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Elife. 2017 May 3;6. pii: e25776. doi: 10.7554/eLife.25776.

CTCF and cohesin regulate chromatin loop stability with distinct dynamics.

Hansen AS1,2,3,4, Pustova I1,2,3,4, Cattoglio C1,2,3,4, Tjian R1,2,3,4, Darzacq X1,2,3.

Author information

1
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
2
Li Ka Shing Center for Biomedical and Health Sciences, University of California, Berkeley, Berkeley, United States.
3
CIRM Center of Excellence, University of California, Berkeley, Berkeley, United States.
4
Howard Hughes Medical Institute, University of California, Berkeley, 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 frequently break and reform throughout the cell cycle.

KEYWORDS:

CTCF; biophysics; chromosomes; cohesin; genes; genome organization; human; imaging; mouse; single-molecule; structural biology

PMID:
28467304
PMCID:
PMC5446243
DOI:
10.7554/eLife.25776
[Indexed for MEDLINE]
Free PMC Article

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