The DOI matches its Crossref record; 56 of the 57 references it cites were found in a registry or an index.
The Energetics and Physiological Impact of Cohesin Extrusion
Open accessAbstract
Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for hours without energy input. Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA. We also identify architectural "stripes," where a loop anchor interacts with entire domains at high frequency. Stripes often tether super-enhancers to cognate promoters, and in B cells, they facilitate Igh transcription and recombination. Stripe anchors represent major hotspots for topoisomerase-mediated lesions, which promote chromosomal translocations and cancer. In plasmacytomas, stripes can deregulate Igh-translocated oncogenes. We propose that higher organisms have coopted cohesin extrusion to enhance transcription and recombination, with implications for tumor development.
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In the citing paper
“Stripe domains tend to anchor at a single CTCF binding site (as opposed to two divergent CTCF sites in the classic case for TADs), which points towards a nearby site for the cohesin-loading factor NIPBL [456, 457].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [456]
In the citing paper
“The presence of so-called stripes or flames on Hi-C maps indicates that unidirectional extrusion from an enhancer is quite common [116,117,118].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [116]
In the citing paper
“The stripes were enriched in super enhancers (Extended Data Fig. 8a-8b), consistent with previous findings 34.”
From Subtype-specific 3D genome alteration in acute myeloid leukaemia (2022) · cites this paper as [34]
Citations
Cites
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Rao, S. S. P., Huntley, M. H., Durand, N. C., Stamenova, E. K., Bochkov, I. D., Robinson, J. T., Sanborn, A. L., Machol, I., Omer, A. D., Lander, E. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.021 · Cited by 9,212
Self-citationComprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome
Lieberman-Aiden, E., van Berkum, N. L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B. R., Sabo, P. J., Dorschner, M. O., et al. (2009) · Science · doi:10.1126/science.1181369 · Cited by 8,898
Self-citationTopological domains in mammalian genomes identified by analysis of chromatin interactions
Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J. S., & Ren, B. (2012) · Nature · doi:10.1038/nature11082 · Cited by 6,829
Spatial partitioning of the regulatory landscape of the X-inactivation centre
Nora, E. P., Lajoie, B. R., Schulz, E. G., Giorgetti, L., Okamoto, I., Servant, N., Piolot, T., van Berkum, N. L., Meisig, J., Sedat, J., et al. (2012) · Nature · doi:10.1038/nature11049 · Cited by 2,895
Disruptions of Topological Chromatin Domains Cause Pathogenic Rewiring of Gene-Enhancer Interactions
Lupiáñez, D. G., Kraft, K., Heinrich, V., Krawitz, P., Brancati, F., Klopocki, E., Horn, D., Kayserili, H., Opitz, J. M., Laxova, R., et al. (2015) · Cell · doi:10.1016/j.cell.2015.04.004 · Cited by 2,132
Formation of chromosomal domains by loop extrusion
Fudenberg, G., Imakaev, M., Lu, C., Goloborodko, A., Abdennur, N., & Mirny, L. A. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.085 · Cited by 2,003
Three-dimensional folding and functional organization principles of the Drosophila genome
Sexton, T., Yaffe, E., Kenigsberg, E., Bantignies, F., Leblanc, B., Hoichman, M., Parrinello, H., Tanay, A., & Cavalli, G. (2012) · Cell · doi:10.1016/j.cell.2012.01.010 · Cited by 1,983
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
Cohesin Loss Eliminates All Loop Domains
Rao, S. S. P., Huang, S.-C., Glenn St Hilaire, B., Engreitz, J. M., Perez, E. M., Kieffer-Kwon, K.-R., Sanborn, A. L., Johnstone, S. E., Bascom, G. D., Bochkov, I. D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.026 · Cited by 1,883
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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
New developments on the Encyclopedia of DNA Elements (ENCODE) data portal
Luo, Y., Hitz, B. C., Gabdank, I., Hilton, J. A., Kagda, M. S., Lam, B. R., Myers, Z., Sud, P., Jou, J., Lin, K. Z., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz1062 · Cited by 982
Cistrome Data Browser: expanded datasets and new tools for gene regulatory analysis
Zheng, R., Wan, C., Mei, S., Qin, Q., Wu, Q., Sun, H., Chen, C.-H., Brown, M. A., Zhang, X., Meyer, C. A., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky1094 · Cited by 908
The 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
Human cohesin compacts DNA by loop extrusion
Kim, Y., Shi, Z., Zhang, H., Finkelstein, I. J., & Yu, H. (2019) · Science · doi:10.1126/science.aaz4475 · Cited by 701
Metadata
- Authors
- Vian, L., Pękowska, A., Rao, S. S. P., Kieffer-Kwon, K.-R., Jung, S., Baranello, L., Huang, S.-C., El Khattabi, L., Dose, M., Pruett, N., Sanborn, A. L., Canela, A., Maman, Y., Oksanen, A., Resch, W., Li, X., Lee, B., Kovalchuk, A. L., Tang, Z., Nelson, S., Di Pierro, M., Cheng, R. R., Machol, I., St Hilaire, B. G., Durand, N. C., Shamim, M. S., Stamenova, E. K., Onuchic, J. N., Ruan, Y., Nussenzweig, A., Levens, D., Aiden, E. L., & Casellas, R.
- Affiliations
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (US)
- Baylor College of Medicine (US)
- National Institutes of Health (US)
- University of Connecticut (US)
- Center for Theoretical Biological Physics (US)
- Corresponding author
- Aiden, Erez Lieberman
- Casellas, Rafael
- ORCID
- Pękowska, Aleksandra
- Rao, Suhas S.P.
- Jung, Seolkyoung
- Baranello, Laura
- Dose, Marei
- Pruett, Nathanael
- Sanborn, Adrian L.
- Maman, Yaakov
- Resch, Wolfgang
- Li, Xingwang
- Lee, Byoungkoo
- Kovalchuk, Alexander L.
- Tang, Zhonghui
- Cheng, Ryan R.
- Machol, Ido
- Durand, Neva C.
- Shamim, Muhammad S.
- Onuchic, José N.
- Ruan, Yijun
- Levens, David
- Aiden, Erez Lieberman
- Casellas, Rafael
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 173
- Issue
- 5
- Pages
- 1165-1178.e20
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6251724
- OpenAlex
- W2800216985
- Cited by
- 581
- References
- 57
- Citations by year
- 2026: 48 · 2025: 57 · 2024: 63 · 2023: 65 · 2022: 68 · 2021: 90 · 2020: 78 · 2019: 80 · 2018: 32
- FWCI
- 25.16
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-09-20)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- UWA Profiles and Research Repository (UWA) (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- NIAMS, NCI
- NIAID
- NIH Helix Systems
- Paul and Daisy Soros Fellowship
- Fannie and John Hertz Foundation Fellowship
- Cornelia de Lange Syndrome Foundation
- NIH New Innovator Award (1DP2OD008540-01)
- NSF Physics Frontiers Center Award (PHY-1427654)
- NHGRI Center for Excellence for Genomic Sciences (HG006193)
- Welch Foundation (Q-1866, C-1792)
- NVIDIA Research Center Award
- IBM University Challenge Award
- Google Research Award
- Cancer Prevention Research Institute of Texas Scholar Award (R1304)
- USDA Agriculture and Food Research Initiative Grant (2017-05741)
- McNair Medical Institute Scholar Award
- NIH Encyclopedia of DNA Elements Mapping Center Award (UM1HG009375)
- President’s Early Career Award in Science and Engineering
- NSF (PHY-1427654, CHE-1614101)
- 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
- 3D genome organization, super-enhancers, chromosomal translocation, plasmacytoma, oncogene deregulation
- MeSH terms
- CCCTC-Binding Factor, Cohesins, Adenosine Triphosphate, Animals, B-Lymphocytes, Cell Line, Chromatin, Chromosomal Proteins, Non-Histone, Chromosomes, DNA-Binding Proteins, Humans, Nuclear Proteins, Phosphoproteins, Chondroitin Sulfate Proteoglycans, Transcription Factors, Transcription, Genetic, Mutagenesis, Genome, Cell Cycle Proteins, Mice
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