Cohesin Disrupts Polycomb-Dependent Chromosome Interactions in Embryonic Stem Cells
Open accessAbstract
How chromosome organization is related to genome function remains poorly understood. Cohesin, loop extrusion, and CCCTC-binding factor (CTCF) have been proposed to create topologically associating domains (TADs) to regulate gene expression. Here, we examine chromosome conformation in embryonic stem cells lacking cohesin and find, as in other cell types, that cohesin is required to create TADs and regulate A/B compartmentalization. However, in the absence of cohesin, we identify a series of long-range chromosomal interactions that persist. These correspond to regions of the genome occupied by the polycomb repressive system and are dependent on PRC1. Importantly, we discover that cohesin counteracts these polycomb-dependent interactions, but not interactions between super-enhancers. This disruptive activity is independent of CTCF and insulation and appears to modulate gene repression by the polycomb system. Therefore, we discover that cohesin disrupts polycomb-dependent chromosome interactions to modulate gene expression in embryonic stem cells.
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Polycomb-mediated looping is likely to work largely independently of CTCF and cohesin and is potentially even counteracted by the looping activities of these factors in ESCs.
“Polycomb-mediated looping is likely to work largely independently of CTCF and cohesin and is potentially even counteracted by the looping activities of these factors in ESCs [357].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [357]
The Introduction and Results report that Polycomb-domain interactions persist without cohesin and are strengthened when cohesin is removed, supporting independence from—and counteraction by—cohesin in ESCs. The Results section ‘Cohesin Counteracts Polycomb Chromatin Domain Interactions Independently of CTCF and Insulation’ says CTCF removal did not strengthen those interactions, so the paper does not support attributing a counteracting effect to CTCF. Page numbers were not provided in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn mammals, PcG-associated promoters and enhancers engage in multitudes of looping contacts, particularly in early development.
“In mammals, PcG-associated promoters and enhancers also engage in multitudes of looping contacts, particularly in early development [139, 141, 276, 357].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [357]
The Results (‘Cohesin-Independent Chromosomal Interactions Exist in ESCs’; page unavailable) report numerous Polycomb-associated interactions in embryonic stem cells, but say the interacting domains were mostly associated with promoters. They note that Polycomb domains can also be associated with enhancers without establishing that PcG-associated enhancers engage in multitudes of looping contacts. The cell-type-specific Results further find much weaker or no obvious interactions in the other mammalian cell types examined, so the broad mammalian wording exceeds this evidence. (LLM, conf=0.85)
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WAPL maintains a cohesin loading cycle to preserve cell-type-specific distal gene regulation
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Polycomb Group Proteins Regulate Chromatin Architecture in Mouse Oocytes and Early Embryos.
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Cohesin is required for long-range enhancer action at the Shh locus
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The Mediator complex regulates enhancer-promoter interactions
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- Authors
- Rhodes, J. D. P., Feldmann, A., Hernández-Rodríguez, B., Díaz, N., Brown, J. M., Fursova, N. A., Blackledge, N. P., Prathapan, P., Dobrinic, P., Huseyin, M. K., Szczurek, A., Kruse, K., Nasmyth, K. A., Buckle, V. J., Vaquerizas, J. M., & Klose, R. J.
- Affiliations
- University of Oxford (GB)
- Max Planck Institute for Molecular Biomedicine (DE)
- Corresponding author
- Vaquerizas, Juan M.
- Klose, Robert J.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 30
- Issue
- 3
- Pages
- 820-835.e10
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6988126
- OpenAlex
- W2994756760
- Cited by
- 187
- References
- 91
- Citations by year
- 2026: 16 · 2025: 28 · 2024: 28 · 2023: 24 · 2022: 34 · 2021: 30 · 2020: 24 · 2019: 3
- FWCI
- 9.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Wolfson Foundation
- Engineering and Physical Sciences Research Council
- Deutsche Forschungsgemeinschaft (VA 1456/1)
- Biotechnology and Biological Sciences Research Council
- Max-Planck-Gesellschaft
- Cancer Research UK (26747, 294401)
- European Research Council (681440)
- Lister Institute of Preventive Medicine
- Medical Research Council (MC_UU_00016/1)
- Wellcome Trust (209400/Z/17/Z)
- 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 › Epigenetics and DNA Methylation
- Keywords
- cohesin, PRC1, topologically associating domains, chromosome conformation, loop extrusion, CTCF, super-enhancers, gene repression, embryonic stem cells, chromatin organization
- MeSH terms
- CCCTC-Binding Factor, Cohesins, Animals, Cell Line, Chromatin, Chromosomal Proteins, Non-Histone, Chromosomes, Gene Expression Regulation, Male, Cell Cycle Proteins, Mice, Embryonic Stem Cells, Polycomb-Group Proteins
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