gene regulation. We conclude that JMJD2B is vital to the TSC transcriptional program and safeguards the trophoblast cell fate via distinctive protein interactors and epigenetic targets.</p>',
			'date' => '2021-01-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33441614',
			'doi' => '10.1038/s41598-020-79601-7',
			'modified' => '2021-12-21 16:43:16',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 46 => array(
			'id' => '4038',
			'name' => 'Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture.',
			'authors' => 'Yusufova, Nevin and Kloetgen, Andreas and Teater, Matt and Osunsade,Adewola and Camarillo, Jeannie M and Chin, Christopher R and Doane, AshleyS and Venters, Bryan J and Portillo-Ledesma, Stephanie and Conway, Josephand Phillip, Jude M and Elemento, Oli',
			'description' => '<p>Linker histone H1 proteins bind to nucleosomes and facilitate chromatin compaction, although their biological functions are poorly understood. Mutations in the genes that encode H1 isoforms B-E (H1B, H1C, H1D and H1E; also known as H1-5, H1-2, H1-3 and H1-4, respectively) are highly recurrent in B&nbsp;cell lymphomas, but the pathogenic relevance of these mutations to cancer and the mechanisms that are involved are unknown. Here we show that lymphoma-associated H1 alleles are genetic driver mutations in lymphomas. Disruption of H1 function results in a profound architectural remodelling of the genome, which is characterized by large-scale yet focal shifts of chromatin from a compacted to a relaxed state. This decompaction drives distinct changes in epigenetic states, primarily owing to a gain of histone H3 dimethylation at lysine 36 (H3K36me2) and/or loss of repressive H3 trimethylation at lysine 27 (H3K27me3). These changes unlock the expression of stem cell genes that are normally silenced during early development. In mice, loss of H1c and H1e (also known as H1f2 and H1f4, respectively) conferred germinal centre B&nbsp;cells with enhanced fitness and self-renewal properties, ultimately leading to aggressive lymphomas with an increased repopulating potential. Collectively, our data indicate that H1 proteins are normally required to sequester early developmental genes into architecturally inaccessible genomic compartments. We also establish H1 as a bona fide tumour suppressor and show that mutations in H1 drive malignant transformation primarily through three-dimensional genome reorganization, which leads to epigenetic reprogramming and derepression of developmentally silenced genes.</p>',
			'date' => '2020-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33299181',
			'doi' => '10.1038/s41586-020-3017-y',
			'modified' => '2021-02-18 17:15:52',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 47 => array(
			'id' => '4056',
			'name' => 'Multi-omic comparison of Alzheimer's variants in human ESC-derivedmicroglia reveals convergence at APOE.',
			'authors' => 'Liu, Tongfei and Zhu, Bing and Liu, Yan and Zhang, Xiaoming and Yin, Junand Li, Xiaoguang and Jiang, LuLin and Hodges, Andrew P and Rosenthal, SaraBrin and Zhou, Lisa and Yancey, Joel and McQuade, Amanda and Blurton-Jones,Mathew and Tanzi, Rudolph E an',
			'description' => '<p>Variations in many genes linked to sporadic Alzheimer's disease (AD) show abundant expression in microglia, but relationships among these genes remain largely elusive. Here, we establish isogenic human ESC-derived microglia-like cell lines (hMGLs) harboring AD variants in CD33, INPP5D, SORL1, and TREM2 loci and curate a comprehensive atlas comprising ATAC-seq, ChIP-seq, RNA-seq, and proteomics datasets. AD-like expression signatures are observed in AD mutant SORL1 and TREM2 hMGLs, while integrative multi-omic analysis of combined epigenetic and expression datasets indicates up-regulation of APOE as a convergent pathogenic node. We also observe cross-regulatory relationships between SORL1 and TREM2, in which SORL1R744X hMGLs induce TREM2 expression to enhance APOE expression. AD-associated SORL1 and TREM2 mutations also impaired hMGL A&beta; uptake in an APOE-dependent manner in vitro and attenuated A&beta; uptake/clearance in mouse AD brain xenotransplants. Using this modeling and analysis platform for human microglia, we provide new insight into epistatic interactions in AD genes and demonstrate convergence of microglial AD genes at the APOE locus.</p>',
			'date' => '2020-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32941599',
			'doi' => '10.1084/jem.20200474',
			'modified' => '2021-02-19 17:18:23',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 48 => array(
			'id' => '4060',
			'name' => 'A genetic variant controls interferon-β gene expression in human myeloidcells by preventing C/EBP-β binding on a conserved enhancer.',
			'authors' => 'Assouvie, Anaïs and Rotival, Maxime and Hamroune, Juliette and Busso,Didier and Romeo, Paul-Henri and Quintana-Murci, Lluis and Rousselet,Germain',
			'description' => '<p>Interferon &beta; (IFN-&beta;) is a cytokine that induces a global antiviral proteome, and regulates the adaptive immune response to infections and tumors. Its effects strongly depend on its level and timing of expression. Therefore, the transcription of its coding gene IFNB1 is strictly controlled. We have previously shown that in mice, the TRIM33 protein restrains Ifnb1 transcription in activated myeloid cells through an upstream inhibitory sequence called ICE. Here, we show that the deregulation of Ifnb1 expression observed in murine Trim33-/- macrophages correlates with abnormal looping of both ICE and the Ifnb1 gene to a 100 kb downstream region overlapping the Ptplad2/Hacd4 gene. This region is a predicted myeloid super-enhancer in which we could characterize 3 myeloid-specific active enhancers, one of which (E5) increases the response of the Ifnb1 promoter to activation. In humans, the orthologous region contains several single nucleotide polymorphisms (SNPs) known to be associated with decreased expression of IFNB1 in activated monocytes, and loops to the IFNB1 gene. The strongest association is found for the rs12553564 SNP, located in the E5 orthologous region. The minor allele of rs12553564 disrupts a conserved C/EBP-&beta; binding motif, prevents binding of C/EBP-&beta;, and abolishes the activation-induced enhancer activity of E5. Altogether, these results establish a link between a genetic variant preventing binding of a transcription factor and a higher order phenotype, and suggest that the frequent minor allele (around 30\% worldwide) might be associated with phenotypes regulated by IFN-&beta; expression in myeloid cells.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33147208',
			'doi' => '10.1371/journal.pgen.1009090',
			'modified' => '2021-02-19 17:29:34',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 49 => 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) 50 => array(
			'id' => '4210',
			'name' => 'Trans- and cis-acting effects of Firre on epigenetic features of theinactive X chromosome.',
			'authors' => 'Fang, He and Bonora, Giancarlo and Lewandowski, Jordan P and Thakur,Jitendra and Filippova, Galina N and Henikoff, Steven and Shendure, Jay andDuan, Zhijun and Rinn, John L and Deng, Xinxian and Noble, William S andDisteche, Christine M',
			'description' => '<p>Firre encodes a lncRNA involved in nuclear organization. Here, we show that Firre RNA expressed from the active X chromosome maintains histone H3K27me3 enrichment on the inactive X chromosome (Xi) in somatic cells. This trans-acting effect involves SUZ12, reflecting interactions between Firre RNA and components of the Polycomb repressive complexes. Without Firre RNA, H3K27me3 decreases on the Xi and the&nbsp;Xi-perinucleolar location is disrupted, possibly due to decreased CTCF binding on the Xi. We also observe widespread gene dysregulation, but not on the Xi. These effects are measurably rescued by ectopic expression of mouse or human Firre/FIRRE transgenes, supporting conserved trans-acting roles. We also find that the compact 3D structure of the Xi partly depends on the Firre locus and its RNA. In common lymphoid progenitors and T-cells Firre exerts a cis-acting effect on maintenance of H3K27me3 in a 26&thinsp;Mb region around the locus, demonstrating cell type-specific trans- and cis-acting roles of this lncRNA.</p>',
			'date' => '2020-11-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33247132',
			'doi' => '10.1038/s41467-020-19879-3',
			'modified' => '2022-01-13 15:03:45',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 51 => array(
			'id' => '4048',
			'name' => 'The histone H2B ubiquitin ligase RNF40 is required for HER2-drivenmammary tumorigenesis.',
			'authors' => 'Wegwitz, Florian and Prokakis, Evangelos and Pejkovska, Anastasija andKosinsky, Robyn Laura and Glatzel, Markus and Pantel, Klaus and Wikman,Harriet and Johnsen, Steven A',
			'description' => '<p>The HER2-positive breast cancer subtype (HER2-BC) displays a particularly aggressive behavior. Anti-HER2 therapies have significantly improved the survival of patients with HER2-BC. However, a large number of patients become refractory to current targeted therapies, necessitating the development of new treatment strategies. Epigenetic regulators are commonly misregulated in cancer and represent attractive molecular therapeutic targets. Monoubiquitination of histone 2B (H2Bub1) by the heterodimeric ubiquitin ligase complex RNF20/RNF40 has been described to have tumor suppressor functions and loss of H2Bub1 has been associated with cancer progression. In this study, we utilized human tumor samples, cell culture models, and a mammary carcinoma mouse model with tissue-specific Rnf40 deletion and identified an unexpected tumor-supportive role of RNF40 in HER2-BC. We demonstrate that RNF40-driven H2B monoubiquitination is essential for transcriptional activation of RHO/ROCK/LIMK pathway components and proper actin-cytoskeleton dynamics through a trans-histone crosstalk with histone 3 lysine 4 trimethylation (H3K4me3). Collectively, this work demonstrates a previously unknown essential role of RNF40 in HER2-BC, revealing the H2B monoubiquitination axis as a possible tumor context-dependent therapeutic target in breast cancer.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33070155',
			'doi' => '10.1038/s41419-020-03081-w',
			'modified' => '2021-02-19 14:03:18',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 52 => array(
			'id' => '4065',
			'name' => 'Polycomb Repressive Complex 2-mediated histone modification H3K27me3 isassociated with embryogenic potential in Norway spruce.',
			'authors' => 'Nakamura, Miyuki and Batista, Rita A and Köhler, Claudia and Hennig, Lars',
			'description' => '<p>Epigenetic reprogramming during germ cell formation is essential to gain pluripotency and thus embryogenic potential. The histone modification H3K27me3, which is catalysed by the Polycomb repressive complex 2 (PRC2), regulates important developmental processes in both plants and animals, and defects in PRC2 components cause pleiotropic developmental abnormalities. Nevertheless, the role of H3K27me3 in determining embryogenic potential in gymnosperms is still elusive. To address this, we generated H3K27me3 profiles of Norway spruce (Picea abies) embryonic callus and non-embryogenic callus using CUT\&amp;RUN, which is a powerful method for chromatin profiling. Here, we show that H3K27me3 mainly accumulated in genic regions in the Norway spruce genome, similarly to what is observed in other plant species. Interestingly, H3K27me3 levels in embryonic callus were much lower than those in the other examined tissues, but markedly increased upon embryo induction. These results show that H3K27me3 levels are associated with the embryogenic potential of a given tissue, and that the early phase of somatic embryogenesis is accompanied by changes in H3K27me3 levels. Thus, our study provides novel insights into the role of this epigenetic mark in spruce embryogenesis and reinforces the importance of PRC2 as a key regulator of cell fate determination across different plant species.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32894759',
			'doi' => '10.1093/jxb/eraa365',
			'modified' => '2021-02-19 17:45:29',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 53 => array(
			'id' => '4384',
			'name' => 'Age-associated cryptic transcription in mammalian stem cells is linked topermissive chromatin at cryptic promoters',
			'authors' => 'McCauley  B. S. et al.',
			'description' => '<p>Suppressing spurious cryptic transcription by a repressive intragenic chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation is critical for maintaining self-renewal capacity in mouse embryonic stem cells. In yeast and nematodes, such cryptic transcription is elevated with age, and reducing the levels of age-associated cryptic transcription extends yeast lifespan. Whether cryptic transcription is also increased during mammalian aging is unknown. We show for the first time an age-associated elevation in cryptic transcription in several stem cell populations, including murine hematopoietic stem cells (mHSCs) and neural stem cells (NSCs) and human mesenchymal stem cells (hMSCs). Using DECAP-seq, we mapped and quantified age-associated cryptic transcription in hMSCs aged in vitro. Regions with significant age-associated cryptic transcription have a unique chromatin signature: decreased H3K36me3 and increased H3K4me1, H3K4me3, and H3K27ac with age. Furthermore, genomic regions undergoing such age-dependent chromatin changes resemble known promoter sequences and are bound by the promoter-associated protein TBP even in young cells. Hence, the more permissive chromatin state at intragenic cryptic promoters likely underlies the increase of cryptic transcription in aged mammalian stem cells.</p>',
			'date' => '2020-10-01',
			'pmid' => 'https://europepmc.org/article/ppr/ppr221829',
			'doi' => '10.21203/rs.3.rs-82156/v1',
			'modified' => '2022-08-04 16:24:46',
			'created' => '2022-08-04 14:55:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 54 => array(
			'id' => '4076',
			'name' => 'RNF40 exerts stage-dependent functions in differentiating osteoblasts andis essential for bone cell crosstalk.',
			'authors' => 'Najafova, Zeynab and Liu, Peng and Wegwitz, Florian and Ahmad, Mubashir andTamon, Liezel and Kosinsky, Robyn Laura and Xie, Wanhua and Johnsen, StevenA and Tuckermann, Jan',
			'description' => '<p>The role of histone ubiquitination in directing cell lineage specification is only poorly understood. Our previous work indicated a role of the histone 2B ubiquitin ligase RNF40 in controlling osteoblast differentiation in vitro. Here, we demonstrate that RNF40 has a stage-dependent function in controlling osteoblast differentiation in vivo. RNF40 expression is essential for early stages of lineage specification, but is dispensable in mature osteoblasts. Paradoxically, while osteoblast-specific RNF40 deletion led to impaired bone formation, it also resulted in increased bone mass due to impaired bone cell crosstalk. Loss of RNF40 resulted in decreased osteoclast number and function through modulation of&nbsp;RANKL expression in OBs. Mechanistically, we demonstrate that&nbsp;Tnfsf11 (encoding RANKL)&nbsp;is an important target gene of H2B monoubiquitination. These data reveal an important role of RNF40-mediated H2B monoubiquitination in bone formation and remodeling and provide a basis for exploring this pathway for the treatment of conditions such as osteoporosis or cancer-associated osteolysis.</p>',
			'date' => '2020-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32901120',
			'doi' => '10.1038/s41418-020-00614-w',
			'modified' => '2021-02-19 18:10:55',
			'created' => '2021-02-18 10:21:53',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 55 => 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) 56 => array(
			'id' => '4010',
			'name' => 'Combined treatment with CBP and BET inhibitors reverses inadvertentactivation of detrimental super enhancer programs in DIPG cells.',
			'authors' => 'Wiese, M and Hamdan, FH and Kubiak, K and Diederichs, C and Gielen, GHand Nussbaumer, G and Carcaboso, AM and Hulleman, E and Johnsen, SA andKramm, CM',
			'description' => '<p>Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation. Hyperacetylation in DIPG favors the action of the Bromodomain and Extra-Terminal (BET) protein BRD4, and leads to the reprogramming of the enhancer landscape contributing to the activation of DIPG super enhancer-driven oncogenes. The activity of the acetyltransferase CREB-binding protein (CBP) is enhanced by BRD4 and associated with acetylation of nucleosomes at super enhancers (SE). In addition, CBP contributes to transcriptional activation through its function as a scaffold and protein bridge. Monotherapy with either a CBP (ICG-001) or BET inhibitor (JQ1) led to the reduction of tumor-related characteristics. Interestingly, combined treatment induced strong cytotoxic effects in H3.3K27M-mutated DIPG cell lines. RNA sequencing and chromatin immunoprecipitation revealed that these effects were caused by the inactivation of DIPG SE-controlled tumor-related genes. However, single treatment with ICG-001 or JQ1, respectively, led to activation of a subgroup of detrimental super enhancers. Combinatorial treatment reversed the inadvertent activation of these super enhancers and rescued the effect of ICG-001 and JQ1 single treatment on enhancer-driven oncogenes in H3K27M-mutated DIPG, but not in H3 wild-type pedHGG cells. In conclusion, combinatorial treatment with CBP and BET inhibitors is highly efficient in H3K27M-mutant DIPG due to reversal of inadvertent activation of detrimental SE programs in comparison with monotherapy.</p>',
			'date' => '2020-08-21',
			'pmid' => 'http://www.pubmed.gov/32826850',
			'doi' => '10.1038/s41419-020-02800-7',
			'modified' => '2020-12-18 13:25:09',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 57 => array(
			'id' => '4011',
			'name' => 'Exploring the virulence gene interactome with CRISPR/dCas9 in the humanmalaria parasite.',
			'authors' => 'Bryant, JM and Baumgarten, S and Dingli, F and Loew, D and Sinha, A andClaës, A and Preiser, PR and Dedon, PC and Scherf, A',
			'description' => '<p>Mutually exclusive expression of the var multigene family is key to immune evasion and pathogenesis in Plasmodium falciparum, but few factors have been shown to play a direct role. We adapted a CRISPR-based proteomics approach to identify novel factors associated with var genes in their natural chromatin context. Catalytically inactive Cas9 ("dCas9") was targeted to var gene regulatory elements, immunoprecipitated, and analyzed with mass spectrometry. Known and novel factors were enriched including structural proteins, DNA helicases, and chromatin remodelers. Functional characterization of PfISWI, an evolutionarily divergent putative chromatin remodeler enriched at the var gene promoter, revealed a role in transcriptional activation. Proteomics of PfISWI identified several proteins enriched at the var gene promoter such as acetyl-CoA synthetase, a putative MORC protein, and an ApiAP2 transcription factor. These findings validate the CRISPR/dCas9 proteomics method and define a new var gene-associated chromatin complex. This study establishes a tool for targeted chromatin purification of unaltered genomic loci and identifies novel chromatin-associated factors potentially involved in transcriptional control and/or chromatin organization of virulence genes in the human malaria parasite.</p>',
			'date' => '2020-08-02',
			'pmid' => 'http://www.pubmed.gov/32816370',
			'doi' => 'https://dx.doi.org/10.15252%2Fmsb.20209569',
			'modified' => '2020-12-18 13:26:33',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 58 => array(
			'id' => '4024',
			'name' => 'Tissue-Specific In Vivo Biotin Chromatin Immunoprecipitation withSequencing in Zebrafish and Chicken',
			'authors' => 'Lukoseviciute, Martyna and Ling, Irving T.C. and Senanayake, Upeka andCandido-Ferreira, Ivan and Taylor, Gunes and Williams, Ruth M. andSauka-Spengler, Tatjana',
			'description' => '<p>Chromatin immunoprecipitation with sequencing (ChIP-seq) has been instrumental in understanding transcription factor (TF) binding during gene regulation. ChIP-seq requires specific antibodies against desired TFs, which are not available for numerous species. Here, we describe a tissue-specific biotin ChIP-seq protocol for zebrafish and chicken embryos which utilizes AVI tagging of TFs, permitting their biotinylation by a co-expressed nuclear biotin ligase. Subsequently, biotinylated factors can be precipitated with streptavidin beads, enabling the user to construct TF genome-wide binding landscapes like conventional ChIP-seq methods.</p>',
			'date' => '2020-07-31',
			'pmid' => 'https://www.sciencedirect.com/science/article/pii/S2666166720300538',
			'doi' => '10.1016/j.xpro.2020.100066',
			'modified' => '2020-12-16 17:50:09',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 59 => array(
			'id' => '4026',
			'name' => 'The gut microbiome switches mutant p53 from tumour-suppressive tooncogenic.',
			'authors' => 'Kadosh, E and Snir-Alkalay, I and Venkatachalam, A and May, S and Lasry, Aand Elyada, E and Zinger, A and Shaham, M and Vaalani, G and Mernberger, Mand Stiewe, T and Pikarsky, E and Oren, M and Ben-Neriah, Y',
			'description' => '<p>Somatic mutations in p53, which inactivate the tumour-suppressor function of p53 and often confer oncogenic gain-of-function properties, are very common in cancer. Here we studied the effects of hotspot gain-of-function mutations in Trp53 (the gene that encodes p53 in mice) in mouse models of WNT-driven intestinal cancer caused by Csnk1a1 deletion or Apc mutation. Cancer in these models is known to be facilitated by loss of p53. We found that mutant versions of p53 had contrasting effects in different segments of the gut: in the distal gut, mutant p53 had the expected oncogenic effect; however, in the proximal gut and in tumour organoids it had a pronounced tumour-suppressive effect. In the tumour-suppressive mode, mutant p53 eliminated dysplasia and tumorigenesis in Csnk1a1-deficient and Apc mice, and promoted normal growth and differentiation of tumour organoids derived from these mice. In these settings, mutant p53 was more effective than wild-type p53 at inhibiting tumour formation. Mechanistically, the tumour-suppressive effects of mutant p53 were driven by disruption of the WNT pathway, through preventing the binding of TCF4 to chromatin. Notably, this tumour-suppressive effect was completely abolished by the gut microbiome. Moreover, a single metabolite derived from the gut microbiota-gallic acid-could reproduce the entire effect of the microbiome. Supplementing gut-sterilized p53-mutant mice and p53-mutant organoids with gallic acid reinstated the TCF4-chromatin interaction and the hyperactivation of WNT, thus conferring a malignant phenotype to the organoids and throughout the gut. Our study demonstrates the substantial plasticity of a cancer mutation and highlights the role of the microenvironment in determining its functional outcome.</p>',
			'date' => '2020-07-29',
			'pmid' => 'http://www.pubmed.gov/32728212',
			'doi' => '10.1038/s41586-020-2541-0',
			'modified' => '2020-12-16 17:52:28',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 60 => array(
			'id' => '3992',
			'name' => 'Egr2-guided histone H2B monoubiquitination is required for peripheral nervous system myelination.',
			'authors' => 'Wüst HM, Wegener A, Fröb F, Hartwig AC, Wegwitz F, Kari V, Schimmel M, Tamm ER, Johnsen SA, Wegner M, Sock E',
			'description' => '<p>Schwann cells are the nerve ensheathing cells of the peripheral nervous system. Absence, loss and malfunction of Schwann cells or their myelin sheaths lead to peripheral neuropathies such as Charcot-Marie-Tooth disease in humans. During Schwann cell development and myelination chromatin is dramatically modified. However, impact and functional relevance of these modifications are poorly understood. Here, we analyzed histone H2B monoubiquitination as one such chromatin modification by conditionally deleting the Rnf40 subunit of the responsible E3 ligase in mice. Rnf40-deficient Schwann cells were arrested immediately before myelination or generated abnormally thin, unstable myelin, resulting in a peripheral neuropathy characterized by hypomyelination and progressive axonal degeneration. By combining sequencing techniques with functional studies we show that H2B monoubiquitination does not influence global gene expression patterns, but instead ensures selective high expression of myelin and lipid biosynthesis genes and proper repression of immaturity genes. This requires the specific recruitment of the Rnf40-containing E3 ligase by Egr2, the central transcriptional regulator of peripheral myelination, to its target genes. Our study identifies histone ubiquitination as essential for Schwann cell myelination and unravels new disease-relevant links between chromatin modifications and transcription factors in the underlying regulatory network.</p>',
			'date' => '2020-07-16',
			'pmid' => 'http://www.pubmed.gov/32672815',
			'doi' => '10.1093/nar/gkaa606',
			'modified' => '2020-09-01 15:02:28',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 61 => array(
			'id' => '4031',
			'name' => 'Battle of the sex chromosomes: competition between X- and Y-chromosomeencoded proteins for partner interaction and chromatin occupancy drivesmulti-copy gene expression and evolution in muroid rodents.',
			'authors' => 'Moretti, C and Blanco, M and Ialy-Radio, C and Serrentino, ME and Gobé,C and Friedman, R and Battail, C and Leduc, M and Ward, MA and Vaiman, Dand Tores, F and Cocquet, J',
			'description' => '<p>Transmission distorters (TDs) are genetic elements that favor their own transmission to the detriments of others. Slx/Slxl1 (Sycp3-like-X-linked and Slx-like1) and Sly (Sycp3-like-Y-linked) are TDs which have been co-amplified on the X and Y chromosomes of Mus species. They are involved in an intragenomic conflict in which each favors its own transmission, resulting in sex ratio distortion of the progeny when Slx/Slxl1 vs. Sly copy number is unbalanced. They are specifically expressed in male postmeiotic gametes (spermatids) and have opposite effects on gene expression: Sly knockdown leads to the upregulation of hundreds of spermatid-expressed genes, while Slx/Slxl1-deficiency downregulates them. When both Slx/Slxl1 and Sly are knocked-down, sex ratio distortion and gene deregulation are corrected. Slx/Slxl1 and Sly are, therefore, in competition but the molecular mechanism remains unknown. By comparing their chromatin binding profiles and protein partners, we show that SLX/SLXL1 and SLY proteins compete for interaction with H3K4me3-reader SSTY1 (Spermiogenesis-specific-transcript-on-the-Y1) at the promoter of thousands of genes to drive their expression, and that the opposite effect they have on gene expression is mediated by different abilities to recruit SMRT/N-Cor transcriptional complex. Their target genes are predominantly spermatid-specific multicopy genes encoded by the sex chromosomes and the autosomal Speer/Takusan. Many of them have co-amplified with Slx/Slxl1/Sly but also Ssty during muroid rodent evolution. Overall, we identify Ssty as a key element of the X vs. Y intragenomic conflict, which may have influenced gene content and hybrid sterility beyond Mus lineage since Ssty amplification on the Y pre-dated that of Slx/Slxl1/Sly.</p>',
			'date' => '2020-07-13',
			'pmid' => 'http://www.pubmed.gov/32658962',
			'doi' => '10.1093/molbev/msaa175/5870835',
			'modified' => '2020-12-18 13:27:51',
			'created' => '2020-10-12 14:54:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 62 => array(
			'id' => '3948',
			'name' => '2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters hepatic polyunsaturated fatty acid metabolism and eicosanoid biosynthesis in female Sprague-Dawley rats.',
			'authors' => 'Doskey CM, Fader KA, Nault R, Lydic T, Matthews J, Potter D, Sharratt B, Williams K, Zacharewski T',
			'description' => '<p>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent aryl hydrocarbon receptor (AhR) agonist that elicits a broad spectrum of dose-dependent hepatic effects including lipid accumulation, inflammation, and fibrosis. To determine the role of inflammatory lipid mediators in TCDD-mediated hepatotoxicity, eicosanoid metabolism was investigated. Female Sprague-Dawley (SD) rats were orally gavaged with sesame oil vehicle or 0.01-10&nbsp;&mu;g/kg TCDD every 4&nbsp;days for 28&nbsp;days. Hepatic RNA-Seq data was integrated with untargeted metabolomics of liver, serum, and urine, revealing dose-dependent changes in linoleic acid (LA) and arachidonic acid (AA) metabolism. TCDD also elicited dose-dependent differential gene expression associated with the cyclooxygenase, lipoxygenase, and cytochrome P450 epoxidation/hydroxylation pathways with corresponding changes in &omega;-6 (e.g. AA and LA) and &omega;-3 polyunsaturated fatty acids (PUFAs), as well as associated eicosanoid metabolites. Overall, TCDD increased the ratio of &omega;-6 to &omega;-3 PUFAs. Phospholipase A2 (Pla2g12a) was induced consistent with increased AA metabolism, while AA utilization by induced lipoxygenases Alox5 and Alox15 increased leukotrienes (LTs). More specifically, TCDD increased pro-inflammatory eicosanoids including leukotriene LTB, and LTB, known to recruit neutrophils to damaged tissue. Dose-response modeling suggests the cytochrome P450 hydroxylase/epoxygenase and lipoxygenase pathways are more sensitive to TCDD than the cyclooxygenase pathway. Hepatic AhR ChIP-Seq analysis found little enrichment within the regulatory regions of differentially expressed genes (DEGs) involved in eicosanoid biosynthesis, suggesting TCDD-elicited dysregulation of eicosanoid metabolism is a downstream effect of AhR activation. Overall, these results suggest alterations in eicosanoid metabolism may play a key role in TCDD-elicited hepatotoxicity associated with the progression of steatosis to steatohepatitis.</p>',
			'date' => '2020-07-01',
			'pmid' => 'http://www.pubmed.gov/32387183',
			'doi' => '10.1016/j.taap.2020.115034',
			'modified' => '2020-08-17 10:04:38',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 63 => 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) 64 => array(
			'id' => '3981',
			'name' => 'Vulnerability of drug-resistant EML4-ALK rearranged lung cancer to transcriptional inhibition.',
			'authors' => 'Paliouras AR, Buzzetti M, Shi L, Donaldson IJ, Magee P, Sahoo S, Leong HS, Fassan M, Carter M, Di Leva G, Krebs MG, Blackhall F, Lovly CM, Garofalo M',
			'description' => '<p>A subset of lung adenocarcinomas is driven by the EML4-ALK translocation. Even though ALK inhibitors in the clinic lead to excellent initial responses, acquired resistance to these inhibitors due to on-target mutations or parallel pathway alterations is a major clinical challenge. Exploring these mechanisms of resistance, we found that EML4-ALK cells parental or resistant to crizotinib, ceritinib or alectinib are remarkably sensitive to inhibition of CDK7/12 with THZ1 and CDK9 with alvocidib or dinaciclib. These compounds robustly induce apoptosis through transcriptional inhibition and downregulation of anti-apoptotic genes. Importantly, alvocidib reduced tumour progression in xenograft mouse models. In summary, our study takes advantage of the transcriptional addiction hypothesis to propose a new treatment strategy for a subset of patients with acquired resistance to first-, second- and third-generation ALK inhibitors.</p>',
			'date' => '2020-06-17',
			'pmid' => 'http://www.pubmed.gov/32558295',
			'doi' => 'https://doi.org/10.15252/emmm.201911099',
			'modified' => '2020-09-01 15:20:40',
			'created' => '2020-08-21 16:41:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 65 => array(
			'id' => '3975',
			'name' => 'Removal of H2Aub1 by ubiquitin-specific proteases 12 and 13 is required for stable Polycomb-mediated gene repression in Arabidopsis.',
			'authors' => 'Kralemann LEM, Liu S, Trejo-Arellano MS, Muñoz-Viana R, Köhler C, Hennig L',
			'description' => '<p>BACKGROUND: Stable gene repression is essential for normal growth and development. Polycomb repressive complexes 1 and 2 (PRC1&amp;2) are involved in this process by establishing monoubiquitination of histone 2A (H2Aub1) and subsequent trimethylation of lysine 27 of histone 3 (H3K27me3). Previous work proposed that H2Aub1 removal by the ubiquitin-specific proteases 12 and 13 (UBP12 and UBP13) is part of the repressive PRC1&amp;2 system, but its functional role remains elusive. RESULTS: We show that UBP12 and UBP13 work together with PRC1, PRC2, and EMF1 to repress genes involved in stimulus response. We find that PRC1-mediated H2Aub1 is associated with gene responsiveness, and its repressive function requires PRC2 recruitment. We further show that the requirement of PRC1 for PRC2 recruitment depends on the initial expression status of genes. Lastly, we demonstrate that removal of H2Aub1 by UBP12/13 prevents loss of H3K27me3, consistent with our finding that the H3K27me3 demethylase REF6 is positively associated with H2Aub1. CONCLUSIONS: Our data allow us to propose a model in which deposition of H2Aub1 permits genes to switch between repression and activation by H3K27me3 deposition and removal. Removal of H2Aub1 by UBP12/13 is required to achieve stable PRC2-mediated repression.</p>',
			'date' => '2020-06-16',
			'pmid' => 'http://www.pubmed.gov/32546254',
			'doi' => '10.1186/s13059-020-02062-8',
			'modified' => '2020-08-12 09:23:32',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 66 => array(
			'id' => '3969',
			'name' => 'Delineating the early transcriptional specification of the mammalian trachea and esophagus.',
			'authors' => 'Kuwahara A, Lewis AE, Coombes C, Leung FS, Percharde M, Bush JO',
			'description' => '<p>The genome-scale transcriptional programs that specify the mammalian trachea and esophagus are unknown. Though NKX2-1 and SOX2 are hypothesized to be co-repressive master regulators of tracheoesophageal fates, this is untested at a whole transcriptomic scale and their downstream networks remain unidentified. By combining single-cell RNA-sequencing with bulk RNA-sequencing of mutants and NKX2-1 ChIP-sequencing in mouse embryos, we delineate the NKX2-1 transcriptional program in tracheoesophageal specification, and discover that the majority of the tracheal and esophageal transcriptome is NKX2-1 independent. To decouple the NKX2-1 transcriptional program from regulation by SOX2, we interrogate the expression of newly-identified tracheal and esophageal markers in / compound mutants. Finally, we discover that NKX2-1 binds directly to and and regulates their expression to control mesenchymal specification to cartilage and smooth muscle, coupling epithelial identity with mesenchymal specification. These findings create a new framework for understanding early tracheoesophageal fate specification at the genome-wide level.</p>',
			'date' => '2020-06-09',
			'pmid' => 'http://www.pubmed.gov/32515350',
			'doi' => '10.7554/eLife.55526',
			'modified' => '2020-08-12 09:32:02',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 67 => array(
			'id' => '3950',
			'name' => 'Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response.',
			'authors' => 'Béguelin W, Teater M, Meydan C, Hoehn KB, Phillip JM, Soshnev AA, Venturutti L, Rivas MA, Calvo-Fernández MT, Gutierrez J, Camarillo JM, Takata K, Tarte K, Kelleher NL, Steidl C, Mason CE, Elemento O, Allis CD, Kleinstein SH, Melnick AM',
			'description' => '<p>Follicular lymphomas (FLs) are slow-growing, indolent tumors containing extensive follicular dendritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations. Paradoxically, FLs originate from highly proliferative germinal center (GC) B cells with proliferation strictly dependent on interactions with T follicular helper cells. Herein, we show that EZH2 mutations initiate FL by attenuating GC B cell requirement for T&nbsp;cell help and driving slow expansion of GC centrocytes that become enmeshed with and dependent on FDCs. By impairing T&nbsp;cell help, mutant EZH2 prevents induction of proliferative MYC programs. Thus, EZH2 mutation fosters malignant transformation by epigenetically reprograming B cells to form an aberrant immunological niche that reflects characteristic features of human FLs, explaining how indolent tumors arise from GC B cells.</p>',
			'date' => '2020-05-11',
			'pmid' => 'http://www.pubmed.gov/32396861',
			'doi' => '10.1016/j.ccell.2020.04.004',
			'modified' => '2020-08-17 09:56:58',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 68 => array(
			'id' => '4206',
			'name' => 'H2A.Z is dispensable for both basal and activated transcription inpost-mitotic mouse muscles.',
			'authors' => 'Belotti E. et al.',
			'description' => '<p>While the histone variant H2A.Z is known to be required for mitosis, it is also enriched in nucleosomes surrounding the transcription start site of active promoters, implicating H2A.Z in transcription. However, evidence obtained so far mainly rely on correlational data generated in actively dividing cells. We have exploited a paradigm in which transcription is uncoupled from the cell cycle by developing an in vivo system to inactivate H2A.Z in terminally differentiated post-mitotic muscle cells. ChIP-seq, RNA-seq and ATAC-seq experiments performed on H2A.Z KO post-mitotic muscle cells show that this histone variant is neither required to maintain nor to activate transcription. Altogether, this study provides in vivo evidence that in the absence of mitosis H2A.Z is dispensable for transcription and that the enrichment of H2A.Z on active promoters is a marker but not an active driver of transcription.</p>',
			'date' => '2020-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32266374',
			'doi' => '10.1093/nar/gkaa157',
			'modified' => '2022-01-13 13:46:38',
			'created' => '2021-12-06 15:53:19',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 69 => array(
			'id' => '3922',
			'name' => 'Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes.',
			'authors' => 'Crespo M, Damont A, Blanco M, Lastrucci E, Kennani SE, Ialy-Radio C, Khattabi LE, Terrier S, Louwagie M, Kieffer-Jaquinod S, Hesse AM, Bruley C, Chantalat S, Govin J, Fenaille F, Battail C, Cocquet J, Pflieger D',
			'description' => '<p>Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and crotonylation on histones H3 and H4 during mouse spermatogenesis. Lysine crotonylation appeared to be of significant abundance compared to acetylation, particularly on Lys27 of histone H3 (H3K27cr) that accumulates in sperm in a cleaved form of H3. We identified the genomic localization of H3K27cr and studied its effects on transcription compared to the classical active mark H3K27ac at promoters and distal enhancers. The presence of both marks was strongly associated with highest gene expression. Assessment of their co-localization with transcription regulators (SLY, SOX30) and chromatin-binding proteins (BRD4, BRDT, BORIS and CTCF) indicated systematic highest binding when both active marks were present and different selective binding when present alone at chromatin. H3K27cr and H3K27ac finally mark the building of some sperm super-enhancers. This integrated analysis of omics data provides an unprecedented level of understanding of gene expression regulation by H3K27cr in comparison to H3K27ac, and reveals both synergistic and specific actions of each histone modification.</p>',
			'date' => '2020-03-17',
			'pmid' => 'http://www.pubmed.gov/32182340',
			'doi' => '10.1093/nar/gkaa163',
			'modified' => '2020-08-17 10:56:19',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 70 => array(
			'id' => '3917',
			'name' => 'Anti-adipogenic signals at the onset of obesity-related inflammation in white adipose tissue.',
			'authors' => 'Caputo T, Tran VDT, Bararpour N, Winkler C, Aguileta G, Trang KB, Giordano Attianese GMP, Wilson A, Thomas A, Pagni M, Guex N, Desvergne B, Gilardi F',
			'description' => '<p>Chronic inflammation that affects primarily metabolic organs, such as white adipose tissue (WAT), is considered as a major cause of human obesity-associated co-morbidities. However, the molecular mechanisms initiating this inflammation in WAT are poorly understood. By combining transcriptomics, ChIP-seq and modeling approaches, we studied the global early and late responses to a high-fat diet (HFD) in visceral (vWAT) and subcutaneous (scWAT) AT, the first being more prone to obesity-induced inflammation. HFD rapidly triggers proliferation of adipocyte precursors within vWAT. However, concomitant antiadipogenic signals limit vWAT hyperplastic expansion by interfering with the differentiation of proliferating adipocyte precursors. Conversely, in scWAT, residing beige adipocytes lose their oxidizing properties and allow storage of excessive fatty acids. This phase is followed by tissue hyperplastic growth and increased angiogenic signals, which further enable scWAT expansion without generating inflammation. Our data indicate that scWAT and vWAT differential ability to modulate adipocyte number and differentiation in response to obesogenic stimuli has a crucial impact on the different susceptibility to obesity-related inflammation of these adipose tissue depots.</p>',
			'date' => '2020-03-11',
			'pmid' => 'http://www.pubmed.gov/32157317',
			'doi' => '10.1007/s00018-020-03485-z',
			'modified' => '2020-08-17 11:01:57',
			'created' => '2020-08-10 12:12:25',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 71 => array(
			'id' => '3888',
			'name' => 'HDAC3 functions as a positive regulator in Notch signal transduction.',
			'authors' => 'Ferrante F, Giaimo BD, Bartkuhn M, Zimmermann T, Close V, Mertens D, Nist A, Stiewe T, Meier-Soelch J, Kracht M, Just S, Klöble P, Oswald F, Borggrefe T',
			'description' => '<p>Aberrant Notch signaling plays a pivotal role in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL). Amplitude and duration of the Notch response is controlled by ubiquitin-dependent proteasomal degradation of the Notch1 intracellular domain (NICD1), a hallmark of the leukemogenic process. Here, we show that HDAC3 controls NICD1 acetylation levels directly affecting NICD1 protein stability. Either genetic loss-of-function of HDAC3 or nanomolar concentrations of HDAC inhibitor apicidin lead to downregulation of Notch target genes accompanied by a local reduction of histone acetylation. Importantly, an HDAC3-insensitive NICD1 mutant is more stable but biologically less active. Collectively, these data show a new HDAC3- and acetylation-dependent mechanism that may be exploited to treat Notch1-dependent leukemias.</p>',
			'date' => '2020-02-28',
			'pmid' => 'http://www.pubmed.gov/32107550',
			'doi' => '10.1093/nar/gkaa088',
			'modified' => '2020-03-20 17:21:31',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 72 => array(
			'id' => '3860',
			'name' => 'Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon.',
			'authors' => 'Zambusi A, Pelin Burhan Ö, Di Giaimo R, Schmid B, Ninkovic J',
			'description' => '<p>Granulins (GRN) are secreted factors that promote neuronal survival and regulate inflammation in various pathological conditions. However, their roles in physiological conditions in the brain remain poorly understood. To address this knowledge gap, we analysed the telencephalon in Grn-deficient zebrafish and identified morphological and transcriptional changes in microglial cells, indicative of a pro-inflammatory phenotype in the absence of any insult. Unexpectedly, activated mutant microglia shared part of their transcriptional signature with aged human microglia. Furthermore, transcriptome profiles of the entire telencephali isolated from young Grn-deficient animals showed remarkable similarities with the profiles of the telencephali isolated from aged wildtype animals. Additionally, 50% of differentially regulated genes during aging were regulated in the telencephalon of young Grn-deficient animals compared to their wildtype littermates. Importantly, the telencephalon transcriptome in young Grn-deficent animals changed only mildly with aging, further suggesting premature aging of Grn-deficient brain. Indeed, Grn loss led to decreased neurogenesis and oligodendrogenesis, and to shortening of telomeres at young ages, to an extent comparable to that observed during aging. Altogether, our data demonstrate a role of Grn in regulating aging kinetics in the zebrafish telencephalon, thus providing a valuable tool for the development of new therapeutic approaches to treat age-associated pathologies.</p>',
			'date' => '2020-02-03',
			'pmid' => 'http://www.pubmed.gov/32028681',
			'doi' => '10.3390/cells9020350',
			'modified' => '2020-03-20 17:55:13',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 73 => array(
			'id' => '3872',
			'name' => 'An inferred fitness consequence map of the rice genome.',
			'authors' => 'Joly-Lopez Z, Platts AE, Gulko B, Choi JY, Groen SC, Zhong X, Siepel A, Purugganan MD',
			'description' => '<p>The extent to which sequence variation impacts plant fitness is poorly understood. High-resolution maps detailing the constraint acting on the genome, especially in regulatory sites, would be beneficial as functional annotation of noncoding sequences remains sparse. Here, we present a fitness consequence (fitCons) map for rice (Oryza sativa). We inferred fitCons scores (&rho;) for 246 inferred genome classes derived from nine functional genomic and epigenomic datasets, including chromatin accessibility, messenger RNA/small RNA transcription, DNA methylation, histone modifications and engaged RNA polymerase activity. These were integrated with genome-wide polymorphism and divergence data from 1,477 rice accessions and 11 reference genome sequences in the Oryzeae. We found &rho; to be multimodal, with ~9% of the rice genome falling into classes where more than half of the bases would probably have a fitness consequence if mutated. Around 2% of the rice genome showed evidence of weak negative selection, frequently at candidate regulatory sites, including a novel set of 1,000 potentially active enhancer elements. This fitCons map provides perspective on the evolutionary forces associated with genome diversity, aids in genome annotation and can guide crop breeding programs.</p>',
			'date' => '2020-02-02',
			'pmid' => 'http://www.pubmed.gov/32042156',
			'doi' => '10.1038/s41477-019-0589-3',
			'modified' => '2020-03-20 17:43:24',
			'created' => '2020-03-13 13:45:54',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 74 => array(
			'id' => '3850',
			'name' => 'Dual-initiation promoters with intertwined canonical and TCT/TOP transcription start sites diversify transcript processing.',
			'authors' => 'Nepal C, Hadzhiev Y, Balwierz P, Tarifeño-Saldivia E, Cardenas R, Wragg JW, Suzuki AM, Carninci P, Peers B, Lenhard B, Andersen JB, Müller F',
			'description' => '<p>Variations in transcription start site (TSS) selection reflect diversity of preinitiation complexes and can impact on post-transcriptional RNA fates. Most metazoan polymerase II-transcribed genes carry canonical initiation with pyrimidine/purine (YR) dinucleotide, while translation machinery-associated genes carry polypyrimidine initiator (5'-TOP or TCT). By addressing the developmental regulation of TSS selection in zebrafish we uncovered a class of dual-initiation promoters in thousands of genes, including snoRNA host genes. 5'-TOP/TCT initiation is intertwined with canonical initiation and used divergently in hundreds of dual-initiation promoters during maternal to zygotic transition. Dual-initiation in snoRNA host genes selectively generates host and snoRNA with often different spatio-temporal expression. Dual-initiation promoters are pervasive in human and fruit fly, reflecting evolutionary conservation. We propose that dual-initiation on shared promoters represents a composite promoter architecture, which can function both coordinately and divergently to diversify RNAs.</p>',
			'date' => '2020-01-10',
			'pmid' => 'http://www.pubmed.gov/31924754',
			'doi' => '10.1038/s41467-019-13687-0',
			'modified' => '2020-02-13 11:09:58',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 75 => 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) 76 => 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) 77 => array(
			'id' => '3845',
			'name' => 'Combinatorial action of NF-Y and TALE at embryonic enhancers defines distinct gene expression programs during zygotic genome activation in zebrafish.',
			'authors' => 'Stanney W, Ladam F, Donaldson IJ, Parsons TJ, Maehr R, Bobola N, Sagerström CG',
			'description' => '<p>Animal embryogenesis is initiated by maternal factors, but zygotic genome activation (ZGA) shifts regulatory control to the embryo during blastula stages. ZGA is thought to be mediated by maternally provided transcription factors (TFs), but few such TFs have been identified in vertebrates. Here we report that NF-Y and TALE TFs bind zebrafish genomic elements associated with developmental control genes already at ZGA. In particular, co-regulation by NF-Y and TALE is associated with broadly acting genes involved in transcriptional control, while regulation by either NF-Y or TALE defines genes in specific developmental processes, such that NF-Y controls a cilia gene expression program while TALE controls expression of hox genes. We also demonstrate that NF-Y and TALE-occupied genomic elements function as enhancers during embryogenesis. We conclude that combinatorial use of NF-Y and TALE at developmental enhancers permits the establishment of distinct gene expression programs at zebrafish ZGA.</p>',
			'date' => '2019-12-17',
			'pmid' => 'http://www.pubmed.gov/31862379',
			'doi' => '10.1016/j.ydbio.2019.12.003',
			'modified' => '2020-02-20 11:13:27',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 78 => array(
			'id' => '3819',
			'name' => 'Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites.',
			'authors' => 'Hammam E, Ananda G, Sinha A, Scheidig-Benatar C, Bohec M, Preiser PR, Dedon PC, Scherf A, Vembar SS',
			'description' => '<p>DNA cytosine modifications are key epigenetic regulators of cellular processes in mammalian cells, with their misregulation leading to varied disease states. In the human malaria parasite Plasmodium falciparum, a unicellular eukaryotic pathogen, little is known about the predominant cytosine modifications, cytosine methylation (5mC) and hydroxymethylation (5hmC). Here, we report the first identification of a hydroxymethylcytosine-like (5hmC-like) modification in P. falciparum asexual blood stages using a suite of biochemical methods. In contrast to mammalian cells, we report 5hmC-like levels in the P. falciparum genome of 0.2-0.4%, which are significantly higher than the methylated cytosine (mC) levels of 0.01-0.05%. Immunoprecipitation of hydroxymethylated DNA followed by next generation sequencing (hmeDIP-seq) revealed that 5hmC-like modifications are enriched in gene bodies with minimal dynamic changes during asexual development. Moreover, levels of the 5hmC-like base in gene bodies positively correlated to transcript levels, with more than 2000 genes stably marked with this modification throughout asexual development. Our work highlights the existence of a new predominant cytosine DNA modification pathway in P. falciparum and opens up exciting avenues for gene regulation research and the development of antimalarials.</p>',
			'date' => '2019-11-28',
			'pmid' => 'http://www.pubmed.gov/31777939',
			'doi' => '10.1093/nar/gkz1093.',
			'modified' => '2020-02-25 13:47:09',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 79 => array(
			'id' => '3820',
			'name' => 'A stress-responsive enhancer induces dynamic drug resistance in acute myeloid leukemia.',
			'authors' => 'Williams MS, Amaral FM, Simeoni F, Somervaille TC',
			'description' => '<p>The drug efflux pump ABCB1 is a key driver of chemoresistance, and high expression predicts for treatment failure in acute myeloid leukemia (AML). In this study, we identified and functionally validated the network of enhancers that controls expression of ABCB1. We show that exposure of leukemia cells to daunorubicin activated an integrated stress response-like transcriptional program to induce ABCB1 through remodeling and activation of an ATF4-bound, stress-responsive enhancer. Protracted stress primed enhancers for rapid increases in activity following re-exposure of cells to daunorubicin, providing an epigenetic memory of prior drug treatment. In primary human AML, exposure of fresh blast cells to daunorubicin activated the stress-responsive enhancer and led to dose-dependent induction of ABCB1. Dynamic induction of ABCB1 by diverse stressors, including chemotherapy, facilitated escape of leukemia cells from targeted third-generation ABCB1 inhibition, providing an explanation for the failure of ABCB1 inhibitors in clinical trials. Stress-induced up regulation of ABCB1 was mitigated by combined use of pharmacologic inhibitors U0126 and ISRIB, which inhibit stress signalling and have potential for use as adjuvants to enhance the activity of ABCB1 inhibitors.</p>',
			'date' => '2019-11-26',
			'pmid' => 'http://www.pubmed.gov/31770110',
			'doi' => '/',
			'modified' => '2020-02-25 13:46:19',
			'created' => '2020-02-13 10:02:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 80 => array(
			'id' => '3810',
			'name' => 'Distinct CoREST complexes act in a cell-type-specific manner.',
			'authors' => 'Mačinković I, Theofel I, Hundertmark T, Kovač K, Awe S, Lenz J, Forné I, Lamp B, Nist A, Imhof A, Stiewe T, Renkawitz-Pohl R, Rathke C, Brehm A',
			'description' => '<p>CoREST has been identified as a subunit of several protein complexes that generate transcriptionally repressive chromatin structures during development. However, a comprehensive analysis of the CoREST interactome has not been carried out. We use proteomic approaches to define the interactomes of two dCoREST isoforms, dCoREST-L and dCoREST-M, in Drosophila. We identify three distinct histone deacetylase complexes built around a common dCoREST/dRPD3 core: A dLSD1/dCoREST complex, the LINT complex and a dG9a/dCoREST complex. The latter two complexes can incorporate both dCoREST isoforms. By contrast, the dLSD1/dCoREST complex exclusively assembles with the dCoREST-L isoform. Genome-wide studies show that the three dCoREST complexes associate with chromatin predominantly at promoters. Transcriptome analyses in S2 cells and testes reveal that different cell lineages utilize distinct dCoREST complexes to maintain cell-type-specific gene expression programmes: In macrophage-like S2 cells, LINT represses germ line-related genes whereas other dCoREST complexes are largely dispensable. By contrast, in testes, the dLSD1/dCoREST complex prevents transcription of germ line-inappropriate genes and is essential for spermatogenesis and fertility, whereas depletion of other dCoREST complexes has no effect. Our study uncovers three distinct dCoREST complexes that function in a lineage-restricted fashion to repress specific sets of genes thereby maintaining cell-type-specific gene expression programmes.</p>',
			'date' => '2019-11-08',
			'pmid' => 'http://www.pubmed.gov/31701127',
			'doi' => '10.1093/nar/gkz1050',
			'modified' => '2019-12-05 11:02:22',
			'created' => '2019-12-02 15:25:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 81 => array(
			'id' => '3782',
			'name' => 'Residual apoptotic activity of a tumorigenic p53 mutant improves cancer therapy responses.',
			'authors' => 'Timofeev O, Klimovich B, Schneikert J, Wanzel M, Pavlakis E, Noll J, Mutlu S, Elmshäuser S, Nist A, Mernberger M, Lamp B, Wenig U, Brobeil A, Gattenlöhner S, Köhler K, Stiewe T',
			'description' => '<p>Engineered p53 mutant mice are valuable tools for delineating p53 functions in tumor suppression and cancer therapy. Here, we have introduced the R178E mutation into the Trp53 gene of mice to specifically ablate the cooperative nature of p53 DNA binding. Trp53 mice show no detectable target gene regulation and, at first sight, are largely indistinguishable from Trp53 mice. Surprisingly, stabilization of p53 in Mdm2 mice nevertheless triggers extensive apoptosis, indicative of residual wild-type activities. Although this apoptotic activity suffices to trigger lethality of Trp53 ;Mdm2 embryos, it proves insufficient for suppression of spontaneous and oncogene-driven tumorigenesis. Trp53 mice develop tumors indistinguishably from Trp53 mice and tumors retain and even stabilize the p53 protein, further attesting to the lack of significant tumor suppressor activity. However, Trp53 tumors exhibit remarkably better chemotherapy responses than Trp53 ones, resulting in enhanced eradication of p53-mutated tumor cells. Together, this provides genetic proof-of-principle evidence that a p53 mutant can be highly tumorigenic and yet retain apoptotic activity which provides a survival benefit in the context of cancer therapy.</p>',
			'date' => '2019-09-04',
			'pmid' => 'http://www.pubmed.gov/31483066',
			'doi' => '10.15252/embj.2019102096',
			'modified' => '2019-10-02 16:50:40',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 82 => array(
			'id' => '3759',
			'name' => 'EOMES interacts with RUNX3 and BRG1 to promote innate memory cell formation through epigenetic reprogramming.',
			'authors' => 'Istaces N, Splittgerber M, Lima Silva V, Nguyen M, Thomas S, Le A, Achouri Y, Calonne E, Defrance M, Fuks F, Goriely S, Azouz A',
			'description' => '<p>Memory CD8 T cells have the ability to provide lifelong immunity against pathogens. Although memory features generally arise after challenge with a foreign antigen, na&iuml;ve CD8 single positive (SP) thymocytes may acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associated with the induction of the T-box transcription factor Eomesodermin (EOMES). However, the underlying molecular mechanisms remain ill-defined. Using epigenomic profiling, we show that these innate memory CD8SP cells acquire only a portion of the active enhancer repertoire of conventional memory cells. This reprograming is secondary to EOMES recruitment, mostly to RUNX3-bound enhancers. Furthermore, EOMES is found within chromatin-associated complexes containing BRG1 and promotes the recruitment of this chromatin remodelling factor. Also, the in vivo acquisition of EOMES-dependent program is BRG1-dependent. In conclusion, our results support a strong epigenetic basis for the EOMES-driven establishment of CD8 T cell innate memory program.</p>',
			'date' => '2019-07-24',
			'pmid' => 'http://www.pubmed.gov/31341159',
			'doi' => '10.1038/s41467-019-11233-6',
			'modified' => '2019-10-03 10:06:15',
			'created' => '2019-10-02 16:16:55',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 83 => 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) 84 => array(
			'id' => '3743',
			'name' => 'ARID1A facilitates KRAS signaling-regulated enhancer activity in an AP1-dependent manner in colorectal cancer cells.',
			'authors' => 'Sen M, Wang X, Hamdan FH, Rapp J, Eggert J, Kosinsky RL, Wegwitz F, Kutschat AP, Younesi FS, Gaedcke J, Grade M, Hessmann E, Papantonis A, Strӧbel P, Johnsen SA',
			'description' => '<p>BACKGROUND: ARID1A (AT-rich interactive domain-containing protein 1A) is a subunit of the BAF chromatin remodeling complex and plays roles in transcriptional regulation and DNA damage response. Mutations in ARID1A that lead to inactivation or&nbsp;loss of expression are frequent and widespread across many cancer types including colorectal cancer (CRC). A tumor suppressor role of ARID1A has been established in a number of tumor types including CRC where the genetic inactivation of Arid1a alone led to the formation of invasive colorectal adenocarcinomas in mice. Mechanistically, ARID1A has been described to largely function through the regulation of enhancer activity. METHODS: To mimic ARID1A-deficient colorectal cancer, we used CRISPR/Cas9-mediated gene editing to inactivate the ARID1A gene in established colorectal cancer cell lines. We integrated gene expression analyses with genome-wide ARID1A occupancy and epigenomic mapping data to decipher ARID1A-dependent transcriptional regulatory mechanisms. RESULTS: Interestingly, we found that CRC cell lines harboring KRAS mutations are critically dependent on ARID1A function. In the absence of ARID1A, proliferation of these cell lines is severely impaired, suggesting an essential role for ARID1A in this context. Mechanistically, we showed that ARID1A acts as a co-factor at enhancers occupied by AP1 transcription factors acting downstream of the MEK/ERK pathway. Consistently, loss of ARID1A led to a disruption of KRAS/AP1-dependent enhancer activity, accompanied by a downregulation of expression of the associated target genes. CONCLUSIONS: We identify a previously unknown context-dependent tumor-supporting function of ARID1A in CRC downstream of KRAS signaling. Upon the loss of ARID1A in KRAS-mutated cells, enhancers that are co-occupied by ARID1A and the AP1 transcription factors become inactive, thereby leading to decreased target gene expression. Thus, targeting of the BAF complex in KRAS-mutated CRC may offer a unique, previously unknown, context-dependent therapeutic option in CRC.</p>',
			'date' => '2019-06-19',
			'pmid' => 'http://www.pubmed.gov/31217031',
			'doi' => '10.1186/s13148-019-0690-5',
			'modified' => '2019-08-06 16:37:28',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 85 => array(
			'id' => '3631',
			'name' => 'Guidelines for optimized gene knockout using CRISPR/Cas9',
			'authors' => 'Campenhout CV et al.',
			'description' => '<p>CRISPR/Cas9 technology has evolved as the most powerful approach to generate genetic models both for fundamental and preclinical research. Despite its apparent simplicity, the outcome of a genome-editing experiment can be substantially impacted by technical parameters and biological considerations. Here, we present guidelines and tools to optimize CRISPR/Cas9 genome-targeting efficiency and specificity. The nature of the target locus, the design of the single guide RNA and the choice of the delivery method should all be carefully considered prior to a genome-editing experiment. Different methods can also be used to detect off-target cleavages and decrease the risk of unwanted mutations. Together, these optimized tools and proper controls are essential to the assessment of CRISPR/Cas9 genome-editing experiments.</p>',
			'date' => '2019-05-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/31039627',
			'doi' => '10.2144/btn-2018-0187',
			'modified' => '2019-05-09 15:37:50',
			'created' => '2019-05-09 15:37:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 86 => array(
			'id' => '3710',
			'name' => 'BRCA1 mutations attenuate super-enhancer function and chromatin looping in haploinsufficient human breast epithelial cells.',
			'authors' => 'Zhang X, Wang Y, Chiang HC, Hsieh YP, Lu C, Park BH, Jatoi I, Jin VX, Hu Y, Li R',
			'description' => '<p>BACKGROUND: BRCA1-associated breast cancer originates from luminal progenitor cells. BRCA1 functions in multiple biological processes, including double-strand break repair, replication stress suppression, transcriptional regulation, and chromatin reorganization. While non-malignant cells carrying cancer-predisposing BRCA1 mutations exhibit increased genomic instability, it remains unclear whether BRCA1 haploinsufficiency affects transcription and chromatin dynamics in breast epithelial cells. METHODS: H3K27ac-associated super-enhancers were compared in primary breast epithelial cells from BRCA1 mutation carriers (BRCA1) and non-carriers (BRCA1). Non-tumorigenic MCF10A breast epithelial cells with engineered BRCA1 haploinsufficiency were used to confirm the H3K27ac changes. The impact of BRCA1 mutations on enhancer function and enhancer-promoter looping was assessed in MCF10A cells. RESULTS: Here, we show that primary mammary epithelial cells from women with BRCA1 mutations display significant loss of H3K27ac-associated super-enhancers. These BRCA1-dependent super-enhancers are enriched with binding motifs for the GATA family. Non-tumorigenic BRCA1 MCF10A cells recapitulate the H3K27ac loss. Attenuated histone mark and enhancer activity in these BRCA1 MCF10A cells can be partially restored with wild-type BRCA1. Furthermore, chromatin conformation analysis demonstrates impaired enhancer-promoter looping in BRCA1 MCF10A cells. CONCLUSIONS: H3K27ac-associated super-enhancer loss is a previously unappreciated functional deficiency in ostensibly normal BRCA1 mutation-carrying breast epithelium. Our findings offer new mechanistic insights into BRCA1 mutation-associated transcriptional and epigenetic abnormality in breast epithelial cells and tissue/cell lineage-specific tumorigenesis.</p>',
			'date' => '2019-04-17',
			'pmid' => 'http://www.pubmed.gov/30995943',
			'doi' => '10.1186/s13058-019-1132-1',
			'modified' => '2019-07-05 14:32:42',
			'created' => '2019-07-04 10:42:34',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 87 => array(
			'id' => '3613',
			'name' => 'Point mutations in the PDX1 transactivation domain impair human β-cell development and function.',
			'authors' => 'Wang X, Sterr M, Ansarullah , Burtscher I, Böttcher A, Beckenbauer J, Siehler J, Meitinger T, Häring HU, Staiger H, Cernilogar FM, Schotta G, Irmler M, Beckers J, Wright CVE, Bakhti M, Lickert H',
			'description' => '<p>OBJECTIVE: Hundreds of missense mutations in the coding region of PDX1 exist; however, if these mutations predispose to diabetes mellitus is unknown. METHODS: In this study, we screened a large cohort of subjects with increased risk for diabetes and identified two subjects with impaired glucose tolerance carrying common, heterozygous, missense mutations in the PDX1 coding region leading to single amino acid exchanges (P33T, C18R) in its transactivation domain. We generated iPSCs from patients with heterozygous PDX1, PDX1 mutations and engineered isogenic cell lines carrying homozygous PDX1, PDX1 mutations and a heterozygous PDX1 loss-of-function mutation (PDX1). RESULTS: Using an in&nbsp;vitro &beta;-cell differentiation protocol, we demonstrated that both, heterozygous PDX1, PDX1 and homozygous PDX1, PDX1 mutations impair &beta;-cell differentiation and function. Furthermore, PDX1 and PDX1 mutations reduced differentiation efficiency of pancreatic progenitors (PPs), due to downregulation of PDX1-bound genes, including transcription factors MNX1 and PDX1 as well as insulin resistance gene CES1. Additionally, both PDX1 and PDX1 mutations in PPs reduced the expression of PDX1-bound genes including the long-noncoding RNA, MEG3 and the imprinted gene NNAT, both involved in insulin synthesis and secretion. CONCLUSIONS: Our results reveal mechanistic details of how common coding mutations in PDX1 impair human pancreatic endocrine lineage formation and &beta;-cell function and contribute to the predisposition for diabetes.</p>',
			'date' => '2019-03-20',
			'pmid' => 'http://www.pubmed.gov/30930126',
			'doi' => '10.1016/j.molmet.2019.03.006',
			'modified' => '2019-04-17 14:43:53',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 88 => 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) 89 => array(
			'id' => '3727',
			'name' => 'Transcriptome-wide dynamics of extensive m6A mRNA methylation during Plasmodium falciparum blood-stage development',
			'authors' => 'Sebastian Baumgarten, Jessica M. Bryant, Ameya Sinha, Thibaud Reyser, Peter R. Preiser, Peter C. Dedon, Artur Scherf',
			'description' => '<p>Malaria pathogenesis results from the asexual replication of Plasmodium falciparum within human red blood cells, which relies on a precisely timed cascade of gene expression over a 48-hour life cycle. Although substantial post-transcriptional regulation of this hardwired program has been observed, it remains unclear how these processes are mediated on a transcriptome-wide level. To this end, we identified mRNA modifications in the P. falciparum transcriptome and performed a comprehensive characterization of N6-methyladenosine (m6A) over the course of blood stage development. Using mass spectrometry and m6A RNA sequencing, we demonstrate that m6A is highly developmentally regulated, exceeding m6A levels known in any other eukaryote. We identify an evolutionarily conserved m6A writer complex and show that knockdown of the putative m6A methyltransferase by CRISPR interference leads to increased levels of transcripts that normally contain m6A. In accordance, we find an inverse correlation between m6A status and mRNA stability or translational efficiency. Our data reveal the crucial role of extensive m6A mRNA methylation in dynamically fine-tuning the transcriptional program of a unicellular eukaryote as well as a new &lsquo;epitranscriptomic&rsquo; layer of gene regulation in malaria parasites.</p>',
			'date' => '2019-03-09',
			'pmid' => 'https://www.nature.com/articles/s41564-019-0521-7',
			'doi' => '10.1101/572891.',
			'modified' => '2022-05-18 19:27:33',
			'created' => '2019-07-31 13:35:50',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 90 => 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) 91 => array(
			'id' => '3662',
			'name' => 'NF-κB p65 dimerization and DNA-binding is important for inflammatory gene expression.',
			'authors' => 'Riedlinger T, Liefke R, Meier-Soelch J, Jurida L, Nist A, Stiewe T, Kracht M, Schmitz ML',
			'description' => '<p>Increasing evidence shows that many transcription factors execute important biologic functions independent from their DNA-binding capacity. The NF-&kappa;B p65 (RELA) subunit is a central regulator of innate immunity. Here, we investigated the relative functional contribution of p65 DNA-binding and dimerization in p65-deficient human and murine cells reconstituted with single amino acid mutants preventing either DNA-binding (p65 E/I) or dimerization (p65 FL/DD). DNA-binding of p65 was required for RelB-dependent stabilization of the NF-&kappa;B p100 protein. The antiapoptotic function of p65 and expression of the majority of TNF-&alpha;-induced genes were dependent on p65's ability to bind DNA and to dimerize. Chromatin immunoprecipitation with massively parallel DNA sequencing experiments revealed that impaired DNA-binding and dimerization strongly diminish the chromatin association of p65. However, there were also p65-independent TNF-&alpha;-inducible genes and a subgroup of p65 binding sites still allowed some residual chromatin association of the mutants. These sites were enriched in activator protein 1 (AP-1) binding motifs and showed increased chromatin accessibility and basal transcription. This suggests a mechanism of assisted p65 chromatin association that can be in part facilitated by chromatin priming and cooperativity with other transcription factors such as AP-1.-Riedlinger, T., Liefke, R., Meier-Soelch, J., Jurida, L., Nist, A., Stiewe, T., Kracht, M., Schmitz, M. L. NF-&kappa;B p65 dimerization and DNA-binding is important for inflammatory gene expression.</p>',
			'date' => '2019-03-01',
			'pmid' => 'http://www.pubmed.gov/30526044',
			'doi' => '10.1096/fj.201801638R',
			'modified' => '2019-07-01 11:42:50',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 92 => array(
			'id' => '3646',
			'name' => 'Differential regulation of RNA polymerase III genes during liver regeneration.',
			'authors' => 'Yeganeh M, Praz V, Carmeli C, Villeneuve D, Rib L, Guex N, Herr W, Delorenzi M, Hernandez N,  ',
			'description' => '<p>Mouse liver regeneration after partial hepatectomy involves cells in the remaining tissue synchronously entering the cell division cycle. We have used this system and H3K4me3, Pol II and Pol III profiling to characterize adaptations in Pol III transcription. Our results broadly define a class of genes close to H3K4me3 and Pol II peaks, whose Pol III occupancy is high and stable, and another class, distant from Pol II peaks, whose Pol III occupancy strongly increases after partial hepatectomy. Pol III regulation in the liver thus entails both highly expressed housekeeping genes and genes whose expression can adapt to increased demand.</p>',
			'date' => '2019-02-28',
			'pmid' => 'http://www.pubmed.gov/30597109',
			'doi' => '10.1093/nar/gky1282',
			'modified' => '2019-06-07 10:14:59',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 93 => array(
			'id' => '3678',
			'name' => 'CBX7 Induces Self-Renewal of Human Normal and Malignant Hematopoietic Stem and Progenitor Cells by Canonical and Non-canonical Interactions.',
			'authors' => 'Jung J, Buisman SC, Weersing E, Dethmers-Ausema A, Zwart E, Schepers H, Dekker MR, Lazare SS, Hammerl F, Skokova Y, Kooistra SM, Klauke K, Poot RA, Bystrykh LV, de Haan G',
			'description' => '<p>In this study, we demonstrate that, among all five CBX Polycomb proteins, only CBX7 possesses the ability to control self-renewal of human hematopoietic stem and progenitor cells (HSPCs). Xenotransplantation of CBX7-overexpressing HSPCs resulted in increased multi-lineage long-term engraftment and myelopoiesis.&nbsp;Gene expression and chromatin analyses revealed perturbations in genes involved in differentiation,&nbsp;DNA and chromatin maintenance, and cell cycle control. CBX7 is upregulated in acute myeloid leukemia (AML), and its genetic or pharmacological repression in AML cells inhibited proliferation and induced differentiation. Mass spectrometry analysis revealed several non-histone protein interactions between CBX7 and the H3K9 methyltransferases SETDB1, EHMT1, and EHMT2. These CBX7-binding proteins possess a trimethylated lysine peptide motif highly similar to the canonical CBX7 target H3K27me3. Depletion of SETDB1 in AML cells phenocopied repression of CBX7. We identify CBX7 as an important regulator of self-renewal and uncover non-canonical crosstalk between distinct pathways, revealing therapeutic opportunities for leukemia.</p>',
			'date' => '2019-02-12',
			'pmid' => 'http://www.pubmed.gov/30759399',
			'doi' => '10.1016/j.celrep.2019.01.050',
			'modified' => '2019-07-01 11:20:46',
			'created' => '2019-06-21 14:55:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 94 => array(
			'id' => '3659',
			'name' => 'Fluorescence-Activated Cell Sorting-Based Isolation and Characterization of Neural Stem Cells from the Adult Zebrafish Telencephalon.',
			'authors' => 'Di Giaimo R, Aschenbroich S, Ninkovic J',
			'description' => '<p>Adult mammalian brain, including humans, has rather limited addition of new neurons and poor regenerative capacity. In contrast, neural stem cells (NSC) with glial identity and neurogenesis are highly abundant throughout the adult zebrafish brain. Importantly, the activation of NSC and production of new neurons in response to injuries lead to the brain regeneration in zebrafish brain. Therefore, understanding of the molecular pathways regulating NSC behavior in response to injury is crucial in order to set the basis for experimental modification of these pathways in glial cells after injury in the mammalian brain and to elicit neuronal regeneration. Here, we describe the procedure that we successfully used to prospectively isolate NSCs from adult zebrafish telencephalon, extract RNA, and prepare cDNA libraries for next generation sequencing (NGS) and full transcriptome analysis as the first step toward understanding regulatory mechanisms leading to restorative neurogenesis in zebrafish. Moreover, we describe an alternative approach to analyze antigenic properties of NSC in the adult zebrafish brain using intracellular fluorescence activated cell sorting (FACS). We employ this method to analyze the number of proliferating NSCs positive for proliferating cell nuclear antigen (PCNA) in the prospectively isolated population of stem cells.</p>',
			'date' => '2019-01-09',
			'pmid' => 'http://www.pubmed.gov/30617972',
			'doi' => '10.1007/978-1-4939-9068-9_4,',
			'modified' => '2019-06-07 08:57:58',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 95 => array(
			'id' => '3651',
			'name' => 'DeltaNp63-dependent super enhancers define molecular identity in pancreatic cancer by an interconnected transcription factor network.',
			'authors' => 'Hamdan FH, Johnsen SA',
			'description' => '<p>Molecular subtyping of cancer offers tremendous promise for the optimization of a precision oncology approach to anticancer therapy. Recent advances in pancreatic cancer research uncovered various molecular subtypes with tumors expressing a squamous/basal-like gene expression signature displaying a worse prognosis. Through unbiased epigenome mapping, we identified deltaNp63 as a major driver of a gene signature in pancreatic cancer cell lines, which we report to faithfully represent the highly aggressive pancreatic squamous subtype observed in vivo, and display the specific epigenetic marking of genes associated with decreased survival. Importantly, depletion of deltaNp63 in these systems significantly decreased cell proliferation and gene expression patterns associated with a squamous subtype and transcriptionally mimicked a subtype switch. Using genomic localization data of deltaNp63 in pancreatic cancer cell lines coupled with epigenome mapping data from patient-derived xenografts, we uncovered that deltaNp63 mainly exerts its effects by activating subtype-specific super enhancers. Furthermore, we identified a group of 45 subtype-specific super enhancers that are associated with poorer prognosis and are highly dependent on deltaNp63. Genes associated with these enhancers included a network of transcription factors, including HIF1A, BHLHE40, and RXRA, which form a highly intertwined transcriptional regulatory network with deltaNp63 to further activate downstream genes associated with poor survival.</p>',
			'date' => '2018-12-26',
			'pmid' => 'http://www.pubmed.gov/30541891',
			'doi' => '10.1073/pnas.1812915116',
			'modified' => '2019-06-07 09:29:25',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 96 => array(
			'id' => '3610',
			'name' => 'The Aryl Hydrocarbon Receptor Pathway Defines the Time Frame for Restorative Neurogenesis.',
			'authors' => 'Di Giaimo R, Durovic T, Barquin P, Kociaj A, Lepko T, Aschenbroich S, Breunig CT, Irmler M, Cernilogar FM, Schotta G, Barbosa JS, Trümbach D, Baumgart EV, Neuner AM, Beckers J, Wurst W, Stricker SH, Ninkovic J',
			'description' => '<p>Zebrafish have a high capacity to replace lost neurons after brain injury. New neurons involved in repair are generated by a specific set of glial cells, known as ependymoglial cells. We analyze changes in the transcriptome of ependymoglial cells and their progeny after injury to infer the molecular pathways governing restorative neurogenesis. We identify the aryl hydrocarbon receptor (AhR) as a regulator of ependymoglia differentiation toward post-mitotic neurons. In&nbsp;vivo imaging shows that high AhR signaling promotes the direct conversion of a specific subset of ependymoglia into post-mitotic neurons, while low AhR signaling promotes ependymoglial proliferation. Interestingly, we observe the inactivation of AhR signaling shortly after injury followed by a return to the basal levels 7&nbsp;days post injury. Interference with timely AhR regulation after injury leads to aberrant restorative neurogenesis. Taken together, we identify AhR signaling as a crucial regulator of restorative neurogenesis timing in the zebrafish brain.</p>',
			'date' => '2018-12-18',
			'pmid' => 'http://www.pubmed.gov/30566853',
			'doi' => '10.1016/j.celrep.2018.11.055',
			'modified' => '2019-04-17 14:47:22',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 97 => array(
			'id' => '3649',
			'name' => 'Genome-wide identification of RETINOBLASTOMA RELATED 1 binding sites in Arabidopsis reveals novel DNA damage regulators.',
			'authors' => 'Bouyer D, Heese M, Chen P, Harashima H, Roudier F, Grüttner C, Schnittger A',
			'description' => '<p>Retinoblastoma (pRb) is a multifunctional regulator, which was likely present in the last common ancestor of all eukaryotes. The Arabidopsis pRb homolog RETINOBLASTOMA RELATED 1 (RBR1), similar to its animal counterparts, controls not only cell proliferation but is also implicated in developmental decisions, stress responses and maintenance of genome integrity. Although most functions of pRb-type proteins involve chromatin association, a genome-wide understanding of RBR1 binding sites in Arabidopsis is still missing. Here, we present a plant chromatin immunoprecipitation protocol optimized for genome-wide studies of indirectly DNA-bound proteins like RBR1. Our analysis revealed binding of Arabidopsis RBR1 to approximately 1000 genes and roughly 500 transposable elements, preferentially MITES. The RBR1-decorated genes broadly overlap with previously identified targets of two major transcription factors controlling the cell cycle, i.e. E2F and MYB3R3 and represent a robust inventory of RBR1-targets in dividing cells. Consistently, enriched motifs in the RBR1-marked domains include sequences related to the E2F consensus site and the MSA-core element bound by MYB3R transcription factors. Following up a key role of RBR1 in DNA damage response, we performed a meta-analysis combining the information about the RBR1-binding sites with genome-wide expression studies under DNA stress. As a result, we present the identification and mutant characterization of three novel genes required for growth upon genotoxic stress.</p>',
			'date' => '2018-11-01',
			'pmid' => 'http://www.pubmed.gov/30500810',
			'doi' => '10.1371/journal.',
			'modified' => '2019-06-07 10:12:16',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 98 => array(
			'id' => '3576',
			'name' => 'SUMO Safeguards Somatic and Pluripotent Cell Identities by Enforcing Distinct Chromatin States',
			'authors' => 'Cossec Jack-Christophe, Theurillat Ilan, Chica Claudia, Búa Aguín Sabela, Gaume Xavier, Andrieux Alexandra, Iturbide Ane, Jouvion Gregory, Li Han, Bossis Guillaume, Seeler Jacob-Sebastian, Torres-Padilla Maria-Elena, Dejean Anne',
			'description' => '<p>Understanding general principles that safeguard cellular identity should reveal critical insights into common mechanisms underlying specification of varied cell types. Here, we show that SUMO modification acts to stabilize cell fate in a variety of contexts. Hyposumoylation enhances pluripotency reprogramming in vitro and in vivo, increases lineage transdifferentiation, and facilitates leukemic cell differentiation. Suppressing sumoylation in embryonic stem cells (ESCs) promotes their conversion into 2-cell-embryo-like (2C-like) cells. During reprogramming to pluripotency, SUMO functions on fibroblastic enhancers to retain somatic transcription factors together with Oct4, Sox2, and Klf4, thus impeding somatic enhancer inactivation. In contrast, in ESCs, SUMO functions on heterochromatin to silence the 2C program, maintaining both proper H3K9me3 levels genome-wide and repression of the Dux locus by triggering recruitment of the sumoylated PRC1.6 and Kap/Setdb1 repressive complexes. Together, these studies show that SUMO acts on chromatin as a glue to stabilize key determinants of somatic and pluripotent states.</p>',
			'date' => '2018-10-25',
			'pmid' => 'http://www.pubmed.gov/30401455',
			'doi' => '10.1016/j.stem.2018.10.001',
			'modified' => '2019-07-22 09:18:55',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 99 => array(
			'id' => '3636',
			'name' => 'Caenorhabditis elegans sperm carry a histone-based epigenetic memory of both spermatogenesis and oogenesis.',
			'authors' => 'Tabuchi TM, Rechtsteiner A, Jeffers TE, Egelhofer TA, Murphy CT, Strome S',
			'description' => '<p>Paternal contributions to epigenetic inheritance are not well understood. Paternal contributions via marked nucleosomes are particularly understudied, in part because sperm in some organisms replace the majority of nucleosome packaging with protamine packaging. Here we report that in Caenorhabditis elegans sperm, the genome is packaged in nucleosomes and carries a histone-based epigenetic memory of genes expressed during spermatogenesis, which unexpectedly include genes well known for their expression during oogenesis. In sperm, genes with spermatogenesis-restricted expression are uniquely marked with both active and repressive marks, which may reflect a sperm-specific chromatin signature. We further demonstrate that epigenetic information provided by sperm is important and in fact sufficient to guide proper germ cell development in offspring. This study establishes one mode of paternal epigenetic inheritance and offers a potential mechanism for how the life experiences of fathers may impact the development and health of their descendants.</p>',
			'date' => '2018-10-17',
			'pmid' => 'http://www.pubmed.gov/30333496',
			'doi' => '10.1038/s41467-018-06236-8',
			'modified' => '2019-06-07 10:26:54',
			'created' => '2019-06-06 12:11:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 100 => array(
			'id' => '3556',
			'name' => 'PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex.',
			'authors' => 'Link S, Spitzer RMM, Sana M, Torrado M, Völker-Albert MC, Keilhauer EC, Burgold T, Pünzeler S, Low JKK, Lindström I, Nist A, Regnard C, Stiewe T, Hendrich B, Imhof A, Mann M, Mackay JP, Bartkuhn M, Hake SB',
			'description' => '<p>Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and cranial-facial development. Here, using in vitro assays, we show that distinct domains of PWWP2A mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly binds H3K36me3-containing gene bodies. Further, PWWP2A binds to an MTA1-specific subcomplex of the NuRD complex (M1HR), which consists solely of MTA1, HDAC1, and RBBP4/7, and excludes CHD, GATAD2 and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as a complex chromatin-binding protein that serves to direct the deacetylase complex M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels.</p>',
			'date' => '2018-10-16',
			'pmid' => 'http://www.pubmed.gov/30327463',
			'doi' => '10.1038/s41467-018-06665-5',
			'modified' => '2019-07-22 09:17:39',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 101 => array(
			'id' => '3498',
			'name' => 'Convergent evolution of complex genomic rearrangements in two fungal meiotic drive elements.',
			'authors' => 'Svedberg J, Hosseini S, Chen J, Vogan AA, Mozgova I, Hennig L, Manitchotpisit P, Abusharekh A, Hammond TM, Lascoux M, Johannesson H',
			'description' => '<p>Meiotic drive is widespread in nature. The conflict it generates is expected to be an important motor for evolutionary change and innovation. In this study, we investigated the genomic consequences of two large multi-gene meiotic drive elements, Sk-2 and Sk-3, found in the filamentous ascomycete Neurospora intermedia. Using long-read sequencing, we generated the first complete and well-annotated genome assemblies of large, highly diverged, non-recombining regions associated with meiotic drive elements. Phylogenetic analysis shows that, even though Sk-2 and Sk-3 are located in the same chromosomal region, they do not form sister clades, suggesting independent origins or at least a long evolutionary separation. We conclude that they have in a convergent manner accumulated similar patterns of tandem inversions and dense repeat clusters, presumably in response to similar needs to create linkage between genes causing drive and resistance.</p>',
			'date' => '2018-10-12',
			'pmid' => 'http://www.pubmed.gov/30315196',
			'doi' => '10.1038/s41467-018-06562-x',
			'modified' => '2019-07-22 09:20:24',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 102 => array(
			'id' => '3507',
			'name' => 'Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclones.',
			'authors' => 'de Boer B, Prick J, Pruis MG, Keane P, Imperato MR, Jaques J, Brouwers-Vos AZ, Hogeling SM, Woolthuis CM, Nijk MT, Diepstra A, Wandinger S, Versele M, Attar RM, Cockerill PN, Huls G, Vellenga E, Mulder AB, Bonifer C, Schuringa JJ',
			'description' => '<p>Intra-tumor heterogeneity caused by clonal evolution is a major problem in cancer treatment. To address this problem, we performed label-free quantitative proteomics on primary acute myeloid leukemia (AML) samples. We identified 50 leukemia-enriched plasma membrane proteins enabling the prospective isolation of genetically distinct subclones from individual AML patients. Subclones differed in their regulatory phenotype, drug sensitivity, growth, and engraftment behavior, as determined by RNA sequencing, DNase I hypersensitive site mapping, transcription factor occupancy analysis, in&nbsp;vitro culture, and xenograft transplantation. Finally, we show that these markers can be used to identify and longitudinally track distinct leukemic clones in patients in routine diagnostics. Our study describes a strategy for a major improvement in stratifying cancer diagnosis and treatment.</p>',
			'date' => '2018-10-08',
			'pmid' => 'http://www.pubmed.gov/30245083',
			'doi' => '10.1016/j.ccell.2018.08.014',
			'modified' => '2019-02-27 16:26:01',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 103 => array(
			'id' => '3505',
			'name' => 'Genomic Location of PRMT6-Dependent H3R2 Methylation Is Linked to the Transcriptional Outcome of Associated Genes.',
			'authors' => 'Bouchard C, Sahu P, Meixner M, Nötzold RR, Rust MB, Kremmer E, Feederle R, Hart-Smith G, Finkernagel F, Bartkuhn M, Savai Pullamsetti S, Nist A, Stiewe T, Philipsen S, Bauer UM',
			'description' => '<p>Protein arginine methyltransferase 6 (PRMT6) catalyzes asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a). This mark has been reported to associate with silent genes. Here, we use a cell model&nbsp;of neural differentiation, which upon PRMT6 knockout exhibits proliferation and differentiation defects. Strikingly, we detect PRMT6-dependent H3R2me2a at active genes, both at promoter and enhancer sites. Loss of H3R2me2a from promoter sites leads to enhanced KMT2A binding and H3K4me3 deposition together with increased target gene transcription, supporting a repressive nature of H3R2me2a. At enhancers, H3R2me2a peaks co-localize with the active enhancer marks H3K4me1 and H3K27ac. Here, loss of H3R2me2a results in reduced KMT2D binding and H3K4me1/H3K27ac deposition together with decreased transcription of associated genes, indicating that H3R2me2a also exerts activation functions. Our work suggests that PRMT6 via H3R2me2a interferes with the deposition of adjacent histone marks and modulates the activity of important differentiation-associated genes by opposing transcriptional effects.</p>',
			'date' => '2018-09-18',
			'pmid' => 'http://www.pubmed.gov/30232013',
			'doi' => '10.1016/j.celrep.2018.08.052',
			'modified' => '2019-02-28 10:05:16',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 104 => array(
			'id' => '3599',
			'name' => 'Enhancer-driven transcriptional regulation is a potential key determinant for human visceral and subcutaneous adipocytes.',
			'authors' => 'Liefke R, Bokelmann K, Ghadimi BM, Dango S',
			'description' => '<p>Obesity is characterized by the excess of body fat leading to impaired health. Abdominal fat is particularly harmful and is associated with cardiovascular and metabolic diseases and cancer. In contrast, subcutaneous fat is generally considered less detrimental. The mechanisms that establish the cellular characteristics of these distinct fat types in humans are not fully understood. Here, we explored whether differences of their gene regulatory mechanisms can be investigated in vitro. For this purpose, we in vitro differentiated human visceral and subcutaneous pre-adipocytes into mature adipocytes and obtained their gene expression profiles and genome-wide H3K4me3, H3K9me3 and H3K27ac patterns. Subsequently, we compared those data with public gene expression data from visceral and subcutaneous fat tissues. We found that the in vitro differentiated adipocytes show significant differences in their transcriptional landscapes, which correlate with biological pathways that are characteristic for visceral and subcutaneous fat tissues, respectively. Unexpectedly, visceral adipocyte enhancers are rich on motifs for transcription factors involved in the Hippo-YAP pathway, cell growth and inflammation, which are not typically associated with adipocyte function. In contrast, enhancers of subcutaneous adipocytes show enrichment of motifs for common adipogenic transcription factors, such as C/EBP, NFI and PPAR&gamma;, implicating substantially disparate gene regulatory networks in visceral and subcutaneous adipocytes. Consistent with the role in obesity, predominantly the histone modification pattern of visceral adipocytes is linked to obesity-associated diseases. Thus, this work suggests that the properties of visceral and subcutaneous fat tissues can be studied in vitro and provides preliminary insights into their gene regulatory processes.</p>',
			'date' => '2018-06-30',
			'pmid' => 'http://www.pubmed.gov/29966764',
			'doi' => '10.1016/j.bbagrm.2018.06.007',
			'modified' => '2019-04-17 15:05:35',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 105 => array(
			'id' => '3621',
			'name' => 'Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx.',
			'authors' => 'Hensel KO, Cantner F, Bangert F, Wirth S, Postberg J',
			'description' => '<p>BACKGROUND: In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of cccDNA and HBx remains unexplored. RESULTS: To identify virus-host genome interactions and the underlying nuclear landscape for the first time, we combined circular chromosome conformation capture (4C) with RNA-seq and ChIP-seq. Moreover, we studied HBx-binding to HBV episomes. In HBV-positive HepaRG hepatocytes, we observed preferential association of HBV episomes and HBx with actively transcribed nuclear domains on the host genome correlating in size with constrained topological units of chromatin. Interestingly, HBx alone occupied transcribed chromatin domains. Silencing of native HBx caused reduced episomal HBV stability. CONCLUSIONS: As part of the HBV episome, HBx might stabilize HBV episomal nuclear localization. Our observations may contribute to the understanding of long-term episomal stability and the facilitation of viral persistence. The exact mechanism by which HBx contributes to HBV nuclear persistence warrants further investigations.</p>',
			'date' => '2018-06-22',
			'pmid' => 'http://www.pubmed.gov/29933745',
			'doi' => '10.1186/s13072-018-0204-2',
			'modified' => '2019-05-16 11:23:59',
			'created' => '2019-04-25 11:11:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 106 => array(
			'id' => '3503',
			'name' => 'Genome-wide rules of nucleosome phasing',
			'authors' => 'Sandro Baldi, Dhawal S. Jain1, Lisa Harpprecht1, Angelika Zabel1, Marion Scheibe, Falk Butter, Tobias Straub and Peter B. Becker',
			'description' => '<p>Regular successions of positioned nucleosomes &ndash; phased nucleosome arrays (PNAs) &ndash; are predominantly known from transcriptional start sites (TSS). It is unclear whether PNAs occur elsewhere in the genome. To generate a comprehensive inventory of PNAs for Drosophila, we applied spectral analysis to nucleosome maps and identified thousands of PNAs throughout the genome. About half of them are not near TSS and strongly enriched for a novel sequence motif. Through genome-wide reconstitution of physiological chromatin in Drosophila embryo extracts we uncovered the molecular basis of PNA formation. We identified Phaser, an unstudied zinc finger protein that positions nucleosomes flanking the new motif. It also revealed how the global activity of the chromatin remodeler CHRAC/ACF, together with local barrier elements, generates islands of regular phasing throughout the genome. Our work demonstrates the potential of chromatin assembly by embryo extracts as a powerful tool to reconstitute chromatin features on a global scale in vitro.</p>',
			'date' => '2018-06-13',
			'pmid' => 'https://doi.org/10.1101/093666',
			'doi' => '10.1101/093666.',
			'modified' => '2019-02-28 10:28:59',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 107 => array(
			'id' => '3562',
			'name' => 'Insulin promoter in human pancreatic β cells contacts diabetes susceptibility loci and regulates genes affecting insulin metabolism.',
			'authors' => 'Jian X, Felsenfeld G',
			'description' => '<p>Both type 1 and type 2 diabetes involve a complex interplay between genetic, epigenetic, and environmental factors. Our laboratory has been interested in the physical interactions, in nuclei of human pancreatic &beta; cells, between the insulin ( gene and other genes that are involved in insulin metabolism. We have identified, using Circularized Chromosome Conformation Capture (4C), many physical contacts in a human pancreatic &beta; cell line between the promoter on chromosome 11 and sites on most other chromosomes. Many of these contacts are associated with type 1 or type 2 diabetes susceptibility loci. To determine whether physical contact is correlated with an ability of the locus to affect expression of these genes, we knock down expression by targeting the promoter; 259 genes are either up or down-regulated. Of these, 46 make physical contact with We analyze a subset of the contacted genes and show that all are associated with acetylation of histone H3 lysine 27, a marker of actively expressed genes. To demonstrate the usefulness of this approach in revealing regulatory pathways, we identify from among the contacted sites the previously uncharacterized gene and show that it plays an important role in controlling the effect of somatostatin-28 on insulin secretion. These results are consistent with models in which clustering of genes supports transcriptional activity. This may be a particularly important mechanism in pancreatic &beta; cells and in other cells where a small subset of genes is expressed at high levels.</p>',
			'date' => '2018-05-15',
			'pmid' => 'http://www.pubmed.gov/29712868',
			'doi' => '10.1073/pnas.1803146115',
			'modified' => '2019-03-25 11:27:48',
			'created' => '2019-03-21 14:12:08',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 108 => array(
			'id' => '3578',
			'name' => 'Modulation of gene transcription and epigenetics of colon carcinoma cells by bacterial membrane vesicles.',
			'authors' => 'Vdovikova S, Gilfillan S, Wang S, Dongre M, Wai SN, Hurtado A',
			'description' => '<p>Interactions between bacteria and colon cancer cells influence the transcription of the host cell. Yet is it undetermined whether the bacteria itself or the communication between the host and bacteria is responsible for the genomic changes in the eukaryotic cell. Now, we have investigated the genomic and epigenetic consequences of co-culturing colorectal carcinoma cells with membrane vesicles from pathogenic bacteria Vibrio cholerae and non-pathogenic commensal bacteria Escherichia coli. Our study reveals that membrane vesicles from pathogenic and commensal bacteria have a global impact on the gene expression of colon-carcinoma cells. The changes in gene expression correlate positively with both epigenetic changes and chromatin accessibility of promoters at transcription start sites of genes induced by both types of membrane vesicles. Moreover, we have demonstrated that membrane vesicles obtained only from V. cholerae induced the expression of genes associated with epithelial cell differentiation. Altogether, our study suggests that the observed genomic changes in host cells might be due to specific components of membrane vesicles and do not require communication by direct contact with the bacteria.</p>',
			'date' => '2018-05-09',
			'pmid' => 'http://www.pubmed.gov/29743643',
			'doi' => '10.1038/s41598-018-25308-9',
			'modified' => '2019-04-17 15:56:24',
			'created' => '2019-04-16 12:25:30',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 109 => array(
			'id' => '3459',
			'name' => 'Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI as a co-repressor for RUNX1.',
			'authors' => 'Feld C, Sahu P, Frech M, Finkernagel F, Nist A, Stiewe T, Bauer UM, Neubauer A',
			'description' => '<p>SKI is a transcriptional co-regulator and overexpressed in various human tumors, for example in acute myeloid leukemia (AML). SKI contributes to the origin and maintenance of the leukemic phenotype. Here, we use ChIP-seq and RNA-seq analysis to identify the epigenetic alterations induced by SKI overexpression in AML cells. We show that approximately two thirds of differentially expressed genes are up-regulated upon SKI deletion, of which &gt;40% harbor SKI binding sites in their proximity, primarily in enhancer regions. Gene ontology analysis reveals that many of the differentially expressed genes are annotated to hematopoietic cell differentiation and inflammatory response, corroborating our finding that SKI contributes to a myeloid differentiation block in HL60 cells. We find that SKI peaks are enriched for RUNX1 consensus motifs, particularly in up-regulated SKI targets upon SKI deletion. RUNX1 ChIP-seq displays that nearly 70% of RUNX1 binding sites overlap with SKI peaks, mainly at enhancer regions. SKI and RUNX1 occupy the same genomic sites and cooperate in gene silencing. Our work demonstrates for the first time the predominant co-repressive function of SKI in AML cells on a genome-wide scale and uncovers the transcription factor RUNX1 as an important mediator of SKI-dependent transcriptional repression.</p>',
			'date' => '2018-04-20',
			'pmid' => 'http://www.pubmed.gov/29471413',
			'doi' => '10.1093/nar/gky119',
			'modified' => '2019-02-15 21:13:23',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 110 => array(
			'id' => '3539',
			'name' => 'A long range distal enhancer controls temporal fine-tuning of PAX6 expression in neuronal precursors.',
			'authors' => 'Lacomme M, Medevielle F, Bourbon HM, Thierion E, Kleinjan DJ, Roussat M, Pituello F, Bel-Vialar S',
			'description' => '<p>Proper embryonic development relies on a tight control of spatial and temporal gene expression profiles in a highly regulated manner. One good example is the ON/OFF switching of the transcription factor PAX6 that governs important steps of neurogenesis. In the neural tube PAX6 expression is initiated in neural progenitors through the positive action of retinoic acid signaling and downregulated in neuronal precursors by the bHLH transcription factor NEUROG2. How these two regulatory inputs are integrated at the molecular level to properly fine tune temporal PAX6 expression is not known. In this study we identified and characterized a 940-bp long distal cis-regulatory module (CRM), located far away from the PAX6 transcription unit and which conveys positive input from RA signaling pathway and indirect repressive signal(s) from NEUROG2. These opposing regulatory signals are integrated through HOMZ, a 94 bp core region within E940 which is evolutionarily conserved in distant organisms such as the zebrafish. We show that within HOMZ, NEUROG2 and RA exert their opposite temporal activities through a short 60 bp region containing a functional RA-responsive element (RARE). We propose a model in which retinoic acid receptors (RARs) and NEUROG2 repressive target(s) compete on the same DNA motif to fine tune temporal PAX6 expression during the course of spinal neurogenesis.</p>',
			'date' => '2018-04-15',
			'pmid' => 'http://www.pubmed.gov/29486153',
			'doi' => '10.1016/j.ydbio.2018.02.015',
			'modified' => '2019-02-28 10:42:57',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 111 => array(
			'id' => '3432',
			'name' => 'HDAC1 and HDAC2 Modulate TGF-β Signaling during Endothelial-to-Hematopoietic Transition.',
			'authors' => 'Thambyrajah R, Fadlullah MZH, Proffitt M, Patel R, Cowley SM, Kouskoff V, Lacaud G',
			'description' => '<p>The first hematopoietic stem and progenitor cells are generated during development from hemogenic endothelium (HE) through trans-differentiation. The molecular mechanisms underlying this endothelial-to-hematopoietic transition (EHT) remain poorly understood. Here, we explored the role of the epigenetic regulators HDAC1 and HDAC2 in the emergence of these first blood cells in&nbsp;vitro and in&nbsp;vivo. Loss of either of these epigenetic silencers through conditional genetic deletion reduced hematopoietic transition from HE, while combined deletion was incompatible with blood generation. We investigated the molecular basis of HDAC1 and HDAC2 requirement and identified TGF-&beta; signaling as one of the pathways controlled by HDAC1 and HDAC2. Accordingly, we experimentally demonstrated that activation of this pathway in HE cells reinforces hematopoietic development. Altogether, our results establish that HDAC1 and HDAC2 modulate TGF-&beta; signaling and suggest that stimulation of this pathway in HE cells would be beneficial for production of hematopoietic cells for regenerative therapies.</p>',
			'date' => '2018-04-10',
			'pmid' => 'http://www.pubmed.gov/29641990',
			'doi' => '10.1016/j.stemcr.2018.03.011',
			'modified' => '2018-12-31 11:55:16',
			'created' => '2018-12-04 09:51:07',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 112 => array(
			'id' => '3468',
			'name' => 'EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma.',
			'authors' => 'Gorthi A, Romero JC, Loranc E, Cao L, Lawrence LA, Goodale E, Iniguez AB, Bernard X, Masamsetti VP, Roston S, Lawlor ER, Toretsky JA, Stegmaier K, Lessnick SL, Chen Y, Bishop AJR',
			'description' => '<p>Ewing sarcoma is an aggressive paediatric cancer of the bone and soft tissue. It results from a chromosomal translocation, predominantly t(11;22)(q24:q12), that fuses the N-terminal transactivation domain of the constitutively expressed EWSR1 protein with the C-terminal DNA binding domain of the rarely expressed FLI1 protein. Ewing sarcoma is highly sensitive to genotoxic agents such as etoposide, but the underlying molecular basis of this sensitivity is unclear. Here we show that Ewing sarcoma cells display alterations in regulation of damage-induced transcription, accumulation of R-loops and increased replication stress. In addition, homologous recombination is impaired in Ewing sarcoma owing to an enriched interaction between BRCA1 and the elongating transcription machinery. Finally, we uncover a role for EWSR1 in the transcriptional response to damage, suppressing R-loops and promoting homologous recombination. Our findings improve the current understanding of EWSR1 function, elucidate the mechanistic basis of the sensitivity of Ewing sarcoma to chemotherapy (including PARP1 inhibitors) and highlight a class of BRCA-deficient-like tumours.</p>',
			'date' => '2018-03-15',
			'pmid' => 'http://www.pubmed.gov/29513652',
			'doi' => '10.1038/nature25748',
			'modified' => '2019-02-15 21:16:23',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 113 => array(
			'id' => '3533',
			'name' => 'A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.',
			'authors' => 'Zanghì G, Vembar SS, Baumgarten S, Ding S, Guizetti J, Bryant JM, Mattei D, Jensen ATR, Rénia L, Goh YS, Sauerwein R, Hermsen CC, Franetich JF, Bordessoulles M, Silvie O, Soulard V, Scatton O, Chen P, Mecheri S, Mazier D, Scherf A',
			'description' => '<p>Heterochromatin plays a central role in the process of immune evasion, pathogenesis, and transmission of the malaria parasite Plasmodium falciparum during blood stage infection. Here, we use ChIP sequencing to demonstrate that sporozoites from mosquito salivary glands expand heterochromatin at subtelomeric regions to silence blood-stage-specific&nbsp;genes. Our data also revealed that heterochromatin enrichment is predictive of the transcription status of clonally variant genes members that mediate cytoadhesion in blood stage parasites. A specific member (here called NF54var) of the var gene family remains euchromatic, and the resultant PfEMP1 (NF54_SpzPfEMP1) is expressed at the&nbsp;sporozoite surface. NF54_SpzPfEMP1-specific antibodies efficiently block hepatocyte infection in&nbsp;a strain-specific manner. Furthermore, human volunteers immunized with infective sporozoites developed antibodies against NF54_SpzPfEMP1. Overall, we show that the epigenetic signature of var genes is reset in mosquito stages. Moreover, the identification of a strain-specific sporozoite PfEMP1 is highly relevant for vaccine design based on sporozoites.</p>',
			'date' => '2018-03-13',
			'pmid' => 'http://www.pubmed.gov/29539423',
			'doi' => '10.1016/j.celrep.2018.02.075',
			'modified' => '2019-02-28 10:47:11',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 114 => array(
			'id' => '3444',
			'name' => 'Genome-wide analysis of PDX1 target genes in human pancreatic progenitors.',
			'authors' => 'Wang X, Sterr M, Burtscher I, Chen S, Hieronimus A, Machicao F, Staiger H, Häring HU, Lederer G, Meitinger T, Cernilogar FM, Schotta G, Irmler M, Beckers J, Hrabě de Angelis M, Ray M, Wright CVE, Bakhti M, Lickert H',
			'description' => '<p>OBJECTIVE: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing &beta;-cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Also, comparative studies of PDX1 binding patterns in pancreatic progenitors and adult &beta;-cells have not been conducted so far. Furthermore, many studies reported the association between single nucleotide polymorphisms (SNPs) and T2DM, and it has been shown that islet enhancers are enriched in T2DM-associated SNPs. Whether regions, harboring T2DM-associated SNPs are PDX1 bound and active at the pancreatic progenitor stage has not been reported so far. METHODS: In this study, we have generated a novel induced pluripotent stem cell (iPSC) line that efficiently differentiates into human pancreatic progenitors (PPs). Furthermore, PDX1 and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) was used to identify PDX1 transcriptional targets and active enhancer and promoter regions. To address potential differences in the function of PDX1 during development and adulthood, we compared PDX1 binding profiles from PPs and adult islets. Moreover, combining ChIP-seq and GWAS meta-analysis data we identified T2DM-associated SNPs in PDX1 binding sites and active chromatin regions. RESULTS: ChIP-seq for PDX1 revealed a total of 8088 PDX1-bound regions that map to 5664 genes in iPSC-derived PPs. The PDX1 target regions include important pancreatic TFs, such as PDX1 itself, RFX6, HNF1B, and MEIS1, which were activated during the differentiation process as revealed by the active chromatin mark H3K27ac and mRNA expression profiling, suggesting that auto-regulatory feedback regulation maintains PDX1 expression and initiates a pancreatic TF program. Remarkably, we identified several PDX1 target genes that have not been reported in the literature in human so far, including RFX3, required for ciliogenesis and endocrine differentiation in mouse, and the ligand of the Notch receptor DLL1, which is important for endocrine induction and tip-trunk patterning. The comparison of PDX1 profiles from PPs and adult human islets identified sets of stage-specific target genes, associated with early pancreas development and adult &beta;-cell function, respectively. Furthermore, we found an enrichment of T2DM-associated SNPs in active chromatin regions from iPSC-derived PPs. Two of these SNPs fall into PDX1 occupied sites that are located in the intronic regions of TCF7L2 and HNF1B. Both of these genes are key transcriptional regulators of endocrine induction and mutations in cis-regulatory regions predispose to diabetes. CONCLUSIONS: Our data provide stage-specific target genes of PDX1 during in&nbsp;vitro differentiation of stem cells into pancreatic progenitors that could be useful to identify pathways and molecular targets that predispose for diabetes. In addition, we show that T2DM-associated SNPs are enriched in active chromatin regions at the pancreatic progenitor stage, suggesting that the susceptibility to T2DM might originate from imperfect execution of a &beta;-cell developmental program.</p>',
			'date' => '2018-03-01',
			'pmid' => 'http://www.pubmed.gov/29396371',
			'doi' => '10.1016/j.molmet.2018.01.011',
			'modified' => '2019-02-15 21:27:03',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 115 => array(
			'id' => '3543',
			'name' => 'A multi-omics study of the grapevine-downy mildew (Plasmopara viticola) pathosystem unveils a complex protein coding- and noncoding-based arms race during infection.',
			'authors' => 'Brilli M, Asquini E, Moser M, Bianchedi PL, Perazzolli M, Si-Ammour A',
			'description' => '<p>Fungicides are applied intensively to prevent downy mildew infections of grapevines (Vitis vinifera) with high impact on the environment. In order to develop alternative strategies we sequenced the genome of the oomycete pathogen Plasmopara viticola causing this disease. We show that it derives from a Phytophthora-like ancestor that switched to obligate biotrophy by losing genes involved in nitrogen metabolism and &gamma;-Aminobutyric acid catabolism. By combining multiple omics approaches we characterized the pathosystem and identified a RxLR effector that trigger an immune response in the wild species V. riparia. This effector is an ideal marker to screen novel grape resistant varieties. Our study reveals an unprecedented bidirectional noncoding RNA-based mechanism that, in one direction might be fundamental for P. viticola to proficiently infect its host, and in the other might reduce the effects of the infection on the plant.</p>',
			'date' => '2018-01-15',
			'pmid' => 'http://www.pubmed.gov/29335535',
			'doi' => '10.1038/s41598-018-19158-8',
			'modified' => '2019-02-28 11:00:21',
			'created' => '2019-02-27 12:54:44',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 116 => array(
			'id' => '3445',
			'name' => 'BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis.',
			'authors' => 'Kaufmann E, Sanz J, Dunn JL, Khan N, Mendonça LE, Pacis A, Tzelepis F, Pernet E, Dumaine A, Grenier JC, Mailhot-Léonard F, Ahmed E, Belle J, Besla R, Mazer B, King IL, Nijnik A, Robbins CS, Barreiro LB, Divangahi M',
			'description' => '<p>The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and&nbsp;location for generating such innate memory responses in&nbsp;vivo remain unknown. Here, we show that access of Bacillus Calmette-Gu&eacute;rin (BCG) to the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), leading to local cell&nbsp;expansion and enhanced myelopoiesis at the&nbsp;expense of lymphopoiesis. Importantly, BCG-educated HSCs generate epigenetically modified macrophages that provide significantly better protection against virulent M.&nbsp;tuberculosis infection than na&iuml;ve macrophages. By using parabiotic and chimeric mice, as well as adoptive transfer approaches, we demonstrate that training of the monocyte/macrophage lineage via BCG-induced HSC reprogramming is sustainable in&nbsp;vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.</p>',
			'date' => '2018-01-11',
			'pmid' => 'http://www.pubmed.gov/29328912',
			'doi' => '10.1016/j.cell.2017.12.031',
			'modified' => '2019-02-15 21:32:25',
			'created' => '2019-02-14 15:01:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 117 => 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) 118 => array(
			'id' => '3355',
			'name' => 'Functional dissection of Drosophila melanogaster SUUR protein influence on H3K27me3 profile',
			'authors' => 'Posukh O. V. et al.',
			'description' => '<div id="__sec1" class="sec sec-first">
<h3>Background</h3>
<p id="Par1" class="p p-first-last">In eukaryotes, heterochromatin replicates late in S phase of the cell cycle and contains specific covalent modifications of histones. <em>SuUR</em> mutation found in Drosophila makes heterochromatin replicate earlier than in wild type and reduces the level of repressive histone modifications. SUUR protein was shown to be associated with moving replication forks, apparently through the interaction with PCNA. The biological process underlying the effects of SUUR on replication and composition of heterochromatin remains unknown.</p>
</div>
<div id="__sec2" class="sec">
<h3>Results</h3>
<p id="Par2" class="p p-first-last">Here we performed a functional dissection of SUUR protein effects on H3K27me3 level. Using hidden Markow model-based algorithm we revealed <em>SuUR</em>-sensitive chromosomal regions that demonstrated unusual characteristics: They do not contain Polycomb and require SUUR function to sustain H3K27me3 level. We tested the role of SUUR protein in the mechanisms that could affect H3K27me3 histone levels in these regions. We found that SUUR does not affect the initial H3K27me3 pattern formation in embryogenesis or Polycomb distribution in the chromosomes. We also ruled out the possible effect of SUUR on histone genes expression and its involvement in DSB repair.</p>
</div>
<div id="__sec3" class="sec">
<h3>Conclusions</h3>
<p id="Par3" class="p p-first-last">Obtained results support the idea that SUUR protein contributes to the heterochromatin maintenance during the chromosome replication. A model that explains major SUUR-associated phenotypes is proposed.</p>
</div>',
			'date' => '2017-12-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709859/',
			'doi' => '',
			'modified' => '2018-04-05 12:28:59',
			'created' => '2018-04-05 12:28:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 119 => array(
			'id' => '3305',
			'name' => 'An endosiRNA-Based Repression Mechanism Counteracts Transposon Activation during Global DNA Demethylation in Embryonic Stem Cells',
			'authors' => 'Berrens R.V. et al.',
			'description' => '<p>Erasure of DNA methylation and repressive chromatin marks in the mammalian germline leads to risk of transcriptional activation of transposable elements (TEs). Here, we used mouse embryonic stem cells (ESCs) to identify an endosiRNA-based mechanism involved in suppression of TE transcription. In ESCs with DNA demethylation induced by acute deletion of Dnmt1, we saw an increase in sense transcription at TEs, resulting in an abundance of sense/antisense transcripts leading to high levels of ARGONAUTE2 (AGO2)-bound small RNAs. Inhibition of Dicer or Ago2 expression revealed that small RNAs are involved in an immediate response to demethylation-induced transposon activation, while the deposition of repressive histone marks follows as a chronic response. In&nbsp;vivo, we also found TE-specific endosiRNAs present during primordial germ cell development. Our results suggest that antisense TE transcription is a "trap" that elicits an endosiRNA response to restrain acute transposon activity during epigenetic reprogramming in the mammalian germline.</p>',
			'date' => '2017-11-02',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/29100015',
			'doi' => '',
			'modified' => '2018-01-03 10:17:40',
			'created' => '2018-01-03 10:17:40',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 120 => array(
			'id' => '3281',
			'name' => 'Epigenome profiling and editing of neocortical progenitor cells during development',
			'authors' => 'Albert M. et al.',
			'description' => '<p>The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resolution are required. Here, we present genomewide histone methylation maps for distinct neural cell populations in the developing mouse neocortex. Using different chromatin features, we identify potential novel regulators of cortical NPCs. Moreover, we identify extensive H3K27me3 changes between NPC subtypes coinciding with major developmental and cell biological transitions. Interestingly, we detect dynamic H3K27me3 changes on promoters of several crucial transcription factors, including the basal progenitor regulator <i>Eomes</i> We use catalytically inactive Cas9 fused with the histone methyltransferase Ezh2 to edit H3K27me3 at the <i>Eomes</i> locus <i>in&nbsp;vivo</i>, which results in reduced Tbr2 expression and lower basal progenitor abundance, underscoring the relevance of dynamic H3K27me3 changes during neocortex development. Taken together, we provide a rich resource of neocortical histone methylation data and outline an approach to investigate its contribution to the regulation of selected genes during neocortical development.</p>',
			'date' => '2017-09-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28765163',
			'doi' => '',
			'modified' => '2017-10-17 10:25:58',
			'created' => '2017-10-17 10:25:58',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 121 => array(
			'id' => '3250',
			'name' => 'Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles',
			'authors' => 'Marincevic-Zuniga Y. et al.',
			'description' => '<div class="">
<h4>BACKGROUND:</h4>
<p><abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL). In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts.</abstracttext></p>
<h4>METHODS:</h4>
<p><abstracttext label="METHODS" nlmcategory="METHODS">We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">We identified 64 unique fusion events distributed among 80 individual patients, of which over 50% have not previously been reported in ALL. Although the majority of the fusion genes were found only in a single patient, we identified several recurrent fusion gene families defined by promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5, and ZNF384, or recurrent fusion genes, such as DUX4-IGH. Our data show that patients harboring these fusion genes displayed characteristic genome-wide DNA methylation and gene expression signatures in addition to distinct patterns in single nucleotide variants and recurrent copy number alterations.</abstracttext></p>
<h4>CONCLUSION:</h4>
<p><abstracttext label="CONCLUSION" nlmcategory="CONCLUSIONS">Our study delineates the fusion gene landscape in pediatric ALL, including both known and novel fusion genes, and highlights fusion gene families with shared molecular etiologies, which may provide additional information for prognosis and therapeutic options in the future.</abstracttext></p>
</div>',
			'date' => '2017-08-14',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28806978',
			'doi' => '',
			'modified' => '2017-09-26 09:49:39',
			'created' => '2017-09-26 09:49:39',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 122 => array(
			'id' => '3259',
			'name' => 'Dynamics of RNA Polymerase II Pausing and Bivalent Histone H3 Methylation during Neuronal Differentiation in Brain Development',
			'authors' => 'Liu J. et al.',
			'description' => '<p>During cellular differentiation, genes important for differentiation are expected to be silent in stem/progenitor cells yet can be readily activated. RNA polymerase II (Pol II) pausing and bivalent chromatin marks are two paradigms suited for establishing such a poised state of gene expression; however, their specific contributions in development are not well understood. Here we characterized Pol II pausing and H3K4me3/H3K27me3 marks in neural progenitor cells (NPCs) and their daughter neurons purified from the developing mouse cortex. We show that genes paused in NPCs or neurons are characteristic of respective cellular functions important for each cell type, although pausing and pause release were not correlated with gene activation. Bivalent chromatin marks poised the marked genes&nbsp;in NPCs for activation in neurons. Interestingly, we&nbsp;observed a positive correlation between H3K27me3 and paused Pol II. This study thus reveals cell type-specific Pol II pausing and gene activation-associated bivalency during mammalian neuronal differentiation.</p>',
			'date' => '2017-08-08',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28793256',
			'doi' => '',
			'modified' => '2017-10-05 11:17:11',
			'created' => '2017-10-05 11:17:11',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 123 => 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) 124 => array(
			'id' => '3282',
			'name' => 'Krox20 hindbrain regulation incorporates multiple modes of cooperation between cis-acting elements',
			'authors' => 'Thierion E. et al.',
			'description' => '<p>Developmental genes can harbour multiple transcriptional enhancers that act simultaneously or in succession to achieve robust and precise spatiotemporal expression. However, the mechanisms underlying cooperation between cis-acting elements are poorly documented, notably in vertebrates. The mouse gene Krox20 encodes a transcription factor required for the specification of two segments (rhombomeres) of the developing hindbrain. In rhombomere 3, Krox20 is subject to direct positive feedback governed by an autoregulatory enhancer, element A. In contrast, a second enhancer, element C, distant by 70 kb, is active from the initiation of transcription independent of the presence of the KROX20 protein. Here, using both enhancer knock-outs and investigations of chromatin organisation, we show that element C possesses a dual activity: besides its classical enhancer function, it is also permanently required in cis to potentiate the autoregulatory activity of element A, by increasing its chromatin accessibility. This work uncovers a novel, asymmetrical, long-range mode of cooperation between cis-acting elements that might be essential to avoid promiscuous activation of positive autoregulatory elements.</p>',
			'date' => '2017-07-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28749941',
			'doi' => '',
			'modified' => '2017-10-23 17:38:21',
			'created' => '2017-10-23 17:38:21',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 125 => array(
			'id' => '3261',
			'name' => 'Ectopic application of the repressive histone modification H3K9me2 establishes post-zygotic reproductive isolation in Arabidopsis thaliana',
			'authors' => 'Jiang H. et al.',
			'description' => '<p>Hybrid seed lethality as a consequence of interspecies or interploidy hybridizations is a major mechanism of reproductive isolation in plants. This mechanism is manifested in the endosperm, a dosage-sensitive tissue supporting embryo growth. Deregulated expression of imprinted genes such as <em>ADMETOS</em> (<em>ADM</em>) underpin the interploidy hybridization barrier in <em>Arabidopsis thaliana</em>; however, the mechanisms of their action remained unknown. In this study, we show that ADM interacts with the AT hook domain protein AHL10 and the SET domain-containing SU(VAR)3&ndash;9 homolog SUVH9 and ectopically recruits the heterochromatic mark H3K9me2 to AT-rich transposable elements (TEs), causing deregulated expression of neighboring genes. Several hybrid incompatibility genes identified in <em>Drosophila</em> encode for dosage-sensitive heterochromatin-interacting proteins, which has led to the suggestion that hybrid incompatibilities evolve as a consequence of interspecies divergence of selfish DNA elements and their regulation. Our data show that imbalance of dosage-sensitive chromatin regulators underpins the barrier to interploidy hybridization in <em>Arabidopsis</em>, suggesting that reproductive isolation as a consequence of epigenetic regulation of TEs is a conserved feature in animals and plants.</p>',
			'date' => '2017-07-25',
			'pmid' => 'http://genesdev.cshlp.org/content/early/2017/07/25/gad.299347.117',
			'doi' => '',
			'modified' => '2017-10-05 11:34:59',
			'created' => '2017-10-05 11:34:59',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 126 => array(
			'id' => '3267',
			'name' => '2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: Alterations in biosynthesis, enterohepatic circulation, and microbial metabolism.',
			'authors' => 'Fader K. et al.',
			'description' => '<p>2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant which elicits hepatotoxicity through activation of the aryl hydrocarbon receptor (AhR). Male C57BL/6 mice orally gavaged with TCDD (0.01-30&thinsp;&micro;g/kg) every 4 days for 28 days exhibited bile duct proliferation and pericholangitis. Mass spectrometry analysis detected a 4.6-fold increase in total hepatic bile acid levels, despite the coordinated repression of genes involved in cholesterol and primary bile acid biosynthesis including Cyp7a1. Specifically, TCDD elicited a &gt;200-fold increase in taurolithocholic acid (TLCA), a potent G protein-coupled bile acid receptor 1 (GPBAR1) agonist associated with bile duct proliferation. Increased levels of microbial bile acid metabolism loci (bsh, baiCD) are consistent with accumulation of TLCA and other secondary bile acids. Fecal bile acids decreased 2.8-fold, suggesting enhanced intestinal reabsorption due to induction of ileal transporters (Slc10a2, Slc51a) and increases in whole gut transit time and intestinal permeability. Moreover, serum bile acids were increased 45.4-fold, consistent with blood-to-hepatocyte transporter repression (Slco1a1, Slc10a1, Slco2b1, Slco1b2, Slco1a4) and hepatocyte-to-blood transporter induction (Abcc4, Abcc3). These results suggest that systemic alterations in enterohepatic circulation, as well as host and microbiota bile acid metabolism, favor bile acid accumulation that contributes to AhR-mediated hepatotoxicity.</p>',
			'date' => '2017-07-19',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28725001',
			'doi' => '',
			'modified' => '2017-10-09 16:22:36',
			'created' => '2017-10-09 16:22:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 127 => 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) 128 => array(
			'id' => '3258',
			'name' => 'CRISPR/Cas9 Genome Editing Reveals That the Intron Is Not Essential for var2csa Gene Activation or Silencing in Plasmodium falciparum',
			'authors' => 'Bryant J.M. et al.',
			'description' => '<p id="p-4"><em>Plasmodium falciparum</em> relies on monoallelic expression of 1 of 60 <em>var</em> virulence genes for antigenic variation and host immune evasion. Each <em>var</em> gene contains a conserved intron which has been implicated in previous studies in both activation and repression of transcription via several epigenetic mechanisms, including interaction with the <em>var</em> promoter, production of long noncoding RNAs (lncRNAs), and localization to repressive perinuclear sites. However, functional studies have relied primarily on artificial expression constructs. Using the recently developed <em>P.&nbsp;falciparum</em> clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, we directly deleted the <em>var2csa P.&nbsp;falciparum</em> 3D7_1200600 (Pf3D7_1200600) endogenous intron, resulting in an intronless <em>var</em> gene in a natural, marker-free chromosomal context. Deletion of the <em>var2csa</em> intron resulted in an upregulation of transcription of the <em>var2csa</em> gene in ring-stage parasites and subsequent expression of the PfEMP1 protein in late-stage parasites. Intron deletion did not affect the normal temporal regulation and subsequent transcriptional silencing of the <em>var</em> gene in trophozoites but did result in increased rates of <em>var</em> gene switching in some mutant clones. Transcriptional repression of the intronless <em>var2csa</em> gene could be achieved via long-term culture or panning with the CD36 receptor, after which reactivation was possible with chondroitin sulfate A (CSA) panning. These data suggest that the <em>var2csa</em> intron is not required for silencing or activation in ring-stage parasites but point to a subtle role in regulation of switching within the <em>var</em> gene family.</p>
<p id="p-5"><strong>IMPORTANCE</strong> <em>Plasmodium falciparum</em> is the most virulent species of malaria parasite, causing high rates of morbidity and mortality in those infected. Chronic infection depends on an immune evasion mechanism termed antigenic variation, which in turn relies on monoallelic expression of 1 of ~60 <em>var</em> genes. Understanding antigenic variation and the transcriptional regulation of monoallelic expression is important for developing drugs and/or vaccines. The <em>var</em> gene family encodes the antigenic surface proteins that decorate infected erythrocytes. Until recently, studying the underlying genetic elements that regulate monoallelic expression in <em>P.&nbsp;falciparum</em> was difficult, and most studies relied on artificial systems such as episomal reporter genes. Our study was the first to use CRISPR/Cas9 genome editing for the functional study of an important, conserved genetic element of <em>var</em> genes&mdash;the intron&mdash;in an endogenous, episome-free manner. Our findings shed light on the role of the <em>var</em> gene intron in transcriptional regulation of monoallelic expression.</p>',
			'date' => '2017-07-11',
			'pmid' => 'http://mbio.asm.org/content/8/4/e00729-17.abstract',
			'doi' => '',
			'modified' => '2017-10-05 11:12:18',
			'created' => '2017-10-05 11:12:18',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 129 => array(
			'id' => '3218',
			'name' => 'Genome-wide mapping and analysis of aryl hydrocarbon receptor (AHR)- and aryl hydrocarbon receptor repressor (AHRR)-binding sites in human breast cancer cells',
			'authors' => 'Sunny Y. Yang, Shaimaa Ahmed, Somisetty V. Satheesh, Jason Matthews',
			'description' => '<p><span>The aryl hydrocarbon receptor (AHR) mediates the toxic actions of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-</span><em class="EmphasisTypeItalic ">&rho;</em><span>-dioxin (TCDD), and also plays roles in vascular development, the immune response, and cell cycle regulation. The AHR repressor (AHRR) is an AHR-regulated gene and a negative regulator of AHR; however, the mechanisms of AHRR-dependent repression of AHR are unclear. In this study, we compared the genome-wide binding profiles of AHR and AHRR in MCF-7 human breast cancer cells treated for 24&nbsp;h with TCDD using chromatin immunoprecipitation followed by next-generation sequencing (ChIP-Seq). We identified 3915 AHR- and 2811 AHRR-bound regions, of which 974 (35%) were common to both datasets. When these 24-h datasets were also compared with AHR-bound regions identified after 45&nbsp;min of TCDD treatment, 67% (1884) of AHRR-bound regions overlapped with those of AHR. This analysis identified 994 unique AHRR-bound regions. AHRR-bound regions mapped closer to promoter regions when compared with AHR-bound regions. The AHRE was identified and overrepresented in AHR:AHRR-co-bound regions, AHR-only regions, and AHRR-only regions. Candidate unique AHR- and AHRR-bound regions were validated by ChIP&ndash;qPCR and their ability to regulate gene expression was confirmed by luciferase reporter gene assays. Overall, this study reveals that AHR and AHRR exhibit similar but also distinct genome-wide binding profiles, supporting the notion that AHRR is a context- and gene-specific repressor of AHR activity.</span></p>',
			'date' => '2017-07-05',
			'pmid' => 'https://link.springer.com/article/10.1007/s00204-017-2022-x',
			'doi' => '10.1007/s00204-017-2022-x',
			'modified' => '2017-07-29 08:23:22',
			'created' => '2017-07-29 08:23:22',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 130 => 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) 131 => array(
			'id' => '3358',
			'name' => 'Characterization of the Polycomb-Group Mark H3K27me3 in Unicellular Algae',
			'authors' => 'Mikulski P. et al.',
			'description' => '<p>Polycomb Group (PcG) proteins mediate chromatin repression in plants and animals by catalyzing H3K27 methylation and H2AK118/119 mono-ubiquitination through the activity of the Polycomb repressive complex 2 (PRC2) and PRC1, respectively. PcG proteins were extensively studied in higher plants, but their function and target genes in unicellular branches of the green lineage remain largely unknown. To shed light on PcG function and <i>modus operandi</i> in a broad evolutionary context, we demonstrate phylogenetic relationship of core PRC1 and PRC2 proteins and H3K27me3 biochemical presence in several unicellular algae of different phylogenetic subclades. We focus then on one of the species, the model red alga <i>Cyanidioschizon merolae</i>, and show that H3K27me3 occupies both, genes and repetitive elements, and mediates the strength of repression depending on the differential occupancy over gene bodies. Furthermore, we report that H3K27me3 in <i>C. merolae</i> is enriched in telomeric and subtelomeric regions of the chromosomes and has unique preferential binding toward intein-containing genes involved in protein splicing. Thus, our study gives important insight for Polycomb-mediated repression in lower eukaryotes, uncovering a previously unknown link between H3K27me3 targets and protein splicing.</p>',
			'date' => '2017-04-26',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28491069',
			'doi' => '',
			'modified' => '2018-04-05 13:09:46',
			'created' => '2018-04-05 13:09:46',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 132 => 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) 133 => array(
			'id' => '3176',
			'name' => 'First landscape of binding to chromosomes for a domesticated mariner transposase in the human genome: diversity of genomic targets of SETMAR isoforms in two colorectal cell lines',
			'authors' => 'Antoine-Lorquin A. et al.',
			'description' => '<p>Setmar is a 3-exons gene coding a SET domain fused to a Hsmar1 transposase. Its different transcripts theoretically encode 8 isoforms with SET moieties differently spliced. In vitro, the largest isoform binds specifically to Hsmar1 DNA ends and with no specificity to DNA when it is associated with hPso4. In colon cell lines, we found they bind specifically to two chromosomal targets depending probably on the isoform, Hsmar1 ends and sites with no conserved motifs. We also discovered that the isoforms profile was different between cell lines and patient tissues, suggesting the isoforms encoded by this gene in healthy cells and their functions are currently not investigated.</p>',
			'date' => '2017-03-09',
			'pmid' => 'http://biorxiv.org/content/early/2017/03/09/115030',
			'doi' => '',
			'modified' => '2017-05-15 10:24:16',
			'created' => '2017-05-15 10:24:16',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 134 => array(
			'id' => '3156',
			'name' => 'Crebbp loss cooperates with Bcl2 over-expression to promote lymphoma in mice',
			'authors' => 'Idoia García-Ramírez, Saber Tadros, Inés González-Herrero, Alberto Martín-Lorenzo, Guillermo Rodríguez-Hernández, Dalia Moore, Lucía Ruiz-Roca, Oscar Blanco, Diego Alonso-López, Javier De Las Rivas, Keenan Hartert, Romain Duval, David Klinkebiel, Martin B',
			'description' => '<p><span>CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits in B-cell development and can cooperate with Bcl2 over-expression to promote B-cell lymphoma. Through transcriptional and epigenetic profiling of these B-cells we found that Crebbp inactivation was associated with broad transcriptional alterations, but no changes in the patterns of histone acetylation at the proximal regulatory regions of these genes. However, B-cells with Crebbp inactivation showed high expression of Myc and patterns of altered histone acetylation that were localized to intragenic regions, enriched for Myc DNA binding motifs, and showed Myc binding. Through the analysis of CREBBP mutations from a large cohort of primary human FL and DLBCL, we show a significant difference in the spectrum of CREBBP mutations in these two diseases, with higher frequencies of nonsense/frameshift mutations in DLBCL compared to FL. Together our data therefore provide important links between Crebbp inactivation and Bcl2 dependence, and show a role for Crebbp inactivation in the induction of Myc expression. We suggest this may parallel the role of CREBBP frameshift/nonsense mutations in DLBCL that result in loss of the protein, but may contrast the role of missense mutations in the lysine acetyltransferase domain that are more frequently observed in FL and yield an inactive protein.</span></p>',
			'date' => '2017-03-05',
			'pmid' => 'http://www.bloodjournal.org/content/early/2017/03/13/blood-2016-08-733469?sso-checked=true',
			'doi' => 'https://doi.org/10.1182/blood-2016-08-733469',
			'modified' => '2017-05-11 11:17:42',
			'created' => '2017-04-10 07:56:37',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 135 => array(
			'id' => '3151',
			'name' => 'Aorta macrophage inflammatory and epigenetic changes in a murine model of obstructive sleep apnea: Potential role of CD36.',
			'authors' => 'Cortese R. et al.',
			'description' => '<p>Obstructive sleep apnea (OSA) affects 8-10% of the population, is characterized by chronic intermittent hypoxia (CIH), and causally associates with cardiovascular morbidities. In CIH-exposed mice, closely mimicking the chronicity of human OSA, increased accumulation and proliferation of pro-inflammatory metabolic M1-like macrophages highly expressing CD36, emerged in aorta. Transcriptomic and MeDIP-seq approaches identified activation of pro-atherogenic pathways involving a complex interplay of histone modifications in functionally-relevant biological pathways, such as inflammation and oxidative stress in aorta macrophages. Discontinuation of CIH did not elicit significant improvements in aorta wall macrophage phenotype. However, CIH-induced aorta changes were absent in CD36 knockout mice, Our results provide mechanistic insights showing that CIH exposures during sleep in absence of concurrent pro-atherogenic settings (i.e., genetic propensity or dietary manipulation) lead to the recruitment of CD36(+)<sup>high</sup> macrophages to the aortic wall and trigger atherogenesis. Furthermore, long-term CIH-induced changes may not be reversible with usual OSA treatment.</p>',
			'date' => '2017-02-27',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28240319',
			'doi' => '',
			'modified' => '2017-03-28 09:16:02',
			'created' => '2017-03-28 09:16:02',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 136 => array(
			'id' => '3138',
			'name' => 'Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia',
			'authors' => 'Chen S. et al.',
			'description' => '<p>Severe neonatal hyperbilirubinemia (SNH) and the onset of bilirubin encephalopathy and kernicterus result in part from delayed expression of UDP-glucuronosyltransferase 1A1 (UGT1A1) and the inability to metabolize bilirubin. Although there is a good understanding of the early events after birth that lead to the rapid increase in serum bilirubin, the events that control delayed expression of UGT1A1 during development remain a mystery. Humanized <em>UGT1</em> (<em>hUGT1</em>) mice develop SNH spontaneously, which is linked to repression of both liver and intestinal UGT1A1. In this study, we report that deletion of intestinal nuclear receptor corepressor 1 (NCoR1) completely diminishes hyperbilirubinemia in <em>hUGT1</em> neonates because of intestinal <em>UGT1A1</em> gene derepression. Transcriptomic studies and immunohistochemistry analysis demonstrate that NCoR1 plays a major role in repressing developmental maturation of the intestines. Derepression is marked by accelerated metabolic and oxidative phosphorylation, drug metabolism, fatty acid metabolism, and intestinal maturation, events that are controlled predominantly by H3K27 acetylation. The control of NCoR1 function and derepression is linked to IKK&beta; function, as validated in <em>hUGT1</em> mice with targeted deletion of intestinal IKK&beta;. Physiological events during neonatal development that target activation of an IKK&beta;/NCoR1 loop in intestinal epithelial cells lead to derepression of genes involved in intestinal maturation and bilirubin detoxification. These findings provide a mechanism of NCoR1 in intestinal homeostasis during development and provide a key link to those events that control developmental repression of UGT1A1 and hyperbilirubinemia.</p>',
			'date' => '2017-02-21',
			'pmid' => 'http://www.pnas.org/content/114/8/E1432.abstract',
			'doi' => '',
			'modified' => '2017-03-21 17:48:23',
			'created' => '2017-03-21 17:48:23',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 137 => array(
			'id' => '3166',
			'name' => 'The Drosophila speciation factor HMR localizes to genomic insulator sites',
			'authors' => 'Gerland T.A. et al.',
			'description' => '<p>Hybrid incompatibility between Drosophila melanogaster and D. simulans is caused by a lethal interaction of the proteins encoded by the Hmr and Lhr genes. In D. melanogaster the loss of HMR results in mitotic defects, an increase in transcription of transposable elements and a deregulation of heterochromatic genes. To better understand the molecular mechanisms that mediate HMR's function, we measured genome-wide localization of HMR in D. melanogaster tissue culture cells by chromatin immunoprecipitation. Interestingly, we find HMR localizing to genomic insulator sites that can be classified into two groups. One group belongs to gypsy insulators and another one borders HP1a bound regions at active genes. The transcription of the latter group genes is strongly affected in larvae and ovaries of Hmr mutant flies. Our data suggest a novel link between HMR and insulator proteins, a finding that implicates a potential role for genome organization in the formation of species.</p>',
			'date' => '2017-02-17',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28207793',
			'doi' => '',
			'modified' => '2017-05-09 10:05:49',
			'created' => '2017-05-09 10:05:49',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 138 => array(
			'id' => '3357',
			'name' => 'Applying the INTACT method to purify endosperm nuclei and to generate parental-specific epigenome profiles.',
			'authors' => 'Moreno-Romero J. et al.',
			'description' => '<p>The early endosperm tissue of dicot species is very difficult to isolate by manual dissection. This protocol details how to apply the INTACT (isolation of nuclei tagged in specific cell types) system for isolating early endosperm nuclei of Arabidopsis at high purity and how to generate parental-specific epigenome profiles. As a Protocol Extension, this article describes an adaptation of an existing Nature Protocol that details the use of the INTACT method for purification of root nuclei. We address how to obtain the INTACT lines, generate the starting material and purify the nuclei. We describe a method that allows purity assessment, which has not been previously addressed. The purified nuclei can be used for ChIP and DNA bisulfite treatment followed by next-generation sequencing (seq) to study histone modifications and DNA methylation profiles, respectively. By using two different Arabidopsis accessions as parents that differ by a large number of single-nucleotide polymorphisms (SNPs), we were able to distinguish the parental origin of epigenetic modifications. Our protocol describes the only working method to our knowledge for generating parental-specific epigenome profiles of the early Arabidopsis endosperm. The complete protocol, from silique collection to finished libraries, can be completed in 2 d for bisulfite-seq (BS-seq) and 3 to 4 d for ChIP-seq experiments.This protocol is an extension to: Nat. Protoc. 6, 56-68 (2011); doi:10.1038/nprot.2010.175; published online 16 December 2010.</p>',
			'date' => '2017-02-01',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/28055034',
			'doi' => '',
			'modified' => '2018-04-05 12:52:20',
			'created' => '2018-04-05 12:52:20',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 139 => array(
			'id' => '3042',
			'name' => 'BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire',
			'authors' => 'Najafova Z. et al.',
			'description' => '<p>Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4.</p>',
			'date' => '2016-09-19',
			'pmid' => 'http://nar.oxfordjournals.org/content/early/2016/09/19/nar.gkw826.abstract',
			'doi' => '',
			'modified' => '2016-10-10 09:58:41',
			'created' => '2016-10-10 09:49:57',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 140 => array(
			'id' => '3043',
			'name' => 'CTCF modulates Estrogen Receptor function through specific chromatin and nuclear matrix interactions',
			'authors' => 'Fiorito E. et al.',
			'description' => '<p>Enhancer regions and transcription start sites of estrogen-target regulated genes are connected by means of Estrogen Receptor long-range chromatin interactions. Yet, the complete molecular mechanisms controlling the transcriptional output of engaged enhancers and subsequent activation of coding genes remain elusive. Here, we report that CTCF binding to enhancer RNAs is enriched when breast cancer cells are stimulated with estrogen. CTCF binding to enhancer regions results in modulation of estrogen-induced gene transcription by preventing Estrogen Receptor chromatin binding and by hindering the formation of additional enhancer-promoter ER looping. Furthermore, the depletion of CTCF facilitates the expression of target genes associated with cell division and increases the rate of breast cancer cell proliferation. We have also uncovered a genomic network connecting loci enriched in cell cycle regulator genes to nuclear lamina that mediates the CTCF function. The nuclear lamina and chromatin interactions are regulated by estrogen-ER. We have observed that the chromatin loops formed when cells are treated with estrogen establish contacts with the nuclear lamina. Once there, the portion of CTCF associated with the nuclear lamina interacts with enhancer regions, limiting the formation of ER loops and the induction of genes present in the loop. Collectively, our results reveal an important, unanticipated interplay between CTCF and nuclear lamina to control the transcription of ER target genes, which has great implications in the rate of growth of breast cancer cells.</p>',
			'date' => '2016-09-15',
			'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/27638884',
			'doi' => '',
			'modified' => '2016-10-10 10:12:33',
			'created' => '2016-10-10 10:12:33',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 141 => array(
			'id' => '3052',
			'name' => 'PionX sites mark the X chromosome for dosage compensation',
			'authors' => 'Villa R et al.',
			'description' => '<p>The rules defining which small fraction of related DNA sequences can be selectively bound by a transcription factor are poorly understood. One of the most challenging tasks in DNA recognition is posed by dosage compensation systems that require the distinction between sex chromosomes and autosomes. In <i>Drosophila melanogaster</i>, the male-specific lethal dosage compensation complex (MSL-DCC) doubles the level of transcription from the single male X chromosome, but the nature of this selectivity is not known<sup><a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref1" title="Lucchesi, J. C. &amp; Kuroda, M. I. Dosage compensation in Drosophila. Cold Spring Harb. Perspect. Biol. 7, a019398 (2015)" id="ref-link-7">1</a></sup>. Previous efforts to identify X-chromosome-specific target sequences were unsuccessful as the identified MSL recognition elements lacked discriminative power<sup><a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref2" title="Alekseyenko, A. A. et al. A sequence motif within chromatin entry sites directs MSL establishment on the Drosophila X chromosome. Cell. 134, 599&ndash;609 (2008)" id="ref-link-8">2</a>, <a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref3" title="Straub, T., Grimaud, C., Gilfillan, G. D., Mitterweger, A. &amp; Becker, P. B. The chromosomal high-affinity binding sites for the Drosophila dosage compensation complex. PLoS Genet. 4, e1000302 (2008)" id="ref-link-9">3</a></sup>. Therefore, additional determinants such as co-factors, chromatin features, RNA and chromosome conformation have been proposed to refine targeting further<sup><a href="http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html#ref4" title="McElroy, K. A., Kang, H. &amp; Kuroda, M. I. Are we there yet? Initial targeting of the Male-Specific Lethal and Polycomb group chromatin complexes in Drosophila. Open Biol. 4, 140006 (2014)" id="ref-link-10">4</a></sup>. Here, using an <i>in vitro</i> genome-wide DNA binding assay, we show that recognition of the X chromosome is an intrinsic feature of the MSL-DCC. MSL2, the male-specific organizer of the complex, uses two distinct DNA interaction surfaces&mdash;the CXC and proline/basic-residue-rich domains&mdash;to identify complex DNA elements on the X chromosome. Specificity is provided by the CXC domain, which binds a novel motif defined by DNA sequence and shape. This motif characterizes a subclass of MSL2-binding sites, which we name PionX (pioneering sites on the X) as they appeared early during the recent evolution of an X chromosome in <i>D. miranda</i> and are the first chromosomal sites to be bound during <i>de novo</i> MSL-DCC assembly. Our data provide the first, to our knowledge, documented molecular mechanism through which the dosage compensation machinery distinguishes the X chromosome from an autosome. They highlight fundamental principles in the recognition of complex DNA elements by protein that will have a strong impact on many aspects of chromosome biology.</p>',
			'date' => '2016-08-31',
			'pmid' => 'http://www.nature.com/nature/journal/v537/n7619/full/nature19338.html',
			'doi' => '',
			'modified' => '2016-10-24 14:23:31',
			'created' => '2016-10-24 14:23:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 142 => 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) 143 => array(
			'id' => '2976',
			'name' => 'Deletion of Polycomb Repressive Complex 2 From Mouse Intestine Causes Loss of Stem Cells',
			'authors' => 'Koppens MA et al.',
			'description' => '<h4>BACKGROUND &amp; AIMS:</h4>
<p><abstracttext label="BACKGROUND &amp; AIMS" nlmcategory="OBJECTIVE">The polycomb repressive complex 2 (PRC2) regulates differentiation by contributing to repression of gene expression and thereby stabilizing the fate of stem cells and their progeny. PRC2 helps to maintain adult stem cell populations, but little is known about its functions in intestinal stem cells. We studied phenotypes of mice with intestine-specific deletion of the PRC2 proteins EED (a subunit required for PRC2 function) and EZH2 (a histone methyltransferase).</abstracttext></p>
<h4>METHODS:</h4>
<p><abstracttext label="METHODS" nlmcategory="METHODS">We performed studies of AhCre;EedLoxP/LoxP (EED knockout) mice and AhCre;Ezh2LoxP/LoxP (EZH2 knockout) mice, which have intestine-specific disruption in EED and EZH2, respectively. Small intestinal crypts were isolated and subsequently cultured to grow organoids. Intestines and organoids were analyzed by immunohistochemical, in situ hybridization, RNA sequence, and chromatin immunoprecipitation methods.</abstracttext></p>
<h4>RESULTS:</h4>
<p><abstracttext label="RESULTS" nlmcategory="RESULTS">Intestines of EED knockout mice had massive crypt degeneration and lower numbers of proliferating cells, compared with wildtype control mice; Cdkn2a became derepressed and we detected increased levels of P21. We did not observe any differences between EZH2 knockout and control mice. Intestinal crypts from EED knockout mice had signs of aberrant differentiation of uncommitted crypt cells-these differentiated toward the secretory cell lineage. Furthermore, crypts from EED-knockout mice had impaired Wnt signaling and concomitant loss of intestinal stem cells; this phenotype was not reversed upon ectopic stimulation of Wnt and Notch signaling in organoids. Analysis of gene expression patterns from intestinal tissues of EED knockout mice revealed dysregulation of several genes involved in Wnt signaling. Wnt signaling was directly regulated by PRC2.</abstracttext></p>
<h4>CONCLUSIONS:</h4>
<p><abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">In intestinal tissues of mice, PRC2 maintains small intestinal stem cells by promoting proliferation and preventing differentiation in the intestinal stem cell compartment. PRC2 controls expression of genes in multiple signaling pathways that regulate intestinal homeostasis.</abstracttext></p>',
			'date' => '2016-06-21',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27342214',
			'doi' => ' 10.1053/j.gastro.2016.06.020',
			'modified' => '2016-07-07 10:04:31',
			'created' => '2016-07-07 10:04:31',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 144 => array(
			'id' => '2949',
			'name' => 'Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells',
			'authors' => 'von Meyenn F et al.',
			'description' => '<p>Global demethylation is part of a conserved program of epigenetic reprogramming to naive pluripotency. The transition from primed hypermethylated embryonic stem cells (ESCs) to naive hypomethylated ones (serum-to-2i) is a valuable model system for epigenetic reprogramming. We present a mathematical model, which accurately predicts global DNA demethylation kinetics. Experimentally, we show that the main drivers of global demethylation are neither active mechanisms (Aicda, Tdg, and Tet1-3) nor the&nbsp;reduction of de novo methylation. UHRF1 protein, the essential targeting factor for DNMT1, is reduced upon transition to 2i, and so is recruitment of the maintenance methylation machinery to replication foci. Concurrently, there is global loss of H3K9me2, which is needed for chromatin binding of UHRF1. These mechanisms synergistically enforce global DNA hypomethylation in a replication-coupled fashion. Our observations establish the molecular mechanism for global demethylation in naive ESCs, which has key parallels with those operating in primordial germ cells and early embryos.</p>',
			'date' => '2016-05-25',
			'pmid' => 'http://www.ncbi.nlm.nih.gov/pubmed/27237052',
			'doi' => '10.1016/j.molcel.2016.04.025',
			'modified' => '2016-06-10 15:23:36',
			'created' => '2016-06-10 15:23:36',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		),
		(int) 145 => array(
			'id' => '2918',
			'name' => 'Parental epigenetic asymmetry of PRC2-mediated histone modifications in the Arabidopsis endosperm',
			'authors' => 'Moreno-Romero J et al.',
			'description' => '<p>Parental genomes in the endosperm are marked by differential DNA methylation and are therefore epigenetically distinct. This epigenetic asymmetry is established in the gametes and maintained after fertilization by unknown mechanisms. In this manuscript, we have addressed the key question whether parentally inherited differential DNA methylation affects <em>de novo</em> targeting of chromatin modifiers in the early endosperm. Our data reveal that polycomb-mediated H3 lysine 27 trimethylation (H3K27me3) is preferentially localized to regions that are targeted by the DNA glycosylase DEMETER (DME), mechanistically linking DNA hypomethylation to imprinted gene expression. Our data furthermore suggest an absence of <em>de novo </em>DNA methylation in the early endosperm, providing an explanation how DME-mediated hypomethylation of the maternal genome is maintained after fertilization. Lastly, we show that paternal-specific H3K27me3-marked regions are located at pericentromeric regions, suggesting that H3K27me3 and DNA methylation are not necessarily exclusive marks at pericentromeric regions in the endosperm.</p>',
			'date' => '2016-04-25',
			'pmid' => 'http://onlinelibrary.wiley.com/doi/10.15252/embj.201593534/abstract',
			'doi' => '10.15252/embj.201593534',
			'modified' => '2016-05-14 00:49:53',
			'created' => '2016-05-13 11:30:16',
			'ProductsPublication' => array(
				[maximum depth reached]
			)
		)
	),
	'Testimonial' => array(
		(int) 0 => array(
			'id' => '68',
			'name' => 'Universidad de Chile',
			'description' => '<p>We sheared the DNA on the Diagenode One and used the MicroPlex Library Preparation v2 Kit to create DNA libraries for whole genome sequencing of four plant species for which there is no reference genome available. Previous attempts with a commercial Tn5-transposase based method gave unsatisfactory results. However, the Diagenode MicroPlex kit was quicker, easier, and gave the expected profile of fragment sizes. In just 30 seconds of sonication, we obtained a fragment distribution centered at 270 bp. The library construction took only 2 hours with this kit. The library was sequenced in a NexSeq 550 in High-Output mode, giving 85% based with&gt;Q30.</p>',
			'author' => 'PhD. Ricardo Verdugo, Assistant Professor, University of Chile',
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			'slug' => 'universidad-de-chile',
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			'modified' => '2018-05-14 14:50:37',
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		),
		(int) 1 => 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',
			'featured' => false,
			'slug' => 'kamila-kwasniewska',
			'meta_keywords' => '',
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			'modified' => '2016-02-01 10:45:40',
			'created' => '2016-02-01 09:56:38',
			'ProductsTestimonial' => array(
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		),
		(int) 2 => array(
			'id' => '45',
			'name' => 'Imperial College London - iDeal ChIP-seq kit for TF + MicroPlex v2',
			'description' => '<p>There are so many ChIP-related products on the market, but I feel so lucky that I have been using the ones from Diagenode since I started my CHIP-seq project. I have used their <a href="../p/ideal-chip-seq-kit-for-transcription-factors-x100-100-rxns">iDeal CHIP-seq Kit for Transcription Factors</a> and <a href="../p/microplex-library-preparation-kit-v2-x48-12-indices-48-rxns">MicroPlex Library Prep Kit v2</a>. Both of them are fantastic and very reproducible. With the very-well written protocols, you will just be home and dry. Particularly, I want to thank the technical support, who is very patient, knowledgeable and extremely helpful. I would definitely recommend my colleagues to use the CHIP products from Diagenode.</p>',
			'author' => 'Dr Kaiyu Lei, Faculty of Medicine, Department of Surgery & Cancer, Imperial College London',
			'featured' => false,
			'slug' => 'testimonial-kaiyu',
			'meta_keywords' => '',
			'meta_description' => '',
			'modified' => '2016-03-09 16:00:31',
			'created' => '2015-12-18 15:40:02',
			'ProductsTestimonial' => array(
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			)
		),
		(int) 3 => array(
			'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',
			'featured' => false,
			'slug' => 'microchip-andrea',
			'meta_keywords' => '',
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			'modified' => '2016-03-09 16:00:08',
			'created' => '2015-12-07 13:04:58',
			'ProductsTestimonial' => array(
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			)
		),
		(int) 4 => array(
			'id' => '35',
			'name' => 'Microplex v2 - Katia Basso',
			'description' => '<p>We used the MicroPlex version 2 kit to generate libraries using ChIP DNA for several transcription factors and compared the results to a standard library generation protocol starting from 5ng of ChIP DNA. Even when we reduced the starting amount of DNA by 10-fold, the MicroPlex Kit produced the same high yields and quality of the libraries. As expected, the number of duplicate reads increased but 15 to 20 million unique reads were sufficient to achieve excellent enrichment data. We found that no information was lost, and the MicroPlex Kit helped produce data that was consistent with the standard protocol despite the lower input. On top of this, the MicroPlex Kit was extremely user-friendly and saved us time. The MicroPlex version 2 kit will make challenging ChIP-seq experiments that rely on very limited amount of starting material much easier with robust results.</p>',
			'author' => 'Katia Basso, PhD, Assistant Professor, Columbia University, New York',
			'featured' => true,
			'slug' => 'microplex-v2-katia-basso',
			'meta_keywords' => '',
			'meta_description' => '',
			'modified' => '2016-03-22 11:32:30',
			'created' => '2015-08-25 10:01:00',
			'ProductsTestimonial' => array(
				[maximum depth reached]
			)
		),
		(int) 5 => array(
			'id' => '30',
			'name' => 'MicroPlex Kit - Sammons',
			'description' => '<p>The Diagenode MicroPlex kit is the quickest and most efficient way to make sequencing libraries, especially from samples with very low inputs. We regularly start with picogram amounts of ChIP material and produce excellent quality libraries that would be impossible to make using normal methods. Sequencing libraries made from the MicroPlex kit give us excellent results even in large genomes. The kit performs very well, and we will use the kit in the future for studies with low cell numbers or starting material.</p>',
			'author' => 'Dr. Morgan Sammons, Lab of Dr. Shelley Berger, University of Pennsylvania',
			'featured' => false,
			'slug' => '',
			'meta_keywords' => '',
			'meta_description' => '',
			'modified' => '2015-08-18 16:27:04',
			'created' => '2015-07-29 10:43:24',
			'ProductsTestimonial' => array(
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		)
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			'countries' => 'GB',
			'modified' => '2021-10-12 14:54:08',
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<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><span>The MicroPlex v2 kit (Cat. No. C05010013) 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>.</span></p>',
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$testimonials = '<blockquote><p>We sheared the DNA on the Diagenode One and used the MicroPlex Library Preparation v2 Kit to create DNA libraries for whole genome sequencing of four plant species for which there is no reference genome available. Previous attempts with a commercial Tn5-transposase based method gave unsatisfactory results. However, the Diagenode MicroPlex kit was quicker, easier, and gave the expected profile of fragment sizes. In just 30 seconds of sonication, we obtained a fragment distribution centered at 270 bp. The library construction took only 2 hours with this kit. The library was sequenced in a NexSeq 550 in High-Output mode, giving 85% based with&gt;Q30.</p><cite>PhD. Ricardo Verdugo, Assistant Professor, University of Chile</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>There are so many ChIP-related products on the market, but I feel so lucky that I have been using the ones from Diagenode since I started my CHIP-seq project. I have used their <a href="../p/ideal-chip-seq-kit-for-transcription-factors-x100-100-rxns">iDeal CHIP-seq Kit for Transcription Factors</a> and <a href="../p/microplex-library-preparation-kit-v2-x48-12-indices-48-rxns">MicroPlex Library Prep Kit v2</a>. Both of them are fantastic and very reproducible. With the very-well written protocols, you will just be home and dry. Particularly, I want to thank the technical support, who is very patient, knowledgeable and extremely helpful. I would definitely recommend my colleagues to use the CHIP products from Diagenode.</p><cite>Dr Kaiyu Lei, Faculty of Medicine, Department of Surgery & Cancer, Imperial College London</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>
<blockquote><p>The Diagenode MicroPlex kit is the quickest and most efficient way to make sequencing libraries, especially from samples with very low inputs. We regularly start with picogram amounts of ChIP material and produce excellent quality libraries that would be impossible to make using normal methods. Sequencing libraries made from the MicroPlex kit give us excellent results even in large genomes. The kit performs very well, and we will use the kit in the future for studies with low cell numbers or starting material.</p><cite>Dr. Morgan Sammons, Lab of Dr. Shelley Berger, University of Pennsylvania</cite></blockquote>
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$featured_testimonials = '<blockquote><span class="label-green" style="margin-bottom:16px;margin-left:-22px">TESTIMONIAL</span><p>We used the MicroPlex version 2 kit to generate libraries using ChIP DNA for several transcription factors and compared the results to a standard library generation protocol starting from 5ng of ChIP DNA. Even when we reduced the starting amount of DNA by 10-fold, the MicroPlex Kit produced the same high yields and quality of the libraries. As expected, the number of duplicate reads increased but 15 to 20 million unique reads were sufficient to achieve excellent enrichment data. We found that no information was lost, and the MicroPlex Kit helped produce data that was consistent with the standard protocol despite the lower input. On top of this, the MicroPlex Kit was extremely user-friendly and saved us time. The MicroPlex version 2 kit will make challenging ChIP-seq experiments that rely on very limited amount of starting material much easier with robust results.</p><cite>Katia Basso, PhD, Assistant Professor, Columbia University, New York</cite></blockquote>
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        <p><strong><input name="data[Cart][quantity]" placeholder="1" value="1" min="1" style="width:60px;display:inline" type="number" id="CartQuantity" required="required"/></strong>iDeal ChIP-seq kit for Transcription Factors個カートに追加。</p>

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<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>
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<td style="width: 144px;"></td>
<td style="width: 267px; text-align: center;"><span style="font-weight: 400;">Amount per IP</span></td>
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<td style="width: 144px;">Cells</td>
<td style="width: 267px; text-align: center;"><strong>4,000,000</strong></td>
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<td style="width: 267px; text-align: center;"><strong>30 mg</strong></td>
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<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>
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<li><span style="font-weight: 400;"><strong>Highly optimized protocol</strong> for ChIP-seq from cells and tissues</span></li>
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<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>
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<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>',
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