Cohesin Loss Eliminates All Loop Domains

Suhas S.P. Rao, Su Chen Huang, Brian Glenn St Hilaire, Jesse M. Engreitz, Elizabeth M. Perez, Kyong Rim Kieffer-Kwon, Adrian L. Sanborn, Sarah E. Johnstone, Gavin D. Bascom, Ivan D. Bochkov, Xingfan Huang, Muhammad S. Shamim, Jaeweon Shin, Douglass Turner, Ziyi Ye, Arina D. Omer, James T. Robinson, Tamar Schlick, Bradley E. Bernstein, Rafael Casellas & 2 others Eric S. Lander, Erez Lieberman Aiden

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)305-320.e24
JournalCell
Volume171
Issue number2
DOIs
StatePublished - Oct 5 2017

Fingerprint

Histone Code
Genes
Chromosomes
Histones
Human Genome
Transcriptional Activation
Extrusion
Chemical activation
cohesins
Recovery
Degradation

Keywords

  • 4D Nucleome
  • chromatin loops
  • cohesion
  • CTCF
  • gene regulation
  • genome architecture
  • Hi-C
  • loop extrusion
  • nuclear compartments
  • superenhancers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Rao, S. S. P., Huang, S. C., Glenn St Hilaire, B., Engreitz, J. M., Perez, E. M., Kieffer-Kwon, K. R., ... Aiden, E. L. (2017). Cohesin Loss Eliminates All Loop Domains. Cell, 171(2), 305-320.e24. https://doi.org/10.1016/j.cell.2017.09.026

Cohesin Loss Eliminates All Loop Domains. / Rao, Suhas S.P.; Huang, Su Chen; Glenn St Hilaire, Brian; Engreitz, Jesse M.; Perez, Elizabeth M.; Kieffer-Kwon, Kyong Rim; Sanborn, Adrian L.; Johnstone, Sarah E.; Bascom, Gavin D.; Bochkov, Ivan D.; Huang, Xingfan; Shamim, Muhammad S.; Shin, Jaeweon; Turner, Douglass; Ye, Ziyi; Omer, Arina D.; Robinson, James T.; Schlick, Tamar; Bernstein, Bradley E.; Casellas, Rafael; Lander, Eric S.; Aiden, Erez Lieberman.

In: Cell, Vol. 171, No. 2, 05.10.2017, p. 305-320.e24.

Research output: Contribution to journalArticle

Rao, SSP, Huang, SC, Glenn St Hilaire, B, Engreitz, JM, Perez, EM, Kieffer-Kwon, KR, Sanborn, AL, Johnstone, SE, Bascom, GD, Bochkov, ID, Huang, X, Shamim, MS, Shin, J, Turner, D, Ye, Z, Omer, AD, Robinson, JT, Schlick, T, Bernstein, BE, Casellas, R, Lander, ES & Aiden, EL 2017, 'Cohesin Loss Eliminates All Loop Domains', Cell, vol. 171, no. 2, pp. 305-320.e24. https://doi.org/10.1016/j.cell.2017.09.026
Rao SSP, Huang SC, Glenn St Hilaire B, Engreitz JM, Perez EM, Kieffer-Kwon KR et al. Cohesin Loss Eliminates All Loop Domains. Cell. 2017 Oct 5;171(2):305-320.e24. https://doi.org/10.1016/j.cell.2017.09.026
Rao, Suhas S.P. ; Huang, Su Chen ; Glenn St Hilaire, Brian ; Engreitz, Jesse M. ; Perez, Elizabeth M. ; Kieffer-Kwon, Kyong Rim ; Sanborn, Adrian L. ; Johnstone, Sarah E. ; Bascom, Gavin D. ; Bochkov, Ivan D. ; Huang, Xingfan ; Shamim, Muhammad S. ; Shin, Jaeweon ; Turner, Douglass ; Ye, Ziyi ; Omer, Arina D. ; Robinson, James T. ; Schlick, Tamar ; Bernstein, Bradley E. ; Casellas, Rafael ; Lander, Eric S. ; Aiden, Erez Lieberman. / Cohesin Loss Eliminates All Loop Domains. In: Cell. 2017 ; Vol. 171, No. 2. pp. 305-320.e24.
@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, chromatin loops, cohesion, CTCF, gene regulation, genome architecture, Hi-C, 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}",
year = "2017",
month = "10",
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",

}

TY - JOUR

T1 - Cohesin Loss Eliminates All Loop Domains

AU - Rao, Suhas S.P.

AU - Huang, Su Chen

AU - Glenn St Hilaire, Brian

AU - Engreitz, Jesse M.

AU - Perez, Elizabeth M.

AU - Kieffer-Kwon, Kyong Rim

AU - Sanborn, Adrian L.

AU - Johnstone, Sarah E.

AU - Bascom, Gavin D.

AU - Bochkov, Ivan D.

AU - Huang, Xingfan

AU - Shamim, Muhammad S.

AU - Shin, Jaeweon

AU - Turner, Douglass

AU - Ye, Ziyi

AU - Omer, Arina D.

AU - Robinson, James T.

AU - Schlick, Tamar

AU - Bernstein, Bradley E.

AU - Casellas, Rafael

AU - Lander, Eric S.

AU - Aiden, Erez Lieberman

PY - 2017/10/5

Y1 - 2017/10/5

N2 - 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.

AB - 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.

KW - 4D Nucleome

KW - chromatin loops

KW - cohesion

KW - CTCF

KW - gene regulation

KW - genome architecture

KW - Hi-C

KW - loop extrusion

KW - nuclear compartments

KW - superenhancers

UR - http://www.scopus.com/inward/record.url?scp=85030538356&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030538356&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2017.09.026

DO - 10.1016/j.cell.2017.09.026

M3 - Article

VL - 171

SP - 305-320.e24

JO - Cell

JF - Cell

SN - 0092-8674

IS - 2

ER -