CTCF and cohesin regulate chromatin loop stability with distinct dynamics
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Abstract
Folding of mammalian genomes into spatial domains is critical for gene regulation. The insulator protein CTCF and cohesin control domain location by folding domains into loop structures, which are widely thought to be stable. Combining genomic and biochemical approaches we show that CTCF and cohesin co-occupy the same sites and physically interact as a biochemically stable complex. However, using single-molecule imaging we find that CTCF binds chromatin much more dynamically than cohesin (~1–2 min vs. ~22 min residence time). Moreover, after unbinding, CTCF quickly rebinds another cognate site unlike cohesin for which the search process is long (~1 min vs. ~33 min). Thus, CTCF and cohesin form a rapidly exchanging 'dynamic complex' rather than a typical stable complex. Since CTCF and cohesin are required for loop domain formation, our results suggest that chromatin loops are dynamic and frequently break and reform throughout the cell cycle.
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Cohesin-mediated chromatin loops are dynamic structures that continuously form and fall apart throughout the cell cycle.
“we propose that cohesin-mediated chromatin loops are dynamic structures that continuously form and fall apart throughout the cell cycle”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [7]
The ΔWAPL Hi-C studies support our conclusion that CTCF binds more dynamically than cohesin.
“Thus, the ΔWAPL Hi-C studies12,14,15 support our conclusion that CTCF binds more dynamically than cohesin.7”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [7]
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Moertelmaier, M., Kögler, E. J., Hesse, J., Sonnleitner, M., Huber, L. A., & Schütz, G. J. (2002) · Single Molecules · doi:10.1002/1438-5171(200208)3:4 · Cited by 17 · see citing works
Skibbens, R. V. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006478 · Cited by 12 · see citing works
FISH-ing for captured contacts: towards reconciling FISH and 3CPreprint
Fudenberg, G., & Imakaev, M. V. (2016) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/081448 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
the 4D Nucleome Network, Dekker, J., Belmont, A. S., Guttman, M., Leshyk, V. O., Lis, J. T., Lomvardas, S., Mirny, L. A., O’Shea, C. C., Park, P. J., et al. (2017) · Nature · doi:10.1038/nature23884 · Cited by 732 · see citing works
Transcription 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 · see citing works
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 · see citing works
Self-citationDistinct Classes of Chromatin Loops Revealed by Deletion of an RNA-Binding Region in CTCF
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 · see citing works
Self-citationRecent 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 · see citing works
Self-citationCohesin and CTCF control the dynamics of chromosome folding
Mach, P., Kos, P. I., Zhan, Y., Cramard, J., Gaudin, S., Tünnermann, J., Marchi, E., Eglinger, J., Zuin, J., Kryzhanovska, M., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01232-7 · Cited by 269 · see citing works
El Khattabi, L., Zhao, H., Kalchschmidt, J., Young, N., Jung, S., Van Blerkom, P., Kieffer-Kwon, P., Kieffer-Kwon, K.-R., Park, S., Wang, X., et al. (2019) · Cell · doi:10.1016/j.cell.2019.07.011 · Cited by 244 · see citing works
Transcription in Living Cells: Molecular Mechanisms of Bursting
Rodriguez, J., & Larson, D. R. (2020) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-011520-105250 · Cited by 224 · see citing works
Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains
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 · see citing works
Chromosome 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 · see citing works
“For typical cohesin residence times (Gerlich et al., 2006b; Hansen et al., 2017; Kueng et al., 2006; Tedeschi et al., 2013; Wutz et al., 2017) , this model suggests that small loops of 10-60 kb (Dauban et al.”
ResultFISH-ing for captured contacts: towards reconciling FISH and 3C
Fudenberg, G., & Imakaev, M. (2017) · Nature Methods · doi:10.1038/nmeth.4329 · Cited by 141 · see citing works
A matter of time: Using dynamics and theory to uncover mechanisms of transcriptional bursting
Lammers, N. C., Kim, Y. J., Zhao, J., & Garcia, H. G. (2020) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2020.08.001 · Cited by 99 · see citing works
“s [86] STAT1 Mammalian cell SMT ˘0.5s [88] TFIIB In vitro reconstitution SMT ˘1.5s [89] TATA-binding protein Mammalian cell SMT 1.5-2min [90] Chromatin Protein Binding CTCF Mammalian cell SMT ˘1-2min [118] Cohesin Mammalian cell SMT ˘22min [118] Enhancer-Promoter Interaction snail shadow enhancer Drosophila embryo MS2…”
MethodInfluentialJpx RNA regulates CTCF anchor site selection and formation of chromosome loops
Oh, H. J., Aguilar, R., Kesner, B., Lee, H.-G., Kriz, A. J., Chu, H.-P., & Lee, J. T. (2021) · Cell · doi:10.1016/j.cell.2021.11.012 · Cited by 84 · see citing works
Brown, J. M., Roberts, N. A., Graham, B., Waithe, D., Lagerholm, C., Telenius, J. M., De Ornellas, S., Oudelaar, A. M., Scott, C., Szczerbal, I., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06248-4 · Cited by 72 · see citing works
Narducci, D. N., & Hansen, A. S. (2025) · Molecular Cell · doi:10.1016/j.molcel.2024.11.032 · Cited by 25 · see citing works
Self-citationGenome-wide absolute quantification of chromatin looping
Jusuf, J. M., Yang, J. H., Toppen, J., Grosse-Holz, S., Gabriele, M., Mach, P., Flyamer, I. M., Zechner, C., Giorgetti, L., Mirny, L. A., et al. (2026) · Nature Structural & Molecular Biology · doi:10.1038/s41594-026-01819-2 · Cited by 22 · see citing works
“CTCF-bound and cohesin-bound sites were identified using CTCF 72,73 and SMC1A 49 ChIP–seq peaks and CTCF binding motifs, promoters were defined as regions ±2 kb from transcription start sites 74 , and enhancers were defined as regions of overlapping H3K4me1 and H3K27ac ChIP– seq peaks 75 .”
Self-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 · see citing works
- Authors
- Hansen, A. S., Pustova, I., Cattoglio, C., Tjian, R., & Darzacq, X.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California, Berkeley (US)
- Corresponding author
- Tjian, Robert
- Darzacq, Xavier
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2017-05-03
- Volume
- 6
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5446243
- OpenAlex
- W2567008309
- Cited by
- 613
- References
- 84
- Citations by year
- 2026: 50 · 2025: 54 · 2024: 61 · 2023: 69 · 2022: 82 · 2021: 89 · 2020: 75 · 2019: 56 · 2018: 57 · 2017: 20
- FWCI
- 23.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Siebel Stem Cell Institute
- Howard Hughes Medical Institute (003061)
- California Institute of Regenerative Medicine (LA1-08013)
- National Institutes of Health (UO1-EB021236, U54-DK107980)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- CTCF, cohesin, chromatin looping, loop stability, chromatin folding, 3D genome organization, protein-protein complex, cell cycle, gene expression regulation, insulator proteins
- MeSH terms
- CCCTC-Binding Factor, Cohesins, Animals, Cells, Cultured, Chromatin, Chromosomal Proteins, Non-Histone, Kinetics, Protein Binding, Cell Cycle Proteins, Protein Interaction Mapping, Mice
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.
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