In vivo analysis reveals that ATP-hydrolysis couples remodeling to SWI/SNF release from chromatin

  1. Ben Tilly  Is a corresponding author
  2. Gillian Chalkley
  3. Jan van der Knaap
  4. Yuri Moshkin
  5. Tsung Wai Kan
  6. Dick HW Dekkers
  7. Jeroen Demmers
  8. Peter Verrijzer  Is a corresponding author
  1. Erasmus University Medical Center, Netherlands
  2. Erasmus MC, Netherlands
  3. ErasmusMC, Netherlands

Abstract

ATP-dependent chromatin remodelers control the accessibility of genomic DNA through nucleosome mobilization. However, the dynamics of genome exploration by remodelers, and the role of ATP hydrolysis in this process remain unclear. We used live-cell imaging of Drosophila polytene nuclei to monitor Brahma (BRM) remodeler interactions with its chromosomal targets. In parallel, we measured local chromatin condensation and its effect on BRM association. Surprisingly, only a small portion of BRM is bound to chromatin at any given time. BRM binds decondensed chromatin but is excluded from condensed chromatin, limiting its genomic search space. BRM-chromatin interactions are highly dynamic, whereas histone-exchange is limited and much slower. Intriguingly, loss of ATP hydrolysis enhanced chromatin retention and clustering of BRM, which was associated with reduced histone turnover. Thus, ATP hydrolysis couples nucleosome remodeling to remodeler release, driving a continuous transient probing of the genome.

Data availability

The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (www.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD025474.All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2 and Figure 2-figure-supplement1

The following data sets were generated

Article and author information

Author details

  1. Ben Tilly

    Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
    For correspondence
    b.tilly@erasmusmc.nl
    Competing interests
    The authors declare that no competing interests exist.
  2. Gillian Chalkley

    Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Jan van der Knaap

    Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Yuri Moshkin

    Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Tsung Wai Kan

    Biochemistry, Erasmus MC, 3015 CN Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Dick HW Dekkers

    Proteomics Center, ErasmusMC, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Jeroen Demmers

    Proteomics Center, ErasmusMC, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  8. Peter Verrijzer

    Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
    For correspondence
    c.verrijzer@erasmusmc.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6476-3264

Funding

FOM-AMOLF (DNA at Work)

  • Peter Verrijzer

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

Copyright

© 2021, Tilly 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. Ben Tilly
  2. Gillian Chalkley
  3. Jan van der Knaap
  4. Yuri Moshkin
  5. Tsung Wai Kan
  6. Dick HW Dekkers
  7. Jeroen Demmers
  8. Peter Verrijzer
(2021)
In vivo analysis reveals that ATP-hydrolysis couples remodeling to SWI/SNF release from chromatin
eLife 10:e69424.
https://doi.org/10.7554/eLife.69424

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https://doi.org/10.7554/eLife.69424

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