Cited by 475Genomics and Chromatin DynamicsChromatin Remodeling and CancerNuclear Structure and Function

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Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl

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Busslinger, Georg A., Stocsits, Roman R., van der Lelij, Petra, Axelsson, Elin, Tedeschi, Antonio, Galjart, Niels, Peters, Jan-Michael·2017·Nature

DOI 10.1038/nature22063PMC PMC6080695

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Abstract

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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Additional file 2 of Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin
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Additional file 1 of Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin
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Additional file 1 of PDS5A and PDS5B differentially affect gene expression without altering cohesin localization across the genome
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Additional file 3 of Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin
Cuadrado, A., Giménez-Llorente, D., Koninck, M. D., Ruiz‐Torres, M., Kojic, A., Rodríguez-Corsino, M., & Losada, A. (2022) · Figshare · doi:10.6084/m9.figshare.21622965
Additional file 2 of Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection
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Additional file 2 of PDS5A and PDS5B differentially affect gene expression without altering cohesin localization across the genome
Arruda, N. L., Bryan, A. F., & Dowen, J. M. (2022) · Figshare · doi:10.6084/m9.figshare.20521075
Additional file 5 of Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin
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Additional file 3 of Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection
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Additional file 4 of Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin
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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: Busslinger, Georg A.
Stocsits, Roman R.
Axelsson, Elin
Tedeschi, Antonio
Galjart, Niels
Peters, Jan-Michael
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2017-04
Volume: 544
Issue: 7651
Pages: 503-507
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature22063
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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Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl

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