Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging
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nihms-1799474 (1).pdf
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Accepted version
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2.03 MB
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Author(s)
Gabriele, Michele
Brandão, Hugo B
Grosse-Holz, Simon
Jha, Asmita
Dailey, Gina M
Cattoglio, Claudia
Hsieh, Tsung-Han S
Mirny, Leonid
Zechner, Christoph
Hansen, Anders S
Date Issued
2022
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Gabriele, Michele, Brandão, Hugo B, Grosse-Holz, Simon, Jha, Asmita, Dailey, Gina M et al. 2022. "Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging." Science, 376 (6592).
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Author's final manuscript
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.
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1126/SCIENCE.ABN6583
