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.
A histone acetylation switch regulates H2A.Z deposition by the SWR-C remodeling enzyme
Watanabe, S.; Radman-Livaja, M.; Rando, O. J.; Peterson, C. L.
2013-04-12 / vol 340 / pages 195-9
1095-9203 (Electronic) 0036-8075 (Linking)
IGMM team(s) involved in this publication
Chromatin and DNA replication
Histones/*metabolism; Acetylation; Saccharomyces cerevisiae Proteins/genetics/*metabolism; *Chromatin Assembly and Disassembly; Adenosine Triphosphatases/*metabolism; Biocatalysis; Multienzyme Complexes/*metabolism; Nucleosomes/*metabolism; Protein Multimerization; Protein Stability; Protein Subunits/metabolism; Saccharomyces cerevisiae/genetics/*metabolism; Substrate Specificity