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

View ORCID ProfileMichele Gabriele, View ORCID ProfileHugo B. Brandão, View ORCID ProfileSimon Grosse-Holz, View ORCID ProfileAsmita Jha, View ORCID ProfileGina M. Dailey, View ORCID ProfileClaudia Cattoglio, View ORCID ProfileTsung-Han S. Hsieh, View ORCID ProfileLeonid Mirny, View ORCID ProfileChristoph Zechner, View ORCID ProfileAnders S. Hansen
doi: https://doi.org/10.1101/2021.12.12.472242
Michele Gabriele
1Department of Biological Engineering, Massachusetts Institute of Technology; Cambridge, 02139, USA
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Hugo B. Brandão
1Department of Biological Engineering, Massachusetts Institute of Technology; Cambridge, 02139, USA
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Simon Grosse-Holz
2Department of Physics, Massachusetts Institute of Technology; Cambridge, MA 02139, USA
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Asmita Jha
1Department of Biological Engineering, Massachusetts Institute of Technology; Cambridge, 02139, USA
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Gina M. Dailey
3Department of Molecular and Cell Biology, University of California, Berkeley; Berkeley, CA 94720, USA
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Claudia Cattoglio
3Department of Molecular and Cell Biology, University of California, Berkeley; Berkeley, CA 94720, USA
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Tsung-Han S. Hsieh
3Department of Molecular and Cell Biology, University of California, Berkeley; Berkeley, CA 94720, USA
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Leonid Mirny
2Department of Physics, Massachusetts Institute of Technology; Cambridge, MA 02139, USA
4Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology; Cambridge, MA 02139, USA
5Institut Curie; Paris 75005, France
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  • For correspondence: leonid@mit.edu zechner@mpi-cbg.de ashansen@mit.edu
Christoph Zechner
6Max Planck Institute of Molecular Cell Biology & Genetics; Dresden, Germany
7Center for Systems Biology Dresden; Dresden, Germany
8Cluster of Excellence Physics of Life, TU Dresden; Dresden, Germany
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  • For correspondence: leonid@mit.edu zechner@mpi-cbg.de ashansen@mit.edu
Anders S. Hansen
1Department of Biological Engineering, Massachusetts Institute of Technology; Cambridge, 02139, USA
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  • For correspondence: leonid@mit.edu zechner@mpi-cbg.de ashansen@mit.edu
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Abstract

Animal genomes are folded into loops and topologically associating domains (TADs) by CTCF and cohesin, but whether these loops are stable or dynamic is unknown. Here, we directly visualize chromatin looping at the Fbn2 TAD in mouse embryonic stem cells using super-resolution live-cell imaging and quantify looping dynamics by Bayesian inference. Our results are consistent with cohesin-mediated loop extrusion in cells, and with CTCF both stopping and stabilizing cohesin. Surprisingly, the Fbn2 loop is both rare and dynamic, with a looped fraction of ~3-6.5% and a median loop lifetime of ~10-30 minutes. Instead of a stable loop, our results establish a highly dynamic view of TADs and loops where the Fbn2 TAD exists predominantly in a partially extruded conformation. This dynamic and quantitative view of TADs may facilitate a mechanistic understanding of their functions.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 13, 2021.
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Dynamics of CTCF and cohesin mediated chromatin looping revealed by live-cell imaging
Michele Gabriele, Hugo B. Brandão, Simon Grosse-Holz, Asmita Jha, Gina M. Dailey, Claudia Cattoglio, Tsung-Han S. Hsieh, Leonid Mirny, Christoph Zechner, Anders S. Hansen
bioRxiv 2021.12.12.472242; doi: https://doi.org/10.1101/2021.12.12.472242
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Dynamics of CTCF and cohesin mediated chromatin looping revealed by live-cell imaging
Michele Gabriele, Hugo B. Brandão, Simon Grosse-Holz, Asmita Jha, Gina M. Dailey, Claudia Cattoglio, Tsung-Han S. Hsieh, Leonid Mirny, Christoph Zechner, Anders S. Hansen
bioRxiv 2021.12.12.472242; doi: https://doi.org/10.1101/2021.12.12.472242

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