ANP32E is a histone chaperone that removes H2A.Z from chromatin
ANP32E is a histone chaperone that removes H2A.Z from chromatin
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DOI：
10.1038/nature12922
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发表时间：
2014-01-30
期刊：
影响因子：
64.8
通讯作者：
Hamiche, Ali
中科院分区：
文献类型：
--
作者：
Obri, Arnaud;Ouararhni, Khalid;Hamiche, Ali
H2A.Z是一种重要的组蛋白变体，参与关键核事件的调控。然而，负责H2A.Z沉积和从染色质中去除的后生动物伴侣蛋白仍然未知。在这里，我们报告的鉴定和表征的人类蛋白质ANP 32 E作为一个特定的H2A.Z分子伴侣。我们表明，ANP 32 E是假定的H2A.Z组蛋白交换复合物p400/TIP 60的成员。ANP 32 E通过称为H2A.Z相互作用结构域（ZID）的新基序与H2A.Z对接结构域的短区域相互作用。ANP 32 E-ZID和H2A.Z/H2 B二聚体之间形成的复合物的1.48埃分辨率晶体结构和生物化学数据支持H2A.Z/H2 B从核小体驱逐的潜在分子机制以及ANP 32 E通过H2A.Z羧基末端α-螺旋的特异性延伸使其稳定。最后，通过染色质免疫沉淀随后测序对ANP 32 E（-/-）细胞中H2A.Z定位的分析显示，H2A.Z在特定染色质控制区，特别是在增强子和绝缘子处的全基因组富集、再分布和积累。
H2A.Z is an essential histone variant implicated in the regulation of key nuclear events. However, the metazoan chaperones responsible for H2A.Z deposition and its removal from chromatin remain unknown. Here we report the identification and characterization of the human protein ANP32E as a specific H2A.Z chaperone. We show that ANP32E is a member of the presumed H2A.Z histone-exchange complex p400/TIP60. ANP32E interacts with a short region of the docking domain of H2A.Z through a new motif termed H2A.Z interacting domain (ZID). The 1.48 angstrom resolution crystal structure of the complex formed between the ANP32E-ZID and the H2A.Z/H2B dimer and biochemical data support an underlying molecular mechanism for H2A.Z/H2B eviction from the nucleosome and its stabilization by ANP32E through a specific extension of the H2A.Z carboxy-terminal alpha-helix. Finally, analysis of H2A.Z localization in ANP32E(-/-) cells by chromatin immunoprecipitation followed by sequencing shows genome-wide enrichment, redistribution and accumulation of H2A.Z at specific chromatin control regions, in particular at enhancers and insulators.