PreprintCited by 45Chromatin Remodeling and CancerGenomics and Chromatin DynamicsEpigenetics and DNA Methylation

Swi/Snf dynamics on stress-responsive genes is governed by competitive bromodomain interactions

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Dutta, Arnob, Gogol, Madelaine, Kim, Jeong-Hoon, Smolle, Michaela, Venkatesh, Swaminathan, Gilmore, Joshua, Florens, Laurence, Washburn, Michael P. +1 more·2014·Genes & Development

Abstract

The Swi/Snf chromatin remodeling complex functions to alter nucleosome positions by either sliding nucleosomes on DNA or the eviction of histones. The presence of histone acetylation and activator-dependent recruitment and retention of Swi/Snf is important for its efficient function. It is not understood, however, why such mechanisms are required to enhance Swi/Snf activity on nucleosomes. Snf2, the catalytic subunit of the Swi/Snf remodeling complex, has been shown to be a target of the Gcn5 acetyltransferase. Our study found that acetylation of Snf2 regulates both recruitment and release of Swi/Snf from stress-responsive genes. Also, the intramolecular interaction of the Snf2 bromodomain with the acetylated lysine residues on Snf2 negatively regulates binding and remodeling of acetylated nucleosomes by Swi/Snf. Interestingly, the presence of transcription activators mitigates the effects of the reduced affinity of acetylated Snf2 for acetylated nucleosomes. Supporting our in vitro results, we found that activator-bound genes regulating metabolic processes showed greater retention of the Swi/Snf complex even when Snf2 was acetylated. Our studies demonstrate that competing effects of (1) Swi/Snf retention by activators or high levels of histone acetylation and (2) Snf2 acetylation-mediated release regulate dynamics of Swi/Snf occupancy at target genes.

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Authors
Dutta, A., Gogol, M., Kim, J.-H., Smolle, M., Venkatesh, S., Gilmore, J., Florens, L., Washburn, M. P., & Workman, J. L.
Affiliations
  • Stowers Institute for Medical Research (US)
  • Korea Research Institute of Bioscience and Biotechnology (KR)
Venue
Genes & Development
Published
2014-10-15
Volume
28
Issue
20
Pages
2314-2330
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2071951467
Cited by
45
References
31
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 7 · 2016: 5 · 2015: 5 · 2014: 1
Type
posted content
Language
en
Open access
Licence
cc-by-nc
Locations
  • Genes & Development (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • KRIBB Repository (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
National Institutes of Health (R01GM047867)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
SWI/SNF complex, SnF2, bromodomain, histone acetylation, GCN5, nucleosome acetylation, stress response genes, transcriptional activator, nucleosome sliding, histone eviction, metabolic genes
MeSH terms
Acetylation, Adenosine Triphosphatases, Nucleosomes, Protein Binding, Saccharomyces cerevisiae, Stress, Physiological, Transcription Factors, Saccharomyces cerevisiae Proteins

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