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

<jats:p> 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 <jats:italic&...

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Main Authors: 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
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2023
Online Access:https://hdl.handle.net/1721.1/147831
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author 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
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
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
author_sort Gabriele, Michele
collection MIT
description <jats:p> 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 <jats:italic>Fbn2</jats:italic> TAD in mouse embryonic stem cells using super-resolution live-cell imaging and quantified looping dynamics by Bayesian inference. Unexpectedly, the <jats:italic>Fbn2</jats:italic> 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 <jats:italic>Fbn2</jats:italic> 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. </jats:p>
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spelling mit-1721.1/1478312023-02-02T03:00:27Z Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging 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 Massachusetts Institute of Technology. Department of Biological Engineering <jats:p> 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 <jats:italic>Fbn2</jats:italic> TAD in mouse embryonic stem cells using super-resolution live-cell imaging and quantified looping dynamics by Bayesian inference. Unexpectedly, the <jats:italic>Fbn2</jats:italic> 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 <jats:italic>Fbn2</jats:italic> 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. </jats:p> 2023-02-01T17:05:13Z 2023-02-01T17:05:13Z 2022 2023-02-01T16:58:06Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147831 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). en 10.1126/SCIENCE.ABN6583 Science Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) PMC
spellingShingle 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
Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging
title Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging
title_full Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging
title_fullStr Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging
title_full_unstemmed Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging
title_short Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging
title_sort dynamics of ctcf and cohesin mediated chromatin looping revealed by live cell imaging
url https://hdl.handle.net/1721.1/147831
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