Cohesin architecture and clustering in vivo
Abstract
Cohesin helps mediate sister chromatid cohesion, chromosome condensation, DNA repair and transcription regulation. We exploited proximity-dependent labeling to define the in vivo interactions of cohesin domains with DNA or with other cohesin domains that lie within the same or in different cohesin complexes. Our results suggest both cohesin's head and hinge domains bind to DNA, and cohesin structure is dynamic with differential folding of its coiled coil regions to generate butterfly confirmations. This method also reveals that cohesins form ordered clusters on and off DNA. The levels of cohesin clusters and their distribution on chromosomes are cell cycle-regulated. Cohesin clustering is likely necessary for cohesion maintenance because clustering and maintenance uniquely require the same subset of cohesin domains and the auxiliary cohesin factor Pds5p. These conclusions provide important new mechanistic and biological insights into the architecture of the cohesin complex, cohesin-cohesin interactions, and cohesin's tethering and loop extruding activities.
Data availability
Sequencing data have been deposited in GEO as GSE157155.
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Chromosome localization of cohesin oligomers in mid-M arrested yeast cellsNCBI Gene Expression Omnibus, GSE157155.
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Cohesin residency determines chromatin loop patternsNCBI Gene Expression Omnibus, GSE151416.
Article and author information
Author details
Funding
Helen Hay Whitney Foundation
- Siheng Xiang
National Institute of General Medical Sciences (1R35 GM-118189-01)
- Douglas Koshland
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Adèle L Marston, University of Edinburgh, United Kingdom
Version history
- Received: August 18, 2020
- Accepted: February 16, 2021
- Accepted Manuscript published: February 17, 2021 (version 1)
- Version of Record published: March 4, 2021 (version 2)
Copyright
© 2021, Xiang & Koshland
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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