The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
DNA loop extrusion by human cohesin
Abstract
Eukaryotic genomes are folded into loops and topologically associating domains, which contribute to chromatin structure, gene regulation, and gene recombination. These structures depend on cohesin, a ring-shaped DNA-entrapping adenosine triphosphatase (ATPase) complex that has been proposed to form loops by extrusion. Such an activity has been observed for condensin, which forms loops in mitosis, but not for cohesin. Using biochemical reconstitution, we found that single human cohesin complexes form DNA loops symmetrically at rates up to 2.1 kilo-base pairs per second. Loop formation and maintenance depend on cohesin's ATPase activity and on NIPBL-MAU2, but not on topological entrapment of DNA by cohesin. During loop formation, cohesin and NIPBL-MAU2 reside at the base of loops, which indicates that they generate loops by extrusion. Our results show that cohesin and NIPBL-MAU2 form an active holoenzyme that interacts with DNA either pseudo-topologically or non-topologically to extrude genomic interphase DNA into loops.
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“Loop extrusion was initially proposed theoretically based on molecular dynamics simulations [342, 435] and then validated in single-molecule assays [436, 437].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [436]
In the citing paper
“loop extrusion mediated by cohesin and CTCF mediates the formation of chromatin loops and self-interacting Topologically Associating Domains (TADs)”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [82]
Citations
Cites
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
Topological 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
Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity
Ran, F. A., Hsu, P. D., Lin, C.-Y., Gootenberg, J. S., Konermann, S., Trevino, A. E., Scott, D. A., Inoue, A., Matoba, S., Zhang, Y., et al. (2013) · Cell · doi:10.1016/j.cell.2013.08.021 · Cited by 3,299
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
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
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
Sanborn, A. L., Rao, S. S. P., Huang, S.-C., Durand, N. C., Huntley, M. H., Jewett, A. I., Bochkov, I. D., Chinnappan, D., Cutkosky, A., Li, J., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1518552112 · Cited by 1,730
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
Cohesin mediates transcriptional insulation by CCCTC-binding factor
Wendt, K. S., Yoshida, K., Itoh, T., Bando, M., Koch, B., Schirghuber, E., Tsutsumi, S., Nagae, G., Ishihara, K., Mishiro, T., et al. (2008) · Nature · doi:10.1038/nature06634 · Cited by 1,193
Cohesins Functionally Associate with CTCF on Mammalian Chromosome Arms
Parelho, V., Hadjur, S., Spivakov, M., Leleu, M., Sauer, S., Gregson, H. C., Jarmuz, A., Canzonetta, C., Webster, Z., Nesterova, T., et al. (2008) · Cell · doi:10.1016/j.cell.2008.01.011 · Cited by 900
Wutz, G., Várnai, C., Nagasaka, K., Cisneros, D. A., Stocsits, R. R., Tang, W., Schoenfelder, S., Jessberger, G., Muhar, M., Hossain, M. J., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201798004 · Cited by 864
Self-citationNasmyth, K. (2001) · Annual Review of Genetics · doi:10.1146/annurev.genet.35.102401.091334 · Cited by 805
The cohesin release factor WAPL restricts chromatin loop extension
Haarhuis, J. H. I., van der Weide, R. H., Blomen, V. A., Yáñez-Cuna, J. O., Amendola, M., van Ruiten, M. S., Krijger, P. H. L., Teunissen, H., Medema, R. H., van Steensel, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.04.013 · Cited by 793
Real-time imaging of DNA loop extrusion by condensin
Ganji, M., Shaltiel, I. A., Bisht, S., Kim, E., Kalichava, A., Haering, C. H., & Dekker, C. (2018) · Science · doi:10.1126/science.aar7831 · Cited by 793
Cohesin’s binding to chromosomes depends on a separate complex consisting of Scc2 and Scc4 proteins
Ciosk, R., Shirayama, M., Shevchenko, A., Tanaka, T., Toth, A., Shevchenko, A., & Nasmyth, K. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80420-7 · Cited by 755
Cohesin relocation from sites of chromosomal loading to places of convergent transcription
Lengronne, A., Katou, Y., Mori, S., Yokobayashi, S., Kelly, G. P., Itoh, T., Watanabe, Y., Shirahige, K., & Uhlmann, F. (2004) · Nature · doi:10.1038/nature02742 · Cited by 588
Self-organization of domain structures by DNA-loop-extruding enzymes
Alipour, E., & Marko, J. F. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks925 · Cited by 540
SMC complexes: from DNA to chromosomes
Uhlmann, F. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.30 · Cited by 536
The cohesin ring concatenates sister DNA molecules
Haering, C. H., Farcas, A.-M., Arumugam, P., Metson, J., & Nasmyth, K. (2008) · Nature · doi:10.1038/nature07098 · Cited by 494
Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl
Busslinger, G. A., Stocsits, R. R., van der Lelij, P., Axelsson, E., Tedeschi, A., Galjart, N., & Peters, J.-M. (2017) · Nature · doi:10.1038/nature22063 · Cited by 468
Self-citationCharacterization of Vertebrate Cohesin Complexes and Their Regulation in Prophase
Sumara, I., Vorlaufer, E., Gieffers, C., Peters, B. H., & Peters, J. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.4.749 · Cited by 414
A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture
Gassler, J., Brandão, H. B., Imakaev, M., Flyamer, I. M., Ladstätter, S., Bickmore, W. A., Peters, J., Mirny, L. A., & Tachibana, K.-E. K. (2017) · The EMBO Journal · doi:10.15252/embj.201798083 · Cited by 382
Condensin and cohesin display different arm conformations with characteristic hinge angles
Anderson, D. E., Losada, A., Erickson, H., & Hirano, T. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200111002 · Cited by 378
Wapl is an essential regulator of chromatin structure and chromosome segregation
Tedeschi, A., Wutz, G., Huet, S., Jaritz, M., Wuensche, A., Schirghuber, E., Davidson, I. F., Tang, W., Cisneros, D. A., Bhaskara, V., et al. (2013) · Nature · doi:10.1038/nature12471 · Cited by 359
Biochemical reconstitution of topological DNA binding by the cohesin ring
Murayama, Y., & Uhlmann, F. (2013) · Nature · doi:10.1038/nature12867 · Cited by 323
Compaction and segregation of sister chromatids via active loop extrusion
Goloborodko, A. A., Imakaev, M., Marko, J. F., & Mirny, L. A. (2016) · eLife · doi:10.7554/elife.14864 · Cited by 317
Strunnikov, A. V., Larionov, V., & Koshland, D. E. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.123.6.1635 · Cited by 312
Bacillus subtilis SMC complexes juxtapose chromosome arms as they travel from origin to terminus
Wang, X., Brandão, H. B., Le, T. B. K., Laub, M. T., & Rudner, D. Z. (2017) · Science · doi:10.1126/science.aai8982 · Cited by 293
The condensin complex is a mechanochemical motor that translocates along DNA
Terakawa, T., Bisht, S., Eeftens, J., Dekker, C., Haering, C., & Greene, E. (2017) · Science · doi:10.1126/science.aan6516 · Cited by 269
Rapid movement and transcriptional re-localization of human cohesin on DNA
Davidson, I. F., Goetz, D., Zaczek, M. P., Molodtsov, M. I., Huis in 't Veld, P. J., Weissmann, F., Litos, G., Cisneros, D. A., Ocampo‐Hafalla, M., Ladurner, R., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201695402 · Cited by 246
Cuartero, S., Weiss, F. D., Dharmalingam, G., Guo, Y., Ing-Simmons, E., Masella, S., Robles-Rebollo, I., Xiao, X., Wang, Y.-F., Barozzi, I., et al. (2018) · Nature Immunology · doi:10.1038/s41590-018-0184-1 · Cited by 210
Releasing cohesin from chromosome arms in early mitosis: opposing actions of Wapl–Pds5 and Sgo1
Shintomi, K., & Hirano, T. (2009) · Genes & Development · doi:10.1101/gad.1844309 · Cited by 203
Recruitment of Xenopus Scc2 and cohesin to chromatin requires the pre-replication complex
Takahashi, T. S., Yiu, P., Chou, M. F., Gygi, S. P., & Walter, J. C. (2004) · Nature Cell Biology · doi:10.1038/ncb1177 · Cited by 201
Scc2 Is a Potent Activator of Cohesin’s ATPase that Promotes Loading by Binding Scc1 without Pds5
Petela, N. J., Gligoris, T. G., Metson, J., Lee, B., Voulgaris, M., Hu, B., Kikuchi, S., Chapard, C., Chen, W., Rajendra, E., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.05.022 · Cited by 196
Characterization of a DNA exit gate in the human cohesin ring
Veld, P. J. H. I. ’., Herzog, F., Ladurner, R., Davidson, I. F., Piric, S., Kreidl, E., Bhaskara, V., Aebersold, R. H., & Peters, J. (2014) · Science · doi:10.1126/science.1256904 · Cited by 189
The fundamental role of chromatin loop extrusion in physiological V(D)J recombination
Zhang, Y., Zhang, X., Ba, Z., Liang, Z., Dring, E. W., Hu, H., Lou, J., Kyritsis, N., Zurita, J., Shamim, M. S., et al. (2019) · Nature · doi:10.1038/s41586-019-1547-y · Cited by 160
Mechanism of APC/C CDC20 activation by mitotic phosphorylation
Qiao, R., Weissmann, F., Yamaguchi, M., Brown, N. G., VanderLinden, R. T., Imre, R., Jarvis, M. A., Brunner, M. R., Davidson, I. F., Litos, G., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1604929113 · Cited by 143
Srinivasan, M., Scheinost, J. C., Petela, N. J., Gligoris, T. G., Wissler, M. F., Ogushi, S., Collier, J., Voulgaris, M., Kurze, A., Chan, K., et al. (2018) · Cell · doi:10.1016/j.cell.2018.04.015 · Cited by 142
Crystal structure of the cohesin loader Scc2 and insight into cohesinopathy
Kikuchi, S., Borek, D., Otwinowski, Z., Tomchick, D. R., & Yu, H. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1611333113 · Cited by 122
Evolution of condensin and cohesin complexes driven by replacement of Kite by Hawk proteins
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Absolute quantification of cohesin, CTCF and their regulators in human cells
Holzmann, J., Politi, A. Z., Nagasaka, K., Hantsche-Grininger, M., Walther, N., Koch, B., Fuchs, J., Dürnberger, G., Tang, W., Ladurner, R., et al. (2019) · eLife · doi:10.7554/elife.46269 · Cited by 113
Scc2/Nipbl hops between chromosomal cohesin rings after loading
Rhodes, J., Mazza, D., Nasmyth, K., & Uphoff, S. (2017) · eLife · doi:10.7554/elife.30000 · Cited by 102
Structure and function of cohesin's Scc3/SA regulatory subunit
Roig, M. B., Löwe, J., Chan, K.-L., Beckouët, F., Metson, J., & Nasmyth, K. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.08.015 · Cited by 91
Pds5 promotes cohesin acetylation and stable cohesin–chromosome interaction
Vaur, S., Feytout, A., Vazquez, S., & Javerzat, J. (2012) · EMBO Reports · doi:10.1038/embor.2012.72 · Cited by 60
Scc2 counteracts a Wapl-independent mechanism that releases cohesin from chromosomes during G1
Srinivasan, M., Petela, N. J., Scheinost, J. C., Collier, J., Voulgaris, M., Roig, M. B., Beckouët, F., Hu, B., & Nasmyth, K. (2019) · eLife · doi:10.7554/elife.44736 · Cited by 48
Expressing Multi-subunit Complexes Using biGBac
Weissmann, F., & Peters, J. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7759-8_21 · Cited by 30
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Metadata
- Authors
- Davidson, I. F., Bauer, B., Goetz, D., Tang, W., Wutz, G., & Peters, J.-M.
- Affiliations
- Research Institute of Molecular Pathology (AT)
- Corresponding author
- Peters, Jan-Michael
- Venue
- Science
- Published
- 2019-12-13
- Volume
- 366
- Issue
- 6471
- Pages
- 1338-1345
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2991248607
- Cited by
- 863
- References
- 46
- Citations by year
- 2026: 117 · 2025: 126 · 2024: 109 · 2023: 121 · 2022: 123 · 2021: 148 · 2020: 113 · 2019: 5
- FWCI
- 32.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Boehringer Ingelheim
- European Molecular Biology Organization (Long-term Fellowship)
- H2020 European Research Council (693949)
- Human Frontier Science Program (Long-term Fellowship)
- Austrian Research Promotion Agency (FFG-852936)
- 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 › Nuclear Structure and Function
- Keywords
- cohesin, DNA loop extrusion, topologically associating domains, chromatin folding, interphase chromatin, holoenzyme, condensin
- MeSH terms
- Cohesins, Chromosomal Proteins, Non-Histone, DNA, DNA-Binding Proteins, Proton-Translocating ATPases, HeLa Cells, Humans, Nucleic Acid Conformation, Cell Cycle Proteins, Holoenzymes
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