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| Status |
Public on Dec 07, 2017 |
| Title |
Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL and PDS5 proteins |
| Organism |
Homo sapiens |
| Experiment type |
Other
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Mammalian genomes are organized into compartments, topologically-associating domains (TADs) and loops to facilitate gene regulation and other chromosomal functions. Compartments are formed by nucleosomal interactions, but how TADs and loops are generated is unknown. It has been proposed that cohesin forms these structures by extruding loops until it encounters CTCF, but direct evidence for this hypothesis is missing. Here we show that cohesin suppresses compartments but is essential for TADs and loops, that CTCF defines their boundaries, and that WAPL and its PDS5 binding partners control the length of chromatin loops. In the absence of WAPL and PDS5 proteins, cohesin passes CTCF sites with increased frequency, forms extended chromatin loops, accumulates in axial chromosomal positions (vermicelli) and condenses chromosomes to an extent normally only seen in mitosis. These results show that cohesin has an essential genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA by WAPL.
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| Overall design |
Analysis of chromatin structure by HiC and ChIP-Seq upon RNAi depletion and auxin-inducible degron (AID) systems.
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| Contributor(s) |
Stocsits RR, Wutz G |
| Citation(s) |
29217591 |
| Submission date |
Aug 21, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Roman R Stocsits |
| E-mail(s) |
roman.stocsits@imp.ac.at
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| Organization name |
IMP - Research Institute of Molecular Pathology
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| Lab |
Jan Michael Peters' Lab
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| Street address |
Campus-Vienna-Biocenter 1
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| City |
Vienna |
| ZIP/Postal code |
1030 |
| Country |
Austria |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (30)
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| GSM2747741 |
Hi-C: Wapl/Pds5A/B RNAi |
| GSM2747742 |
Hi-C: Pro-M control sync. |
| GSM2747743 |
Hi-C: S control sync. |
| GSM2747744 |
Hi-C: G2 control sync. |
| GSM2747745 |
Hi-C: Scc1-AID control + auxin, 0 min 1 |
| GSM2747746 |
Hi-C: Scc1-AID control + auxin, 15 min |
| GSM2747747 |
Hi-C: Scc1-AID control + auxin, 180 min |
| GSM2747748 |
Hi-C: Scc1-AID control + auxin, 0 min 2 |
| GSM2747749 |
Hi-C: Scc1-AID control + auxin, 120 min |
| GSM2747750 |
Hi-C: control |
| GSM2747751 |
Hi-C: CTCF-AID control + auxin, 0 min |
| GSM2747752 |
Hi-C: CTCF-AID control + auxin, 120 min |
| GSM2747753 |
Hi-C: Scc1-AID WAB + auxin, 0 min |
| GSM2747754 |
Hi-C: Scc1-AID WAB + auxin, 15 min |
| GSM2747755 |
Hi-C: Scc1-AID WAB + auxin, 180 min |
| GSM2747756 |
ChIP-Seq: SMC3 control rep1 |
| GSM2747757 |
ChIP-Seq: SMC3 control rep2 |
| GSM2747758 |
ChIP-Seq: SMC3 WAPL-depleted rep1 |
| GSM2747759 |
ChIP-Seq: SMC3 WAPL-depleted rep2 |
| GSM2747760 |
ChIP-Seq: SMC3 PDS5-depleted rep1 |
| GSM2747761 |
ChIP-Seq: SMC3 PDS5-depleted rep2 |
| GSM2747762 |
ChIP-Seq: SMC3 WAPL+PDS5-depleted rep1 |
| GSM2747763 |
ChIP-Seq: SMC3 WAPL+PDS5-depleted rep2 |
| GSM2747764 |
ChIP-Seq: CTCF control |
| GSM2747765 |
ChIP-Seq: CTCF WAPL-depleted |
| GSM2747766 |
ChIP-Seq: CTCF PDS5-depleted |
| GSM2747767 |
ChIP-Seq: CTCF WAPL-+PDS%-depleted |
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| Relations |
| BioProject |
PRJNA399157 |
| SRA |
SRP115913 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE102884_RAW.tar |
11.9 Gb |
(http)(custom) |
TAR (of HIC, WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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