title: A histone acetylation switch regulates H2A.Z deposition by the SWR-C remodeling enzyme.
abstract: The histone variant H2A.Z plays key roles in gene expression, DNA repair, and centromere function. H2A.Z deposition is controlled by SWR-C chromatin remodeling enzymes that catalyze the nucleosomal exchange of canonical H2A with H2A.Z. Here we report that acetylation of histone H3 on lysine 56 (H3-K56Ac) alters the substrate specificity of SWR-C, leading to promiscuous dimer exchange in which either H2A.Z or H2A can be exchanged from nucleosomes. This result was confirmed in vivo, where genome-wide analysis demonstrated widespread decreases in H2A.Z levels in yeast mutants with hyperacetylated H3K56. Our work also suggests that a conserved SWR-C subunit may function as a "lock" that prevents removal of H2A.Z from nucleosomes. Our study identifies a histone modification that regulates a chromatin remodeling reaction and provides insights into how histone variants and nucleosome turnover can be controlled by chromatin regulators.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Shinya
authors.initials: S
authors.lastname: Watanabe
authors.forename: Marta
authors.initials: M
authors.lastname: Radman-Livaja
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Rando
authors.forename: Craig L
authors.initials: CL
authors.lastname: Peterson
mesh_terms: D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D055162:Biocatalysis; D042002:Chromatin Assembly and Disassembly; D006657:Histones / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism*; D055503:Protein Multimerization; D055550:Protein Stability; D021122:Protein Subunits / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D006657:Histones; D009097:Multienzyme Complexes; D009707:Nucleosomes; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C481261:Swr1 protein, S cerevisiae