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

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.

SUBMITTER: Gabriele M

PROVIDER: S-EPMC9069445 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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

Gabriele Michele M Brandão Hugo B HB Grosse-Holz Simon S Jha Asmita A Dailey Gina M GM Cattoglio Claudia C Hsieh Tsung-Han S TS Mirny Leonid L Zechner Christoph C Hansen Anders S AS

Science (New York, N.Y.) 20220414 6592

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 <i>Fbn2</i> TAD in mouse embryonic stem cells using super-resolution live-cell imaging and quantified looping dynamics by Bayesian inference. Unexpectedly, the <i>Fbn2</i> loop was both rare and dynamic, with a looped fraction of approximately 3 to 6.5% and ...[more]

PMID: 35420890

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