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

  1. Jee Min Kim
  2. Pat Visanpattanasin
  3. Vivian Jou
  4. Sheng Liu
  5. Xiaona Tang
  6. Qinsi Zheng
  7. Kai Yu Li
  8. Jonathan Snedeker
  9. Luke D Lavis
  10. Timothee Lionnet
  11. Carl Wu  Is a corresponding author
  1. Johns Hopkins University, United States
  2. Janelia Research Campus, United States
  3. Janelia Research Campus, Howard Hughes Medical Institute, United States
  4. New York University, United States

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.

Data availability

All custom scripts and imaging data files have been deposited in Mendeley Data and are publicly available via: https://data.mendeley.com/datasets/ydwcx9yhpp/2 (DOI: 10.17632/ydwcx9yhpp.2).

Article and author information

Author details

  1. Jee Min Kim

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    No competing interests declared.
  2. Pat Visanpattanasin

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9506-8360
  3. Vivian Jou

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    No competing interests declared.
  4. Sheng Liu

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    No competing interests declared.
  5. Xiaona Tang

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    No competing interests declared.
  6. Qinsi Zheng

    Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, United States
    Competing interests
    Qinsi Zheng, L.D.L. and Q.Z. are listed as inventors on patents and patent applications whose value might be affected by publication. US Patent 9,933,417 and Patent Application 2021/0085805 describing azetidine-containing fluorophores and variant compositions (with inventors Q.Z., L.D.L., and T.L.) are assigned to HHMI..
  7. Kai Yu Li

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    No competing interests declared.
  8. Jonathan Snedeker

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    No competing interests declared.
  9. Luke D Lavis

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    Luke D Lavis, L.D.L. and Q.Z. are listed as inventors on patents and patent applications whose value might be affected by publication. US Patent 9,933,417 and Patent Application 2021/0085805 describing azetidine-containing fluorophores and variant compositions (with inventors Q.Z., L.D.L., and T.L.) are assigned to HHMI..
  10. Timothee Lionnet

    Langone Medical Center, Institute of System Genetics, New York University, New York, United States
    Competing interests
    Timothee Lionnet, T.L. holds intellectual property rights related to Janelia Fluor dyes used in this publication. US Patent 9,933,417 and Patent Application 2021/0085805 describing azetidine-containing fluorophores and variant compositions (with inventors Q.Z., L.D.L., and T.L.) are assigned to HHMI..
  11. Carl Wu

    Department of Biology, Johns Hopkins University, Baltimore, United States
    For correspondence
    wuc@jhu.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6933-5763

Funding

National Institutes of Health (GM132290)

  • Carl Wu

National Institutes of Health (GM127538)

  • Timothee Lionnet

Korean Foundation for Advanced Studies Fellowship

  • Jee Min Kim

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Sebastian Deindl, Uppsala University, Sweden

Version history

  1. Received: April 13, 2021
  2. Preprint posted: April 21, 2021 (view preprint)
  3. Accepted: July 26, 2021
  4. Accepted Manuscript published: July 27, 2021 (version 1)
  5. Version of Record published: August 9, 2021 (version 2)

Copyright

© 2021, Kim et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jee Min Kim
  2. Pat Visanpattanasin
  3. Vivian Jou
  4. Sheng Liu
  5. Xiaona Tang
  6. Qinsi Zheng
  7. Kai Yu Li
  8. Jonathan Snedeker
  9. Luke D Lavis
  10. Timothee Lionnet
  11. Carl Wu
(2021)
Single-molecule imaging of chromatin remodelers reveals role of ATPase in promoting fast kinetics of target search and dissociation from chromatin
eLife 10:e69387.
https://doi.org/10.7554/eLife.69387

Share this article

https://doi.org/10.7554/eLife.69387

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