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A Histone Acetylation Switch Regulates H2A.Z Deposition by the SWR-C Remodeling Enzyme

Science  12 Apr 2013:
Vol. 340, Issue 6129, pp. 195-199
DOI: 10.1126/science.1229758

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Variants and Regulation

Genomic DNA is packaged into nucleosomes by spooling around histone proteins. Histone variants and the composition of nucleosomes can influence gene expression, as well as other chromatin-mediated processes. For example, the H2A.Z histone variant flanks RNA polII promoters, and such nucleosomes show rapid turnover, as well as enrichment for histone H3 acetylated at lysine 56 (H3-K56Ac). Watanabe et al. (p. 195) show that H3-K56Ac alters the substrate specificity of the chromatin remodeling enzyme SWR-C, which normally evicts nucleosomal H2A.Z such that it now rapidly exchanges both canonical H2A and the variant H2A.Z, modulating nucleosome turnover and therefore influencing gene regulation. Pathways are dramatically simplified, promoting proper folding.

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.

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