Animal genomes are folded into loops and topologically associating domains (TADs) by CTCF and loop-extruding cohesins, but the live dynamics of loop formation and stability remain unknown. Here, we directly visualized chromatin looping at the Fbn2 TAD in mouse embryonic stem cells using super-resolution live-cell imaging and quantified looping dynamics by Bayesian inference. Unexpectedly, the Fbn2 loop was both rare and dynamic, with a looped fraction of approximately 3 to 6.5% and a median loop lifetime of approximately 10 to 30 minutes. Our results establish that the Fbn2 TAD is highly dynamic, and about 92% of the time, cohesin-extruded loops exist within the TAD without bridging both CTCF boundaries. This suggests that single CTCF boundaries, rather than the fully CTCF-CTCF looped state, may be the primary regulators of functional interactions.

Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging / Gabriele, M.; Brandao, H. B.; Grosse-Holz, S.; Jha, A.; Dailey, G. M.; Cattoglio, C.; Hsieh, T. -H. S.; Mirny, L.; Zechner, C.; Hansen, A. S.. - In: SCIENCE. - ISSN 0036-8075. - 376:6592(2022), pp. 476-501. [10.1126/science.abn6583]

Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging

Zechner C.
;
2022-01-01

Abstract

Animal genomes are folded into loops and topologically associating domains (TADs) by CTCF and loop-extruding cohesins, but the live dynamics of loop formation and stability remain unknown. Here, we directly visualized chromatin looping at the Fbn2 TAD in mouse embryonic stem cells using super-resolution live-cell imaging and quantified looping dynamics by Bayesian inference. Unexpectedly, the Fbn2 loop was both rare and dynamic, with a looped fraction of approximately 3 to 6.5% and a median loop lifetime of approximately 10 to 30 minutes. Our results establish that the Fbn2 TAD is highly dynamic, and about 92% of the time, cohesin-extruded loops exist within the TAD without bridging both CTCF boundaries. This suggests that single CTCF boundaries, rather than the fully CTCF-CTCF looped state, may be the primary regulators of functional interactions.
2022
376
6592
476
501
https://www.biorxiv.org/content/10.1101/2021.12.12.472242v1.abstract
https://pubmed.ncbi.nlm.nih.gov/35420890/
Gabriele, M.; Brandao, H. B.; Grosse-Holz, S.; Jha, A.; Dailey, G. M.; Cattoglio, C.; Hsieh, T. -H. S.; Mirny, L.; Zechner, C.; Hansen, A. S.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/145859
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