Synthetic maize centromeres transmit chromosomes across generations. Published: March, 2023 Abstract:
Centromeres are long, often repetitive regions of genomes that bind kinetochore proteins and ensure normal chromosome segregation. Engineering centromeres that function in vivo has proven to be difficult. Here we describe a tethering approach that... Read more »
The effect of Jun dimerization on neurite outgrowth and motif binding. Published: August, 2018 Abstract:
Axon regeneration is a necessary step toward functional recovery after spinal cord injury. The AP-1 transcription factor c-Jun has long been known to play an important role in directing the transcriptional response of Dorsal Root Ganglion (DRG) ne... Read more »
Wnt receptor Frizzled 8 is a target of ERG in prostate cancer Published: July, 2018 Abstract:
Prostate cancer (PCa) is one of the most frequently diagnosed cancers among men. Many molecular changes have been detailed during PCa progression. The gene encoding the transcription factor ERG shows recurrent rearrangement, resulting in the overe... Read more »
MYC drives overexpression of telomerase RNA (hTR/TERC) in prostate cancer Published: September, 2017 Abstract:
Telomerase consists of at least two essential elements, an RNA component hTR or TERC that contains the template for telomere DNA addition and a catalytic reverse transcriptase (TERT). While expression of TERT has been considered the key rate-limit... Read more »
SOX2 as a New Regulator of HPV16 Transcription Published: July, 2017 Abstract:
Persistent infections with high-risk human papillomavirus (HPV) constitute the main risk factor for cervical cancer development. HPV16 is the most frequent type associated to squamous cell carcinomas (SCC), followed by HPV18. The long control regi... Read more »
Ezh2 represses the basal cell lineage during lung endoderm development. Published: January, 2015 Abstract:
The development of the lung epithelium is regulated in a stepwise fashion to generate numerous differentiated and stem cell lineages in the adult lung. How these different lineages are generated in a spatially and temporally restricted fashion rem... Read more »
ChIPping Away at the Drosophila Clock Published: December, 2014 Abstract:
In eukaryotes, the circadian clock controls 24 h rhythms in physiology, metabolism, and behavior via cell autonomous transcriptional feedback loops. These feedback loops keep circadian time and control rhythmic outputs by driving rhythms in transc... Read more »
Methods to Study Molecular Mechanisms of the Neurospora Circadian Clock Published: December, 2014 Abstract:
Eukaryotic circadian clocks are comprised of interlocked autoregulatory feedback loops that control gene expression at the levels of transcription and translation. The filamentous fungus Neurospora crassa is an excellent model for the complex mole... Read more »
NFAT Targets Signaling Molecules to Gene Promoters in Pancreatic β Cells. Published: December, 2014 Abstract:
Nuclear factor of activated T cells (NFAT) is activated by calcineurin in response to calcium signals derived by metabolic and inflammatory stress to regulate genes in pancreatic islets. Here we show that NFAT targets MAPKs, p300, and histone deac... Read more »
MiR-98 delays skeletal muscle differentiation by downregulating E2F5. Published: November, 2014 Abstract:
A genome-wide screen had previously shown that knocking down miR-98 and let-7g, two miRNAs of the let-7 family, leads to a dramatic increase of terminal myogenic differentiation. Here we report that a transcriptomic analysis of human myoblasts whe... Read more »
RNA helicase DDX21 coordinates transcription and ribosomal RNA processing. Published: November, 2014 Abstract:
DEAD-box RNA helicases are vital for the regulation of various aspects of the RNA life cycle, but the molecular underpinnings of their involvement, particularly in mammalian cells, remain poorly understood. Here we show that the DEAD-box RNA helic... Read more »
Epigenetic regulation of inflammatory gene expression in macrophages by selenium. Published: October, 2014 Abstract:
Acetylation of histone and non-histone proteins by histone acetyltransferases plays a pivotal role in the expression of proinflammatory genes. Given the importance of dietary selenium in mitigating inflammation, we hypothesized that selenium suppl... Read more »
KDM5 Interacts with Foxo to Modulate Cellular Levels of Oxidative Stress Published: October, 2014 Abstract:
Increased cellular levels of oxidative stress are implicated in a large number of human diseases. Here we describe the transcription co-factor KDM5 (also known as Lid) as a new critical regulator of cellular redox state. Moreover, this occurs thro... Read more »
Cross-talking noncoding RNAs contribute to cell-specific neurodegeneration in SCA7. Published: October, 2014 Abstract:
What causes the tissue-specific pathology of diseases resulting from mutations in housekeeping genes? Specifically, in spinocerebellar ataxia type 7 (SCA7), a neurodegenerative disorder caused by a CAG-repeat expansion in ATXN7 (which encodes an e... Read more »
Head formation: OTX2 regulates Dkk1 and Lhx1 activity in the anterior mesendoderm. Published: October, 2014 Abstract:
The Otx2 gene encodes a paired-type homeobox transcription factor that is essential for the induction and the patterning of the anterior structures in the mouse embryo. Otx2 knockout embryos fail to form a head. Whereas previous studies have shown... Read more »
Shigella flexneri targets the HP1γ subcode through the phosphothreonine lyase OspF. Published: September, 2014 Abstract:
HP1 proteins are transcriptional regulators that, like histones, are targets for post-translational modifications defining an HP1-mediated subcode. HP1γ has multiple phosphorylation sites, including serine 83 (S83) that marks it to sites of active... Read more »
Determinants of G quadruplex-induced epigenetic instability in REV1-deficient cells. Published: September, 2014 Abstract:
REV1-deficient chicken DT40 cells are compromised in replicating G quadruplex (G4)-forming DNA. This results in localised, stochastic loss of parental chromatin marks and changes in gene expression. We previously proposed that this epigenetic inst... Read more »
Nanog induces hyperplasia without initiating tumors. Published: September, 2014 Abstract:
Though expression of the homeobox transcription factor Nanog is generally restricted to pluripotent cells and early germ cells, many contradictory reports about Nanog's involvement in tumorigenesis exist. To address this, a modified Tet-On system ... Read more »
KMTase Set7/9 is a critical regulator of E2F1 activity upon genotoxic stress. Published: August, 2014 Abstract:
During the recent years lysine methyltransferase Set7/9 ((Su(var)-3-9, Enhancer-of-Zeste, Trithorax) domain containing protein 7/9) has emerged as an important regulator of different transcription factors. In this study, we report a novel function... Read more »
Inappropriate p53 activation during development induces features of CHARGE syndrome. Published: August, 2014 Abstract:
CHARGE syndrome is a multiple anomaly disorder in which patients present with a variety of phenotypes, including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genitourinary hypoplasia and ear abnormalities. Desp... Read more »
Active CREB1 Promotes a Malignant TGFβ2 Autocrine Loop in Glioblastoma. Published: August, 2014 Abstract:
In advanced cancer, including glioblastoma, the TGFβ pathway acts as an oncogenic factor. Some tumors exhibit aberrantly high TGFβ activity, and the mechanisms underlying this phenomenon are not well understood. We have observed that TGFβ can indu... Read more »
Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Published: June, 2014 Abstract:
Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-κB induces premature ageing in mice. We a... Read more »
A phosphotyrosine switch determines the antitumor activity of ERβ Published: June, 2014 Abstract:
Estrogen receptors ERα and ERβ share considerable sequence homology yet exert opposite effects on breast cancer cell proliferation. While the proliferative role of ERα in breast tumors is well characterized, it is not clear whether the antitumor a... Read more »
RNAi-Mediated Gene silencing in Zebrafish Triggered by Convergent Transcription. Published: June, 2014 Abstract:
RNAi based strategies to induce gene silencing are commonly employed in numerous model organisms but have not been extensively used in zebrafish. We found that introduction of transgenes containing convergent transcription units in zebrafish embry... Read more »
Hippo pathway activity influences liver cell fate. Published: June, 2014 Abstract:
The Hippo-signaling pathway is an important regulator of cellular proliferation and organ size. However, little is known about the role of this cascade in the control of cell fate. Employing a combination of lineage tracing, clonal analysis, and o... Read more »
Dendritic cell development requires histone deacetylase activity. Published: May, 2014 Abstract:
DCs develop from multipotent progenitors (MPPs), which commit into DC-restricted common dendritic cell progenitors (CDPs). CDPs further differentiate into classical DCs (cDCs) and plasmacytoid DCs (pDCs). Here, we studied the impact of histone ace... Read more »
Myostatin Regulates Energy Homeostasis in the Heart and Prevents Heart Failure. Published: May, 2014 Abstract:
RATIONALE: Myostatin is a major negative regulator of skeletal muscle mass and initiates multiple metabolic changes including enhanced insulin sensitivity. However, the function of Myostatin in the heart is barely understood although it is upregul... Read more »
Early-life stress reduces DNA methylation of the pomc gene in male mice. Published: May, 2014 Abstract:
Early-life stress (ELS) increases the vulnerability thresholds for stress-related diseases such as major depression and anxiety by inducing alterations in the structure and function of neural circuits and endocrine pathways. We previously demonstr... Read more »
The myc 3' wnt-responsive element suppresses colonic tumorigenesis. Published: May, 2014 Abstract:
Mutations in components of the Wnt/β-catenin signaling pathway are commonly found in colorectal cancers, and these mutations cause aberrant expression of genes controlled by Wnt-responsive DNA elements (WREs). While the c-Myc proto-oncogene (Myc) ... Read more »
CHD7 interacts with BMP R-SMADs to epigenetically regulate cardiogenesis in mice. Published: April, 2014 Abstract:
Haploinsufficiency for CHD7, an ATP-dependent nucleosome remodeling factor, is the leading cause of CHARGE syndrome. While congenital heart defects (CHDs) are major clinical features of CHARGE syndrome, affecting >75% of patients, it remains uncle... Read more »
Rif1 controls DNA replication timing in yeast through the PP1 phosphatase Glc7. Published: April, 2014 Abstract:
The Rif1 protein, originally identified as a telomere-binding factor in yeast, has recently been implicated in DNA replication control from yeast to metazoans. Here, we show that budding yeast Rif1 protein inhibits activation of prereplication com... Read more »
ApoER2 processing by presenilin-1 modulates reelin expression. Published: April, 2014 Abstract:
The reelin signaling protein and its downstream components have been associated with synaptic plasticity and neurotransmission. The reelin signaling pathway begins with the binding of reelin to the transmembrane lipoprotein receptor apolipoprotein... Read more »
Length-dependent processing of telomeres in the absence of telomerase. Published: April, 2014 Abstract:
In the absence of telomerase, telomeres progressively shorten with every round of DNA replication, leading to replicative senescence. In telomerase-deficient Saccharomyces cerevisiae, the shortest telomere triggers the onset of senescence by activ... Read more »
HMGA1 recruits CTIP2-repressed P-TEFb to the HIV-1 and cellular target promoters. Published: April, 2014 Abstract:
Active positive transcription elongation factor b (P-TEFb) is essential for cellular and human immunodeficiency virus type 1 (HIV-1) transcription elongation. CTIP2 represses P-TEFb activity in a complex containing 7SK RNA and HEXIM1. Recently, th... Read more »
Rad51-Rad52 mediated maintenance of centromeric chromatin in Candida albicans. Published: April, 2014 Abstract:
Specification of the centromere location in most eukaryotes is not solely dependent on the DNA sequence. However, the non-genetic determinants of centromere identity are not clearly defined. While multiple mechanisms, individually or in concert, m... Read more »
TAp73 is essential for germ cell adhesion and maturation in testis. Published: March, 2014 Abstract:
A core evolutionary function of the p53 family is to protect the genomic integrity of gametes. However, the role of p73 in the male germ line is unknown. Here, we reveal that TAp73 unexpectedly functions as an adhesion and maturation factor of the... Read more »
Hmga2 is required for canonical WNT signaling during lung development. Published: March, 2014 Abstract:
BACKGROUND: The high-mobility-group (HMG) proteins are the most abundant non-histone chromatin-associated proteins. HMG proteins are present at high levels in various undifferentiated tissues during embryonic development and their levels are stron... Read more »
Counteracting Activities of OCT4 and KLF4 during Reprogramming to Pluripotency. Published: March, 2014 Abstract:
Differentiated cells can be reprogrammed into induced pluripotent stem cells (iPSCs) after overexpressing four transcription factors, of which Oct4 is essential. To elucidate the role of Oct4 during reprogramming, we investigated the immediate tra... Read more »
Citrullination regulates pluripotency and histone H1 binding to chromatin. Published: March, 2014 Abstract:
Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried o... Read more »
Cyclin-dependent kinase inhibitor 2B regulates efferocytosis and atherosclerosis. Published: March, 2014 Abstract:
Genetic variation at the chromosome 9p21 risk locus promotes cardiovascular disease; however, it is unclear how or which proteins encoded at this locus contribute to disease. We have previously demonstrated that loss of one candidate gene at this ... Read more »
Decreased genetic dosage of hepatic yin yang 1 causes diabetic-like symptoms. Published: March, 2014 Abstract:
Insulin sensitivity in liver is characterized by the ability of insulin to efficiently inhibit glucose production and fatty acid oxidation as well as promote de novo lipid biosynthesis. Specific dysregulation of glucose and lipid metabolism in liv... Read more »
Epigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in mice. Published: February, 2014 Abstract:
"Epigenetherapy" alters epigenetic status of the targeted chromatin and modifies expression of the endogenous therapeutic gene. In this study we used lentiviral in vivo delivery of small hairpin RNA (shRNA) into hearts in a murine infarction model... Read more »
Geriatric muscle stem cells switch reversible quiescence into senescence. Published: February, 2014 Abstract:
Regeneration of skeletal muscle depends on a population of adult stem cells (satellite cells) that remain quiescent throughout life. Satellite cell regenerative functions decline with ageing. Here we report that geriatric satellite cells are incap... Read more »
Sumoylation of the THO complex regulates the biogenesis of a subset of mRNPs. Published: February, 2014 Abstract:
Assembly of messenger ribonucleoparticles (mRNPs) is a pivotal step in gene expression, but only a few molecular mechanisms contributing to its regulation have been described. Here, through a comprehensive proteomic survey of mRNP assembly, we dem... Read more »
A highly conserved region within H2B is important for FACT to act on nucleosomes. Published: February, 2014 Abstract:
Histone N-terminal tails play crucial roles in chromatin-related processes. The tails of histones H3 and H4 are highly conserved and well characterized, but much less is known about the functions of the tails of histones H2A and H2B and their sequ... Read more »
The role of DNA methylation in regulation of the murine Lhx3 gene. Published: January, 2014 Abstract:
LHX3 is a LIM-homeodomain transcription factor with critical roles in pituitary and nervous system development. Mutations in the LHX3 gene are associated with pediatric diseases featuring severe hormone deficiencies, hearing loss, developmental de... Read more »
The thyroid hormone receptor β induces DNA damage and premature senescence. Published: January, 2014 Abstract:
There is increasing evidence that the thyroid hormone (TH) receptors (THRs) can play a role in aging, cancer and degenerative diseases. In this paper, we demonstrate that binding of TH T3 (triiodothyronine) to THRB induces senescence and deoxyribo... Read more »
A role for FACT in repopulation of nucleosomes at inducible genes. Published: January, 2014 Abstract:
Xenobiotic drugs induce Pleiotropic Drug Resistance (PDR) genes via the orthologous Pdr1/Pdr3 transcription activators. We previously identified the Mediator transcription co-activator complex as a key target of Pdr1 orthologs and demonstrated tha... Read more »
Integrated transcriptome analysis of mouse spermatogenesis. Published: January, 2014 Abstract:
BACKGROUND: Differentiation of primordial germ cells into mature spermatozoa proceeds through multiple stages, one of the most important of which is meiosis. Meiotic recombination is in turn a key part of meiosis. To achieve the highly specialized... Read more »
Regulation of the neuronal transcription factor NPAS4 by REST and microRNAs. Published: January, 2014 Abstract:
NPAS4 is a brain restricted, activity-induced transcription factor which regulates the expression of inhibitory synapse genes to control homeostatic excitatory/inhibitory balance in neurons. NPAS4 is required for normal social interaction and cont... Read more »
Inactivating CUX1 mutations promote tumorigenesis. Published: January, 2014 Abstract:
A major challenge in cancer genetics is to determine which low-frequency somatic mutations are drivers of tumorigenesis. Here we interrogate the genomes of 7,651 diverse human cancers and find inactivating mutations in the homeodomain transcriptio... Read more »
H19 lncRNA controls gene expression of the Imprinted Gene Network by recruiting MBD1. Published: December, 2013 Abstract:
The H19 gene controls the expression of several genes within the Imprinted Gene Network (IGN), involved in growth control of the embryo. However, the underlying mechanisms of this control remain elusive. Here, we identified the methyl-CpG-binding ... Read more »
UTX coordinates steroid hormone-mediated autophagy and cell death. Published: December, 2013 Abstract:
Correct spatial and temporal induction of numerous cell type-specific genes during development requires regulated removal of the repressive histone H3 lysine 27 trimethylation (H3K27me3) modification. Here we show that the H3K27me3 demethylase dUT... Read more »
Reprogramming of lysosomal gene expression by interleukin-4 and Stat6 Published: December, 2013 Abstract:
Background Lysosomes play important roles in multiple aspects of physiology, but the problem of how the transcription of lysosomal genes is coordinated remains incompletely understood. The goal of this study was to illuminate the physiological c... Read more »
The role of Ctk1 kinase in termination of small non-coding RNAs. Published: December, 2013 Abstract:
Transcription termination in Saccharomyces cerevisiae can be performed by at least two distinct pathways and is influenced by the phosphorylation status of the carboxy-terminal domain (CTD) of RNA polymerase II (Pol II). Late termination of mRNAs ... Read more »
Transcriptional activation of Mina by Sp1/3 factors. Published: December, 2013 Abstract:
Mina is an epigenetic gene regulatory protein known to function in multiple physiological and pathological contexts, including pulmonary inflammation, cell proliferation, cancer and immunity. We showed previously that the level of Mina gene expres... Read more »
MAP Kinase Signaling Mediates Phosphorylation of Polycomb Ortholog Cbx7. Published: November, 2013 Abstract:
Cbx7 is one of five mammalian orthologs of the Drosophila Polycomb (Pc). Cbx7 recognizes methylated lysine residues on the histone H3 tail and contributes to gene silencing in the context of the Polycomb Repressive Complex 1 (PRC1). However, our k... Read more »
Combined modulation of polycomb and trithorax genes rejuvenates β cell replication. Published: October, 2013 Abstract:
Inadequate functional β cell mass underlies both type 1 and type 2 diabetes. β Cell growth and regeneration also decrease with age through mechanisms that are not fully understood. Age-dependent loss of enhancer of zeste homolog 2 (EZH2) prevents ... Read more »
Class I Lysine Deacetylases Facilitate Glucocorticoid-induced Transcription. Published: October, 2013 Abstract:
Nuclear receptors use lysine acetyltransferases and lysine deacetylases (KDACs) in regulating transcription through histone acetylation. Lysine acetyltransferases interact with steroid receptors upon binding of an agonist and are recruited to targ... Read more »
Geminin Is Required for the Maintenance of Pluripotency Published: September, 2013 Abstract:
Pluripotency requires the expression of the three core transcriptions factors Oct4, Sox2 and Nanog, as well as further, complementary proteins. The geminin protein is part of this network, and was shown to play a role in the regulation of DNA repl... Read more »
MiR-210 Is Induced by Oct-2, Regulates B Cells, and Inhibits Autoantibody Production. Published: September, 2013 Abstract:
MicroRNAs (MiRs) are small, noncoding RNAs that regulate gene expression posttranscriptionally. In this study, we show that MiR-210 is induced by Oct-2, a key transcriptional mediator of B cell activation. Germline deletion of MiR-210 results in t... Read more »
Multivalent Engagement of TFIID to Nucleosomes. Published: September, 2013 Abstract:
The process of eukaryotic transcription initiation involves the assembly of basal transcription factor complexes on the gene promoter. The recruitment of TFIID is an early and important step in this process. Gene promoters contain distinct DNA seq... Read more »
Evidence from mouse and man for a role of neuregulin 3 in nicotine dependence. Published: September, 2013 Abstract:
Addiction to nicotine and the ability to quit smoking are influenced by genetic factors. We used functional genomic approaches (chromatin immunoprecipitation (ChIP) and whole-genome sequencing) to identify cAMP response element-binding protein (CR... Read more »
Endogenous Nuclear RNAi Mediates Behavioral Adaptation to Odor. Published: August, 2013 Abstract:
Most eukaryotic cells express small regulatory RNAs. The purpose of one class, the somatic endogenous siRNAs (endo-siRNAs), remains unclear. Here, we show that the endo-siRNA pathway promotes odor adaptation in C. elegans AWC olfactory neurons. In... Read more »
PRC2 Controls Drosophila Oocyte Cell Fate by Repressing Cell Cycle Genes. Published: August, 2013 Abstract:
The oocyte is a unique cell type that undergoes extensive chromosome changes on its way to fertilization, but the chromatin determinants of its fate are unknown. Here, we show that Polycomb group (PcG) proteins of the Polycomb repressive complex 2... Read more »
Optical control of mammalian endogenous transcription and epigenetic states. Published: August, 2013 Abstract:
The dynamic nature of gene expression enables cellular programming, homeostasis and environmental adaptation in living systems. Dissection of causal gene functions in cellular and organismal processes therefore necessitates approaches that enable ... Read more »
Conserved Regulators of Nucleolar Size Revealed by Global Phenotypic Analyses Published: August, 2013 Abstract:
Regulation of cell growth is a fundamental process in development and disease that integrates a vast array of extra- and intracellular information. A central player in this process is RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA... Read more »
WT1 regulates the expression of inhibitory chemokines during heart development. Published: August, 2013 Abstract:
The embryonic epicardium is an important source of cardiovascular precursor cells and paracrine factors that are required for adequate heart formation. Signaling pathways regulated by WT1 that promote heart development have started to be described... Read more »
A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis. Published: August, 2013 Abstract:
In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185(BCR-ABL+) B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the ... Read more »
A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. Published: August, 2013 Abstract:
Pathogens dramatically affect host cell transcription programs for their own profit during infection, but in most cases, the underlying mechanisms remain elusive. We found that during infection with the bacterium Listeria monocytogenes, the host d... Read more »
Androgen Receptor Drives Transcription of Rat PACAP in Gonadotrope Cells. Published: August, 2013 Abstract:
Gonadotropin expression is precisely regulated within the hypothalamic-pituitary-gonadal axis through the complex interaction of neuropeptides, gonadal steroids. and both gonadal- and pituitary-derived peptides. In the anterior pituitary gland, th... Read more »
Noncoding RNAs prevent spreading of a repressive histone mark. Published: August, 2013 Abstract:
Transcription of eukaryotic genomes is more widespread than was previously anticipated and results in the production of many non-protein-coding RNAs (ncRNAs) whose functional relevance is poorly understood. Here we demonstrate that ncRNAs can coun... Read more »
Genome-wide measurement of protein-DNA binding dynamics using competition ChIP. Published: July, 2013 Abstract:
Competition chromatin immunoprecipitation (competition ChIP) enables experimenters to measure protein-DNA dynamics at a single locus or across the entire genome, depending on the detection method. Competition ChIP relies on a cell containing two c... Read more »
Jpx RNA activates Xist by evicting CTCF. Published: June, 2013 Abstract:
In mammals, dosage compensation between XX and XY individuals occurs through X chromosome inactivation (XCI). The noncoding Xist RNA is expressed and initiates XCI only when more than one X chromosome is present. Current models invoke a dependency... Read more »
Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk Published: June, 2013 Abstract:
The Wnt/β-catenin signalling and autophagy pathways each play important roles during development, adult tissue homeostasis and tumorigenesis. Here we identify the Wnt/β-catenin signalling pathway as a negative regulator of both basal and stress-in... Read more »
Nuclear receptor/microRNA circuitry links muscle fiber type to energy metabolism. Published: June, 2013 Abstract:
The mechanisms involved in the coordinate regulation of the metabolic and structural programs controlling muscle fitness and endurance are unknown. Recently, the nuclear receptor PPARβ/δ was shown to activate muscle endurance programs in transgeni... Read more »
KDM4B is a Master Regulator of the Estrogen Receptor Signalling Cascade. Published: May, 2013 Abstract:
The importance of the estrogen receptor (ER) in breast cancer (BCa) development makes it a prominent target for therapy. Current treatments, however, have limited effectiveness, and hence the definition of new therapeutic targets is vital. The ER ... Read more »
Progesterone receptors induce FOXO1-dependent senescence in ovarian cancer cells. Published: May, 2013 Abstract:
Loss of nuclear progesterone receptors (PR) and low circulating progesterone levels are associated with increased ovarian cancer (OC) risk. However, PR are abundantly expressed in a significant percentage of serous and endometrioid ovarian tumors;... Read more »
A vitamin D receptor/SMAD genomic circuit gates hepatic fibrotic response. Published: April, 2013 Abstract:
Liver fibrosis is a reversible wound-healing response involving TGFβ1/SMAD activation of hepatic stellate cells (HSCs). It results from excessive deposition of extracellular matrix components and can lead to impairment of liver function. Here, we ... Read more »
The response of human macrophages to β-glucans depends on the inflammatory milieu. Published: April, 2013 Abstract:
BACKGROUND: β-glucans are fungal cell wall components that bind to the C-type lectin-like receptor dectin-1. Polymorphisms of dectin-1 gene are associated with susceptibility to invasive fungal infection and medically refractory ulcerative colitis... Read more »
Single-cell dynamics of genome-nuclear lamina interactions. Published: March, 2013 Abstract:
The nuclear lamina (NL) interacts with hundreds of large genomic regions termed lamina associated domains (LADs). The dynamics of these interactions and the relation to epigenetic modifications are poorly understood. We visualized the fate of LADs... Read more »
Fission yeast CSL proteins function as transcription factors. Published: March, 2013 Abstract:
BACKGROUND: Transcription factors of the CSL (CBF1/RBP-Jk/Suppressor of Hairless/LAG-1) family are key regulators of metazoan development and function as the effector components of the Notch receptor signalling pathway implicated in various cell f... Read more »
PRC1 coordinates timing of sexual differentiation of female primordial germ cells. Published: March, 2013 Abstract:
In mammals, sex differentiation of primordial germ cells (PGCs) is determined by extrinsic cues from the environment. In mouse female PGCs, expression of stimulated by retinoic acid gene 8 (Stra8) and meiosis are induced in response to retinoic ac... Read more »
Chromatin immunoprecipitation of adult murine cardiomyocytes. Published: March, 2013 Abstract:
This unit describes a streamlined two-step protocol for the isolation of adult murine cardiomyocytes with subsequent Chromatin ImmunoPrecipitation (ChIP). Isolation and culturing of cardiomyocytes is a delicate process and the protocol presented h... Read more »
Krüppel-like factor 2 is required for normal mouse cardiac development. Published: February, 2013 Abstract:
Krüppel-like factor 2 (KLF2) is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV) canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure an... Read more »
Bifurcation of Arabidopsis NLR immune signaling via Ca²⁺-dependent protein kinases. Published: January, 2013 Abstract:
Nucleotide-binding domain leucine-rich repeat (NLR) protein complexes sense infections and trigger robust immune responses in plants and humans. Activation of plant NLR resistance (R) proteins by pathogen effectors launches convergent immune respo... Read more »
Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression Published: January, 2013 Abstract:
E-cadherin expression is repressed by ZEB2/SIP1 while it is induced by KLF4. Independent data from the literature indicate that these two transcription factors could bind close to each other in the proximal region of the E-cadherin gene promoter. ... Read more »
Valproic acid inhibits the proliferation of cancer cells by re-expressing cyclin D2. Published: January, 2013 Abstract:
In this study, primary murine prostate cancer (PCa) cells were derived using the well-established TRAMP model (transgenic adenocarcinoma mouse prostate). These PCa cells were treated with the histone deacetylase inhibitor (HDACi), valproic acid (V... Read more »
Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment. Published: January, 2013 Abstract:
Long noncoding RNAs (lncRNAs) are often expressed in a development-specific manner, yet little is known about their roles in lineage commitment. Here, we identified Braveheart (Bvht), a heart-associated lncRNA in mouse. Using multiple embryonic st... Read more »
Dual function of MIPS1 as a metabolic enzyme and transcriptional regulator. Published: January, 2013 Abstract:
Because regulation of its activity is instrumental either to support cell proliferation and growth or to promote cell death, the universal myo-inositol phosphate synthase (MIPS), responsible for myo-inositol biosynthesis, is a critical enzyme of p... Read more »
Pre-mRNA Splicing Is a Determinant of Nucleosome Organization Published: January, 2013 Abstract:
Chromatin organization affects alternative splicing and previous studies have shown that exons have increased nucleosome occupancy compared with their flanking introns. To determine whether alternative splicing affects chromatin organization we de... Read more »
Conserved boundary elements from the Hox complex of mosquito, Anopheles gambiae. Published: December, 2012 Abstract:
The conservation of hox genes as well as their genomic organization across the phyla suggests that this system of anterior-posterior axis formation arose early during evolution and has come under strong selection pressure. Studies in the split Hox... Read more »
ATF4 orchestrates a program of BH3-only protein expression in severe hypoxia. Published: December, 2012 Abstract:
Intratumoral hypoxia is associated with poor prognosis, regardless of the mode of therapy. Cancer cells survive this condition through activating several adaptive signaling pathways, including the integrated stress response (ISR) and autophagy. Ac... Read more »
Gene regulation by the lysine demethylase KDM4A in Drosophila. Published: November, 2012 Abstract:
Lysine methylation of histones is associated with both transcriptionally active chromatin and with silent chromatin, depending on what residue is modified. Histone methyltransferases and demethylases ensure that histone methylations are dynamic an... Read more »
Regulation of delta-aminolevulinic Acid dehydratase by krüppel-like factor 1. Published: October, 2012 Abstract:
Krüppel-like factor 1(KLF1) is a hematopoietic-specific zinc finger transcription factor essential for erythroid gene expression. In concert with the transacting factor GATA1, KLF1 modulates the coordinate expression of the genes encoding the mult... Read more »
The histone demethylase PHF8 is essential for cytoskeleton dynamics. Published: October, 2012 Abstract:
PHF8 is a histone demethylase associated with X-linked mental retardation. It has been described as a transcriptional co-activator involved in cell cycle progression, but its physiological role is still poorly understood. Here we show that PHF8 co... Read more »
Multigenerational epigenetic adaptation of the hepatic wound-healing response. Published: September, 2012 Abstract:
We investigated whether ancestral liver damage leads to heritable reprogramming of hepatic wound healing in male rats. We found that a history of liver damage corresponds with transmission of an epigenetic suppressive adaptation of the fibrogenic ... Read more »
KAP1/TRIM28: an inhibitor of IRF5 function in inflammatory macrophages Published: August, 2012 Abstract:
IRF5 plays a key role in the induction of pro-inflammatory cytokines, contributing to the plasticity and polarisation of macrophages to an M1 phenotype and initiation of a potent TH1-TH17 response. To better understand the means of IRF5 transcript... Read more »
IRF-1 and miRNA126 Modulate VCAM-1 Expression in Response to a High Fat Meal. Published: August, 2012 Abstract:
Rationale: A high-fat diet accompanied by hypertriglyceridemia increases an individual's risk for developing atherosclerosis. An early event in this process is monocyte recruitment through binding to VCAM-1 upregulated on inflamed arterial endothe... Read more »
Chromatin Immunoprecipitation Analysis of Xenopus Embryos Published: August, 2012 Abstract:
Chromatin immunoprecipitation (ChIP) is a powerful technique to study epigenetic regulation and transcription factor binding events in the nucleus. It is based on immune-affinity capture of epitopes that have been cross-linked to genomic DNA in vi... Read more »
The human CST complex is a terminator of telomerase activity. Published: July, 2012 Abstract:
The lengths of human telomeres, which protect chromosome ends from degradation and end fusions, are crucial determinants of cell lifespan. During embryogenesis and in cancer, the telomerase enzyme counteracts telomeric DNA shortening. As shown in ... Read more »
Aberrant expression of IFN-γ in Th2 cells from Th2 LCR-deficient mice. Published: July, 2012 Abstract:
The Th2 locus control region (LCR) has been shown to be a crucial cis-acting element for Th2 cytokine expression and Th2 cell differentiation. To study the role of Th2 LCR in ifng locus regulation, we examined the expression of IFN-γ in Th2 cells ... Read more »
Occludin is a direct target of thyroid transcription factor-1 (TTF-1/NKX2-1). Published: July, 2012 Abstract:
The thyroid transcription factor 1 gene (TTF-1 or NKX2-1) is essential to lung development; however, it is also a critical factor in lung cancer. TTF-1 is amplified in lung cancers, suggesting that it is a gain-of-function lung oncogene. Conversel... Read more »
ZRF1 controls oncogene-induced senescence through the INK4-ARF locus. Published: June, 2012 Abstract:
The reactivation of the INK4-ARF locus, which is epigenetically repressed by Polycomb proteins in healthy cells, is a hallmark of senescence. One mechanism of reactivating Polycomb-silenced genes is mediated by the epigenetic factor ZRF1, which as... Read more »
A Cell Cycle Role for the Epigenetic Factor CTCF-L/BORIS. Published: June, 2012 Abstract:
CTCF is a ubiquitous epigenetic regulator that has been proposed as a master keeper of chromatin organisation. CTCF-like, or BORIS, is thought to antagonise CTCF and has been found in normal testis, ovary and a large variety of tumour cells. The c... Read more »
Transcriptional networks driving enhancer function in the CFTR gene. Published: June, 2012 Abstract:
A critical cis-regulatory element for the cystic fibrosis transmembrane conductance regulator (CFTR) gene is located in intron 11, 100 kb distal to the promoter, with which it interacts. This sequence contains an intestine-selective enhancer and a... Read more »
GSK3 Temporally Regulates Neurogenin 2 Proneural Activity in the Neocortex. Published: June, 2012 Abstract:
The neocortex is comprised of six neuronal layers that are generated in a defined temporal sequence. While extrinsic and intrinsic cues are known to regulate the sequential production of neocortical neurons, how these factors interact and function... Read more »
FOXO1 in the ventromedial hypothalamus regulates energy balance. Published: June, 2012 Abstract:
The transcription factor FOXO1 plays a central role in metabolic homeostasis by regulating leptin and insulin activity in many cell types, including neurons. However, the neurons mediating these effects and the identity of the molecular targets th... Read more »
The linker histone plays a dual role during gametogenesis in S. cerevisiae. Published: May, 2012 Abstract:
The differentiation of gametes involves dramatic changes to chromatin, affecting transcription, meiosis, and cell morphology. Sporulation in S. cerevisiae shares many chromatin features with spermatogenesis, including a ten-fold compaction of the ... Read more »
BIM promoter directly targeted by EBNA3C in polycomb-mediated repression by EBV. Published: May, 2012 Abstract:
Detailed analyses of the chromatin around the BIM promoter has revealed that latent Epstein-Barr virus (EBV) triggers the recruitment of polycomb repressive complex 2 (PRC2) core subunits and the trimethylation of histone H3 lysine 27 (H3K27me3) a... Read more »
The histone demethylase Kdm3a is essential to progression through differentiation. Published: May, 2012 Abstract:
Histone demethylation has important roles in regulating gene expression and forms part of the epigenetic memory system that regulates cell fate and identity by still poorly understood mechanisms. Here, we examined the role of histone demethylase K... Read more »
RBE controls microRNA164 expression to effect floral organogenesis. Published: May, 2012 Abstract:
The establishment and maintenance of organ boundaries are vital for animal and plant development. In the Arabidopsis flower, three microRNA164 genes (MIR164a, b and c) regulate the expression of CUP-SHAPED COTYLEDON1 (CUC1) and CUC2, which encode ... Read more »
piRNA-mediated transgenerational inheritance of an acquired trait. Published: May, 2012 Abstract:
The maintenance of genome integrity is an essential trait to the successful transmission of genetic information. In animal germ cells, piRNAs guide PIWI proteins to silence transposable elements (TEs) in order to maintain genome integrity. In inse... Read more »
HDAC1 Regulates Fear Extinction in Mice. Published: April, 2012 Abstract:
Histone acetylation has been implicated with the pathogenesis of neuropsychiatric disorders and targeting histone deacetylases (HDACs) using HDAC inhibitors was shown to be neuroprotective and to initiate neuroregenerative processes. However, litt... Read more »
Miz1 Is a Critical Repressor of cdkn1a during Skin Tumorigenesis. Published: April, 2012 Abstract:
The transcription factor Miz1 forms repressive DNA-binding complexes with the Myc, Gfi-1 and Bcl-6 oncoproteins. Known target genes of these complexes encode the cyclin-dependent kinase inhibitors (CKIs) cdkn2b (p15(Ink4)), cdkn1a (p21(Cip1)), and... Read more »
Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation. Published: April, 2012 Abstract:
The ability of skeletal muscle to enhance lipid utilization during exercise is a form of metabolic plasticity essential for survival. Conversely, metabolic inflexibility in muscle can cause organ dysfunction and disease. Although the transcription... Read more »
DLK2 is a transcriptional target of KLF4 in the early stages of adipogenesis. Published: March, 2012 Abstract:
The epidermal growth factor-like protein DLK2, highly homologous to DLK1, has been identified as a modulator of adipogenesis in vitro. Knocking down Dlk2 expression prevents adipogenesis of 3T3-L1 cells but enhances that of the mesenchymal cell li... Read more »
Resveratrol Inhibits KSHV Reactivation by Lowering the Levels of Cellular EGR-1. Published: March, 2012 Abstract:
In the field of herpesvirus research, the exact molecular mechanism by which such viruses reactivate from latency remains elusive. Kaposi's sarcoma-associated herpesvirus (KSHV) primarily exists in a latent state, while only 1-3% of cells support ... Read more »
CBX4-mediated SUMO modification regulates BMI1 recruitment at sites of DNA damage. Published: March, 2012 Abstract:
Polycomb group (PcG) proteins are involved in epigenetic silencing where they function as major determinants of cell identity, stem cell pluripotency and the epigenetic gene silencing involved in cancer development. Recently numerous PcG proteins,... Read more »
EZH2 couples pancreatic regeneration to neoplastic progression. Published: March, 2012 Abstract:
Although the polycomb group protein Enhancer of Zeste Homolog 2 (EZH2) is well recognized for its role as a key regulator of cell differentiation, its involvement in tissue regeneration is largely unknown. Here we show that EZH2 is up-regulated fo... Read more »
Transcriptional Activation of the Adenoviral Genome Is Mediated by Capsid Protein VI Published: February, 2012 Abstract:
Gene expression of DNA viruses requires nuclear import of the viral genome. Human Adenoviruses (Ads), like most DNA viruses, encode factors within early transcription units promoting their own gene expression and counteracting cellular antiviral d... Read more »
Circadian rhythms govern cardiac repolarization and arrhythmogenesis Published: February, 2012 Abstract:
Sudden cardiac death exhibits diurnal variation in both acquired and hereditary forms of heart disease1,2, but the molecular basis of this variation is unknown. A common mechanism that underlies susceptibility to ventricular arrhythmias is abnorma... Read more »
Anticheckpoint pathways at telomeres in yeast Published: February, 2012 Abstract:
Telomeres hide (or ‘cap’) chromosome ends from DNA-damage surveillance mechanisms that arrest the cell cycle and promote repair, but the checkpoint status of telomeres is not well understood. Here we characterize the response in Saccharomyces cere... Read more »
The composition and signaling of the IL-35 receptor are unconventional. Published: February, 2012 Abstract:
Interleukin 35 (IL-35) belongs to the IL-12 family of heterodimeric cytokines but has a distinct functional profile. IL-35 suppresses T cell proliferation and converts naive T cells into IL-35-producing induced regulatory T cells (iTr35 cells). He... Read more »
The Spt5 C-terminal region recruits yeast 3’-RNA cleavage factor I Published: January, 2012 Abstract:
During transcription elongation, RNA polymerase (Pol) II binds the general elongation factor Spt5. Spt5 contains a repetitive C-terminal region (CTR) that is required for co-transcriptional recruitment of the Paf1 complex (44, 88). Here we report ... Read more »
Histone deacetylase 1 is required for Carbamazepine-induced CYP3A4 expression. Published: January, 2012 Abstract:
Carbamazepine (CBZ) is a commonly prescribed antiepileptic drug. Adverse effects and drug-drug interaction are the two major concerns for its clinic application. CBZ is mainly metabolized by cytochrome P450 (CYP) 3A4, a strong inducer of CYP3A4 as... Read more »
A novel retinoblastoma therapy from genomic and epigenetic analyses Published: January, 2012 Abstract:
Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the ret... Read more »
Characterization of a proximal Sp1 response element in the mouse Dlk2 gene promoter. Published: December, 2011 Abstract:
ABSTRACT: BACKGROUND: DLK2 is an EGF-like membrane protein, closely related to DLK1, which is involved in adipogenesis. Both proteins interact with the NOTCH1 receptor and are able to modulate its activation. The expression of the gene Dlk2 is co... Read more »
Notch Activation of Jagged1 Contributes to the Assembly of the Arterial Wall Published: December, 2011 Abstract:
BACKGROUND: Notch signaling in vascular smooth muscle precursors is required for smooth muscle differentiation. Jagged1 expression on endothelium activates Notch in vascular smooth muscle precursors including those of neural crest origin to initi... Read more »
Etsrp/Etv2 Is Directly Regulated by Foxc1a/b in the Zebrafish Angioblast. Published: December, 2011 Abstract:
Rationale:Endothelial cells are developmentally derived from angioblasts specified in the mesodermal germ cell layer. The transcription factor etsrp/etv2 is at the top of the known genetic hierarchy for angioblast development. The transcriptional ... Read more »
Human tRNA genes function as chromatin insulators Published: November, 2011 Abstract:
nsulators help separate active chromatin domains from silenced ones. In yeast, gene promoters act as insulators to block the spread of Sir and HP1 mediated silencing while in metazoans most insulators are multipartite autonomous entities. tDNAs ar... Read more »
Osteocalcin gene expression is regulated by wild-type p53. Published: November, 2011 Abstract:
The tumor-suppressor p53 is a transcription factor that regulates a number of genes in the process of cell-cycle inhibition, apoptosis, and DNA damage. Recent studies have revealed a crucial role for p53 in bone remodeling. In our previous studies... Read more »
R432 is a key residue for the multiple functions of Ndt80p in Candida albicans. Published: October, 2011 Abstract:
Ndt80p is an important transcription modulator to various stress-response genes in Candida albicans, the most common human fungal pathogen in systemic infections. We found that Ndt80p directly regulated its target genes, such as YHB1, via the mid-... Read more »
CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing. Published: October, 2011 Abstract:
Alternative splicing of pre-messenger RNA is a key feature of transcriptome expansion in eukaryotic cells, yet its regulation is poorly understood. Spliceosome assembly occurs co-transcriptionally, raising the possibility that DNA structure may di... Read more »
BRCA1 tumour suppression occurs via heterochromatin-mediated silencing. Published: September, 2011 Abstract:
Mutations in the tumour suppressor gene BRCA1 lead to breast and/or ovarian cancer. Here we show that loss of Brca1 in mice results in transcriptional de-repression of the tandemly repeated satellite DNA. Brca1 deficiency is accompanied by a reduc... Read more »
Smad3-mediated upregulation of miR-21 promotes renal fibrosis. Published: September, 2011 Abstract:
TGF-β/Smad signaling plays a role in fibrogenesis, but therapies targeting TGF-β are ineffective in treating renal fibrosis. Here, we explored the therapeutic potential of targeting TGF-β-induced microRNA in the progression of renal fibrosis. Micr... Read more »
SIRT6 is required for maintenance of telomere position effect in human cells. Published: August, 2011 Abstract:
In Saccharomyces cerevisiae, the repressive chromatin environment at telomeres gives rise to telomere position effect (TPE), the epigenetic silencing of telomere-proximal genes. Chromatin-modifying factors that control TPE in yeast have been exten... Read more »
Polycomb eviction as a new distant enhancer function. Published: August, 2011 Abstract:
Remote distal enhancers may be located tens or thousands of kilobases away from their promoters. How they control gene expression is still poorly understood. Here, we analyze the influence of a remote enhancer on the balance between repression (Po... Read more »
Analysis of HP1α regulation in human breast cancer cells. Published: August, 2011 Abstract:
The three mammalian HP1 proteins, HP1α/CBX5, HP1β/CBX1, and HPγ/CBX3, are involved in chromatin packing and gene regulation. The HP1α protein is down-regulated in invasive compared to non-invasive breast cancer cells and HP1α is a suppressor of ce... Read more »
Regulation of adipocyte differentiation by the zinc finger protein ZNF638. Published: July, 2011 Abstract:
Zinc finger proteins constitute the largest family of transcription regulators in eukaryotes. These factors are involved in diverse processes in many tissues, including development and differentiation. We report here the characterization of the zi... Read more »
Defective GATA-3 expression in Th2 LCR-deficient mice. Published: July, 2011 Abstract:
Th2 cell differentiation is critically influenced by transcription factor GATA-3 and by various cis-acting elements including enhancers, silencers and a locus control region (LCR) in the Th2 cytokine locus. Th2 LCR-deficient Th2 cells completely l... Read more »
DNA methylation status predicts cell type-specific enhancer activity Published: June, 2011 Abstract:
Cell-selective glucocorticoid receptor (GR) binding to distal regulatory elements is associated with cell type-specific regions of locally accessible chromatin. These regions can either pre-exist in chromatin (pre-programmed) or be induced by the ... Read more »
Mediator influences telomeric silencing and cellular life span. Published: June, 2011 Abstract:
The Mediator complex is required for the regulated transcription of nearly all RNA polymerase II-dependent genes. Here we demonstrate a new role for Mediator which appears to be separate from its function as a transcriptional coactivator. Mediator... Read more »
Functional analysis of KAP1 genomic recruitment. Published: May, 2011 Abstract:
TRIM28 (KAP1) is upregulated in many cancers and has been implicated in both transcriptional activation and repression. Using chromatin immunoprecipitation and sequencing, we show that KAP1 binding sites fall into several categories, specifically,... Read more »
Mechanism of 1α,25-dihydroxyvitamin D(3)-dependent repression of interleukin-12B. Published: May, 2011 Abstract:
Interleukin 12 (IL-12) is a heterodimeric, pro-inflammatory cytokine that plays a central role in activation and differentiation of CD4(+) T cells into interferon-γ secreting T-helper type 1 cells. IL-12B, a gene encoding the larger subunit of act... Read more »
The histone demethylase JARID1A regulates progesterone receptor expression. Published: May, 2011 Abstract:
Transcriptional control of the progesterone receptor gene by estrogen is a complex mechanism. It involves estrogen receptor α which uses several enzymes that locally modify histone tails as cofactors. Using MCF-7 cells as a model, we found that Ju... Read more »
TLE3 is a dual-function transcriptional coregulator of adipogenesis. Published: April, 2011 Abstract:
PPARγ and Wnt signaling are central positive and negative regulators of adipogenesis, respectively. Here we identify the groucho family member TLE3 as a transcriptional integrator of the PPARγ and Wnt pathways. TLE3 is a direct target of PPARγ tha... Read more »
HDAC-mediated deacetylation of NF-κB is critical for Schwann cell myelination. Published: April, 2011 Abstract:
Schwann cell myelination is tightly regulated by timely expression of key transcriptional regulators that respond to specific environmental cues, but the molecular mechanisms underlying such a process are poorly understood. We found that the acety... Read more »
The multifunctional Ccr4-Not complex directly promotes transcription elongation. Published: March, 2011 Abstract:
The Ccr4-Not complex has been implicated in the control of multiple steps of mRNA metabolism; however, its functions in transcription remain ambiguous. The discovery that Ccr4/Pop2 is the major cytoplasmic mRNA deadenylase and the detection of Not... Read more »
Role for miR-204 in human pulmonary arterial hypertension. Published: March, 2011 Abstract:
Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Because microRNAs have been recently implicated in the regulation of cell proliferation and ap... Read more »
Histone H3 lysine 9 trimethylation and HP1γ favor inclusion of alternative exons. Published: March, 2011 Abstract:
Pre-messenger RNAs (pre-mRNAs) maturation is initiated cotranscriptionally. It is therefore conceivable that chromatin-borne information participates in alternative splicing. Here we find that elevated levels of trimethylation of histone H3 on Lys... Read more »
Involvement of placental growth factor in Wallerian degeneration. Published: March, 2011 Abstract:
Wallerian degeneration (WD) is an inflammatory process of nerve degeneration, which occurs more rapidly in the peripheral nervous system compared with the central nervous system, resulting, respectively in successful and aborted axon regeneration.... Read more »
DNA methylation and histone H3-K9 modifications contribute to MUC17 expression. Published: February, 2011 Abstract:
MUC17 glycoprotein is a membrane-associated mucin that is mainly expressed in the digestive tract. It has been suggested that MUC17 expression is correlated with the malignancy potential of pancreatic ductal adenocarcinomas (PDACs). In the present... Read more »
Effects of nickel treatment on H3K4 trimethylation and gene expression. Published: January, 2011 Abstract:
Occupational exposure to nickel compounds has been associated with lung and nasal cancers. We have previously shown that exposure of the human lung adenocarcinoma A549 cells to NiCl(2) for 24 hr significantly increased global levels of trimethylat... Read more »
Epigenetic regulation of miR-212 expression in lung cancer. Published: January, 2011 Abstract:
Many studies have shown that microRNA expression in cancer may be regulated by epigenetic events. Recently, we found that in lung cancer miR-212 was strongly down-regulated. However, mechanisms involved in the regulation of miR-212 expression are ... Read more »
Nucleosome-interacting proteins regulated by DNA and histone methylation. Published: October, 2010 Abstract:
Modifications on histones or on DNA recruit proteins that regulate chromatin function. Here, we use nucleosomes methylated on DNA and on histone H3 in an affinity assay, in conjunction with a SILAC-based proteomic analysis, to identify "crosstalk"... Read more »
Transcriptional regulation of lipid homeostasis in mycobacteria. Published: October, 2010 Abstract:
Mycolic acids are major components of the cell envelope of mycobacteria, such as Mycobacterium tuberculosis, and play an important role in its architecture, impermeability and interaction with the environment. Synthesis of mycolic acids is carried... Read more »
DNA methylation and Yin Yang-1 repress adenosine A2A receptor levels in human brain. Published: October, 2010 Abstract:
Adenosine A(2A) receptors (A(2A) Rs) are G-protein coupled receptors that stimulate adenylyl cyclase activity. The most A(2A) Rs-enriched brain region is the striatum, in which A(2A) Rs are largely restricted to GABAergic neurons of the indirect p... Read more »
HAATI survivors replace canonical telomeres with blocks of generic heterochromatin. Published: September, 2010 Abstract:
The notion that telomeres are essential for chromosome linearity stems from the existence of two chief dangers: inappropriate DNA damage response (DDR) reactions that mistake natural chromosome ends for double-strand DNA breaks (DSBs), and the pro... Read more »
miR-192 mediates TGF-beta/Smad3-driven renal fibrosis. Published: August, 2010 Abstract:
TGF-beta/Smad3 promotes renal fibrosis, but the mechanisms that regulate profibrotic genes remain unclear. We hypothesized that miR-192, a microRNA expressed in the kidney may mediate renal fibrosis in a Smad3-dependent manner. Microarray and real... Read more »
The impact of intragenic CpG content on gene expression. Published: July, 2010 Abstract:
The development of vaccine components or recombinant therapeutics critically depends on sustained expression of the corresponding transgene. This study aimed to determine the contribution of intragenic CpG content to expression efficiency in trans... Read more »
Vertebrate homologue of Drosophila GAGA factor. Published: June, 2010 Abstract:
Polycomb group (PcG) and trithorax group (trxG) proteins are chromatin-mediated regulators of a number of developmentally important genes including the homeotic genes. In Drosophila melanogaster, one of the trxG members, Trithorax like (Trl), enco... Read more »
Regulation of cyclin B2 expression and cell cycle G2/m transition by menin. Published: June, 2010 Abstract:
Multiple endocrine neoplasia type 1 (MEN1) results from mutations in tumor suppressor gene Men1, which encodes nuclear protein menin. Menin up-regulates certain cyclin-dependent kinase inhibitors through increasing histone H3 lysine 4 (H3K4) methy... Read more »
CDKL5 is a brain MeCP2 target gene regulated by DNA methylation. Published: June, 2010 Abstract:
Rett syndrome and its "early-onset seizure" variant are severe neurodevelopmental disorders associated with mutations within the MECP2 and the CDKL5 genes. Antidepressants and drugs of abuse induce the expression of the epigenetic factor MeCP2, th... Read more »
Regulation of Epstein-Barr virus OriP replication by poly(ADP-ribose) polymerase 1. Published: May, 2010 Abstract:
Poly(ADP-ribose) polymerase (PARP) is an abundant, chromatin-associated, NAD-dependent enzyme that functions in multiple chromosomal processes, including DNA replication and chromatin remodeling. The Epstein-Barr virus (EBV) origin of plasmid repl... Read more »
The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Published: April, 2010 Abstract:
The critical initial step in V(D)J recombination, binding of RAG1 and RAG2 to recombination signal sequences flanking antigen receptor V, D, and J gene segments, has not previously been characterized in vivo. Here, we demonstrate that RAG protein ... Read more »
Long intronic GAA repeats causing Friedreich ataxia impede transcription elongation. Published: April, 2010 Abstract:
Friedreich ataxia is a degenerative disease caused by deficiency of the protein frataxin (FXN). An intronic expansion of GAA triplets in the FXN-encoding gene, FXN, causes gene silencing and thus reduced FXN protein levels. Although it is widely a... Read more »
Autonomous silencing of the imprinted Cdkn1c gene in stem cells Published: April, 2010 Abstract:
Parent-of-origin specific expression of imprinted genes relies on the differential DNA methylation of specific genomic regions. Differentially methylated regions (DMRs) acquire DNA methylation either during gametogenesis (primary DMR) or after fer... Read more »
DNA methylation regulates adenosine A(2A) receptor cell surface expression levels. Published: March, 2010 Abstract:
Adenosine A(2A) receptors (A(2A)Rs) appear to play important roles in inflammation and in certain diseases of the nervous system. Pharmacological modulation of A(2A)Rs is particularly useful in Parkinson's disease and has been tested in schizophre... Read more »
Splicing factor Spf30 assists exosome-mediated gene silencing in fission yeast. Published: March, 2010 Abstract:
Heterochromatin assembly in fission yeast relies on the processing of cognate noncoding RNAs by both the RNA interference and the exosome degradation pathways. Recent evidence indicates that splicing factors facilitate the cotranscriptional proces... Read more »
Dr1 (NC2) is present at tRNA genes and represses their transcription in human cells. Published: March, 2010 Abstract:
Dr1 (also known as NC2beta) was identified as a repressor of RNA polymerase (pol) II transcription. It was subsequently shown to inhibit pol III transcription when expressed at high levels in vitro or in yeast cells. However, endogenous Dr1 was no... Read more »
Polycomb target genes are silenced in multiple myeloma. Published: January, 2010 Abstract:
Multiple myeloma (MM) is a genetically heterogeneous disease, which to date remains fatal. Finding a common mechanism for initiation and progression of MM continues to be challenging. By means of integrative genomics, we identified an underexpress... Read more »
A paucity of heterochromatin at functional human neocentromeres. Published: January, 2010 Abstract:
BACKGROUND: Centromeres are responsible for the proper segregation of replicated chromatids during cell division. Neocentromeres are fully functional ectopic human centromeres that form on low-copy DNA sequences and permit analysis of centromere s... Read more »
Antagonism of aryl hydrocarbon receptor signaling by 6,2',4'-trimethoxyflavone. Published: January, 2010 Abstract:
The aryl hydrocarbon receptor (AHR) is regarded as an important homeostatic transcriptional regulator within physiological and pathophysiological processes, including xenobiotic metabolism, endocrine function, immunity, and cancer. Agonist activat... Read more »
CTCF prevents the epigenetic drift of EBV latency promoter Qp. Published: January, 2010 Abstract:
The establishment and maintenance of Epstein-Barr Virus (EBV) latent infection requires distinct viral gene expression programs. These gene expression programs, termed latency types, are determined largely by promoter selection, and controlled thr... Read more »
Paired hormone response elements predict caveolin-1 as a glucocorticoid target gene. Published: January, 2010 Abstract:
Glucocorticoids act in part via glucocorticoid receptor binding to hormone response elements (HREs), but their direct target genes in vivo are still largely unknown. We developed the criterion that genomic occurrence of paired HREs at an inter-HRE... Read more »
Histone H1 binding is inhibited by histone variant H3.3 Published: December, 2009 Abstract:
Linker histones are involved in the formation of higher-order chromatin structure and the regulation of specific genes, yet it remains unclear what their principal binding determinants are. We generated a genome-wide high-resolution binding map fo... Read more »
CpG-island promoters drive transcription of human telomeres. Published: December, 2009 Abstract:
The longstanding dogma that telomeres, the heterochromatic extremities of linear eukaryotic chromosomes, are transcriptionally silent was overturned by the discovery that DNA-dependent RNA polymerase II (RNAPII) transcribes telomeric DNA into telo... Read more »
Dynamic DNA methylation programs persistent adverse effects of early-life stress. Published: December, 2009 Abstract:
Adverse early life events can induce long-lasting changes in physiology and behavior. We found that early-life stress (ELS) in mice caused enduring hypersecretion of corticosterone and alterations in passive stress coping and memory. This phenotyp... Read more »
JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Published: October, 2009 Abstract:
Activation of Janus kinase 2 (JAK2) by chromosomal translocations or point mutations is a frequent event in haematological malignancies. JAK2 is a non-receptor tyrosine kinase that regulates several cellular processes by inducing cytoplasmic signa... Read more »
Transcription independent insulation at TFIIIC-dependent insulators. Published: September, 2009 Abstract:
Chromatin insulators separate active from repressed chromatin domains. In yeast the RNA pol III transcription machinery bound to tRNA genes function with histone acetylases and chromatin remodelers to restrict the spread of heterochromatin. Our re... Read more »
HIC1 interacts with a specific subunit of SWI/SNF complexes, ARID1A/BAF250A. Published: August, 2009 Abstract:
HIC1, a tumor suppressor gene epigenetically silenced in many human cancers encodes a transcriptional repressor involved in regulatory loops modulating p53-dependent and E2F1-dependent cell survival and stress responses. HIC1 is also implicated in... Read more »
BRG1 increases transcription of proinflammatory genes in renal ischemia. Published: August, 2009 Abstract:
Acute kidney injury stimulates renal production of inflammatory mediators, including TNF-alpha and monocyte chemoattractant protein 1 (MCP-1). These responses reflect, in part, injury-induced transcription of proinflammatory genes by proximal tubu... Read more »
CpG methylation controls reactivation of HIV from latency. Published: August, 2009 Abstract:
DNA methylation of retroviral promoters and enhancers localized in the provirus 5' long terminal repeat (LTR) is considered to be a mechanism of transcriptional suppression that allows retroviruses to evade host immune responses and antiretroviral... Read more »
Endoplasmic reticulum stress regulates adipocyte resistin expression. Published: August, 2009 Abstract:
OBJECTIVE: Resistin is a secreted polypeptide that impairs glucose metabolism and, in rodents, is derived exclusively from adipocytes. In murine obesity, resistin circulates at elevated levels but its gene expression in adipose tissue is paradoxic... Read more »
Regulon-specific control of transcription elongation across the yeast genome. Published: August, 2009 Abstract:
Transcription elongation by RNA polymerase II was often considered an invariant non-regulated process. However, genome-wide studies have shown that transcriptional pausing during elongation is a frequent phenomenon in tightly-regulated metazoan ge... Read more »
Gfi1 integrates progenitor versus granulocytic transcriptional programming. Published: May, 2009 Abstract:
In patients with severe congenital neutropenia (SCN) and mice with growth factor independent-1 (Gfi1) loss of function, arrested myeloid progenitors accumulate, whereas terminal granulopoiesis is blocked. One might assume that Gfi-null progenitors... Read more »
Characterization of the murine Ephrin-B2 promoter. Published: May, 2009 Abstract:
Eph/ephrin signaling is pivotal in prenatal angiogenesis. Although their role in these processes has been extensively studied the mechanisms controlling eph/ephrin expression is not fully understood. To better understand the transcriptional regula... Read more »
Differential chromatin marking of introns and expressed exons by H3K36me3. Published: March, 2009 Abstract:
Variation in patterns of methylations of histone tails reflects and modulates chromatin structure and function. To provide a framework for the analysis of chromatin function in Caenorhabditis elegans, we generated a genome-wide map of histone H3 t... Read more »
Temporal regulation of Ath5 gene expression during eye development. Published: February, 2009 Abstract:
During central nervous system development the timing of progenitor differentiation must be precisely controlled to generate the proper number and complement of neuronal cell types. Proneural basic helix-loop-helix (bHLH) transcription factors play... Read more »
p53-Responsive micrornas 192 and 215 are capable of inducing cell cycle arrest. Published: December, 2008 Abstract:
microRNAs provide a novel layer of regulation for gene expression by interfering with the stability and/or translation of specific target mRNAs. Overall levels of microRNAs are frequently down-regulated in cancer cells, and reducing general microR... Read more »
Genome-associated RNA polymerase II includes the dissociable Rpb4/7 subcomplex. Published: September, 2008 Abstract:
Yeast RNA polymerase (Pol) II consists of a 10-subunit core enzyme and the Rpb4/7 subcomplex, which is dispensable for catalytic activity and dissociates in vitro. To investigate whether Rpb4/7 is an integral part of DNA-associated Pol II in vivo,... Read more »
BACH1 is a specific repressor of HMOX1 that is inactivated by arsenite. Published: August, 2008 Abstract:
Intracellular heme is a redox active molecule that can be detrimental to cells at high concentrations or under oxidizing conditions. To prevent accumulation, the inducible enzyme heme oxygenase-1 (HMOX1) catalyzes degradation of heme. In the absen... Read more »
Transcriptional regulation of autocrine IL-6 expression in multiple myeloma cells. Published: August, 2008 Abstract:
Multiple myeloma (MM) is an as to date incurable hematopoietic malignancy. The importance of Interleukin-6 (IL-6) as an autocrine growth factor for MM cells is widely accepted, yet very little is known about the mechanisms at the basis of deregula... Read more »
Regulation of p53 target gene expression by peptidylarginine deiminase 4. Published: August, 2008 Abstract:
Histone Arg methylation has been correlated with transcriptional activation of p53 target genes. However, whether this modification is reversed to repress the expression of p53 target genes is unclear. Here, we report that peptidylarginine deimina... Read more »
Nucleotide excision repair driven by the dissociation of CAK from TFIIH. Published: July, 2008 Abstract:
The transcription/DNA repair factor TFIIH is organized into a core that associates with the CDK-activating kinase (CAK) complex. Using chromatin immunoprecipitation, we have followed the composition of TFIIH over time after UV irradiation of repai... Read more »
Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene. Published: June, 2008 Abstract:
In the present report we have determined the molecular mechanisms, which govern the expression of the human IL-10 gene when induced by the glucocorticoid Methyl-Prednisolone (MP). Treatment of cells with MP at 10(-6) M will readily induce IL-10 in... Read more »
Modulation of RNA polymerase assembly dynamics in transcriptional regulation. Published: May, 2008 Abstract:
The interaction of transcription factors with target genes is highly dynamic. Whether the dynamic nature of these interactions is merely an intrinsic property of transcription factors or serves a regulatory role is unknown. Here we have used singl... Read more »
SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Published: March, 2008 Abstract:
The Sir2 deacetylase regulates chromatin silencing and lifespan in Saccharomyces cerevisiae. In mice, deficiency for the Sir2 family member SIRT6 leads to a shortened lifespan and a premature ageing-like phenotype. However, the molecular mechanism... Read more »
Differential regulation of NAB corepressor genes in Schwann cells. Published: December, 2007 Abstract:
BACKGROUND: Myelination of peripheral nerves by Schwann cells requires not only the Egr2/Krox-20 transactivator, but also the NGFI-A/Egr-binding (NAB) corepressors, which modulate activity of Egr2. Previous work has shown that axon-dependent expre... Read more »
Molecular basis for estrogen receptor alpha deficiency in BRCA1-linked breast cancer. Published: November, 2007 Abstract:
BACKGROUND: BRCA1-mutant breast tumors are typically estrogen receptor alpha (ER alpha) negative, whereas most sporadic tumors express wild-type BRCA1 and are ER alpha positive. We examined a possible mechanism for the observed ER alpha-negative p... Read more »
Analysis of transcription, chromatin dynamics and epigenetic changes in neural genes. Published: November, 2007 Abstract:
The ways in which gene transcription is investigated have undergone radical change since the turn of the millennium. Piece-meal approaches focussed upon model genes have increasingly been complemented by genome-wide approaches that allow interroga... Read more »
Protein arginine-methyltransferase-dependent oncogenesis. Published: October, 2007 Abstract:
Enzymes that mediate reversible epigenetic modifications have not only been recognized as key in regulating gene expression and oncogenesis, but also provide potential targets for molecular therapy. Although the methylation of arginine 3 of histon... Read more »
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Published: August, 2007 Abstract:
We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generate... Read more »
MTERF3 is a negative regulator of mammalian mtDNA transcription. Published: July, 2007 Abstract:
Regulation of mammalian mtDNA gene expression is critical for altering oxidative phosphorylation capacity in response to physiological demands and disease processes. The basal machinery for initiation of mtDNA transcription has been molecularly de... Read more »
Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Published: February, 2007 Abstract:
The mechanisms underlying microRNA (miRNA) disruption in human disease are poorly understood. In cancer cells, the transcriptional silencing of tumor suppressor genes by CpG island promoter hypermethylation has emerged as a common hallmark. We won... Read more »
Architecture of a polycomb nucleoprotein complex. Published: October, 2006 Abstract:
Polycomb group (PcG) epigenetic silencing proteins act through cis-acting DNA sequences, named Polycomb response elements (PREs). Within PREs, Pleiohomeotic (PHO) binding sites and juxtaposed Pc binding elements (PBEs) function as an integrated DN... Read more »
Influenza virus inhibits RNA polymerase II elongation. Published: July, 2006 Abstract:
The influenza virus RNA-dependent RNA polymerase interacts with the serine-5 phosphorylated carboxy-terminal domain (CTD) of the large subunit of RNA polymerase II (Pol II). It was proposed that this interaction allows the viral RNA polymerase to ... Read more »
Menin links estrogen receptor activation to histone H3K4 trimethylation. Published: May, 2006 Abstract:
The product of the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor gene, menin, is an integral component of MLL1/MLL2 histone methyltransferase complexes specific for Lys4 of histone H3 (H3K4). We show that menin is a transcriptional c... Read more »
The Polycomb group protein EZH2 directly controls DNA methylation. Published: February, 2006 Abstract:
The establishment and maintenance of epigenetic gene silencing is fundamental to cell determination and function. The essential epigenetic systems involved in heritable repression of gene activity are the Polycomb group (PcG) proteins and the DNA ... Read more »
Transcriptional regulation of epidermal barrier formation. Abstract:
The mammalian epidermis is a self-renewing stratified squamous epithelium. Its basal cell layer contains proliferating keratinocytes that exit the cell cycle when they move into the suprabasal compartment. These cells activate a gene differentiati... Read more »
In Vivo ChIP for the Analysis of Microdissected Tissue Samples Abstract:
The development of chromatin immunoprecipitation assays (ChIP) as a tool to examine the interactions between nuclear proteins and DNA has enhanced essentially our understanding of the dynamic association of transcription factors and chromatin modi... Read more »
Fatty acids regulate perilipin5 in muscle by activating PPARδ Abstract:
The surface of lipid droplets (LDs) in various cell types is coated with perilipin proteins encoded by the Plin genes. Perilipins regulate LD metabolism by selectively recruiting lipases and other proteins to LDs. We have studied the expression of... Read more »
ChIP for Hox proteins from Drosophila imaginal discs. Abstract:
Chromatin immunoprecipitation (ChIP) is a technique that reveals in vivo location of a protein bound to DNA. ChIP coupled with DNA microarrays (ChIP-chip) or next-generation sequencing (ChIP-seq) allows for identification of binding sites of trans... Read more »
Chromatin immunoprecipitation analysis in filamentous fungi. Abstract:
Chromatin immunoprecipitation (ChIP) is used to map the interaction between proteins and DNA at a specific genomic locus in the living cell. The protein-DNA complexes are stabilized already in vivo by reversible crosslinking and the DNA is sheared... Read more »
Chromatin Immunoprecipitation Abstract:
Chromatin plays important functions in regulating many biological processes, including DNA transcription, replication, and repair. The use of chromatin immunoprecipitation (ChIP) assays has contributed enor- mously to identify interactions between... Read more »
Chromatin Immunoprecipitation in Mouse Hippocampal Cells and Tissues Abstract:
Chromatin immunoprecipitation (ChIP) has been developed for studying protein-DNA interactions and has been extensively used for mapping the localization of posttranslationally modified histones, histone variants, transcription factors, or chromati... Read more »
