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Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl
Open accessAbstract
Mammalian genomes are spatially organized by CCCTC-binding factor (CTCF) and cohesin into chromatin loops and topologically associated domains, which have important roles in gene regulation and recombination. By binding to specific sequences, CTCF defines contact points for cohesin-mediated long-range chromosomal cis-interactions. Cohesin is also present at these sites, but has been proposed to be loaded onto DNA elsewhere and to extrude chromatin loops until it encounters CTCF bound to DNA. How cohesin is recruited to CTCF sites, according to this or other models, is unknown. Here we show that the distribution of cohesin in the mouse genome depends on transcription, CTCF and the cohesin release factor Wings apart-like (Wapl). In CTCF-depleted fibroblasts, cohesin cannot be properly recruited to CTCF sites but instead accumulates at transcription start sites of active genes, where the cohesin-loading complex is located. In the absence of both CTCF and Wapl, cohesin accumulates in up to 70 kilobase-long regions at 3'-ends of active genes, in particular if these converge on each other. Changing gene expression modulates the position of these 'cohesin islands'. These findings indicate that transcription can relocate mammalian cohesin over long distances on DNA, as previously reported for yeast cohesin, that this translocation contributes to positioning cohesin at CTCF sites, and that active genes can be freed from cohesin either by transcription-mediated translocation or by Wapl-mediated release.
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“Since cohesin can remain topologically engaged and slide on both naked DNA42–44 and chromatin,45,46”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [46]
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“…36 | No 24 | 2017 that cohesin’s function in gene regulation is related to CTCF, as this DNA binding protein recruits cohesin to specific sites in mammalian genomes and depends on cohesin for its ability to mediate gene regulation (Parelho et al, 2008; Wendt et al, 2008; Busslinger et al, 2017).”
InfluentialSelf-citation
Metadata
- Authors
- Busslinger, G. A., Stocsits, R. R., van der Lelij, P., Axelsson, E., Tedeschi, A., Galjart, N., & Peters, J.-M.
- Affiliations
- Research Institute of Molecular Pathology (AT)
- Erasmus MC (NL)
- Corresponding author
- Peters, Jan-Michael
- ORCID
- Venue
- Nature
- Published
- 2017-04
- Volume
- 544
- Issue
- 7651
- Pages
- 503-507
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6080695
- OpenAlex
- W2607008467
- Cited by
- 468
- References
- 51
- Citations by year
- 2026: 30 · 2025: 36 · 2024: 36 · 2023: 45 · 2022: 58 · 2021: 52 · 2020: 59 · 2019: 67 · 2018: 50 · 2017: 35
- FWCI
- 23.91
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- cohesin, CTCF, WAPL, transcription, cohesin loading, chromatin looping, topologically associating domains, 3D genome organization, transcription start sites, mouse genome, cis-interactions, gene expression regulation, recombination, mouse fibroblasts
- MeSH terms
- CCCTC-Binding Factor, Cohesins, Animals, Binding Sites, Cells, Cultured, Chromatin, Chromosomal Proteins, Non-Histone, DNA, Female, Fibroblasts, Male, Proteins, Chondroitin Sulfate Proteoglycans, Repressor Proteins, Transcription, Genetic, Genome, Cell Cycle Proteins, Protein Transport, Transcription Initiation Site, Chromosomes, Mammalian, Mice
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