CTCF and cohesin regulate chromatin loop stability with distinct dynamics
- University of California, Berkeley, United States
Abstract
Folding of mammalian genomes into spatial domains is critical for gene regulation. The insulator protein CTCF and cohesin control domain location by folding domains into loop structures, which are widely thought to be stable. Combining genomic and biochemical approaches we show that CTCF and cohesin co-occupy the same sites and physically interact as a biochemically stable complex. However, using single-molecule imaging we find that CTCF binds chromatin much more dynamically than cohesin (~1-2 min vs. ~22 min residence time). Moreover, after unbinding, CTCF quickly rebinds another cognate site unlike cohesin for which the search process is long (~1 min vs. ~33 min). Thus, CTCF and cohesin form a rapidly exchanging "dynamic complex" rather than a typical stable complex. Since CTCF and cohesin are required for loop domain formation, our results suggest that chromatin loops are dynamic and constantly break and reform throughout the cell cycle.
Data availability
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Nuclear organization and dynamics of CTCF and cohesinPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE90994).
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he Cohesin Complex Cooperates with Pluripotency Transcription Factors in the Maintenance of Embryonic Stem Cell IdentityPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE24030).
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CTCF-Mediated Functional Chromatin Interactome in Pluripotent CellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE28247).
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A draft map of cis-regulatory sequences in the mouse genome [ChIP-Seq]Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE29218).
Article and author information
Author details
Funding
Siebel Stem Cell Institute (NA)
- Anders S Hansen
Howard Hughes Medical Institute (3061)
- Robert Tjian
California Institute of Regenerative Medicine (LA1-08013)
- Xavier Darzacq
National Institutes of Health (UO1-EB021236 U54-DK107980)
- Xavier Darzacq
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- David Sherratt, University of Oxford, United Kingdom
Publication history
- Received: February 6, 2017
- Accepted: April 30, 2017
- Accepted Manuscript published: May 3, 2017 (version 1)
- Version of Record published: May 26, 2017 (version 2)
Copyright
© 2017, Hansen 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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CTCF and cohesin regulate chromatin loop stability with distinct dynamics
eLife 6:e25776.
https://doi.org/10.7554/eLife.25776
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