A histone acetylation switch regulates H2A.Z deposition by the SWR-C remodeling enzyme
Department of Biochemistry and Molecular Pharmacology; Program in Molecular Medicine
Acetylation; Adenosine Triphosphatases; Biocatalysis; *Chromatin Assembly and Disassembly; Histones; Multienzyme Complexes; Nucleosomes; Protein Multimerization; Protein Stability; Protein Subunits; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Substrate Specificity
Biochemistry | Molecular Biology
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.
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Citation: Science. 2013 Apr 12;340(6129):195-9. doi: 10.1126/science.1229758. Link to article on publisher's site
Science (New York, N.Y.)
Watanabe, Shinya; Radman-Livaja, Marta; Rando, Oliver J.; and Peterson, Craig L., "A histone acetylation switch regulates H2A.Z deposition by the SWR-C remodeling enzyme" (2013). University of Massachusetts Medical School Faculty Publications. 97.