Cohesin Loss Eliminates All Loop Domains.

Cell
Authors
Keywords
Abstract

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.

Year of Publication
2017
Journal
Cell
Volume
171
Issue
2
Pages
305-320.e24
Date Published
2017 Oct 05
ISSN
1097-4172
DOI
10.1016/j.cell.2017.09.026
PubMed ID
28985562
PubMed Central ID
PMC5846482
Links
Grant list
U01 HL130010 / HL / NHLBI NIH HHS / United States
UM1 HG009375 / HG / NHGRI NIH HHS / United States
U54 DK107967 / DK / NIDDK NIH HHS / United States
T32 GM008294 / GM / NIGMS NIH HHS / United States
DP2 OD008540 / OD / NIH HHS / United States
T32 CA009216 / CA / NCI NIH HHS / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
R01 GM055164 / GM / NIGMS NIH HHS / United States
T32 GM008307 / GM / NIGMS NIH HHS / United States
U24 CA210004 / CA / NCI NIH HHS / United States
RM1 HG006193 / HG / NHGRI NIH HHS / United States
Additional Materials