Transcription factor cooperativity in early adipogenic hotspots and super-enhancers
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE56872 | GEO | 2014/04/17
SECONDARY ACCESSION(S): PRJNA244848
REPOSITORIES: GEO
Similar Datasets
Project description:Here we have used a combination of advanced proteomics and genomics approaches to investigate the extent and mechanisms of transcription factor cross-talk at genomic hotspots. We identify ~12,000 transcription factor hotspots in the early phase of adipogenesis, and we find evidence of both simultaneous and sequential binding of transcription factors at these regions. We demonstrate for the first time that hotspots are highly enriched in large super-enhancer regions and that these drive the early adipogenic reprogramming of gene expression. Our results indicate that cooperativity between transcription factors at the level of hotspots as well as super-enhancers is very important for enhancer activity and transcriptional reprogramming. Thus, hotspots and super-enhancers constitute important regulatory hubs integrating external stimuli on chromatin. Genome-wide profiling of transcription factor and co-factor binding, epigenomic marks, and gene expression in 3T3-L1 pre-adipocytes.
2014-04-17 | E-GEOD-56872 | biostudies-arrayexpress
Project description:Transcription factor cooperativity in early adipogenic hotspots and super-enhancers
| PRJNA244848 | ENA
Project description:We sought to identify hotspots of aberrant enhancer activity in colorectal cancer (CRC) through interrogation of the enhancer epigenomes of a large cohort of genetically diverse CRC samples and normal colonic crypts, representing the cell type of origin for CRC. Through characterization of loci that exhibit differential enhancer activity, we identified sets of enhancers that are recurrently commissioned and decommissioned in CRC relative to normal crypts. The set of recurrently commissioned, or “acquired”, enhancers are of particular interest. Many originate from primed chromatin and activate known and potentially novel oncogenes in CRC. They are also frequently constituents of super enhancers and loaded with AP-1 and cohesin complex proteins. Nearly half of all GWAS CRC risk loci identified to date map to these enhancer hotspots. Through functional studies and integrative analyses we further demonstrate that CRC growth can be mitigated through pharmacologic inhibition or targeted knockout of genes activated by recurrent enhancers.
2017-02-08 | GSE77737 | GEO
Project description:We recently developed high-throughput sequencing approaches, eXcision Repair sequencing (XR-seq) and Damage-seq, to generate genome-wide mapping of DNA damage formation and excision repair, respectively, with single-nucleotide resolution. Here, we adopted time-course XR-seq data to profile UV-induced excision repair dynamics, paired with Damage-seq data to quantify the overall induced DNA damage. We identified genome-wide repair hotspots that are subject to exemplified amount of repair very soon after UV irradiation. We show that such repair hotspots do not result from hypersensitivity to DNA damage and are thus not damage hotspots. We find that the earliest repair occur preferentially in promoters and enhancers from open-chromatin regions. The repair hotspots are also significantly enriched for frequently interacting regions and super-enhancers, both of which are hotspots for local chromatin interactions. We further extend the interrogation of chromatin organization to DNA replication timing and conclude that early-repair hotspots are enriched for early-replication domains. Collectively, we report genome-wide early-repair hotspots of UV-induced damage, in association with chromatin states and epigenetic compartmentalization of the human genome.
2020-04-09 | GSE148303 | GEO
Project description:Cellular differentiation involves widespread epigenetic reprogramming, including modulation of DNA methylation patterns. We have investigated DNA genome-wide methylation dynamics in embryonic stem cells, primary myoblasts, terminal differentiated myotubes and mature myofibers. About 1.000 differentially methylated regions (DMRs) have been indentified during muscle-lineage determination and terminal differentiation. As a whole, muscle lineage commitment was characterized by a major gain of DNA methylation, while muscle differentiation was accompanied by loss of DNA methylation in CpG-poor regions. Notably, hypomethylated regions in muscle cells were neighboured by enhancer-type chromatin, suggesting the involvement of DNA methylation in the regulation of cell-type specific enhancers. Indeed, one of the hypomethylations detected in muscle cells affected the super-enhancer of the master transcription factor Myf5. Super-enhancers have been defined as large clusters of transcriptional enhancers driving cell-identity and gene expression, but how these lineage-specific super-enhancers are specifically activated or repressed in different tissues is not well understood. We demonstrated that the binding of the transcription factor USF1 to Myf5 locus occurs upon DNA demethylation of the super-enhancer region in myogenic committed cells. Taken all together, we have characterized the unique DNA methylation signatures of muscle-committed cells and highlighted the importance of DNA methylation mediated regulation of cell identity super-enhancers. We have investigated DNA genome-wide methylation dynamics in embryonic stem cells, primary myoblasts, terminal differentiated myotubes and mature myofibers by AIMS-seq techniques and coupled to microarray expression data by SurePrint G3 Mouse 8x60K from Agilent Technologies. Samples were in triplicates, except for ESCs (quadruplicates).
2015-01-16 | E-GEOD-65037 | biostudies-arrayexpress
Project description:The master transcription factors Oct4, Sox2 and Nanog bind enhancer elements and recruit the Mediator co-activator to activate much of the gene expression program of embryonic stem cells (ESCs). We report here that the ESC master transcription factors and Mediator form “super-enhancers” at most genes known to control the pluripotent state, including those encoding the master transcription factors themselves. These super-enhancers consist of extraordinarily large genomic domains occupied by exceptional amounts of Oct4, Sox2, Nanog, Klf4, Esrrb and Mediator. Super-enhancers stimulate considerably higher transcription than typical enhancers in vivo and in reporter vectors. Reduced levels of Oct4 or Mediator cause preferential loss of expression of super-enhancer-associated genes relative to other genes, suggesting how changes in gene expression programs might be accomplished during development. In other more differentiated cells, super-enhancers containing cell-type-specific master transcription factors are also found at genes that define cell identity. These results implicate super-enhancers in the control of mammalian cell identity and differentiation. ChIP-Seq and controls associated with Super-Enhancers in murine cell types
2013-02-13 | E-GEOD-44286 | biostudies-arrayexpress
Project description:The master transcription factors Oct4, Sox2 and Nanog bind enhancer elements and recruit the Mediator co-activator to activate much of the gene expression program of embryonic stem cells (ESCs). We report here that the ESC master transcription factors and Mediator form M-bM-^@M-^\super-enhancersM-bM-^@M-^] at most genes known to control the pluripotent state, including those encoding the master transcription factors themselves. These super-enhancers consist of extraordinarily large genomic domains occupied by exceptional amounts of Oct4, Sox2, Nanog, Klf4, Esrrb and Mediator. Super-enhancers stimulate considerably higher transcription than typical enhancers in vivo and in reporter vectors. Reduced levels of Oct4 or Mediator cause preferential loss of expression of super-enhancer-associated genes relative to other genes, suggesting how changes in gene expression programs might be accomplished during development. In other more differentiated cells, super-enhancers containing cell-type-specific master transcription factors are also found at genes that define cell identity. These results implicate super-enhancers in the control of mammalian cell identity and differentiation. Time-course of gene expression following shRNA knockdown of Oct4 and Med12.
2013-02-13 | E-GEOD-44287 | biostudies-arrayexpress
Project description:Super-enhancers are principal determinants of cell transcription, development, phenotype, and oncogenesis, not yet implicated in host-pathogen interactions. We found four Epstein-Barr virus (EBV) oncoproteins and five EBV-activated NF-M-oM-^AM-+B subunits co-occupying thousand of enhancer sites in EBV-transformed lymphoblastoid cells (LCLs). Of these, 187 had markedly higher and broader histone H3K27ac signals characteristic of super-enhancer formation, and were designated M-bM-^@M-^\EBV super-enhancersM-bM-^@M-^]. EBV super-enhancer associated genes included MYC and BCL2, which enable LCL proliferation and survival. EBV super-enhancers were enriched for specific B cell transcription factor motifs and had high STAT5 and NFAT co-occupancy. EBV super-enhancer associated genes were more highly expressed than other LCL genes. Disruption of EBV super-enhancers by the bromo-domain inhibitor, JQ1, by conditional inactivation of an EBV oncoprotein or NF-M-oM-^AM-+B, decreased MYC or BCL2 gene expression and arrested LCL growth. These findings provide novel insights into the mechanisms by which EBV causes lymphoproliferation and identify opportunities for therapeutic intervention. ChIP-seq was used to define the BRD4 genome-wide landscape in GM12878 lymphoblastoid cells.
2014-11-01 | E-GEOD-62912 | biostudies-arrayexpress
Project description:The master transcription factors Oct4, Sox2 and Nanog bind enhancer elements and recruit the Mediator co-activator to activate much of the gene expression program of embryonic stem cells (ESCs). We report here that these ESC master transcription factors and Mediator form M-bM-^@M-^\super-enhancersM-bM-^@M-^] at most genes that are known to control the pluripotent state, including those encoding the master transcription factors themselves. These super-enhancers consist of extraordinarily large genomic domains occupied by exceptional amounts of Oct4 and Mediator. Super-enhancers stimulate considerably higher transcription than typical enhancers in reporter vectors. ESC differentiation causes preferential loss of expression of super-enhancer -associated genes. Super-enhancers are also found at key cell identity genes in differentiated cells. These results implicate super-enhancers in the control of mammalian cell identity and differentiation and suggest that these elements might generally be used to identify genes that control cell-type specific gene expression programs in many mammalian cells. ChIP-Seq and RNA-seq of Med1 in ZHBTc4 ES during treatment with doxycycline. ChIP-Seq data of Med1 in 38B9 pro-B cells.
2013-01-02 | E-GEOD-42474 | biostudies-arrayexpress
Project description:Super-enhancers are large clusters of transcriptional enhancers that drive expression of genes that control and define cell identity. Improved understanding of the roles super-enhancers play in biology would be afforded by knowing the constellation of factors that constitute these domains and by identifying super-enhancers across the spectrum of human cell types. We describe here the population of transcription factors, cofactors, chromatin regulators and core transcription apparatus that occupy super-enhancers in embryonic stem cells (ESCs) and evidence that super-enhancers are highly transcribed. We then use epigenomic data to produce a catalogue of super-enhancers in a broad range of human cell types. These super-enhancer domains are associated with genes encoding master transcription factors and other components that play important roles in the biology of these cells. Interestingly, sequence variation associated with a broad spectrum of diseases is especially enriched in the super-enhancers of disease-relevant cell types. Furthermore, we find that cancer cells generate super-enhancers at oncogenes and other genes that play important roles in tumor pathogenesis. We discuss these insights and their implications for future study of human health and disease. ChIP-Seq for transcription factors in mouse embryonic stem cells and H3K27ac in Jurkat T-ALL cell line RNA-Seq for mouse embryonic stem cells
2013-10-23 | E-GEOD-51522 | biostudies-arrayexpress