1. Chromosomes and Gene Expression

RSC primes the quiescent genome for hypertranscription upon cell cycle re-entry

  1. Christine E Cucinotta
  2. Rachel H Dell
  3. Keean CA Braceros
  4. Toshio Tsukiyama  Is a corresponding author
  1. Fred Hutchinson Cancer Research Center, United States
https://doi.org/10.7554/eLife.67033
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  1. Christine E Cucinotta
  2. Rachel H Dell
  3. Keean CA Braceros
  4. Toshio Tsukiyama
(2021)
RSC primes the quiescent genome for hypertranscription upon cell cycle re-entry
eLife 10:e67033.
https://doi.org/10.7554/eLife.67033
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Abstract

Quiescence is a reversible G0 state essential for differentiation, regeneration, stem cell renewal, and immune cell activation. Necessary for long-term survival, quiescent chromatin is compact, hypoacetylated, and transcriptionally inactive. How transcription activates upon cell-cycle re-entry is undefined. Here we report robust, widespread transcription within the first minutes of quiescence exit. During quiescence, the chromatin-remodeling enzyme RSC was already bound to the genes induced upon quiescence exit. RSC depletion caused severe quiescence exit defects: a global decrease in RNA polymerase II (Pol II) loading, Pol II accumulation at transcription start sites, initiation from ectopic upstream loci, and aberrant antisense transcription. These phenomena were due to a combination of highly robust Pol II transcription and severe chromatin defects in the promoter regions and gene bodies. Together, these results uncovered multiple mechanisms by which RSC facilitates initiation and maintenance of large-scale, rapid gene expression despite a globally repressive chromatin state.

Data availability

All sequencing data are uploading on the NCBI Gene Expression Omnibus under the accession number GSE166789.

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

Article and author information

Author details

  1. Christine E Cucinotta

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9644-3126

  2. Rachel H Dell

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

  3. Keean CA Braceros

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

  4. Toshio Tsukiyama

    Basic Sciences Division, 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

NCI (T32CA009657)

  • Christine E Cucinotta

NIGMS (F32GM131554)

  • Christine E Cucinotta

NIGMS (R01 GM111428)

  • Toshio Tsukiyama

NIGMS (R35GM139429)

  • Toshio Tsukiyama

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

Copyright

© 2021, Cucinotta 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. Christine E Cucinotta
  2. Rachel H Dell
  3. Keean CA Braceros
  4. Toshio Tsukiyama
(2021)
RSC primes the quiescent genome for hypertranscription upon cell cycle re-entry
eLife 10:e67033.
https://doi.org/10.7554/eLife.67033

Share this article

https://doi.org/10.7554/eLife.67033

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