ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesinSTAG1 from WAPL
- Research Institute of Molecular Pathology, Austria
- Baylor College of Medicine, United States
- Stanford University, United States
- University of Birmingham, United Kingdom
- The Francis Crick Institute, United Kingdom
- The Babraham Institute, United Kingdom
- University of Washington, United States
- Gregor Mendel Institute of Molecular Plant Biology, Austria
- Institute of Molecular Biotechnology, Austria
- Cited 8
- Views 2,084
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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.
Article and author information
Author details
Stefan Schoenfelder
Jan-Michael Peters
Funding
NIH Clinical Center (5U01HL130010-05)
- Erez Lieberman-Aiden
The Austrian Science Fund (Z196-B20 Wittgenstein award)
- Jan-Michael Peters
The European community's Seventh Frame- work Programme (FP7/2007-2013 241548)
- Jan-Michael Peters
Human Frontier Science Program (RGP0057/2018)
- Jan-Michael Peters
NIH Clinical Center (5UM1HG009375-03)
- Erez Lieberman-Aiden
National Science Foundation (PHY-1427654)
- Erez Lieberman-Aiden
Horizon 2020 Framework Programme (EPIC-XS 823839)
- Karl Mechtler
Austrian Science Fund by ERA-CAPS (3686 International Project)
- Karl Mechtler
H2020 European Research Council (No 693949)
- Jan-Michael Peters
Vienna Science and Technology Fund (WWTF LS09-13)
- Jan-Michael Peters
The Austrian Science Fund (SFB F34)
- Jan-Michael Peters
Austrian Research Promotion Agency (FFG-852936)
- Jan-Michael Peters
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jeannie T Lee, Massachusetts General Hospital, United States
Publication history
- Received: September 22, 2019
- Accepted: February 10, 2020
- Accepted Manuscript published: February 17, 2020 (version 1)
- Version of Record published: March 3, 2020 (version 2)
- Version of Record updated: March 6, 2020 (version 3)
Copyright
© 2020, Wutz et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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