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Live-cell imaging and physical modeling reveal control of chromosome folding dynamics by cohesin and CTCF

Pia Mach, Pavel I. Kos, Yinxiu Zhan, Julie Cramard, Simon Gaudin, Jana Tünnermann, Edoardo Marchi, Jan Eglinger, Jessica Zuin, Mariya Kryzhanovska, Sebastien Smallwood, Laurent Gelman, Gregory Roth, Elphège P. Nora, Guido Tiana, Luca Giorgetti
doi: https://doi.org/10.1101/2022.03.03.482826
Pia Mach
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
2University of Basel, Basel, Switzerland
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  • For correspondence: luca.giorgetti@fmi.ch
Pavel I. Kos
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
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Yinxiu Zhan
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
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Julie Cramard
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
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Simon Gaudin
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
3École Normale Supérieure de Lyon and Université Claude Bernard Lyon I, Université de Lyon, Lyon, France
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Jana Tünnermann
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
2University of Basel, Basel, Switzerland
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Edoardo Marchi
4Università degli Studi di Milano and INFN, Milan, Italy.
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Jan Eglinger
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
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Jessica Zuin
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
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Mariya Kryzhanovska
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
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Sebastien Smallwood
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
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Laurent Gelman
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
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Gregory Roth
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
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Elphège P. Nora
5Cardiovascular Research Institute, University of California San Francisco; Department of Biochemistry and Biophysics, University of California San Francisco; San Francisco, CA, USA
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Guido Tiana
4Università degli Studi di Milano and INFN, Milan, Italy.
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Luca Giorgetti
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
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  • For correspondence: luca.giorgetti@fmi.ch
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Abstract

Physical proximity between genomic sequences in mammalian chromosomes controls key biological processes such as transcriptional regulation and DNA repair. Yet it is currently unknown if chromosomal contacts are rare and stable or instead frequent and dynamic, and how they depend on the loop extrusion activity of cohesin or barriers such as CTCF. By imaging chromosomal locations at high spatial and temporal resolution over several hours in living cells, we show that sequences within topological associating domains (TADs) frequently come into physical proximity during the course of a cell cycle and remain close to each other only for a few minutes. Such contacts become nonetheless substantially longer and more frequent in the presence of convergent CTCF sites, resulting in a suppression of variability in chromosome folding in single cells across time. Supported by physical models of chromosome dynamics, our data additionally suggests that individual CTCF-anchored loops last around 10 minutes. The estimates of chromosomal contact dynamics in our study provide a novel quantitative framework to link chromosome structure to function and show that cohesin and CTCF stabilize otherwise highly dynamic chromosome structures to facilitate selected subsets of chromosomal interactions.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
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-ND 4.0 International license.
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Posted March 03, 2022.
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Live-cell imaging and physical modeling reveal control of chromosome folding dynamics by cohesin and CTCF
Pia Mach, Pavel I. Kos, Yinxiu Zhan, Julie Cramard, Simon Gaudin, Jana Tünnermann, Edoardo Marchi, Jan Eglinger, Jessica Zuin, Mariya Kryzhanovska, Sebastien Smallwood, Laurent Gelman, Gregory Roth, Elphège P. Nora, Guido Tiana, Luca Giorgetti
bioRxiv 2022.03.03.482826; doi: https://doi.org/10.1101/2022.03.03.482826
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Live-cell imaging and physical modeling reveal control of chromosome folding dynamics by cohesin and CTCF
Pia Mach, Pavel I. Kos, Yinxiu Zhan, Julie Cramard, Simon Gaudin, Jana Tünnermann, Edoardo Marchi, Jan Eglinger, Jessica Zuin, Mariya Kryzhanovska, Sebastien Smallwood, Laurent Gelman, Gregory Roth, Elphège P. Nora, Guido Tiana, Luca Giorgetti
bioRxiv 2022.03.03.482826; doi: https://doi.org/10.1101/2022.03.03.482826

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