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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Cited by
Sorted by citations
Items 401–500 of 880
Toward precise CRISPR DNA fragment editing and predictable 3D genome engineering
Wu, Q., & Shou, J. (2020) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjaa060 · Cited by 15
“In addition, consistent with the model of cohesin ‘loop extrusion’, deletion of WAPL, a cohesin releasing factor, thus increasing cohesin enrichments on chromatin, results in a significant increase of TAD size (Gassler et al., 2017; Haarhuis et al., 2017; Wutz et al., 2017).”
BackgroundA Cohesin Traffic Pattern Genetically Linked to Gene Regulation
Valton, A.-L., Dekker, J., Venev, S. V., Mair, B., Khokhar, E. S., Pai, A. A., & Moffat, J. (2021) · HAL · Cited by 18
MoDLE: high-performance stochastic modeling of DNA loop extrusion interactions
Rossini, R., Kumar, V., Mathelier, A., Rognes, T., & Paulsen, J. (2022) · bioRxiv · doi:10.1186/s13059-022-02815-7 · Cited by 14
“Similarly, depletion of CTCF induces loss of loops and TADs [24, 27].”
BackgroundPrinciples of Meiotic Chromosome AssemblyPreprint
Schalbetter, S., Fudenberg, G., Baxter, J., Pollard, K., & Neale, M. (2018) · bioRxiv · doi:10.1101/442038 · Cited by 16
A cohesin traffic pattern genetically linked to gene regulationPreprint
Valton, A.-L., Venev, S. V., Mair, B., Khokhar, E. S., Tong, A. H. Y., Ušaj, M., Chan, K. S. K., Pai, A. A., Moffat, J., & Dekker, J. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.29.454218 · Cited by 15
“In this model, the cohesin complex dynamically extrudes loops and accumulates at sites where it gets blocked, most prominently at CTCF sites during interphase (Nora et al., 2017; Nuebler et al., 2018; Wutz et al., 2017).”
BackgroundResultBeckwith, K. S., Ødegård-Fougner, Ø., Morero, N. R., Barton, C., Schueder, F., Tang, W., Alexander, S., Peters, J. M., Jungmann, R., Birney, E., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61689-y · Cited by 13
“S5c), which is consistent with HiC data also showing a similar contact frequency after Cohesin depletion for genomic distances below 50 − 100kb 5,6 .”
InfluentialSelf-citationCis-Regulatory Control of Mammalian Sex Determination
Ridnik, M., Schoenfelder, S., & Gonen, N. (2021) · Sexual Development · doi:10.1159/000519244 · Cited by 14
“Several studies have depleted CTCF or cohesin from mammalian nuclei, and as expected, this results in significant weakening (CTCF depletion) or complete loss of TAD structures (cohesin depletion) [Haarhuis et al., 2017; Nora et al., 2017; Rao et al., 2017; Schwarzer et al., 2017; Wutz et al., 2017].”
BackgroundSelf-citationPolymer simulations guide the detection and quantification of chromatin loop extrusion by imaging
Sabaté, T., Lelandais, B., Bertrand, E., & Zimmer, C. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad034 · Cited by 13
“by depleting the CTCF protein or mutating CTCF binding sites (19,24).”
BackgroundMethodYin Yang 1 regulates cohesin complex protein SMC3 in mouse hematopoietic stem cells
Lu, Z., Wang, Y., Assumpção, A. L. F. V., Liu, P., Kopp, A., Saka, S., McIlwain, S. J., Viny, A. D., Brand, M., & Pan, X. (2024) · Blood Advances · doi:10.1182/bloodadvances.2023011411 · Cited by 15
Molecular mechanism and functional significance of Wapl interaction with the Cohesin complex
Yuan, X., Yan, L., Chen, Q., Zhu, S., Zhou, X., Zeng, L., Liu, M., He, X., Huang, J., Lü, W., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2405177121 · Cited by 13
“Loss of Wapl protein stabilizes Cohesin on chromatin, resulting in the formation of vermicelli - like chromosomes characterized by increased chromatin loop size (20, 42, 57).”
Maeshima, K. (2025) · Proceedings of the Japan Academy Series B · doi:10.2183/pjab.101.020 · Cited by 18
A (3D-Nuclear) Space Odyssey: Making Sense of Hi-C Maps
Mota-Gómez, I., & Lupiáñez, D. G. (2019) · Genes · doi:10.3390/genes10060415 · Cited by 16
“Studies depleting the cohesin-releasing factor WAPL increase the persistence of the cohesin complex on chromatin, thus providing important insights on the nature of the loop extrusion process [34,38,39].”
BackgroundInfluentialBiology and Physics of Heterochromatin-Like Domains/Complexes
Singh, P. B., Belyakin, S. N., & Laktionov, P. P. (2020) · Cells · doi:10.3390/cells9081881 · Cited by 15
Functional impact of cancer-associated cohesin variants on gene expression and cellular identity
Rittenhouse, N., Carico, Z. M., Liu, Y. F., Stefan, H. C., Arruda, N. L., Zhou, J., & Dowen, J. M. (2021) · Genetics · doi:10.1093/genetics/iyab025 · Cited by 13
“Whereas inactivation of RAD21 or NIPBL was shown to cause a strong breakdown of TADs, depletion of STAG2 caused modest reductions in the number and strength of TADs (Haarhuis et al. 2017; Rao et al. 2017; Schwarzer et al. 2017; Wutz et al. 2017; Kojic et al. 2018; Cuadrado et al. 2019).”
BackgroundA Newly Assigned Role of CTCF in Cellular Response to Broken DNAs
Kang, M. A., & Lee, J.-S. (2021) · Biomolecules · doi:10.3390/biom11030363 · Cited by 14
“This model is supported by degradation or depletion of RAD21 and CTCF loss [30,53,54].”
BackgroundMethodScourzic, L., Salataj, E., & Apostolou, E. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.669881 · Cited by 16
The two waves in single-cell 3D genomics
Ulianov, S. V., & Razin, S. V. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.05.021 · Cited by 15
Fiber-Like Organization as a Basic Principle for Euchromatin Higher-Order Structure
Zakirov, A. N., Sosnovskaya, S., Ryumina, E. D., Kharybina, E., Strelkova, O. S., Zhironkina, O. A., Golyshev, S. A., Moiseenko, A. V., & Kireev, I. I. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.784440 · Cited by 13
“Recent studies including Hi-C and single-molecule imaging suggested the dynamic nature of the loops with cohesin complex serving as both a loop-forming and a loop-maintaining factor (Gassler et al., 2017; Wutz et al., 2017; Nuebler et al., 2018; Davidson et al., 2019).”
Contribution of Immunoglobulin Enhancers to B Cell Nuclear Organization
Bruzeau, C., Cook‐Moreau, J., Pinaud, E., & Noir, S. L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.877930 · Cited by 12
“In addition to histone mark patterns that reflect the nucleosomal context, the emergence of new molecular biology approaches led to the discovery of Topologically Associated Domains (TADs) and the dynamic loop extrusion model (5).”
BackgroundThe Interplay of Transcription and Genome Topology Programs T Cell Development and Differentiation
Zhao, X., Zhu, S., Peng, W., & Xue, H. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2200625 · Cited by 14
Enhancers are genes that express organizational RNAs
Mattick, J. S. (2023) · Frontiers in RNA Research · doi:10.3389/frnar.2023.1194526 · Cited by 10
“TAD boundaries are maintained by the interplay of the Cohesin and Mediator complexes and the zinc finger “transcription factor” CTCF (Kagey et al., 2010; Lee and Iyer, 2012; Wutz et al., 2017; Hansen et al., 2018; Popay and Dixon, 2022), all of which bind RNA or RNA/DNA hybrids (Yao et al., 2010; Saldana-Meyer et al.,…”
BackgroundMarshall, A. E., Ishak, C. A., & Dick, F. A. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00452-19 · Cited by 13
Architectural proteins for the formation and maintenance of the 3D genome
Li, M., Gan, J., Sun, Y., Xu, Z., Yang, J., Sun, Y., & Li, C. (2020) · Science China Life Sciences · doi:10.1007/s11427-019-1613-3 · Cited by 15
“Consistently, NIPBL (also known as SCC2) is the major subunit of the cohesin loading complex, and its loss results in shorter loops (Gassler et al., 2017; Haarhuis et al., 2017; Wutz et al., 2017).”
BackgroundAdaptation of the AID system for stem cell and transgenic mouse research
Pryzhkova, M. V., Xu, M. J., & Jordan, P. W. (2020) · Stem Cell Research · doi:10.1016/j.scr.2020.102078 · Cited by 12
“cells have relied on random integration using viral vectors and, most recently, CRISPRCas9-mediated AAVS1 safe harbor locus targeting (Holland et al., 2012; Natsume et al., 2016; Wutz et al., 2017).”
BackgroundSingh, P., & Neumann, D. M. (2021) · Journal of Virology · doi:10.1128/jvi.00364-21 · Cited by 13
Huang, H., Zhu, Q.-S., Jussila, A. P., Han, Y., Bintu, B., Kern, C., Conte, M., Zhang, Y.-X., Bianco, S., Chiariello, A., et al. (2020) · bioRxiv · doi:10.1101/2020.07.07.192526 · Cited by 14
Emerging roles of cohesin-STAG2 in cancer
Scott, J. S., Ayadi, L. A., Epeslidou, E., van Scheppingen, R. H., Mukha, A., Kaaij, L. J. T., Lutz, C., & Preković, S. (2024) · Oncogene · doi:10.1038/s41388-024-03221-y · Cited by 15
Characterization of induced cohesin loop extrusion trajectories in living cells
Han, R., Huang, Y., Robers, M. J., Magnitov, M. D., Vaandrager, I., Allahyar, A., Verstegen, M. J. A. M., Zhang, K., de Wit, E., de Laat, W. L., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02358-0 · Cited by 20
“PDS5A is thought to restrict chromatin loop sizes by competing with and displacing NIPBL from cohesin 3,29,30 .”
Multi-Scale Imaging of the Dynamic Organization of Chromatin
Fernández, F. G., Huet, S., & Miné-Hattab, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242115975 · Cited by 13
“…strength [77]. cohesin, which results in less contact specificity within compartments and a weakening in compartmentalization strength [77] Consistent with an increased long-range interaction in cells lacking cohesin, Consistent with an increased long-range interaction in cells…”
BackgroundDNA replication and replication stress response in the context of nuclear architecture
González‐Acosta, D., & Lopes, M. (2023) · Chromosoma · doi:10.1007/s00412-023-00813-7 · Cited by 12
“…imaging experiments show that the MCM complex is a physical barrier for loop extruding cohesin (Dequeker et al. 2022), as previously shown for converging CTCF binding sites (Gassler et al. 2017; Nora et al. 2017; Wutz et al. 2017) and transcription (Jeppsson et al. 2022; Banigan et al. 2023).”
BackgroundRIF1 regulates early replication timing in murine B cells
Malzl, D., Peycheva, M., Rahjouei, A., Gnan, S., Klein, K. N., Nazarova, M., Schoeberl, U. E., Gilbert, D. M., Buonomo, S. B. C., Virgilio, M. D., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43778-y · Cited by 12
A non-canonical role of the inner kinetochore in regulating sister-chromatid cohesion at centromeres
Yan, L., Yuan, X., Liu, M., Chen, Q., Zhang, M., Xu, J., Zeng, L., Zhang, L., Huang, J., Lü, W., et al. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00104-6 · Cited by 12
“CTCF enables the formation of chromatin loops by cohesin, which can be released by Wapl (Davidson and Peters, 2021; Haarhuis et al, 2017; Hoencamp and Rowland, 2023; Wutz et al, 2017).”
PHF2 regulates genome topology and DNA replication in neural stem cells via cohesin
Feng, J., Chuah, Y. H., Liang, Y., Cipta, N. O., Zeng, Y., Warrier, T., Elfar, G. A., Yoon, J., Grinchuk, O. V., Tay, E. X. Y., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae457 · Cited by 12
“In addition, cohesin is an important regulator of topologically-associated domains (TADs) ( 4 ,5 ), which are spatially organized DNA domains that are defined by preferential contacts between loci inside the same TAD and insulation from loci in adjacent TADs.”
CTCF/RAD21 organize the ground state of chromatin–nuclear speckle association
Yu, R., Roseman, S. A., Siegenfeld, A. P., Gardner, Z., Nguyen, S. C., Tran, K. A., Joyce, E. F., Jain, R., Liau, B. B., Krantz, I. D., et al. (2025) · Nature Structural & Molecular Biology · doi:10.1038/s41594-024-01465-6 · Cited by 22
“We used a RAD21-AID system in HeLa 24 , in which endogenous RAD21 is degraded rapidly (within 1 h) after auxin treatment (validation in Extended Data Fig.”
InfluentialTwo CTCF motifs impede cohesin-mediated DNA loop extrusion
Barth, R., Janissen, R., Muras, L., van der Torre, J., Litos, G., van der Sluis, E. O., van den Berg, A., Davidson, I. F., Peters, J., & Dekker, C. (2025) · Molecular Cell · doi:10.1016/j.molcel.2025.11.001 · Cited by 14
Self-citationPredictive Polymer Models for 3D Chromosome Organization
Chiang, M., Forte, G., Gilbert, N., Marenduzzo, D., & Brackley, C. A. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-1390-0_14 · Cited by 16
S. cerevisiae Cells Can Grow without the Pds5 Cohesin Subunit
Choudhary, K., Itzkovich, Z., Alonso‐Perez, E., Bishara, H., Dunn, B. L., Sherlock, G., & Kupiec, M. (2022) · mBio · doi:10.1128/mbio.01420-22 · Cited by 13
“The loop extrusion function of Pds5 is linked to its cohesin stabilization activity (55, 56).”
BackgroundLohia, R., Fox, N., & Gillis, J. (2022) · Genome biology · doi:10.1186/s13059-022-02790-z · Cited by 11
“[60], SRP186277, SRP115913 [61], SRP157799 [62], SRP110964, SRP194362 [63], SRP151075 [64], SRP157894 [65], SRP160101, SRP157048 [66], SRP221518 [67], SRP225696 [68], ERP104251, SRP105082 [9], SRP223060 [69], SRP234897 [70], SRP250333 [71], SRP113633 [72], SRP186012 [73], SRP199225 [74], SRP107176 [75], SRP105181 [76]…”
Costea, J., Schoeberl, U. E., Malzl, D., von der Linde, M., Fitz, J., Gupta, A., Makharova, M., Goloborodko, A. A., & Pavri, R. (2022) · Molecular Cell · doi:10.1016/j.molcel.2023.01.014 · Cited by 12
Through the lens of phase separation: intrinsically unstructured protein and chromatin looping
Cai, L., & Wang, G. G. (2023) · Nucleus · doi:10.1080/19491034.2023.2179766 · Cited by 14
“[39] Wutz G, Varnai C, Nagasaka K, et al.”
BackgroundEpigenetics, Enhancer Function and 3D Chromatin Organization in Reprogramming to Pluripotency
Hörnblad, A., & Remeseiro, S. (2022) · Cells · doi:10.3390/cells11091404 · Cited by 14
A streamlined cohesin apparatus is sufficient for mitosis and meiosis in the protist Tetrahymena
Ali, E. I., Loidl, J., & Howard-Till, R. A. (2018) · Chromosoma · doi:10.1007/s00412-018-0673-x · Cited by 12
“looping supports formation of topologically associated domains (TADs) of several hundred kilobase (Gassler et al. 2017; Wutz et al. 2017; Zhan et al. 2017).”
BackgroundDefining the relative and combined contribution of CTCF and CTCFL to genomic regulationPreprint
Nishana, M., Ha, C. J., Rodriguez-Hernaez, J., Ranjbaran, A., Chio, E., Nora, E. P., Badri, S., Kloetgen, A., Bruneau, B. G., Tsirigos, A., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2019.12.14.874560 · Cited by 12
CTCF is a DNA-tension-dependent barrier to cohesin-mediated DNA loop extrusionPreprint
Davidson, I., Barth, R., Zaczek, M., van der Torre, J., Tang, W., Nagasaka, K., Janissen, R., Kerssemakers, J., Wutz, G., Dekker, C., et al. (2022) · bioRxiv · doi:10.1101/2022.09.08.507093 · Cited by 3
Self-citationChromatin insulators in gene regulation and 3D genome organization
Sultana, H., Kunar, R., & Matera, A. G. (2025) · Biochemical Society Transactions · doi:10.1042/bst20253036 · Cited by 12
“Removal of WAPL leads to stronger binding of cohesin to chromatin resulting in stronger TADs [59,60].”
De novo formation of cis-regulatory contacts in the absence of NIPBL-driven chromatin loop extrusion
Aboreden, N. G., Zhao, H., Yang, J., Shan, F., Liu, F., Hansen, A. S., Zhang, H., & Blobel, G. A. (2026) · Nature Genetics · doi:10.1038/s41588-026-02565-3 · Cited by 21
PDS5 proteins control genome architecture by limiting the lifetime of cohesin-NIPBL complexes
Wutz, G., Davidson, I. F., Banigan, E. J., Stocsits, R. R., Kawasumi, R., Tang, W., Nagasaka, K., Costantino, L., Jansen, R., Hirota, K., et al. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.03.025 · Cited by 12
Self-citationInterplay between epigenome and 3D chromatin structure
Han, M.-H., Issagulova, D., & Park, M. (2023) · BMB Reports · doi:10.5483/bmbrep.2023-0197 · Cited by 13
“Importantly, loop extrusion and compartmentalization operate through distinct mechanisms, and perturbing one may influence, though not necessarily abolish, the other (29-33).”
BackgroundLocus folding mechanisms determine modes of antigen receptor gene assembly
Allyn, B. M., Hayer, K. E., Oyeniran, C., Nganga, V. K., Lee, K. D., Mishra, B., Saçan, A., Oltz, E. M., & Bassing, C. H. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20230985 · Cited by 10
“Additional impediments to cohesin can anchor loops, including active transcription and chromatin-bound proteins other than CTCF (Busslinger et al., 2017; Jeppsson et al., 2022; Wutz et al., 2017; Zhang et al., 2019).”
BackgroundQi, S., Shi, Z., & Yu, H. (2025) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2025.102310 · Cited by 13
Developing landscapes: genome architecture during early embryogenesis
van der Weide, R. H., & de Wit, E. (2019) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2019.04.009 · Cited by 10
Stress as a Chromatin Landscape Architect
Vertii, A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.790138 · Cited by 11
“CTCF, together with cohesin, mediates long-range chromatin loops and defines TAD borders (Wutz et al., 2017).”
BackgroundFluorescence-based super-resolution-microscopy strategies for chromatin studies
Burgers, T. C. Q., & Vlijm, R. (2023) · Chromosoma · doi:10.1007/s00412-023-00792-9 · Cited by 14
The DNA-binding protein CST associates with the cohesin complex and promotes chromosome cohesion
Schuck, P. L., Ball, L. E., & Stewart, J. A. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101026 · Cited by 11
“complex is involved in organizing topologically associated domains for cellular processes such as DNA repair and gene expression (6).”
BackgroundIntegrative approaches in genome structure analysis
Boninsegna, L., Yıldırım, A., Zhan, Y., & Alber, F. (2021) · Structure · doi:10.1016/j.str.2021.12.003 · Cited by 11
CDK activity sensors: genetically encoded ratiometric biosensors for live analysis of the cell cycle
Martinez, M. A. Q., & Matus, D. Q. (2022) · Biochemical Society Transactions · doi:10.1042/bst20211131 · Cited by 11
Stolper, R. J., Tsang, F. H., Georgiades, E., Hansen, L. L. P., Downes, D. J., Harrold, C. L., Hughes, J. R., Beagrie, R. A., Davies, B., Kassouf, M. T., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.07.556660 · Cited by 11
The material properties of mitotic chromosomes
Spicer, M. F. D., & Gerlich, D. W. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102617 · Cited by 10
STAG2: Computational Analysis of Missense Variants Involved in Disease
Ros‐Pardo, D., Gómez‐Puertas, P., & Marcos‐Alcalde, Í. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021280 · Cited by 10
SMC-mediated chromosome organization: Does loop extrusion explain it all?
Hirano, T., & Kinoshita, K. (2024) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2024.102447 · Cited by 10
Cohesin prevents local mixing of condensed euchromatic domains in living human cells
Shimazoe, M. A., Iida, S., Minami, K., Higashi, K., Tamura, S., Kobayashi, Y., Fujishiro, S., Xiong, L., Nakazato, K., Ashwin, S. S., et al. (2026) · Nature Genetics · doi:10.1038/s41588-026-02736-2 · Cited by 12
Meiotic cohesin RAD21L shapes 3D genome structure and transcription in the male germline
Marín-Gual, L., Vara, C., Sainz-Urruela, R., Cuartero, Y., Álvarez-González, L., Felipe‐Medina, N., Garcia, F., Llano, E., Martı́-Renom, M. A., Pendás, A. M., et al. (2025) · Science Advances · doi:10.1126/sciadv.adv2283 · Cited by 10
“These findings echo previous observations in mouse one-cell embryos, where deletion of the somatic subunit RAD21 impaired loops and TAD formation ( 28 ) and are consistent with studies showing altered chromatin organization following auxin-induced RAD21 degradation in somatic cells ( 52 ).”
The physical chemistry of interphase loop extrusion
Tortora, M. M. C., & Fudenberg, G. (2025) · Cell Genomics · doi:10.1016/j.xgen.2025.101098 · Cited by 9
“18 At this depletion level, cohesin residence time was predicted to increase 8-fold after Δ WAPL or 2-fold after Δ PDS5 (Figure 4E), in close agreement with experimental FRAP after either Δ WAPL or Δ PDS5A + B by RNAi.”
InfluentialKaryotype engineering reveals spatio-temporal control of replication firing and gene contacts
Lazar‐Stefanita, L., Luo, J., Montagne, R., Thierry, A., Sun, X., Mercy, G., Mozziconacci, J., Koszul, R., & Boeke, J. D. (2022) · Cell Genomics · doi:10.1016/j.xgen.2022.100163 · Cited by 10
Cohesin and CTCF complexes mediate contacts in chromatin loops depending on nucleosome positions
Attou, A., Zülske, T., & Wedemann, G. (2022) · Biophysical Journal · doi:10.1016/j.bpj.2022.10.044 · Cited by 9
Pezić, D., Weeks, S., Varsally, W., Dewari, P. S., Pollard, S. M., Branco, M. R., & Hadjur, S. (2023) · Stem Cell Reports · doi:10.1016/j.stemcr.2023.09.004 · Cited by 12
Dysregulation of the cohesin subunit RAD21 by Hepatitis C virus mediates host–virus interactions
Perez, S., Gevor, M., Davidovich, A., Kaspi, A., Yamin, K., Domovich, T., Meirson, T., Matityahu, A., Brody, Y., Stemmer, S. M., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz052 · Cited by 10
“It has been suggested that WAPL restricts the size of TADs, and WAPL depletion results in increased loop size and hypercondensation (23,71).”
BackgroundCohesin disrupts polycomb-dependent chromosome interactionsPreprint
Rhodes, J., Feldmann, A., Hernández-Rodríguez, B., Díaz, N., Brown, J., Fursova, N. A., Blackledge, N. P., Prathapan, P., Dobrinić, P., Huseyin, M. K., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/593970 · Cited by 10
“Consistent with previous findings (Rao et al., 2017; Schwarzer et al., 2017; Wutz et al., 2017), removal of cohesin caused a complete loss of TADs (Figure S1B and C) and modestly enhanced A/B compartmentalisation (Figure S1D).”
ResultCis-regulatory chromatin contacts form de novo in the absence of loop extrusionPreprint
Aboreden, N. G., Zhao, H., Shan, F., Liu, F., Zhang, H., & Blobel, G. A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.12.632634 · Cited by 10
Permeable TAD boundaries and their impact on genome‐associated functions
Chang, L., & Noordermeer, D. (2024) · BioEssays · doi:10.1002/bies.202400137 · Cited by 10
Callegari, A., Kueblbeck, M., Morero, N. R., Serrano‐Solano, B., & Ellenberg, J. (2024) · Nature Protocols · doi:10.1038/s41596-024-01043-6 · Cited by 10
Self-citationCohesin positions the epigenetic reader Phf2 within the genome
Tang, W., Costantino, L., Stocsits, R. R., Wutz, G., Ladurner, R., Hudecz, O., Mechtler, K., & Peters, J. (2025) · The EMBO Journal · doi:10.1038/s44318-024-00348-2 · Cited by 9
“Many chromatin loops are generated by cohesin (Gassler et al, 2017; Rao et al, 2017; Schwarzer et al, 2017; Wutz et al, 2017), a ‘ structural maintenance of chromosomes ’ (SMC) complex, which extrudes DNA into loops in vitro (Davidson et al, 2019; Kim et al, 2019).”
InfluentialSelf-citationHistone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells
Dunjić, M., Jonas, F., Yaakov, G., More, R., Mayshar, Y., Rais, Y., Orenbuch, A.-H., Cheng, S., Barkai, N., & Stelzer, Y. (2023) · Nature Communications · doi:10.1038/s41467-023-39477-3 · Cited by 9
“In the prevailing model, CTCF proteinscreateabaseofchromatinloopsbythwartingtheprogression of cohesin-mediated loop extrusion 60,63,67,72 – 74 .”
Al-Jibury, E., King, J. W. D., Guo, Y., Lenhard, B., Fisher, A. G., Merkenschlager, M., & Rueckert, D. (2023) · Nature Communications · doi:10.1038/s41467-023-40547-9 · Cited by 9
“This was expected, as NIPBL is required for cohesinloading, and the lossof cohesinfrom chromosomes abrogates the formation of contact domains and loops 3,15,26 .”
BackgroundEffect of loops on the mean-square displacement of Rouse-model chromatin
Yuan, T., Yan, H., Bailey, M. L. P., Williams, J. F., Surovtsev, I. V., King, M. C., & Mochrie, S. G. J. (2024) · Physical review. E · doi:10.1103/physreve.109.044502 · Cited by 9
“On the experimental side, the structural maintenance of chromosomes (SMC) complexes, cohesin and condensin, have been identified as possible LEFs, with TADs disappearing from Hi-C maps in the absence of cohesin [55, 56].”
Xu, W., Kim, J.-S., Yang, T., Ya, A., Sadzewicz, L., Tallon, L. J., Harris, B. T., Sarkaria, J. N., Jin, F., & Waldman, T. A. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107341 · Cited by 10
“Inactivation of cohesin subunits RAD21 and NIPBL has been shown to cause the immediate complete collapse of TADs (9 – 12).”
BackgroundForm and function of archaeal genomes
Bell, S. (2022) · Biochemical Society Transactions · doi:10.1042/bst20221396 · Cited by 8
Toward understanding the dynamic state of 3D genome
Shinkai, S., Onami, S., & Nakato, R. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.08.014 · Cited by 9
“As Wapl-deficient cells accumulate contact at multi-TAD corners [52,51], chromatin formation becomes more compact.”
BackgroundMethodInfluentialZuilkoski, C. M., & Skibbens, R. V. (2020) · Cell Cycle · doi:10.1080/15384101.2020.1804221 · Cited by 9
PCNA antagonizes cohesin-dependent roles in genomic stability
Zuilkoski, C. M., & Skibbens, R. V. (2020) · PLoS ONE · doi:10.1371/journal.pone.0235103 · Cited by 9
Insight Into Chromatin-Enriched RNA: A Key Chromatin Regulator in Tumors
Zhang, J., Ding, T., & Zhang, H. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.649605 · Cited by 8
Comoglio, F., Park, H. J., Schoenfelder, S., Barozzi, I., Bode, D., Fraser, P., & Green, A. R. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/163113 · Cited by 9
Self-citationCTCF/cohesin organize the ground state of chromatin-nuclear speckle associationPreprint
Yu, R., Roseman, S. A., Siegenfeld, A. P., Nguyen, S. C., Joyce, E. F., Liau, B. B., Krantz, I. D., Alexander, K. A., & Berger, S. L. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.22.550178 · Cited by 9
“To evaluate whether the Nterminal domain of CTCF was important for nuclear speckle contacts, we constructed N-terminal deletion (1-266) and C-terminal deletion (576-727) mutations in a transient expression plasmid with FLAG-tagged CTCF.”
BackgroundMethodInfluentialRinzema, 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. (2021) · doi:10.1101/2021.10.05.463209 · Cited by 8
Differential oligomerization regulates PHF13 chromatin affinity and function
Rossi, F., Magalhães, A. P., Buschow, R., Schubert, T., Glaser, L. V., Fontana, A., Mai, J., Staege, H., Grimme, A., Will, H., et al. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf572 · Cited by 8
“This phenomenon of global interphase chromatin compaction has only been previously described for a few complexes, namely cohesin [ 66 , 67 ], condensin [ 68 ], and poly-comb [ 31 , 81 ].”
NIPBL and STAG1 enable loop extrusion by providing differential DNA–cohesin affinity
van Wee, R., Asor, R., Li, Y., Drechsel, D. N., Popova, M., Litos, G., Davidson, I. F., Peters, J., & Kukura, P. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2514190122 · Cited by 8
Self-citationBass, T. E., Fleenor, D. E., Burrell, P. E., & Kastan, M. B. (2022) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-22-0399 · Cited by 8
Super-enhancer landscape rewiring in cancer: The epigenetic control at distal sites
Giorgio, E. D., Benetti, R., Kerschbamer, E., Xodo, L. E., & Brancolini, C. (2023) · International review of cytology · doi:10.1016/bs.ircmb.2023.03.013 · Cited by 9
Huber, J., Tanasie, N.-L., Zernia, S., & Stigler, J. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae391 · Cited by 8
“As individual CTCF molecules could not be spatially separated on 4 × CBSs constructs, a model was developed that describes the disappearance of the last molecule on a multi-binding-site array.”
Single-nucleus Hi-C of mammalian oocytes and zygotes
Gassler, J., Flyamer, I. M., & Tachibana, K.-E. K. (2018) · Methods in cell biology · doi:10.1016/bs.mcb.2018.03.032 · Cited by 8
Role of chromosomal architecture in germinal center B cells and lymphomagenesis
Rivas, M. A., & Melnick, A. M. (2019) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000505 · Cited by 8
“Cohesin loading and unloading requires accessory proteins such as Pds5a/Pds5b, Wapl, and Nipbl [10].”
BackgroundCoutiño, B. C., Cornhill, Z. E., Couto, A., Mack, N. A., Rusu, A. D., Nagarajan, U., Fan, Y. N., Hadjicharalambous, M. R., Castellanos, M., Burrows, A., et al. (2020) · iScience · doi:10.1016/j.isci.2020.101237 · Cited by 8
Golov, A. K., Golova, A., Gavrilov, A. A., & Razin, S. V. (2021) · Epigenetics & Chromatin · doi:10.1186/s13072-021-00411-w · Cited by 8
Chromatin Organization and Transcriptional Programming of Breast Cancer Cell Identity
Bobbitt, J. R., Seachrist, D. D., & Keri, R. A. (2023) · Endocrinology · doi:10.1210/endocr/bqad100 · Cited by 9
Three-dimensional genome organization in normal and malignant haematopoiesis
Cuartero, S., & Merkenschlager, M. (2018) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000436 · Cited by 8
Ruiz, Y., Ramos‐González, P. L., Soto, J., Rodríguez, M., Carlos, N., Reyes, A., Callard, D., Sánchez, Y., Pujol, M., & Fuentes, A. D. (2020) · Transgenic Research · doi:10.1007/s11248-019-00187-6 · Cited by 8
Despang, A., Schöpflin, R., Franke, M., Ali, S., Jerković, I., Paliou, C., Chan, W.-L., Timmermann, B., Wittler, L., Vingron, M., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/566562 · Cited by 8
Topologically Associating Domain Boundaries are Commonly Required for Normal Genome FunctionPreprint
Rajderkar, S. S., Barozzi, I., Zhu, Y., Hu, R., Zhang, Y., Li, B., Fukuda, Y., Kelman, G., Akeza, A., Blow, M. J., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.06.443037 · Cited by 8
Dynamic barriers modulate cohesin positioning and genome folding at fixed occupancy
Rahmaninejad, H., Xiao, Y., Tortora, M. M. C., & Fudenberg, G. (2025) · Genome Research · doi:10.1101/gr.280108.124 · Cited by 8
“If we increased extruder lifetime sevenfold (as estimated experimentally [Wutz et al. 2017]) with transient barriers ( τ b << τ E ), we observed vermicelli formation in simulations (Fig.”
Influential
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
