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Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins
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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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“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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“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]
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“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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Cites
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382
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
Comprehensive 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
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
Juicer Provides a One-Click System for Analyzing Loop-Resolution Hi-C Experiments
Durand, N. C., Shamim, M. S., Machol, I., Rao, S. S. P., Huntley, M. H., Lander, E. S., & Aiden, E. L. (2016) · Cell Systems · doi:10.1016/j.cels.2016.07.002 · Cited by 3,860
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
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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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
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Schoenfelder, S., & Fraser, P. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0128-0 · Cited by 1,102
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Davidson, I. F., Bauer, B., Goetz, D., Tang, W., Wutz, G., & Peters, J.-M. (2019) · Science · doi:10.1126/science.aaz3418 · Cited by 863
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Zheng, H., & Xie, W. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0132-4 · Cited by 742
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Misteli, T. (2020) · Cell · doi:10.1016/j.cell.2020.09.014 · Cited by 742
“(B) TADs form via loop-extrusion generated by the cohesin motor (light blue).”
InfluentialHuman 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
Chromatin organization by an interplay of loop extrusion and compartmental segregation
Nuebler, J., Fudenberg, G., Imakaev, M., Abdennur, N. A., & Mirny, L. A. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1717730115 · Cited by 638
“The characteristic hump in contact probability scaling extends to significantly larger distances, reflecting larger loops (14).”
BackgroundInfluentialPrinciples of genome folding into topologically associating domains
Szabo, Q., Bantignies, F., & Cavalli, G. (2019) · Science Advances · doi:10.1126/sciadv.aaw1668 · Cited by 631
Transcription factors and 3D genome conformation in cell-fate decisions
Stadhouders, R., Filion, G. J. P., & Graf, T. (2019) · Nature · doi:10.1038/s41586-019-1182-7 · Cited by 530
Genome folding through loop extrusion by SMC complexes
Davidson, I. F., & Peters, J. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00349-7 · Cited by 531
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Li, Y., Haarhuis, J. H. I., Sedeño Cacciatore, Á., Oldenkamp, R., van Ruiten, M. S., Willems, L., Teunissen, H., Muir, K. W., de Wit, E., Rowland, B. D., et al. (2020) · Nature · doi:10.1038/s41586-019-1910-z · Cited by 459
Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging
Gabriele, M., Brandão, H. B., Grosse-Holz, S., Jha, A., Dailey, G. M., Cattoglio, C., Hsieh, T.-H. S., Mirny, L., Zechner, C., & Hansen, A. S. (2022) · Science · doi:10.1126/science.abn6583 · Cited by 506
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BackgroundTranscription Elongation Can Affect Genome 3D Structure
Heinz, S., Texari, L., Hayes, M. G. B., Urbanowski, M., Chang, M. W., Givarkes, N., Rialdi, A., White, K. M., Albrecht, R. A., Pache, L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.047 · Cited by 453
Extensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization
Finn, E. H., Pegoraro, G., Brandão, H. B., Valton, A.-L., Oomen, M. E., Dekker, J., Mirny, L., & Misteli, T. (2019) · Cell · doi:10.1016/j.cell.2019.01.020 · Cited by 459
Hsieh, T.-H. S., Cattoglio, C., Slobodyanyuk, E., Hansen, A. S., Darzacq, X., & Tjian, R. (2022) · Nature Genetics · doi:10.1038/s41588-022-01223-8 · Cited by 406
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Jerković, I., & Cavalli, G. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00362-w · Cited by 413
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
“Both TADs and loops were stronger in Wapl Δ compared to control zygotes (Figs 3B and EV3C; see also Tables EV1 and EV2), in agreement with what has been observed in Wapl Δ HAP1 and Wapl RNAi HeLa cells (Haarhuis et al , 2017; Wutz et al , 2017).”
BackgroundResultInfluentialSelf-citationSLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis
Muhar, M., Ebert, A., Neumann, T., Umkehrer, C., Jude, J., Wieshofer, C., Rescheneder, P., Lipp, J., Herzog, V. A., Reichholf, B., et al. (2018) · Science · doi:10.1126/science.aao2793 · Cited by 371
Self-citationHighly rearranged chromosomes reveal uncoupling between genome topology and gene expression
Ghavi-Helm, Y., Jankowski, A., Meiers, S., Viales, R. R., Korbel, J. O., & Furlong, E. E. M. (2019) · Nature Genetics · doi:10.1038/s41588-019-0462-3 · Cited by 354
Organization of Chromosomal DNA by SMC Complexes
Yatskevich, S., Rhodes, J., & Nasmyth, K. (2019) · Annual Review of Genetics · doi:10.1146/annurev-genet-112618-043633 · Cited by 349
Loop extrusion as a mechanism for formation of DNA damage repair foci
Arnould, C., Rocher, V., Finoux, A.-L., Clouaire, T., Li, K., Zhou, F., Caron, P., Mangeot, P. E., Ricci, E. P., Mourad, R., et al. (2021) · Nature · doi:10.1038/s41586-021-03193-z · Cited by 341
The relationship between genome structure and function
Oudelaar, A. M., & Higgs, D. R. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-020-00303-x · Cited by 304
Despang, A., Schöpflin, R., Franke, M., Ali, S., Jerković, I., Paliou, C., Chan, W.-L., Timmermann, B., Wittler, L., Vingron, M., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0466-z · Cited by 321
Emerging Evidence of Chromosome Folding by Loop ExtrusionPreprint
Fudenberg, G., Abdennur, N. A., Imakaev, M., Goloborodko, A. A., & Mirny, L. A. (2017) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2017.82.034710 · Cited by 298
“…of active LEFs, depletion of the cohesin loader Nipbl (Scc2) (Schwarzer et al. 2017) and acute degradation of the cohesin kleisin Rad21 (Scc1) (Wutz et al. 2017; Rao et al. 2017) during interphase led to both: (i) complete erasure of TADs and Hi-C peaks (ii) and decompaction, as evidenced by…”
BackgroundMethodInfluentialPredicting 3D genome folding from DNA sequence with Akita
Fudenberg, G., Kelley, D. R., & Pollard, K. S. (2020) · Nature Methods · doi:10.1038/s41592-020-0958-x · Cited by 300
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Hansen, A. S., Hsieh, T.-H. S., Cattoglio, C., Pustova, I., Saldaña-Meyer, R., Reinberg, D., Darzacq, X., & Tjian, R. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.07.039 · Cited by 279
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Hildebrand, E. M., & Dekker, J. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.01.002 · Cited by 284
Recent evidence that TADs and chromatin loops are dynamic structures
Hansen, A. S., Cattoglio, C., Darzacq, X., & Tjian, R. (2018) · Nucleus · doi:10.1080/19491034.2017.1389365 · Cited by 266
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Goel, V. Y., Huseyin, M. K., & Hansen, A. S. (2023) · Nature Genetics · doi:10.1038/s41588-023-01391-1 · Cited by 271
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van Steensel, B., & Furlong, E. E. M. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0114-6 · Cited by 247
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Galupa, R., & Heard, É. (2018) · Annual Review of Genetics · doi:10.1146/annurev-genet-120116-024611 · Cited by 257
Transcription shapes 3D chromatin organization by interacting with loop extrusion
Banigan, E. J., Tang, W., van den Berg, A. A., Stocsits, R. R., Wutz, G., Brandão, H. B., Busslinger, G. A., Peters, J., & Mirny, L. A. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2210480120 · Cited by 238
“While cohesin frequently colocalizes with CTCF in WT cells (6, 11, 12, 17, 53, 54), cohesin islands are not associated with CTCF sites (6), and contacts between CTCF sites are reduced in DKO (Fig.”
BackgroundMethodSelf-citationTwo major mechanisms of chromosome organization
Mirny, L. A., Imakaev, M., & Abdennur, N. A. (2019) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2019.05.001 · Cited by 232
“Consistently, an increase in cohesin activity (in Wapl knockout cells) leads to weakened compartmentalization signal [29,30,43].”
BackgroundMethodCryo-EM structure of the human cohesin-NIPBL-DNA complex
Shi, Z., Gao, H., Bai, X., & Yu, H. (2020) · Science · doi:10.1126/science.abb0981 · Cited by 228
Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome
Lu, J. Y., Chang, L., Li, T., Wang, T., Yin, Y., Zhan, G., Han, X., Zhang, K., Tao, Y., Percharde, M., et al. (2021) · Cell Research · doi:10.1038/s41422-020-00466-6 · Cited by 205
CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention
Pugacheva, E. M., Kubo, N., Loukinov, D. I., Tajmul, M., Kang, S., Kovalchuk, A. L., Strunnikov, A. V., Zentner, G. E., Ren, B., & Lobanenkov, V. V. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1911708117 · Cited by 224
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Meyer, A., Schloissnig, S., Franchini, P., Du, K., Woltering, J. M., Irisarri, I., Wong, W. Y., Nowoshilow, S., Kneitz, S., Kawaguchi, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03198-8 · Cited by 211
Molecular basis of CTCF binding polarity in genome folding
Nora, E. P., Caccianini, L., Fudenberg, G., So, K., Kameswaran, V., Nagle, A., Uebersohn, A., Hajj, B., Saux, A. L., Coulon, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19283-x · Cited by 206
Catarino, R. R., & Stark, A. (2018) · Genes & Development · doi:10.1101/gad.310367.117 · Cited by 215
“…disrupts TADs and seems to instead favor contacts within active or respressive compartments (Hou et al. 2012; Seitan et al. 2013; Zuin et al. 2014; Ing-Simmons et al. 2015; Ulianov et al. 2016; Haarhuis et al. 2017; Nora et al. 2017; Rao et al. 2017; Schwarzer et al. 2017; Wutz et al. 2017).”
BackgroundMcCord, R. P., Kaplan, N., & Giorgetti, L. (2020) · Molecular Cell · doi:10.1016/j.molcel.2019.12.021 · Cited by 220
“Formation of interactions associated with CTCF requires the cohesin complex (Hadjur et al. 2009; Rao et al. 2017; Wutz et al. 2017), which has been proposed to extrude DNA loops until it is arrested by CTCF bound to DNA in a certain orientation or other barrier proteins (Fudenberg et al.”
BackgroundCanela, A., Maman, Y., Huang, S.-Y. N., Wutz, G., Tang, W., Zagnoli-Vieira, G., Callén, E., Wong, N., Day, A., Peters, J., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.04.030 · Cited by 202
“In WAPL-deficient cells, chromatin loops are enlarged because of the increased residence time of cohesin on DNA (Haarhuis et al., 2017; Wutz et al., 2017), and we observed a concomitant increase in ETOinduced damage genome-wide (Figures S1E–S1G).”
Self-citationRegulation of single-cell genome organization into TADs and chromatin nanodomains
Szabo, Q., Donjon, A., Jerković, I., Papadopoulos, G. L., Cheutin, T., Bonev, B., Nora, E. P., Bruneau, B. G., Bantignies, F., & Cavalli, G. (2020) · Nature Genetics · doi:10.1038/s41588-020-00716-8 · Cited by 194
“In mammals, most TADs are defined by the binding of CTCF in a convergent manner at their borders and by the action of the cohesin complex 9–16 .”
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Oudelaar, A. M., Davies, J. O. J., Hanssen, L. L. P., Telenius, J. M., Schwessinger, R., Liu, Y., Brown, J. M., Downes, D. J., Chiariello, A. M., Bianco, S., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0253-2 · Cited by 196
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Davidson, I. F., Barth, R., Zaczek, M., van der Torre, J., Tang, W., Nagasaka, K., Janissen, R., Kerssemakers, J. W. J., Wutz, G., Dekker, C., et al. (2023) · Nature · doi:10.1038/s41586-023-05961-5 · Cited by 198
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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
“We therefore suggest that CTCF might block LE by somehow hindering replacement of Pds5 by Scc2, as discussed in Wutz et al. (2017).”
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Walther, N., Hossain, M. J., Politi, A., Koch, B., Kueblbeck, M., Ødegård-Fougner, Ø., Lampe, M., & Ellenberg, J. (2018) · bioRxiv · doi:10.1083/jcb.201801048 · Cited by 181
“Comparison of FWHM for the same Condensin subunit between prometa- and anaphase: CAP-D2 (p = 0.0067), CAP-D3 (p = 0.0064), CAP-H (p = 0.3966), CAP- H2 (p = 0.0391).”
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“, 2017), and HeLa (Wutz et al., 2017), we did not observe obvious punctate interactions between polycomb chromatin domains in control cells, and these sites did not interact following removal of SCC1 (HCT116 and HeLa) or removal of the cohesin loader component SCC4 (HAP1).”
BackgroundResultInfluentialHuang, H., Zhu, Q., Jussila, A., Han, Y., Bintu, B., Kern, C., Conte, M., Zhang, Y., Bianco, S., Chiariello, A. M., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00863-6 · Cited by 187
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Wutz, G., Ladurner, R., Hilaire, B. G. S., Stocsits, R. R., Nagasaka, K., Pignard, B., Sanborn, A. L., Tang, W., Várnai, C., Ivanov, M. P., et al. (2020) · eLife · doi:10.7554/elife.52091 · Cited by 173
“Third, aggregate peak analysis using loop coordinates identified in control or WAPL-depleted cells (Wutz et al., 2017) revealed that genome wide loops were weakest in STAG1-depleted cells, strongest in WAPL-depleted cells and of intermediate strength in STAG2-depleted cells (Figure S11A).”
BackgroundMethodResultInfluentialSelf-citationDistinct roles of cohesin-SA1 and cohesin-SA2 in 3D chromosome organization
Kojic, A., Cuadrado, A., Koninck, M. D., Giménez-Llorente, D., Rodríguez-Corsino, M., Goméz-López, G., Dily, F. L., Martí-Renom, M. A., & Losada, A. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0070-4 · Cited by 183
Thiecke, M. J., Wutz, G., Muhar, M., Tang, W., Bevan, S., Malysheva, V., Stocsits, R., Neumann, T., Zuber, J., Fraser, P., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107929 · Cited by 177
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Zhang, S., Übelmesser, N., Barbieri, M., & Papantonis, A. (2023) · Nature Genetics · doi:10.1038/s41588-023-01364-4 · Cited by 165
“Removing CTCF from chromatin leads to the loss of insulation at domain boundaries (Nora et al., 2017), while cohesin removal leads to the elimination of CTCF-anchored loops (Rao et al., 2017; Wutz et al, 2017).”
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“, 5 μg per ChIP), (7) MED1 (A300-793A, Bethyl Laboratories, 5 μg per ChIP), (8) H3K4me3 (pAb-003-050, Diagenode, 5 μg per ChIP), and (9) H3K27ac (ab4729, Abcam, 5 μg per ChIP).”
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Concia, L., Veluchamy, A., Ramirez-Prado, J. S., Martin-Ramirez, A., Huang, Y., Perez, M., Domenichini, S., Rodriguez-Granados, N. R., Kim, S., Blein, T., et al. (2020) · Genome Biology · doi:10.1186/s13059-020-01998-1 · Cited by 120
Rinzema, N. J., Sofiadis, K., Tjalsma, S. J. D., Verstegen, M. J. A. M., Oz, Y., Valdes-Quezada, C., Felder, A.-K., Filipovska, T., van der Elst, S., de Andrade dos Ramos, Z., et al. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00787-7 · Cited by 166
Uyehara, C. M., & Apostolou, E. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112068 · Cited by 143
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Du, Z., Zheng, H., Kawamura, Y., Zhang, K., Gassler, J., Powell, S. T., Xu, Q., Lin, Z., Xu, K., Zhou, Q., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.11.011 · Cited by 163
Topologically associating domain boundaries are required for normal genome function
Rajderkar, S., Barozzi, I., Zhu, Y., Hu, R., Zhang, Y., Li, B., Alcaina‐Caro, A., Fukuda-Yuzawa, Y., Kelman, G., Akeza, A., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-04819-w · Cited by 172
“Loss of CTCF, cohesin, or the cohesin loading factor Nipbl results in TAD disruption, while loss of cohesin release factor, Wapl, results in reinforcement of TAD boundaries 20,21 .”
Kaaij, L. J. T., Mohn, F., van der Weide, R. H., de Wit, E., & Bühler, M. (2019) · Cell · doi:10.1016/j.cell.2019.08.007 · Cited by 161
Loop extrusion: theory meets single-molecule experiments
Banigan, E. J., & Mirny, L. A. (2020) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2020.04.011 · Cited by 169
Hi-C analyses with GENOVA: a case study with cohesin variants
van der Weide, R. H., van den Brand, T., Haarhuis, J. H. I., Teunissen, H., Rowland, B. D., & de Wit, E. (2021) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqab040 · Cited by 161
Systemic Loss and Gain of Chromatin Architecture throughout Zebrafish Development
Kaaij, L. J. T., van der Weide, R. H., Ketting, R. F., & de Wit, E. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.003 · Cited by 156
Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning
Ing-Simmons, E., Vaid, R., Bing, X. Y., Levine, M., Mannervik, M., & Vaquerizas, J. M. (2021) · Nature Genetics · doi:10.1038/s41588-021-00799-x · Cited by 159
The cohesin complex in mammalian meiosis
Ishiguro, K. (2018) · Genes to Cells · doi:10.1111/gtc.12652 · Cited by 157
Dynamic reorganization of the genome shapes the recombination landscape in meiotic prophase
Patel, L., Kang, R., Rosenberg, S., Qiu, Y., Raviram, R., Chee, S., Hu, R., Ren, B., Cole, F., & Corbett, K. D. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0187-0 · Cited by 157
“Cohesin depletion causes an almost immediate loss of TADs in aggregate Hi-C data, strengthening and in some cases fragmentation of the A/B compartment structure, and the formation of multivalent enhancer clusters, or “superenhancer hubs” 20–22 .”
InfluentialDynamic chromatin organization without the 30-nm fiber
Maeshima, K., Ide, S., & Babokhov, M. (2019) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2019.02.003 · Cited by 165
Chromatin accessibility: methods, mechanisms, and biological insights
Mansisidor, A., & Risca, V. I. (2022) · Nucleus · doi:10.1080/19491034.2022.2143106 · Cited by 168
“First, the compartment associations are independent of active loop extrusion and are antagonized by it, as observed when compartment contacts appear stronger when cohesin is depleted from chromatin and appear weaker when cohesin’s stability on chromatin is enhanced [234,236,237].”
BackgroundMCM complexes are barriers that restrict cohesin-mediated loop extrusion
Dequeker, B., Scherr, M. J., Brandão, H. B., Gassler, J., Powell, S. T., Gáspár, I., Flyamer, I. M., Lalic, A., Tang, W., Stocsits, R. R., et al. (2020) · Nature · doi:10.1038/s41586-022-04730-0 · Cited by 132
Self-citationChromosome organization by one-sided and two-sided loop extrusion
Banigan, E. J., van den Berg, A. A., Brandão, H. B., Marko, J. F., & Mirny, L. A. (2020) · eLife · doi:10.7554/elife.53558 · Cited by 146
Genome control by SMC complexes
Hoencamp, C., & Rowland, B. D. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00609-8 · Cited by 147
Diverse silent chromatin states modulate genome compartmentalization and loop extrusion barriers
Spracklin, G., Abdennur, N. A., Imakaev, M., Chowdhury, N., Pradhan, S., Mirny, L. A., & Dekker, J. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00892-7 · Cited by 144
RNA polymerases as moving barriers to condensin loop extrusion
Brandão, H. B., Paul, P., van den Berg, A. A., Rudner, D. Z., Wang, X., & Mirny, L. A. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1907009116 · Cited by 143
“If eukaryotic RNAPs turn out as permeable to SMC as bacterial RNAPs, transcription in eukaryotes may not have a major effect on chromosome organization by loop extrusion, as compared to other molecules that specifically (and directionally) impede loop extrusion, like CTCF (20, 60).”
BackgroundInfluentialWapl repression by Pax5 promotes V gene recombination by Igh loop extrusion
Hill, L., Ebert, A., Jaritz, M., Wutz, G., Nagasaka, K., Tagoh, H., Kostanova‐Poliakova, D., Schindler, K., Sun, Q., Bönelt, P., et al. (2020) · Nature · doi:10.1038/s41586-020-2454-y · Cited by 143
Self-citationLiquid chromatin Hi-C characterizes compartment-dependent chromatin interaction dynamics
Belaghzal, H., Borrman, T. M., Stephens, A. D., Lafontaine, D. L. J., Venev, S. V., Weng, Z., Marko, J. F., & Dekker, J. (2021) · Nature Genetics · doi:10.1038/s41588-021-00784-4 · Cited by 136
Three-dimensional chromatin packing and positioning of plant genomes
Doğan, E. S., & Liu, C. (2018) · Nature Plants · doi:10.1038/s41477-018-0199-5 · Cited by 147
Acute depletion of CTCF directly affects MYC regulation through loss of enhancer–promoter looping
Hyle, J. W., Zhang, Y., Wright, S., Xu, B., Shao, Y., Easton, J. B., Tian, L., Feng, R., Xu, P., & Li, C. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz462 · Cited by 132
“Our data supported the recent reported data that acute loss of Ctcf does not affect nuclear compartmentalization on the multi-Mb scale, but does significantly disrupt TAD boundary integrity and enhancer–promoter looping (29,34).”
ResultDetermining cellular CTCF and cohesin abundances to constrain 3D genome models
Cattoglio, C., Pustova, I., Walther, N., Ho, J. J., Hantsche-Grininger, M., Inouye, C. J., Hossain, M. J., Dailey, G. M., Ellenberg, J., Darzacq, X., et al. (2019) · eLife · doi:10.7554/elife.40164 · Cited by 133
Self-citationPrinciples of meiotic chromosome assembly revealed in S. cerevisiae
Schalbetter, S. A., Fudenberg, G., Baxter, J., Pollard, K. S., & Neale, M. J. (2019) · Nature Communications · doi:10.1038/s41467-019-12629-0 · Cited by 140
Computer vision for pattern detection in chromosome contact maps
Matthey-Doret, C., Baudry, L., Breuer, A., Montagne, R., Guiglielmoni, N., Scolari, V. F., Jean, É., Campeas, A., Chanut, P. H., Oriol, E., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19562-7 · Cited by 133
CTCF shapes chromatin structure and gene expression in health and disease
Dehingia, B., Milewska, M., Janowski, M., & Pękowska, A. (2022) · EMBO Reports · doi:10.15252/embr.202255146 · Cited by 141
Luppino, J. M., Park, D. S., Nguyen, S. C., Lan, Y., Xu, Z., Yunker, R., & Joyce, E. F. (2020) · Nature Genetics · doi:10.1038/s41588-020-0647-9 · Cited by 122
Mitotic Chromosome Mechanics: How Cells Segregate Their Genome
Batty, P., & Gerlich, D. W. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.05.007 · Cited by 121
Principles of Chromosome Architecture Revealed by Hi-C
Eagen, K. P. (2018) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2018.03.006 · Cited by 120
“Auxin-mediated, acute protein degradation of CTCF [37,38] or cohesin [38,39] altered chromatin looping.”
BackgroundMethodInfluentialRowley, M. J., Lyu, X., Rana, V., Ando‐Kuri, M., Karns, R., Bosco, G., & Corces, V. G. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.116 · Cited by 114
“The loss of Rad21 or CTCF results in the demise of these loops (Nora et al., 2017; Rao et al., 2017; Schwarzer et al., 2017; Wutz et al., 2017).”
Aljahani, A., Hua, P., Karpinska, M. A., Quililan, K., Davies, J. O. J., & Oudelaar, A. M. (2022) · Nature Communications · doi:10.1038/s41467-022-29696-5 · Cited by 121
CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning
Ba, Z., Lou, J., Ye, A. Y., Dai, H., Dring, E. W., Lin, S. G., Jain, S., Kyritsis, N., Kieffer-Kwon, K.-R., Casellas, R. C., et al. (2020) · Nature · doi:10.1038/s41586-020-2578-0 · Cited by 115
Looping the Genome with SMC Complexes
Kim, E., Barth, R., & Dekker, C. (2023) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-032620-110506 · Cited by 96
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
“CTCF consensus binding sites are frequently oriented convergently at TAD borders (Rao et al., 2014; de Wit et al., 2015; Vietri Rudan et al., 2015) and depletion of CTCF leads to a loss of insulation between TADs (Nora et al., 2017; Wutz et al., 2017).”
BackgroundInfluentialSelf-citationConformation of sister chromatids in the replicated human genome
Mitter, M., Gasser, C., Takács, Z., Langer, C. C. H., Tang, W., Jessberger, G., Beales, C. T., Neuner, E., Ameres, S. L., Peters, J., et al. (2020) · Nature · doi:10.1038/s41586-020-2744-4 · Cited by 111
Self-citationThe solid and liquid states of chromatin
Hansen, J. C., Maeshima, K., & Hendzel, M. J. (2021) · Epigenetics & Chromatin · doi:10.1186/s13072-021-00424-5 · Cited by 118
CTCF and R-loops are boundaries of cohesin-mediated DNA looping
Zhang, H., Shi, Z., Banigan, E. J., Kim, Y., Yu, H., Bai, X., & Finkelstein, I. J. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.07.006 · Cited by 123
Emerging themes in cohesin cancer biology
Waldman, T. A. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0270-1 · Cited by 117
Condensed but liquid-like domain organization of active chromatin regions in living human cells
Nozaki, T., Shinkai, S., Ide, S., Higashi, K., Tamura, S., Shimazoe, M. A., Nakagawa, M., Suzuki, Y., Okada, Y., Sasai, M., et al. (2023) · Science Advances · doi:10.1126/sciadv.adf1488 · Cited by 110
Cohesin residency determines chromatin loop patterns
Costantino, L., Hsieh, T.-H. S., Lamothe, R. C., Darzacq, X., & Koshland, D. E. (2020) · eLife · doi:10.7554/elife.59889 · Cited by 125
The role of chromatin loop extrusion in antibody diversification
Zhang, Y., Zhang, X., Dai, H., Hu, H., & Alt, F. W. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00679-3 · Cited by 106
Chromatin topology, condensates and gene regulation: shifting paradigms or just a phase?
Mir, M., Bickmore, W. A., Furlong, E. E. M., & Narlikar, G. J. (2019) · Development · doi:10.1242/dev.182766 · Cited by 113
“If TAD formation is widely disrupted, for example through the removal or depletion of cohesin (Sofueva et al., 2013; Wutz et al., 2017; Schwarzer et al., 2017; Rao et al., 2017; Haarhuis et al., 2017) or CTCF (Nora et al., 2017), the activity of only a subset of genes is disrupted, whereas the…”
Chromatin features constrain structural variation across evolutionary timescales
Fudenberg, G., & Pollard, K. S. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1808631116 · Cited by 107
“, 2012), largely dependent on the binding of CTCF (Nora et al., 2017; Wutz et al., 2017), are structural features of the genome of much recent interest and are hypothesized to play an important role in gene regulation.”
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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