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SRX1609501: GSM2078272: Input1-4; Mus musculus; ChIP-Seq
1 ILLUMINA (NextSeq 500) run: 7.5M spots, 558M bases, 202Mb downloads

Submitted by: NCBI (GEO)
Study: The cohesin associated protein Wapal is required for proper polycomb-mediated gene silencing [Ring1b ChIP-seq]
show Abstracthide Abstract
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. Overall design: ChIP-seq for Ring1b, before or after depletion of Wapal by RNAi
Sample: Input1-4
SAMN04528747 • SRS1318971 • All experiments • All runs
Organism: Mus musculus
Library:
Instrument: NextSeq 500
Strategy: ChIP-Seq
Source: GENOMIC
Selection: ChIP
Layout: SINGLE
Construction protocol: Briefly, cells were crosslinked for 5 min at room temperature with 1% fresh formaldehyde. Reaction was quenched with glycine (125 mM final concentration) for 5 min at room temperature. Cells were lysed in 0.1% SDS lysis buffer (0.1% SDS, 1% Triton X-100, 2 mM EDTA, 20 mM Tris-HCl pH8.0,150 mM NaCl). Chromatin was sonicated to a mean size of 300-500bp. Lysed cells were cleared by centrifugation and anti-Ring1b (Active Motif 39664) was added to chromatin extracts and incubated overnight. Protein A/G Dynal beads were added for 2 hours and beads were isolated with a magnet and then washed with 0.1% SDS Lysis Buffer, Low Salt Buffer ( 0.1% SDS, 1% Triton X-100, 2mM EDTA, 20 mM Tris-HCl pH 8.0, 150 mM NaCl), LiCl Wash Buffer (250 mM LiCl, 0.5% NP-40, 0.5% Deoxycholate, 1 mM EDTA, 10 mM Tris-HCl pH 8.0), and TE x2. DNA was eluted and decrosslinked overnight at 65 oC in SDS Elution Buffer (1% SDS, 10mM EDTA, 50 mM Tris-HCl pH 8.0). The next day RNase A and proteinase K were added, and the DNA was precipitated in the presence of glycogen. DNA for downstream applications were quantitated by flourometry (Qubit, Invitrogen), and equal DNA was used for each ChIP-qPCR and normalized to sheared, non-IP’d genomic DNA (Input). NEB ChIp-seq library prep kit (cat# E7645)
Experiment attributes:
GEO Accession: GSM2078272
Links:
Runs: 1 run, 7.5M spots, 558M bases, 202Mb
Run# of Spots# of BasesSizePublished
SRR31996517,517,431558M202Mb2016-03-21

ID:
2301759

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