Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Cell. 2011 Jan 21;144(2):200-13. doi: 10.1016/j.cell.2010.12.021.
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 mislocalized, 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 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 mechanism to promote genome stability.
INO80 是一种进化上保守的、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 通过控制组蛋白变体 H2A.Z 的全基因组分布至少部分地促进了这些不同的过程。在没有 INO80 的情况下，H2A.Z 核小体发生定位错误，启动子处的 H2A.Z 水平对转录变化的反应性降低，表明 INO80 控制 H2A.Z 的动力学。此外，我们证明 INO80 具有组蛋白交换活性，其中该酶可以用游离的 H2A/H2B 二聚体取代核小体中的 H2A.Z/H2B。ino80 和 htz1 之间的遗传相互作用支持了这样一种模型，即 INO80 作为一种促进基因组稳定性的机制，催化从染色质中去除未乙酰化的 H2A.Z。
