Local chromatin fiber folding represses transcription and loop extrusion in quiescent cells
- Fred Hutchinson Cancer Research Center, United States
- University of Washington, United States
- New York University, United States
- Academia Sinica, Taiwan
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
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Rpd3 drives transcriptional quiescenceNCBI Gene Expression Omnibus, GSE67151.
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Condensin-dependent chromatin condensation represses transcription globally during quiescenceNCBI Gene Expression Omnibus, GSE120905.
Article and author information
Author details
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.
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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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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