Swi/Snf dynamics on stress-responsive genes is governed by competitive bromodomain interactions
Open accessAbstract
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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SWI/SNF modulates nucleosome position to regulate the expression of a subset of genes including stress-responsive genes.
“SWI/SNF modulates nucleosome position to regulate the expression of a subset of genes including stress-responsive genes20,37–40.”
From SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes (2022) · cites this paper as [39]
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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)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2014-10-15
- Volume
- 28
- Issue
- 20
- Pages
- 2314-2330
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC4201291
- 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
- hybrid
- doi.org
- 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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