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Control of Embryonic Stem Cell State by Mediator and Cohesin (Agilent gene expression data)

ABSTRACT: The key transcription factors that control the embryonic stem cell gene expression program have been identified, but how they function to implement this program is not well understood. While screening for genes essential for maintenance of ES cell state, we identified many components of the Mediator and Cohesin complexes. Mediator and Cohesin were found to physically and functionally connect the enhancers and core promoters of active genes. An ES cell Mediator complex was found to copurify with Cohesin and its loading factor Nipbl, and normal levels of these proteins were essential for expression of the genes they occupy and for maintenance of ES cell state. See associated publication.

ORGANISM(S): Mus musculus

SUBMITTER: Richard Young

PROVIDER: E-GEOD-22556 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Mediator and cohesin connect gene expression and chromatin architecture.

Kagey Michael H MH Newman Jamie J JJ Bilodeau Steve S Zhan Ye Y Orlando David A DA van Berkum Nynke L NL Ebmeier Christopher C CC Goossens Jesse J Rahl Peter B PB Levine Stuart S SS Taatjes Dylan J DJ Dekker Job J Young Richard A RA

Nature 20100818 7314

Transcription factors control cell-specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. Here we report that mediator and cohesin physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells. Mediat ...[more]

PMID: 20720539

Similar Datasets

Control of Embryonic Stem Cell State by Mediator and Cohesin

Project description:This SuperSeries is composed of the following subset Series: GSE22556: Control of Embryonic Stem Cell State by Mediator and Cohesin (Agilent gene expression data) GSE22562: Control of Embryonic Stem Cell State by Mediator and Cohesin (Illumina ChIP-Seq data) Refer to individual Series

2010-08-11 | E-GEOD-22557 | biostudies-arrayexpress

Control of Embryonic Stem Cell State by Mediator and Cohesin (Illumina ChIP-Seq data)

Project description:The key transcription factors that control the embryonic stem cell gene expression program have been identified, but how they function to implement this program is not well understood. While screening for genes essential for maintenance of ES cell state, we identified many components of the Mediator and Cohesin complexes. Mediator and Cohesin were found to physically and functionally connect the enhancers and core promoters of active genes. An ES cell Mediator complex was found to copurify with Cohesin and its loading factor Nipbl, and normal levels of these proteins were essential for expression of the genes they occupy and for maintenance of ES cell state. See associated publication.

2010-08-12 | E-GEOD-22562 | biostudies-arrayexpress

Cell-Type-Specific TGF-beta Signaling is Targeted to Genes that Control Cell Identity: Gene Expression

Project description:Smad3 co-occupies DNA binding sites with master transcription factors. Treated (Cy5) vs. untreated (Cy3).

2011-08-23 | E-GEOD-21608 | biostudies-arrayexpress

Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes [gene expression]

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

Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation (expression)

Project description:Transcription factors and chromatin modifiers play important roles in programming and reprogramming of cellular states during development. Much is known about the role of these regulators in gene activation, but relatively little is known about the critical process of enhancer silencing during differentiation. Here we show that the H3K4/K9 histone demethylase LSD1 plays an essential role in decommissioning enhancers during differentiation of embryonic stem cells (ESCs). LSD1 occupies enhancers of active genes critical for control of ESC state. However, LSD1 is not essential for maintenance of ESC identity. Instead, ESCs lacking LSD1 activity fail to fully differentiate and ESC-specific enhancers fail to undergo the histone demethylation events associated with differentiation. At enhancers, LSD1 is a component of the NuRD complex, which contains additional subunits that are necessary for ESC differentiation. We propose that the LSD1-NuRD complex decommissions enhancers of the pluripotency program upon differentiation, which is essential for complete shutdown of the ESC gene expression program and the transition to new cell states. This represents the expression part of the study.

2012-01-03 | E-GEOD-27714 | biostudies-arrayexpress

Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation

Project description:This SuperSeries is composed of the following subset Series: GSE27714: Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation (expression) GSE27841: Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation (ChIP-seq) Refer to individual Series

2012-01-03 | E-GEOD-27844 | biostudies-arrayexpress

The X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex specific manner [Agilent array data]

Project description:Embryogenesis requires the timely and coordinated activation of developmental regulators. It has been suggested that the recently discovered class of histone demethylases (UTX and JMJD3) that specifically target the repressive H3K27me3 modification play an important role in the activation of M-bM-^@M-^\bivalentM-bM-^@M-^] genes in response to specific developmental cues. To determine the requirements for UTX in pluripotency and development, we have generated Utx null ES cells and mutant mice. The loss of UTX had a profound effect during embryogenesis. Utx null embryos had reduced somite counts, neural tube closure defects and heart malformation which presented between E9.5 and E13.5. Unexpectedly, homozygous mutant female embryos were more severely affected than hemizygous mutant male embryos. In fact, we observed the survival of a subset of UTX-deficient males which were smaller in size and had reduced life-span. Interestingly, these animals were fertile with normal spermatogenesis. Consistent with a mid-gestation lethality, UTX null male and female ES cells gave rise to all three germ layers in teratoma assays although sex-specific differences could be observed in the activation of developmental regulators in embryoid body assays. Lastly, ChIP-seq analysis revealed an increase in H3K27me3 in Utx null male ES cells. In summary, our data demonstrate sex-specific requirements for this X-linked gene while suggesting a role for UTY during development. Keywords: Expression profiling by array Four-condition experiment, Wt (V6.5) ES vs. RA-treated Wt (V6.5) ES cells; UtxKO ES vs RA-treated UtxKO ES cells. This Series represents the Agilent microarray data only (not ChIP-Seq).

2012-07-31 | E-GEOD-39473 | biostudies-arrayexpress

Architectural protein subclasses shape 3-D organization of genomes during lineage commitment

Project description:Understanding the topological configurations of chromatin can reveal valuable insights into how the genome and epigenome act in concert to control cell fate during development. Here we generate high-resolution architecture maps across seven genomic loci in embryonic stem cells and neural progenitor cells. We observe a hierarchy of 3-D interactions that undergo marked reorganization at the sub-Mb scale during differentiation. Distinct combinations of CTCF, Mediator, and cohesin show widespread enrichment in architecture at different length scales. CTCF/cohesin anchor long-range constitutive interactions that might form the topological basis for invariant sub-domains. Conversely, Mediator/cohesin together with pioneer factors bridge short-range enhancer-promoter interactions within and between larger sub-domains. Knockdown of Smc1 or Med12 in ES cells results in disruption of spatial architecture and down-regulation of genes found in cohesin-mediated interactions. We conclude that cell type-specific chromatin organization occurs at the sub-Mb scale and that architectural proteins shape the genome in hierarchical length scales. Analysis of higher-order chromatin chromatin architecture in mouse ES cells and ES-derived NPCs. Analysis of CTCF and Smc1 occupied sites in ES-derived NPCs.

2013-05-24 | E-GEOD-36203 | biostudies-arrayexpress

Control of Embryonic Stem Cell State by Mediator and Cohesin (Illumina ChIP-Seq data)

2010-08-12 | GSE22562 | GEO

Control of Embryonic Stem Cell State by Mediator and Cohesin (Agilent gene expression data)

2010-08-12 | GSE22556 | GEO