Cited by 613Genomics and Chromatin DynamicsDiffusion and Search DynamicsChromatin Remodeling and Cancer

CTCF and cohesin regulate chromatin loop stability with distinct dynamics

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Hansen, Anders S, Pustova, Iryna, Cattoglio, Claudia, Tjian, Robert, Darzacq, Xavier·2017·eLife

Published version of a preprint

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.

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  • Cohesin-mediated chromatin loops are dynamic structures that continuously form and fall apart throughout the cell cycle.

    “we propose that cohesin-mediated chromatin loops are dynamic structures that continuously form and fall apart throughout the cell cycle”
  • The ΔWAPL Hi-C studies support our conclusion that CTCF binds more dynamically than cohesin.

    “Thus, the ΔWAPL Hi-C studies12,14,15 support our conclusion that CTCF binds more dynamically than cohesin.7”

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Authors
Hansen, A. S., Pustova, I., Cattoglio, C., Tjian, R., & Darzacq, X.
Affiliations
  • Howard Hughes Medical Institute (US)
  • University of California, Berkeley (US)
Corresponding author
  • Tjian, Robert
  • Darzacq, Xavier
Venue
eLife
Published
2017-05-03
Volume
6
ISSN
2050-084X (ISSN-L)
OpenAlex
W2567008309
Cited by
613
References
84
Citations by year
2026: 50 · 2025: 54 · 2024: 61 · 2023: 69 · 2022: 82 · 2021: 89 · 2020: 75 · 2019: 56 · 2018: 57 · 2017: 20
FWCI
23.45
Type
journal article
Language
en
Open access
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Siebel Stem Cell Institute
  • Howard Hughes Medical Institute (003061)
  • California Institute of Regenerative Medicine (LA1-08013)
  • National Institutes of Health (UO1-EB021236, U54-DK107980)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
CTCF, cohesin, chromatin looping, loop stability, chromatin folding, 3D genome organization, protein-protein complex, cell cycle, gene expression regulation, insulator proteins
MeSH terms
CCCTC-Binding Factor, Cohesins, Animals, Cells, Cultured, Chromatin, Chromosomal Proteins, Non-Histone, Kinetics, Protein Binding, Cell Cycle Proteins, Protein Interaction Mapping, Mice

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