Cohesins Functionally Associate with CTCF on Mammalian Chromosome Arms
Open accessAbstract
Cohesins mediate sister chromatid cohesion, which is essential for chromosome segregation and postreplicative DNA repair. In addition, cohesins appear to regulate gene expression and enhancer-promoter interactions. These noncanonical functions remained unexplained because knowledge of cohesin-binding sites and functional interactors in metazoans was lacking. We show that the distribution of cohesins on mammalian chromosome arms is not driven by transcriptional activity, in contrast to S. cerevisiae. Instead, mammalian cohesins occupy a subset of DNase I hypersensitive sites, many of which contain sequence motifs resembling the consensus for CTCF, a DNA-binding protein with enhancer blocking function and boundary-element activity. We find cohesins at most CTCF sites and show that CTCF is required for cohesin localization to these sites. Recruitment by CTCF suggests a rationale for noncanonical cohesin functions and, because CTCF binding is sensitive to DNA methylation, allows cohesin positioning to integrate DNA sequence and epigenetic state.
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Open chromatin regions are not limited to active enhancers, and also harbour active gene promoters, regulatory elements in a poised chromatin configuration, and some structural regions such as tissue-invariant binding sites for CTCF.
“However, open chromatin regions are not limited to active enhancers, and also harbour other regions including active gene promoters, regulatory elements in a ‘poised’ chromatin configuration (discussed below), as well as some structural regions such as tissue-invariant binding sites for the architectural protein CCCTC-binding factor (CTCF) [129–132].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [132]
CTCF associates with the cohesin complex.
“A key insight into how CTCF mediates chromosomal looping was the discovery of its association with the cohesin complex [132, 334, 335].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [132]
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- Authors
- Parelho, V., Hadjur, S., Spivakov, M., Leleu, M., Sauer, S., Gregson, H. C., Jarmuz, A., Canzonetta, C., Webster, Z., Nesterova, T., Cobb, B. S., Yokomori, K., Dillon, N., Aragon, L., Fisher, A. G., & Merkenschlager, M.
- Affiliations
- Imperial College London (GB)
- University of California, Irvine (US)
- Corresponding author
- Merkenschlager, Matthias
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 132
- Issue
- 3
- Pages
- 422-433
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2028022357
- Cited by
- 900
- References
- 2
- Citations by year
- 2026: 17 · 2025: 19 · 2024: 16 · 2023: 35 · 2022: 34 · 2021: 37 · 2020: 52 · 2019: 50 · 2018: 42 · 2017: 41 · 2016: 53 · 2015: 55 · 2014: 54 · 2013: 74 · 2012: 64
- FWCI
- 34.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1993 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- RVC Research Online (Royal Veterinary College) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- China Scholarship Council
- National Institute of General Medical Sciences (R01GM059150, GM-59150)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- cohesin, CTCF, sister chromatid cohesion, chromosome arms, DNase I hypersensitive sites, enhancer-promoter interactions, enhancer blocking, DNA methylation, epigenetic regulation, gene expression regulation
- MeSH terms
- CCCTC-Binding Factor, Cohesins, Animals, Base Sequence, Cell Differentiation, Cell Line, Chromosomal Proteins, Non-Histone, Deoxyribonuclease I, DNA-Binding Proteins, Humans, Mice, Transgenic, Nuclear Proteins, Repressor Proteins, T-Lymphocytes, Gene Expression, Cytokines, Cell Cycle Proteins, Chromosomes, Mammalian, Chromatin Assembly and Disassembly, Chromatin Immunoprecipitation, Mice
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