A histone acetylation switch regulates H2A.Z deposition by the SWR-C remodeling enzyme.

A histone acetylation switch regulates H2A.Z deposition by the SWR-C remodeling enzyme.
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DOI:
10.1126/science.1229758
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发表时间:
2013-04-12
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Peterson CL
Peterson CL
中科院分区:
其他
文献类型:
--
作者:
Watanabe S;Radman-Livaja M;Rando OJ;Peterson CL

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组蛋白变体H2 A. Z在基因表达、DNA修复和着丝粒功能中起关键作用。H2A.Z沉积由SWR-C染色质重塑酶控制,所述酶催化典型H2 A与H2A.Z的核小体交换。在这里,我们报告了组蛋白H3对赖氨酸56(H3-K56 Ac)的乙酰化改变了SWR-C的底物特异性,导致混杂的二聚体交换,其中H2A.Z或H2 A可以从核小体交换。这一结果在体内得到了证实,其中全基因组分析证明了具有超乙酰化H3 K56的酵母突变体中H2A.Z水平的广泛降低。我们的工作还表明,一个保守的SWR-C亚基可能作为一个“锁”,防止从核小体去除H2A.Z。我们的研究确定了一个组蛋白修饰,调节染色质重塑反应,并提供了深入了解组蛋白变体和核小体营业额可以控制染色质调节剂。
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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