RSC primes the quiescent genome for hypertranscription upon cell cycle re-entry
- Fred Hutchinson Cancer Research Center, United States
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.
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RSC primes the quiescent genome for hypertranscription upon cell cycle re-entrNCBI Gene Expression Omnibus under the accession number, GSE166789.
Article and author information
Author details
Christine E Cucinotta
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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RSC primes the quiescent genome for hypertranscription upon cell cycle re-entry
eLife 10:e67033.
https://doi.org/10.7554/eLife.67033
