CTCF and cohesin regulate chromatin loop stability with distinct dynamics

Abstract
Data availability
Article and author information
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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

The following data sets were generated

(2017) Nuclear organization and dynamics of CTCF and cohesin
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE90994).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE90994

The following previously published data sets were used

1. Nitzsche A
2. Paszkowski-Rogacz M
(2011) he Cohesin Complex Cooperates with Pluripotency Transcription Factors in the Maintenance of Embryonic Stem Cell Identity
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE24030).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE24030
1. Handoko L
2. Xu H
3. Li G
4. Ruan Y
5. Wei C
(2011) CTCF-Mediated Functional Chromatin Interactome in Pluripotent Cells
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE28247).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE28247
1. Shen Y
2. Yue F
3. Ren B
(2012) A draft map of cis-regulatory sequences in the mouse genome [ChIP-Seq]
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE29218).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE29218

Article and author information

Author details

Anders S Hansen

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0001-7540-7858
Iryna Pustova

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Claudia Cattoglio

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Robert Tjian

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
Robert Tjian, President of the Howard Hughes Medical Institute (2009-present), one of the three founding funders of eLife, and a member of eLife's Board of Directors..

"This ORCID iD identifies the author of this article:" 0000-0003-0539-8217
Xavier Darzacq

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

For correspondence
darzacq@berkeley.edu

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0003-2537-8395

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.

Copyright

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.