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

  1. Gordana Wutz
  2. Rene Ladurner
  3. Brian Glenn St Hilaire
  4. Roman R Stocsits
  5. Kota Nagasaka
  6. Benoit Pignard
  7. Adrian Sanborn
  8. Wen Tang
  9. Csilla Várnai
  10. Miroslav P Ivanov
  11. Stefan Schoenfelder
  12. Petra van der Lelij
  13. Xingfan Huang
  14. Gerhard Dürnberger
  15. Elisabeth Roitinger
  16. Karl Mechtler
  17. Iain Finley Davidson
  18. Peter J Fraser
  19. Erez Lieberman-Aiden  Is a corresponding author
  20. Jan-Michael Peters  Is a corresponding author
  1. Research Institute of Molecular Pathology, Austria
  2. Baylor College of Medicine, United States
  3. Stanford University, United States
  4. University of Birmingham, United Kingdom
  5. The Francis Crick Institute, United Kingdom
  6. The Babraham Institute, United Kingdom
  7. University of Washington, United States
  8. Gregor Mendel Institute of Molecular Plant Biology, Austria
  9. Institute of Molecular Biotechnology, Austria

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.

Data availability

Sequencing data have been deposited in GEO under accession code GSE138405. Please go to https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138405

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Gordana Wutz

    Research Institute of Molecular Pathology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6842-0795
  2. Rene Ladurner

    Research Institute of Molecular Pathology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  3. Brian Glenn St Hilaire

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Roman R Stocsits

    Research Institute of Molecular Pathology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  5. Kota Nagasaka

    Research Institute of Molecular Pathology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0765-638X
  6. Benoit Pignard

    Research Institute of Molecular Pathology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  7. Adrian Sanborn

    Department of Computer Science, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Wen Tang

    Research Institute of Molecular Pathology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  9. Csilla Várnai

    Centre for Computational Biology, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Miroslav P Ivanov

    DSB Repair Metabolism, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9352-0969
  11. Stefan Schoenfelder

    Epigenetics Programme, The Babraham Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3200-8133
  12. Petra van der Lelij

    Research Institute of Molecular Pathology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  13. Xingfan Huang

    Departments of Computer Science and Genome Sciences, University of Washington, Washington, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Gerhard Dürnberger

    Gregor Mendel Institute of Molecular Plant Biology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  15. Elisabeth Roitinger

    Mechtler Laboratory, Institute of Molecular Biotechnology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  16. Karl Mechtler

    Research Institute of Molecular Pathology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  17. Iain Finley Davidson

    Research Institute of Molecular Pathology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  18. Peter J Fraser

    Nuclear Dynamics Programme, The Babraham Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  19. Erez Lieberman-Aiden

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    For correspondence
    erez@erez.com
    Competing interests
    The authors declare that no competing interests exist.
  20. Jan-Michael Peters

    Research Institute of Molecular Pathology, Vienna, Austria
    For correspondence
    Jan-Michael.Peters@imp.ac.at
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2820-3195

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

  1. Jeannie T Lee, Massachusetts General Hospital, United States

Publication history

  1. Received: September 22, 2019
  2. Accepted: February 10, 2020
  3. Accepted Manuscript published: February 17, 2020 (version 1)
  4. Version of Record published: March 3, 2020 (version 2)
  5. 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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  1. Gordana Wutz
  2. Rene Ladurner
  3. Brian Glenn St Hilaire
  4. Roman R Stocsits
  5. Kota Nagasaka
  6. Benoit Pignard
  7. Adrian Sanborn
  8. Wen Tang
  9. Csilla Várnai
  10. Miroslav P Ivanov
  11. Stefan Schoenfelder
  12. Petra van der Lelij
  13. Xingfan Huang
  14. Gerhard Dürnberger
  15. Elisabeth Roitinger
  16. Karl Mechtler
  17. Iain Finley Davidson
  18. Peter J Fraser
  19. Erez Lieberman-Aiden
  20. Jan-Michael Peters
(2020)
ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesinSTAG1 from WAPL
eLife 9:e52091.
https://doi.org/10.7554/eLife.52091

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