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Elife. 2020 Feb 17;9. pii: e52091. doi: 10.7554/eLife.52091.

ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesinSTAG1 from WAPL.

Author information

1
Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
2
The Center for Genome Architecture, Baylor College of Medicine, Houston, United States.
3
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
4
Center for Theoretical Biological Physics, Rice University, Houston, United States.
5
Department of Computer Science, Stanford University, Stanford, United States.
6
Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom.
7
Centre for Computational Biology, University of Birmingham, Birmingham, United Kingdom.
8
Departments of Computer Science and Computational and Applied Mathematics, Rice University, Houston, United States.
9
Departments of Computer Science and Genome Sciences, University of Washington, Seattle, United States.
10
Institute of Molecular Biotechnology, Vienna Biocenter (VBC), Vienna, Austria.
11
Department of Biological Science, Florida State University, Tallahassee, United States.
12
Broad Institute of MIT and Harvard, Cambridge, United States.
13
Shanghai Institute for Advanced Immunochemical Studies, Shanghai Tech University, Shanghai, China.

Abstract

Eukaryotic genomes are folded into loops. It is thought that these are formed by cohesin complexes via extrusion, either until loop expansion is arrested by CTCF or until cohesin is removed from DNA by WAPL. Although WAPL limits cohesin's chromatin residence time to minutes, it has been reported that some loops exist for hours. How these loops can persist is unknown. We show that during G1-phase, mammalian cells contain acetylated cohesinSTAG1 which binds chromatin for hours, whereas cohesinSTAG2 binds chromatin for minutes. Our results indicate that CTCF and the acetyltransferase ESCO1 protect a subset of cohesinSTAG1 complexes from WAPL, thereby enable formation of long and presumably long-lived loops, and that ESCO1, like CTCF, contributes to boundary formation in chromatin looping. Our data are consistent with a model of nested loop extrusion, in which acetylated cohesinSTAG1 forms stable loops between CTCF sites, demarcating the boundaries of more transient cohesinSTAG2 extrusion activity.

KEYWORDS:

CTCF; TADs; cell biology; chromatin structure; chromosomes; cohesin; gene expression; genome organization; human; loops

Conflict of interest statement

GW, RL, BS, RS, KN, BP, AS, WT, CV, MI, SS, Pv, XH, GD, ER, KM, ID, PF, EL, JP No competing interests declared

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