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

Elife. 2021 Jul 27:10:e69424. doi: 10.7554/eLife.69424.


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.

Keywords: ATP-dependent chromatin remodeling; D. melanogaster; RNA polymerase II; SWI/SNF; biochemistry; brahma; chemical biology; chromosomes; gene expression; live-cell imaging; polytene chromosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism*
  • Animals
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Chromatin Assembly and Disassembly*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Histones / metabolism
  • Hydrolysis
  • Nucleosomes / metabolism
  • Ribonucleoprotein, U1 Small Nuclear / metabolism*
  • Trans-Activators / metabolism*


  • Cell Cycle Proteins
  • Drosophila Proteins
  • Histones
  • Nucleosomes
  • Ribonucleoprotein, U1 Small Nuclear
  • Trans-Activators
  • brm protein, Drosophila
  • snf protein, Drosophila
  • Adenosine Triphosphate
  • Adenosine Triphosphatases

Grants and funding

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