1. Chromosomes and Gene Expression
  2. Genetics and Genomics

Local chromatin fiber folding represses transcription and loop extrusion in quiescent cells

  1. Sarah G Swygert  Is a corresponding author
  2. Dejun Lin
  3. Stephanie Portillo-Ledesma
  4. Po-Yen Lin
  5. Dakota R Hunt
  6. Cheng-Fu Kao
  7. Tamar Schlick
  8. William S Noble
  9. Toshio Tsukiyama  Is a corresponding author
  1. Fred Hutchinson Cancer Research Center, United States
  2. University of Washington, United States
  3. New York University, United States
  4. Academia Sinica, Taiwan
https://doi.org/10.7554/eLife.72062
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  1. Sarah G Swygert
  2. Dejun Lin
  3. Stephanie Portillo-Ledesma
  4. Po-Yen Lin
  5. Dakota R Hunt
  6. Cheng-Fu Kao
  7. Tamar Schlick
  8. William S Noble
  9. Toshio Tsukiyama
(2021)
Local chromatin fiber folding represses transcription and loop extrusion in quiescent cells
eLife 10:e72062.
https://doi.org/10.7554/eLife.72062
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Abstract

A longstanding hypothesis is that chromatin fiber folding mediated by interactions between nearby nucleosomes represses transcription. However, it has been difficult to determine the relationship between local chromatin fiber compaction and transcription in cells. Further, global changes in fiber diameters have not been observed, even between interphase and mitotic chromosomes. We show that an increase in the range of local inter-nucleosomal contacts in quiescent yeast drives the compaction of chromatin fibers genome-wide. Unlike actively dividing cells, inter-nucleosomal interactions in quiescent cells require a basic patch in the histone H4 tail. This quiescence-specific fiber folding globally represses transcription and inhibits chromatin loop extrusion by condensin. These results reveal that global changes in chromatin fiber compaction can occur during cell state transitions, and establish physiological roles for local chromatin fiber folding in regulating transcription and chromatin domain formation.

Data availability

All genomics data have been deposited to GEO and are available under accession code GSE167020. Genomics and mesoscale modeling analysis scripts are publicly available on GitHub at the following address: https://github.com/sswygert/Local-Chromatin-Fiber-Folding-Represses-Transcription-and-Loop-Extrusion-in-Quiescent-Cells

The following previously published data sets were used

Article and author information

Author details

  1. Sarah G Swygert

    Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    sarah.g.swygert@gmail.com
    Competing interests
    The authors declare that no competing interests exist.

  2. Dejun Lin

    University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Stephanie Portillo-Ledesma

    New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Po-Yen Lin

    Academia Sinica, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.

  5. Dakota R Hunt

    Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Cheng-Fu Kao

    Academia Sinica, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.

  7. Tamar Schlick

    New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. William S Noble

    University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Toshio Tsukiyama

    Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    ttsukiya@fredhutch.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6478-6207

Funding

National Cancer Institute (T32CA009657)

  • Sarah G Swygert

National Institute of General Medical Sciences (R35GM139429)

  • Toshio Tsukiyama

National Institute of General Medical Sciences (F32GM120962)

  • Sarah G Swygert

National Institute of General Medical Sciences (K99GM134150)

  • Sarah G Swygert

Academia Sinica (AS-CFII-108-119)

  • Po-Yen Lin

National Institute of General Medical Sciences (R01GM055264)

  • Tamar Schlick

National Institute of General Medical Sciences (R35GM122562)

  • Tamar Schlick

National Science Foundation (2030277)

  • Tamar Schlick

National Institute of Diabetes and Digestive and Kidney Diseases (U54DK107979)

  • William S Noble

National Institute of General Medical Sciences (R01GM111428)

  • Toshio Tsukiyama

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Geeta J Narlikar, University of California, San Francisco, United States

Version history

  1. Preprint posted: November 24, 2020 (view preprint)
  2. Received: July 8, 2021
  3. Accepted: November 3, 2021
  4. Accepted Manuscript published: November 4, 2021 (version 1)
  5. Version of Record published: November 17, 2021 (version 2)

Copyright

© 2021, Swygert 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. Sarah G Swygert
  2. Dejun Lin
  3. Stephanie Portillo-Ledesma
  4. Po-Yen Lin
  5. Dakota R Hunt
  6. Cheng-Fu Kao
  7. Tamar Schlick
  8. William S Noble
  9. Toshio Tsukiyama
(2021)
Local chromatin fiber folding represses transcription and loop extrusion in quiescent cells
eLife 10:e72062.
https://doi.org/10.7554/eLife.72062

Share this article

https://doi.org/10.7554/eLife.72062

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