@article{34c8690c0e214a7a95e951570441777a,
title = "Cohesin Loss Eliminates All Loop Domains",
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. Mapping the nucleome in 4D during cohesin loss and recovery reveals that cohesin degradation eliminates loop domains but has only modest transcriptional consequences.",
keywords = "4D Nucleome, CTCF, Hi-C, chromatin loops, cohesion, gene regulation, genome architecture, loop extrusion, nuclear compartments, superenhancers",
author = "Rao, {Suhas S.P.} and Huang, {Su Chen} and {Glenn St Hilaire}, Brian and Engreitz, {Jesse M.} and Perez, {Elizabeth M.} and Kieffer-Kwon, {Kyong Rim} and Sanborn, {Adrian L.} and Johnstone, {Sarah E.} and Bascom, {Gavin D.} and Bochkov, {Ivan D.} and Xingfan Huang and Shamim, {Muhammad S.} and Jaeweon Shin and Douglass Turner and Ziyi Ye and Omer, {Arina D.} and Robinson, {James T.} and Tamar Schlick and Bernstein, {Bradley E.} and Rafael Casellas and Lander, {Eric S.} and Aiden, {Erez Lieberman}",
note = "Funding Information: This work was supported by a Paul and Daisy Soros Fellowship , a Fannie and John Hertz Foundation Fellowship , a Cornelia de Lange Syndrome Foundation grant, and a Stanford Medical Scholars Fellowship to S.S.P.R.; NIGMS award R01GM055164 to T.S.; and an NIH New Innovator Award ( 1DP2OD008540-01 ), an NSF Physics Frontier Center Grant ( PHY-1427654 , Center for Theoretical Biological Physics), the NHGRI Center for Excellence for Genomic Sciences ( HG006193 ), the Welch Foundation ( Q-1866 ), an NVIDIA Research Center Award , an IBM University Challenge Award , a Google Research Award , a Cancer Prevention Research Institute of Texas Scholar Award ( R1304 ), a McNair Medical Institute Scholar Award , an NIH 4D Nucleome Grant ( U01HL130010 ), an NIH Encyclopedia of DNA Elements Mapping Center Award ( UM1HG009375 ), and the President{\textquoteright}s Early Career Award in Science and Engineering ( 4DP2OD008540 ) to E.L.A. B.E.B. holds equity in Fulcrum Therapeutics. We thank Masato Kanemaki for sharing the HCT-116 RAD21-mAID-mClover cell line; Roger Kornberg, Olga Dudchenko, Peter Geiduschek, and Miriam Huntley for their thoughtful comments on the manuscript; Neva Durand for assistance with computation; Fabio Stossi and Hannah Johnson for assistance with microscopy; Sigrid Knemeyer, Nathaniel Musial, and Lynn Zhu for assistance with figures; and Novogene for assistance with sequencing. The experiments in this study were informed by discussions with E. Nora regarding his experiments on domain structure after CTCF degradation, and we thank him and his collaborators. All contact maps reported here can be explored interactively via Juicebox at http://www.aidenlab.org/juicebox/ . Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = oct,
day = "5",
doi = "10.1016/j.cell.2017.09.026",
language = "English (US)",
volume = "171",
pages = "305--320.e24",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}