title: Swi/Snf dynamics on stress-responsive genes is governed by competitive bromodomain interactions.
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.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Arnob
authors.initials: A
authors.lastname: Dutta
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Madelaine
authors.initials: M
authors.lastname: Gogol
authors.affiliation: Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806, Korea;
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Michaela
authors.initials: M
authors.lastname: Smolle
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Swaminathan
authors.initials: S
authors.lastname: Venkatesh
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Joshua
authors.initials: J
authors.lastname: Gilmore
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: 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.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
mesh_terms: D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C499333:SNF2 protein, S cerevisiae
keywords: Swi/Snf; activator; histone acetylation; stress