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Single-molecule imaging of chromatin remodelers reveals role of ATPase in promoting fast kinetics of target search and dissociation from chromatin

Jee Min Kim, View ORCID ProfilePat Visanpattanasin, Vivian Jou, Sheng Liu, Xiaona Tang, Qinsi Zheng, Kai Yu Li, Jonathan Snedeker, Luke D. Lavis, Timothée Lionnet, View ORCID ProfileCarl Wu
doi: https://doi.org/10.1101/2021.04.21.440742
Jee Min Kim
1Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
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Pat Visanpattanasin
1Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
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  • ORCID record for Pat Visanpattanasin
Vivian Jou
1Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
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Sheng Liu
1Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
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Xiaona Tang
1Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
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Qinsi Zheng
2Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA
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Kai Yu Li
1Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
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Jonathan Snedeker
1Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
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Luke D. Lavis
2Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA
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Timothée Lionnet
3Institute of Systems Genetics, Langone Medical Center, New York University, New York, NY 10016, USA
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Carl Wu
1Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
4Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA
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  • ORCID record for Carl Wu
  • For correspondence: [email protected]
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ABSTRACT

Conserved ATP-dependent chromatin remodelers establish and maintain genome-wide chromatin architectures of regulatory DNA during cellular lifespan, but the temporal interactions between remodelers and chromatin targets have been obscure. We performed live-cell single-molecule tracking for RSC, SWI/SNF, CHD1, ISW1, ISW2, and INO80 remodeling complexes in budding yeast and detected hyperkinetic behaviors for chromatin-bound molecules that frequently transition to the free state for all complexes. Chromatin-bound remodelers display notably higher diffusion than nucleosomal histones, and strikingly fast dissociation kinetics with 4-7 s mean residence times. These enhanced dynamics require ATP binding or hydrolysis by the catalytic ATPase, uncovering an additional function to its established role in nucleosome remodeling. Kinetic simulations show that multiple remodelers can repeatedly occupy the same promoter region on a timescale of minutes, implicating an unending ‘tug-of-war’ that controls a temporally shifting window of accessibility for the transcription initiation machinery.

Competing Interest Statement

T.L. holds intellectual property rights related to Janelia Fluor dyes used in this publication. L.D.L. and Q.Z. are listed as inventors on patents and patent applications whose value might be affected by publication. The remaining authors declare no competing interests.

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 4.0 International license.
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Posted April 21, 2021.
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Single-molecule imaging of chromatin remodelers reveals role of ATPase in promoting fast kinetics of target search and dissociation from chromatin
Jee Min Kim, Pat Visanpattanasin, Vivian Jou, Sheng Liu, Xiaona Tang, Qinsi Zheng, Kai Yu Li, Jonathan Snedeker, Luke D. Lavis, Timothée Lionnet, Carl Wu
bioRxiv 2021.04.21.440742; doi: https://doi.org/10.1101/2021.04.21.440742
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Single-molecule imaging of chromatin remodelers reveals role of ATPase in promoting fast kinetics of target search and dissociation from chromatin
Jee Min Kim, Pat Visanpattanasin, Vivian Jou, Sheng Liu, Xiaona Tang, Qinsi Zheng, Kai Yu Li, Jonathan Snedeker, Luke D. Lavis, Timothée Lionnet, Carl Wu
bioRxiv 2021.04.21.440742; doi: https://doi.org/10.1101/2021.04.21.440742

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