RecG Directs DNA Synthesis during Double-Strand Break Repair Published: February, 2016 Abstract:
Homologous recombination provides a mechanism of DNA double-strand break repair (DSBR) that requires an intact, homologous template for DNA synthesis. When DNA synthesis associated with DSBR is convergent, the broken DNA strands are replaced and r... Read more »
Transducin-like enhancer of split-1 is expressed and functional in human macrophages Published: December, 2015 Abstract:
Macrophages display heterogeneous phenotypes, including the classical M1 proinflammatory and the alternative M2 anti-inflammatory polarization states. The transducin-like enhancer of split-1 (TLE1) is a transcriptional corepressor whose functions ... Read more »
Opposing role for Egr3 in nucleus accumbens cell subtypes in cocaine action. Published: May, 2015 Abstract:
An imbalance in molecular signaling cascades and transcriptional regulation in nucleus accumbens (NAc) medium spiny neuron (MSN) subtypes, those enriched in dopamine D1 versus D2 receptors, is implicated in the behavioral responses to psychostimul... Read more »
Involvement of RNA Polymerase III in Immune Responses. Published: May, 2015 Abstract:
Inflammation in the tumor microenvironment has many tumor-promoting effects. In particular, tumor-associated macrophages (TAMs) produce many cytokines which can support tumor growth by promoting survival of malignant cells, angiogenesis, and metas... Read more »
Interaction with WDR5 Promotes Target Gene Recognition and Tumorigenesis by MYC. Published: May, 2015 Abstract:
MYC is an oncoprotein transcription factor that is overexpressed in the majority of malignancies. The oncogenic potential of MYC stems from its ability to bind regulatory sequences in thousands of target genes, which depends on interaction of MYC ... Read more »
C2H2 zinc finger proteins greatly expand the human regulatory lexicon. Published: May, 2015 Abstract:
Cys2-His2 zinc finger (C2H2-ZF) proteins represent the largest class of putative human transcription factors. However, for most C2H2-ZF proteins it is unknown whether they even bind DNA or, if they do, to which sequences. Here, by combining data f... Read more »
Global regulation of heterochromatin spreading by Leo1. Published: May, 2015 Abstract:
Heterochromatin plays important roles in eukaryotic genome regulation. However, the repressive nature of heterochromatin combined with its propensity to self-propagate necessitates robust mechanisms to contain heterochromatin within defined bounda... Read more »
Spt6 Is Essential for rRNA Synthesis by RNA Polymerase I Published: April, 2015 Abstract:
Spt6 has many roles in transcription initiation and elongation by RNA polymerase (Pol) II. These effects are mediated through interactions with histones, transcription factors, and the RNA polymerase. Two lines of evidence suggest that Spt6 also p... Read more »
Transcriptional co-repressor function of the hippo pathway transducers YAP and TAZ. Published: April, 2015 Abstract:
YAP (yes-associated protein) and TAZ are oncogenic transcriptional co-activators downstream of the Hippo tumor-suppressor pathway. However, whether YAP and/or TAZ (YAP/TAZ) engage in transcriptional co-repression remains relatively unexplored. Her... Read more »
The Paf1 complex represses small-RNA-mediated epigenetic gene silencing. Published: April, 2015 Abstract:
RNA interference (RNAi) refers to the ability of exogenously introduced double-stranded RNA to silence expression of homologous sequences. Silencing is initiated when the enzyme Dicer processes the double-stranded RNA into small interfering RNAs (... Read more »
Targeting the MLL complex in castration-resistant prostate cancer. Published: April, 2015 Abstract:
Resistance to androgen deprivation therapies and increased androgen receptor (AR) activity are major drivers of castration-resistant prostate cancer (CRPC). Although prior work has focused on targeting AR directly, co-activators of AR signaling, w... Read more »
Oxyntomodulin regulates resetting of the liver circadian clock by food Published: March, 2015 Abstract:
Circadian clocks coordinate 24-hr rhythms of behavior and physiology. In mammals, a master clock residing in the suprachiasmatic nucleus (SCN) is reset by the light-dark cycle, while timed food intake is a potent synchronizer of peripheral clocks ... Read more »
Genome wide expression profiling of p53 regulated miRNAs in neuroblastoma. Published: March, 2015 Abstract:
Restoration of the antitumor activity of p53 could offer a promising approach for the treatment of neuroblastoma. MicroRNAs (miRNAs) are important mediators of p53 activity, but their role in the p53 response has not yet been comprehensively addre... Read more »
Bacterial Infection Remodels the DNA Methylation Landscape of Human Dendritic Cells Published: March, 2015 Abstract:
DNA methylation is thought to be robust to environmental perturbations on a short time scale. Here, we challenge that view by demonstrating that the infection of human dendritic cells (DCs) with a pathogenic bacteria is associated with rapid chang... Read more »
Exon-intron circular RNAs regulate transcription in the nucleus. Published: March, 2015 Abstract:
Noncoding RNAs (ncRNAs) have numerous roles in development and disease, and one of the prominent roles is to regulate gene expression. A vast number of circular RNAs (circRNAs) have been identified, and some have been shown to function as microRNA... Read more »
The DREAM complex promotes gene body H2A.Z for target repression. Published: March, 2015 Abstract:
The DREAM (DP, Retinoblastoma [Rb]-like, E2F, and MuvB) complex controls cellular quiescence by repressing cell cycle genes, but its mechanism of action is poorly understood. Here we show that Caenorhabditis elegans DREAM targets have an unusual p... Read more »
Genome-wide redistribution of BRD4 binding sites in transformation resistant cells. Published: March, 2015 Abstract:
Hutchinson-Gilford progeria syndrome (HGPS) patients do not develop cancer despite a significant accumulation of DNA damage in their cells. We have recently reported that HGPS cells are refractory to experimental oncogenic transformation and we id... Read more »
FUBP1: a new protagonist in splicing regulation of the DMD gene. Published: February, 2015 Abstract:
We investigated the molecular mechanisms for in-frame skipping of DMD exon 39 caused by the nonsense c.5480T>A mutation in a patient with Becker muscular dystrophy. RNase-assisted pull down assay coupled with mass spectrometry revealed that the mu... Read more »
Reduced Expression of MYC Increases Longevity and Enhances Healthspan. Published: January, 2015 Abstract:
MYC is a highly pleiotropic transcription factor whose deregulation promotes cancer. In contrast, we find that Myc haploinsufficient (Myc(+/-)) mice exhibit increased lifespan. They show resistance to several age-associated pathologies, including ... Read more »
Ligand-dependent enhancer activation regulated by topoisomerase-I activity. Published: January, 2015 Abstract:
The discovery that enhancers are regulated transcription units, encoding eRNAs, has raised new questions about the mechanisms of their activation. Here, we report an unexpected molecular mechanism that underlies ligand-dependent enhancer activatio... Read more »
Dynamic Regulation of Schwann Cell Enhancers after Peripheral Nerve Injury. Published: January, 2015 Abstract:
Myelination of the peripheral nervous system is required for axonal function and long term stability. After peripheral nerve injury, Schwann cells transition from axon myelination to a demyelinated state that supports neuronal survival and ultimat... Read more »
USP7 COOPERATES WITH SCML2 TO REGULATE THE ACTIVITY OF PRC1. Published: January, 2015 Abstract:
USP7 is a protein deubiquitinase with an essential role in development. Here, we provide evidence that USP7 regulates the activity of the Polycomb Repressive Complex 1 (PRC1) in coordination with SCML2. There are six versions of PRC1 defined by th... 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 »
RNA Chromatin Immunoprecipitation (RNA-ChIP) in Caenorhabditis elegans Published: December, 2014 Abstract:
The RNA chromatin immunoprecipitation assay (RNA-ChIP) allows detection and quantification of RNA–protein interactions using in vivo cross-linking with formaldehyde followed by immunoprecipitation of the RNA–protein complexes. Here we describe th... Read more »
An AUTS2-Polycomb complex activates gene expression in the CNS. Published: December, 2014 Abstract:
Naturally occurring variations of Polycomb repressive complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, autism susceptibility candidate 2 (AUTS2). Although AUTS2 is often disrup... 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 »
DNA Copy-Number Control through Inhibition of Replication Fork Progression. Published: November, 2014 Abstract:
Proper control of DNA replication is essential to ensure faithful transmission of genetic material and prevent chromosomal aberrations that can drive cancer progression and developmental disorders. DNA replication is regulated primarily at the lev... 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 »
AF9 YEATS Domain Links Histone Acetylation to DOT1L-Mediated H3K79 Methylation. Published: October, 2014 Abstract:
The recognition of modified histones by "reader" proteins constitutes a key mechanism regulating gene expression in the chromatin context. Compared with the great variety of readers for histone methylation, few protein modules that recognize histo... 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 »
ETS1 is a genome-wide effector of RAS/ERK signaling in epithelial cells. Published: October, 2014 Abstract:
The RAS/ERK pathway is commonly activated in carcinomas and promotes oncogenesis by altering transcriptional programs. However, the array of cis-regulatory elements and trans-acting factors that mediate these transcriptional changes is still uncle... 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 »
Genome-wide map of regulatory interactions in the human genome. Published: September, 2014 Abstract:
Increasing evidence suggests that interactions between regulatory genomic elements play an important role in regulating gene expression. We generated a genome-wide interaction map of regulatory elements in human cells (ENCODE tier 1 cells, K562, G... 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 »
Chromatin enrichment for proteomics. Published: September, 2014 Abstract:
During interphase, chromatin hosts fundamental cellular processes, such as gene expression, DNA replication and DNA damage repair. To analyze chromatin on a proteomic scale, we have developed chromatin enrichment for proteomics (ChEP), which is a ... Read more »
Immunogenetics. Chromatin state dynamics during blood formation. Published: August, 2014 Abstract:
Chromatin modifications are crucial for development, yet little is known about their dynamics during differentiation. Hematopoiesis provides a well-defined model to study chromatin state dynamics; however, technical limitations impede profiling of... 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 »
FUS is sequestered in nuclear aggregates in ALS patient fibroblasts. Published: July, 2014 Abstract:
Mutations in the RNA-binding protein FUS have been shown to cause the neurodegenerative disease amyotrophic lateral sclerosis. We investigate whether mutant FUS protein in ALS patient-derived fibroblasts affects normal FUS functions in the nucleus... 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 »
Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells. Published: April, 2014 Abstract:
Bacterial type II CRISPR-Cas9 systems have been widely adapted for RNA-guided genome editing and transcription regulation in eukaryotic cells, yet their in vivo target specificity is poorly understood. Here we mapped genome-wide binding sites of a... 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 »
Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1. Published: April, 2014 Abstract:
Genetic deficiencies in transcription factors can lead to the loss of certain types of cells and tissue. The steroidogenic tissue-specific nuclear receptor Ad4BP/SF-1 (NR5A1) is one such gene, because mice in which this gene is disrupted fail to d... 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 »
ZBED6 Modulates the Transcription of Myogenic Genes in Mouse Myoblast Cells. Published: April, 2014 Abstract:
ZBED6 is a recently discovered transcription factor, unique to placental mammals, that has evolved from a domesticated DNA transposon. It acts as a repressor at the IGF2 locus. Here we show that ZBED6 acts as a transcriptional modulator in mouse m... 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 »
CpG domains downstream of TSSs promote high levels of gene expression. Published: April, 2014 Abstract:
CpG dinucleotides are known to play a crucial role in regulatory domains, affecting gene expression in their natural context. Here, we demonstrate that intragenic CpG frequency and distribution impacts transgene and genomic gene expression levels ... 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 »
Identification of HilD-regulated genes in Salmonella enterica serovar Typhimurium. Published: March, 2014 Abstract:
Salmonella enterica serovar Typhimurium (S. Typhimurium) pathogenicity island 1 (SPI-1) encodes a type III secretion system required for invasion of host gut epithelial cells. Expression of SPI-1 virulence genes is controlled by a complex hierarch... 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 »
Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Published: February, 2014 Abstract:
Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not furth... 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 »
Genome-wide binding patterns of thyroid hormone receptor beta. Published: February, 2014 Abstract:
Thyroid hormone (TH) receptors (TRs) play central roles in metabolism and are major targets for pharmaceutical intervention. Presently, however, there is limited information about genome wide localizations of TR binding sites. Thus, complexities o... 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 cohesin-independent role for NIPBL at promoters provides insights in CdLS. Published: February, 2014 Abstract:
The cohesin complex is crucial for chromosome segregation during mitosis and has recently also been implicated in transcriptional regulation and chromatin architecture. The NIPBL protein is required for the loading of cohesin onto chromatin, but h... 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 »
CLOCK:BMAL1 is a pioneer-like transcription factor. Published: January, 2014 Abstract:
The mammalian circadian clock relies on the master genes CLOCK and BMAL1 to drive rhythmic gene expression and regulate biological functions under circadian control. Here we show that rhythmic CLOCK:BMAL1 DNA binding promotes rhythmic chromatin op... 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 »
Large conserved domains of low DNA methylation maintained by Dnmt3a. Published: January, 2014 Abstract:
Gains and losses in DNA methylation are prominent features of mammalian cell types. To gain insight into the mechanisms that promote shifts in DNA methylation and contribute to changes in cell fate, including malignant transformation, we performed... 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 »
Nfatc1 orchestrates aging in hair follicle stem cells. Published: December, 2013 Abstract:
Hair production is fueled by stem cells (SCs), which transition between cyclical bouts of rest and activity. Here, we explore why hair growth wanes with age. We show that aged hair follicle SCs (HFSCs) in mice exhibit enhanced resting and abbrevia... 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 »
Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment. Published: December, 2013 Abstract:
Mediator is a large multiprotein complex conserved in all eukaryotes. The crucial function of Mediator in transcription is now largely established. However, we found that this complex also plays an important role by connecting transcription with D... 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 »
Coupling transcription factor occupancy to nucleosome architecture with DNase-FLASH. Published: November, 2013 Abstract:
It is currently not possible to resolve the genome-wide relationship of transcription factors (TFs) and nucleosomes at the level of individual chromatin templates despite rapidly increasing data on TF and nucleosome occupancy in the human genome. ... Read more »
Promiscuous RNA binding by Polycomb repressive complex 2. Published: November, 2013 Abstract:
Polycomb repressive complex 2 (PRC2) is a histone methyltransferase required for epigenetic silencing during development and cancer. Long noncoding RNAs (lncRNAs) recruit PRC2 to chromatin, but the general role of RNA in maintaining repressed chro... Read more »
PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells. Published: November, 2013 Abstract:
EZH2 is the catalytic subunit of PRC2, a central epigenetic repressor essential for development processes in vivo and for the differentiation of embryonic stem cells (ESCs) in vitro. The biochemical function of PRC2 in depositing repressive H3K27m... Read more »
Gene dysregulation by histone variant H2A.Z in bladder cancer Published: October, 2013 Abstract:
Background The incorporation of histone variants into nucleosomes is one of the main strategies that the cell uses to regulate the structure and function of chromatin. Histone H2A.Z is an evolutionarily conserved histone H2A variant that is pref... 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 »
Genomic organization of human transcription initiation complexes. Published: October, 2013 Abstract:
The human genome is pervasively transcribed, yet only a small fraction is coding. Here we address whether this non-coding transcription arises at promoters, and detail the interactions of initiation factors TATA box binding protein (TBP), transcri... Read more »
Gene regulation and priming by topoisomerase IIα in embryonic stem cells. Published: September, 2013 Abstract:
Topoisomerases resolve torsional stress, while their function in gene regulation, especially during cellular differentiation, remains unknown. Here we find that the expression of topo II isoforms, topoisomerase IIα and topoisomerase IIβ, is the ch... Read more »
Addiction of t(8;21) and inv(16) acute myeloid leukemia to native RUNX1. Published: September, 2013 Abstract:
The t(8;21) and inv(16) chromosomal aberrations generate the oncoproteins AML1-ETO (A-E) and CBFβ-SMMHC (C-S). The role of these oncoproteins in acute myeloid leukemia (AML) etiology has been well studied. Conversely, the function of native RUNX1 ... 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 »
Ras-Induced Changes in H3K27me3 Occur after Those in Transcriptional Activity. Published: August, 2013 Abstract:
Oncogenic signaling pathways regulate gene expression in part through epigenetic modification of chromatin including DNA methylation and histone modification. Trimethylation of histone H3 at lysine-27 (H3K27), which correlates with transcriptional... 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 »
Chromatin tandem affinity purification sequencing. Published: August, 2013 Abstract:
Chromatin immunoprecipitation coupled with ultra-high-throughput sequencing (ChIP-seq) is a widely used method for mapping the interactions of proteins with DNA. However, the requirements for ChIP-grade antibodies impede wider application of this ... 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 »
De Novo Mutations in the Genome Organizer CTCF Cause Intellectual Disability. Published: July, 2013 Abstract:
An increasing number of genes involved in chromatin structure and epigenetic regulation has been implicated in a variety of developmental disorders, often including intellectual disability. By trio exome sequencing and subsequent mutational screen... Read more »
Uniform, optimal signal processing of mapped deep-sequencing data. Published: July, 2013 Abstract:
Despite their apparent diversity, many problems in the analysis of high-throughput sequencing data are merely special cases of two general problems, signal detection and signal estimation. Here we adapt formally optimal solutions from signal proce... 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 »
Estrogen-dependent dynamic profile of eNOS-DNA associations in prostate cancer. Published: May, 2013 Abstract:
In previous work we have documented the nuclear translocation of endothelial NOS (eNOS) and its participation in combinatorial complexes with Estrogen Receptor Beta (ERβ) and Hypoxia Inducible Factors (HIFs) that determine localized chromatin remo... 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 proteomic characterization of factors enriched at nascent DNA molecules. Published: April, 2013 Abstract:
DNA replication is facilitated by multiple factors that concentrate in the vicinity of replication forks. Here, we developed an approach that combines the isolation of proteins on nascent DNA chains with mass spectrometry (iPOND-MS), allowing a co... Read more »
Placing the HIRA histone chaperone complex in the chromatin landscape. Published: April, 2013 Abstract:
The HIRA chaperone complex, comprised of HIRA, UBN1, and CABIN1, collaborates with histone-binding protein ASF1a to incorporate histone variant H3.3 into chromatin in a DNA replication-independent manner. To better understand HIRA's function and m... 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 »
Genome-wide control of RNA polymerase II activity by cohesin. Published: March, 2013 Abstract:
Cohesin is a well-known mediator of sister chromatid cohesion, but it also influences gene expression and development. These non-canonical roles of cohesin are not well understood, but are vital: gene expression and development are altered by mode... Read more »
Polycomb domain formation depends on short and long distance regulatory cues. Published: February, 2013 Abstract:
BACKGROUND: Polycomb group (PcG) proteins dynamically define cellular identities through the epigenetic repression of key developmental genes. In Drosophila, cis-regulatory regions termed PcG response elements (PREs) act as nucleation sites for Pc... Read more »
Multiple roles for Piwi in silencing Drosophila transposons. Published: February, 2013 Abstract:
Silencing of transposons in the Drosophila ovary relies on three Piwi family proteins--Piwi, Aubergine (Aub), and Ago3--acting in concert with their small RNA guides, the Piwi-interacting RNAs (piRNAs). Aub and Ago3 are found in the germ cell cyto... 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 »
Specificity and Function of Archaeal DNA Replication Initiator Proteins. Published: January, 2013 Abstract:
Chromosomes with multiple DNA replication origins are a hallmark of Eukaryotes and some Archaea. All eukaryal nuclear replication origins are defined by the origin recognition complex (ORC) that recruits the replicative helicase MCM(2-7) via Cdc6 ... Read more »
MeCP2 modulates gene expression pathways in astrocytes. Published: January, 2013 Abstract:
ABSTRACT: BACKGROUND: Mutations in MECP2 encoding methyl-CpG-binding protein 2 (MeCP2) cause the X-linked neurodevelopmental disorder Rett syndrome. Rett syndrome patients exhibit neurological symptoms that include irregular breathing, impaired mo... 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 »
In Vivo Epigenomic Profiling of Germ Cells Reveals Germ Cell Molecular Signatures. Published: January, 2013 Abstract:
The limited number of in vivo germ cells poses an impediment to genome-wide studies. Here, we applied a small-scale chromatin immunoprecipitation sequencing (ChIP-seq) method on purified mouse fetal germ cells to generate genome-wide maps of four ... 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 »
Histone methyltransferase MLL3 contributes to genome-scale circadian transcription. Published: January, 2013 Abstract:
Daily cyclical expression of thousands of genes in tissues such as the liver is orchestrated by the molecular circadian clock, the disruption of which is implicated in metabolic disorders and cancer. Although we understand much about the circadian... Read more »
A Molecular Roadmap of Reprogramming Somatic Cells into iPS Cells. Published: December, 2012 Abstract:
Factor-induced reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is inefficient, complicating mechanistic studies. Here, we examined defined intermediate cell populations poised to becoming iPSCs by genome-wide analyses. W... 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 »
Cdk11-CyclinL Controls the Assembly of the RNA Polymerase II Mediator Complex. Published: November, 2012 Abstract:
The large Mediator (L-Mediator) is a general coactivator of RNA polymerase II transcription and is formed by the reversible association of the small Mediator (S-Mediator) and the kinase-module-harboring Cdk8. It is not known how the kinase module ... 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 »
Limitations and possibilities of low cell number ChIP-seq. Published: November, 2012 Abstract:
ABSTRACT: BACKGROUND: Chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq) offers high resolution, genome-wide analysis of DNA-protein interactions. However, current standard methods require abundant starting materi... 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 »
A genome-wide signature of glucocorticoid receptor binding in neuronal PC12 cells. Published: October, 2012 Abstract:
ABSTRACT: BACKGROUND: Glucocorticoids, secreted by the adrenals in response to stress, profoundly affect structure and plasticity of neurons. Glucocorticoid action in neurons is mediated by glucocorticoid receptors (GR) that operate as transcripti... 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 »
Argonaute proteins couple chromatin silencing to alternative splicing. Published: September, 2012 Abstract:
Argonaute proteins play a major part in transcriptional gene silencing in many organisms, but their role in the nucleus of somatic mammalian cells remains elusive. Here, we have immunopurified human Argonaute-1 and Argonaute-2 (AGO1 and AGO2) chro... 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 »
Widespread plasticity in CTCF occupancy linked to DNA methylation. Published: September, 2012 Abstract:
CTCF is a ubiquitously expressed regulator of fundamental genomic processes including transcription, intra- and interchromosomal interactions, and chromatin structure. Because of its critical role in genome function, CTCF binding patterns have lon... Read more »
Molecular basis for the specification of floral organs by APETALA3 and PISTILLATA. Published: August, 2012 Abstract:
How different organs are formed from small sets of undifferentiated precursor cells is a key question in developmental biology. To understand the molecular mechanisms underlying organ specification in plants, we studied the function of the homeoti... 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 »
A Key Role for Chd1 in Histone H3 Dynamics at the 3′ Ends of Long Genes in Yeast Published: July, 2012 Abstract:
Chd proteins are ATP–dependent chromatin remodeling enzymes implicated in biological functions from transcriptional elongation to control of pluripotency. Previous studies of the Chd1 subclass of these proteins have implicated them in diverse role... Read more »
SATB1-mediated Functional Packaging of Chromatin into Loops. Published: July, 2012 Abstract:
Mammalian genomes are organized into multiple layers of higher-order chromatin structure, and in this organization chromatin looping is a striking and crucial feature that brings together distal genomic loci into close spatial proximity. Such thre... 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 »
Cohesins Repress KSHV Immediate Early Gene Transcription During Latency. Published: June, 2012 Abstract:
Chromatin-organizing factors, like CTCF and cohesins, have been implicated in the control of complex viral regulatory programs. We investigated the role of CTCF and cohesin in the control of the latent to lytic switch for Kaposi's Sarcoma-Associat... 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 »
Functional Genomic Methods to Study Estrogen Receptor Activity. Published: May, 2012 Abstract:
Estrogen Receptor (ER) is a nuclear receptor that mediates the actions of estrogen and tamoxifen. ER is expressed in a major fraction of human breast cancers. Recently, genomic maps for estrogen- and tamoxifen-ER have been published. Interestingly... 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 »
Genome Wide Analysis Of Pax8 Binding Provides New Insights Into Thyroid Functions. Published: April, 2012 Abstract:
ABSTRACT: BACKGROUND: The transcription factor Pax8 is essential for the differentiation of thyroid cells. However, there are few data on genes transcriptionally regulated by Pax8 other than thyroid-related genes. To better understand the role of ... Read more »
A dual role of linker histone H1.4 Lys 34 acetylation in transcriptional activation. Published: April, 2012 Abstract:
The linker histone H1 is a key player in chromatin organization, yet our understanding of the regulation of H1 functions by post-translational modifications is very limited. We provide here the first functional characterization of H1 acetylation. ... 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 »
Analysis of Chromatin Dynamics during Glucocorticoid Receptor Activation. Published: March, 2012 Abstract:
Steroid hormone receptors initiate a genetic program tightly regulated by the chromatin environment of the responsive regions. Using the glucocorticoid receptor (GR) as a model factor for transcriptional initiation, we classified chromatin structu... Read more »
Genome-wide analysis of histone H3.1 and H3.3 variants in Arabidopsis thaliana. Published: March, 2012 Abstract:
Nucleosomes package eukaryotic DNA and are composed of four different histone proteins, designated H3, H4, H2A, and H2B. Histone H3 has two main variants, H3.1 and H3.3, which show different genomic localization patterns in animals. We profiled H3... 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 »
Chromatin-modifying enzymes as modulators of reprogramming. Published: March, 2012 Abstract:
Generation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming involves global epigenetic remodelling. Whereas several proteins are known to regulate chromatin marks associated with the distinct epigenetic states of cells befor... 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 »
Widespread site-dependent buffering of human regulatory polymorphism. Published: March, 2012 Abstract:
The average individual is expected to harbor thousands of variants within non-coding genomic regions involved in gene regulation. However, it is currently not possible to interpret reliably the functional consequences of genetic variation within a... Read more »
Dynamic MicroRNA Gene Transcription and Processing during T Cell Development. Published: February, 2012 Abstract:
By disrupting microRNA (miRNA) biogenesis, we previously showed that this pathway is critical for the differentiation and function of T cells. Although various cloning studies have shown that many miRNAs are expressed during T cell development, an... 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 »
A workflow for genome-wide mapping of archaeal transcription factors with ChIP-seq. Published: February, 2012 Abstract:
Deciphering the structure of gene regulatory networks across the tree of life remains one of the major challenges in postgenomic biology. We present a novel ChIP-seq workflow for the archaea using the model organism Halobacterium salinarum sp. NRC... Read more »
Research Resource: The Pdx1 Cistrome of Pancreatic Islets. Published: February, 2012 Abstract:
The homeodomain transcription factor pancreas duodenal homeobox 1 (Pdx1, also known as insulin promoter factor 1) is a master regulator of pancreas development, as mice or humans lacking Pdx1 function are a pancreatic. Importantly, heterozygous mu... 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 »
The little elongation complex regulates small nuclear RNA transcription. Published: December, 2011 Abstract:
Eleven-nineteen lysine-rich leukemia (ELL) participates in the super elongation complex (SEC) with the RNA polymerase II (Pol II) CTD kinase P-TEFb. SEC is a key regulator in the expression of HOX genes in mixed lineage leukemia (MLL)-based hemato... 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 »
