Global regulation of H2A.Z localization by the INO80 chromatin-remodeling enzyme is essential for genome integrity.
Global regulation of H2A.Z localization by the INO80 chromatin-remodeling enzyme is essential for genome integrity.
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DOI：
10.1016/j.cell.2010.12.021
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发表时间：
2011-01-21
期刊：
影响因子：
64.5
通讯作者：
Peterson CL
中科院分区：
文献类型：
--
作者：
Papamichos-Chronakis M;Watanabe S;Rando OJ;Peterson CL
INO80是一种进化保守的、依赖于ATP的染色质重塑酶，在转录、DNA修复和复制中发挥作用。在这里，我们表明酵母INO80至少部分地通过控制组蛋白变异体H2A.Z在全基因组的分布来促进这些不同的过程。在没有INO80的情况下，H2A.Z核小体被错误定位，并且启动子上的H2A.Z水平显示对转录变化的反应性降低，这表明INO80控制着H2A.Z的动态。此外，我们还证明了INO80具有一种新的组蛋白交换活性，该酶可以用游离的H_2A/H_2B二聚体取代核小体H_2A/H_2B。INO80和htz1之间的遗传相互作用支持一种模型，在该模型中，INO80催化从染色质中去除未乙酰化的H2A.Z，这是促进基因组稳定性的一种新机制。
INO80 is an evolutionarily conserved, ATP-dependent chromatin remodeling enzyme that plays roles in transcription, DNA repair, and replication. Here, we show that yeast INO80 facilitates these diverse processes at least in part by controlling genome-wide distribution of the histone variant H2A.Z. In the absence of INO80, H2A.Z nucleosomes are mis-localized, and H2A.Z levels at promoters show reduced responsiveness to transcriptional changes, suggesting that INO80 controls H2A.Z dynamics. Additionally, we demonstrate that INO80 has a novel histone exchange activity in which the enzyme can replace nucleosomal H2A.Z/H2B with free H2A/H2B dimers. Genetic interactions between ino80 and htz1 support a model in which INO80 catalyzes the removal of unacetylated H2A.Z from chromatin as a novel mechanism to promote genome stability.
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