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The cohesin associated factor Wapal is required for proper polycomb-mediated gene silencing

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE63325 | GEO | 2016/03/21

SECONDARY ACCESSION(S): PRJNA267500

REPOSITORIES: GEO

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The cohesin-associated protein Wapal is required for proper Polycomb-mediated gene silencing.

Project description: Not available

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The cohesin offloading factor Wapal is required for proper polycomb-mediated gene silencing [array]

Project description:The cohesin offloading protein Wapal also acts as a polycomb factor in flies. We examined its role in transcriptional role in murine embryonic stem cells (ESCs)

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The cohesin offloading factor Wapal is required for proper polycomb-mediated gene silencing [ChIP-Seq]

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The cohesin associated protein Wapal is required for proper polycomb-mediated gene silencing [Ring1b ChIP-seq]

Project description:The cohesin complex consists of multiple core subunits that play critical roles in mitosis and transcriptional regulation. The cohesin-associated protein Wapal plays a central role in offloading cohesin to facilitate sister chromatid separation, but its role in regulating mammalian gene expression is not understood. We used embryonic stem cells (ESCs) as a model given the well-defined transcriptional regulatory circuits established through master transcription factors and epigenetic pathways that regulate their ability to maintain a pluripotent state. RNAi-mediated depletion of Wapal causes a loss of pluripotency, phenocopying loss of core cohesin subunits. Using chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq) we determine that Wapal occupies genomic sites distal to genes in combination with CTCF and core cohesin subunits such as Rad21. Interestingly, genomic sites occupied by Wapal appear enriched for cohesin, implying Wapal does not offload cohesin at regions it occupies. Wapal depletion induces derepression of Polycomb Group (PcG) target genes without altering total levels of Polycomb-mediated histone modifications, implying that PcG enzymatic activity is preserved. By integrating ChIP-seq and gene expression changes data we identify that Wapal binding is enriched at the promoters of PcG silenced genes and is required for proper Polycomb Repressive Complex 2 (PRC2) recruitment. Lastly, we demonstrate that Wapal is required for the interaction of a distal cis-regulatory element (CRE) with the c-Fos promoter. Collectively, this work indicates that Wapal plays a critical role in silencing of PcG target genes through the interaction of distal CREs with promoters.

2016-03-21 | GSE78826 | GEO

Widespread rearrangement of 3D chromatin organization underlies Polycomb-mediated stress-induced silencing

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-02-23 | E-GEOD-63518 | biostudies-arrayexpress

Wapl antagonizes cohesin binding and promotes Polycomb-group silencing in Drosophila.

Project description: Not available

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The Histone H3 Lysine 9 Methyltransferases G9a and GLP Regulate Polycomb Repressive Complex 2-Mediated Gene Silencing

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Widespread rearrangement of 3D chromatin organization underlies Polycomb-mediated stress-induced silencing

Project description:This SuperSeries is composed of the SubSeries listed below.