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Genes Dev. 2014 Oct 15;28(20):2314-30. doi: 10.1101/gad.243584.114.

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

Author information

1
Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
2
Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806, Korea;
3
Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.

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.

KEYWORDS:

Swi/Snf; activator; histone acetylation; stress

PMID:
25319830
PMCID:
PMC4201291
DOI:
10.1101/gad.243584.114
[Indexed for MEDLINE]
Free PMC Article

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