The DOI matches its Crossref record; 96 of the 97 references it cites were found in a registry or an index.
Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins
Open accessPublished version of a preprint
Abstract
Mammalian genomes are spatially organized into compartments, topologically associating domains (TADs), and loops to facilitate gene regulation and other chromosomal functions. How compartments, TADs, and loops are generated is unknown. It has been proposed that cohesin forms TADs and loops by extruding chromatin loops until it encounters CTCF, but direct evidence for this hypothesis is missing. Here, we show that cohesin suppresses compartments but is required for TADs and loops, that CTCF defines their boundaries, and that the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops. In the absence of WAPL and PDS5 proteins, cohesin forms extended loops, presumably by passing CTCF sites, accumulates in axial chromosomal positions (vermicelli), and condenses chromosomes. Unexpectedly, PDS5 proteins are also required for boundary function. These results show that cohesin has an essential genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA by WAPL.
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In the citing paper
“Contacts between convergent CTCF binding sites are established by the extrusion of chromatin loops with cohesin [42,46,48,93].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [48]
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In the citing paper
“Convergent binding sites for the versatile transcription factor CTCF (CCCTC-binding factor) located at TAD borders [46] block the movement of loop extruders [47,48,49].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [48]
In the citing paper
“The CTCF Y226A F228A mutation, like CTCF depletion, only slightly affects the contact probability profile.”
From The structural basis for cohesin–CTCF-anchored loops (2020) · cites this paper as [12]
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Citations
Cites
Model-based Analysis of ChIP-Seq (MACS)
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A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
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Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome
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Juicer Provides a One-Click System for Analyzing Loop-Resolution Hi-C Experiments
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Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity
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Spatial partitioning of the regulatory landscape of the X-inactivation centre
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Mediator and cohesin connect gene expression and chromatin architecture
Kagey, M. H., Newman, J. J., Bilodeau, S., Zhan, Y., Orlando, D. A., van Berkum, N. L., Ebmeier, C. C., Goossens, J., Rahl, P. B., Levine, S. S., et al. (2010) · Nature · doi:10.1038/nature09380 · Cited by 1,939
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Organizational principles of 3D genome architecture
Rowley, M. J., & Corces, V. G. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0060-8 · Cited by 1,171
Two independent modes of chromatin organization revealed by cohesin removal
Schwarzer, W., Abdennur, N., Goloborodko, A., Pekowska, A., Fudenberg, G., Loe-Mie, Y., Fonseca, N. A., Huber, W., Haering, C. H., Mirny, L., et al. (2017) · Nature · doi:10.1038/nature24281 · Cited by 1,196
Long-range enhancer–promoter contacts in gene expression control
Schoenfelder, S., & Fraser, P. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0128-0 · Cited by 1,102
Self-citationDNA loop extrusion by human cohesin
Davidson, I. F., Bauer, B., Goetz, D., Tang, W., Wutz, G., & Peters, J.-M. (2019) · Science · doi:10.1126/science.aaz3418 · Cited by 863
Self-citationThe role of 3D genome organization in development and cell differentiation
Zheng, H., & Xie, W. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0132-4 · Cited by 742
Metadata
- Authors
- Wutz, G., Várnai, C., Nagasaka, K., Cisneros, D. A., Stocsits, R. R., Tang, W., Schoenfelder, S., Jessberger, G., Muhar, M., Hossain, M. J., Walther, N., Koch, B., Kueblbeck, M., Ellenberg, J., Zuber, J., Fraser, P., & Peters, J.
- Affiliations
- Research Institute of Molecular Pathology (AT)
- Babraham Institute (GB)
- European Molecular Biology Laboratory (DE)
- Florida State University (US)
- Corresponding author
- Peters, Jan‐Michael
- ORCID
- Venue
- The EMBO Journal
- Published
- 2017-12-07
- Volume
- 36
- Issue
- 24
- Pages
- 3573-3599
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC5730888
- OpenAlex
- W2775505403
- Cited by
- 864
- References
- 97
- Citations by year
- 2026: 83 · 2025: 77 · 2024: 102 · 2023: 97 · 2022: 119 · 2021: 127 · 2020: 112 · 2019: 87 · 2018: 49 · 2017: 11
- FWCI
- 29.61
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Boehringer Ingelheim
- Austrian Research Promotion Agency (FFG‐834223)
- UK Biotechnology and Biological Sciences Research Council (BB/J004480/1)
- European Research Council Advanced Grant (DEVOCHROMO)
- EMBO Long Term Fellowship (ALTF 1335‐2016)
- Austrian Science Fund (SFB F34, Z196‐B20)
- Human Frontier Science Program (LT001527/2017)
- 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
- topologically associating domains, chromatin looping, cohesin, CTCF, WAPL, Pds5, loop extrusion, chromatin compartments, long-range chromatin interactions, chromosome condensation, vermicelli, 3D genome organization
- MeSH terms
- CCCTC-Binding Factor, Cohesins, Carrier Proteins, Chromatin, Chromosomal Proteins, Non-Histone, Chromosomes, DNA-Binding Proteins, HeLa Cells, Humans, Nuclear Proteins, Proto-Oncogene Proteins, Transcription Factors, Genome, Human, Cell Cycle Proteins
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