Local chromatin fiber folding represses transcription and loop extrusion in quiescent cells
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
-
Rpd3 drives transcriptional quiescenceNCBI Gene Expression Omnibus, GSE67151.
-
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.
Metrics
-
- 2,966
- views
-
- 497
- downloads
-
- 26
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Chromosomes and Gene Expression
Specialized magnetic beads that bind target proteins to a cryogenic electron microscopy grid make it possible to study the structure of protein complexes from dilute samples.
-
- Chromosomes and Gene Expression
The association between late replication timing and low transcription rates in eukaryotic heterochromatin is well known, yet the specific mechanisms underlying this link remain uncertain. In Saccharomyces cerevisiae, the histone deacetylase Sir2 is required for both transcriptional silencing and late replication at the repetitive ribosomal DNA (rDNA) arrays. We have previously reported that in the absence of SIR2, a de-repressed RNA PolII repositions MCM replicative helicases from their loading site at the ribosomal origin, where they abut well-positioned, high-occupancy nucleosomes, to an adjacent region with lower nucleosome occupancy. By developing a method that can distinguish activation of closely spaced MCM complexes, here we show that the displaced MCMs at rDNA origins have increased firing propensity compared to the nondisplaced MCMs. Furthermore, we found that both activation of the repositioned MCMs and low occupancy of the adjacent nucleosomes critically depend on the chromatin remodeling activity of FUN30. Our study elucidates the mechanism by which Sir2 delays replication timing, and it demonstrates, for the first time, that activation of a specific replication origin in vivo relies on the nucleosome context shaped by a single chromatin remodeler.