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Publication

Cohesin Loss Eliminates All Loop Domains.

Cell | 2017

The human genome folds to create thousands of intervals, called "contact domains," that exhibit enhanced contact frequency within themselves. "Loop domains" form because of tethering between two loci-almost always bound by CTCF and cohesin-lying on the same chromosome. "Compartment domains" form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes. In particular, cohesin loss causes superenhancers to co-localize, forming hundreds of links within and across chromosomes and affecting the regulation of nearby genes. We then restore cohesin and monitor the re-formation of each loop. Although re-formation rates vary greatly, many megabase-sized loops recovered in under an hour, consistent with a model where loop extrusion is rapid.

Pubmed ID: 28985562 RIS Download

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Associated grants

Agency: NHLBI NIH HHS, United States
Id: U01 HL130010
Agency: NHGRI NIH HHS, United States
Id: UM1 HG009375
Agency: NIDDK NIH HHS, United States
Id: U54 DK107967
Agency: NIGMS NIH HHS, United States
Id: T32 GM008294
Agency: NIH HHS, United States
Id: DP2 OD008540
Agency: NCI NIH HHS, United States
Id: T32 CA009216
Agency: NHGRI NIH HHS, United States
Id: P50 HG006193
Agency: NIGMS NIH HHS, United States
Id: R01 GM055164
Agency: NIGMS NIH HHS, United States
Id: T32 GM008307
Agency: NCI NIH HHS, United States
Id: U24 CA210004
Agency: NHGRI NIH HHS, United States
Id: RM1 HG006193

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RRID:SCR_005476

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BWA (tool)

RRID:SCR_010910

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Encode (tool)

RRID:SCR_015482

Consortium to build comprehensive parts list of functional elements in human genome. This includes elements that act at protein and RNA levels, and regulatory elements that control cells and circumstances in which gene is active. Data from 2012-present.

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