1] Département de Génomique Fonctionnelle et Cancer, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, CNRS, INSERM, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France [2].
Département de Biologie Structurale Intégrative, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, CNRS, INSERM, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France.
Nature. 2014 Jan 30;505(7485):648-53. doi: 10.1038/nature12922. Epub 2014 Jan 22.
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 Å 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 α-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.
H2A.Z 是一种重要的组蛋白变体，参与调控关键的核事件。然而，负责 H2A.Z 沉积及其从染色质中去除的后生动物伴侣蛋白仍不清楚。本文报道了人蛋白 ANP32E 作为一种特定的 H2A.Z 伴侣蛋白的鉴定和特性。研究表明，ANP32E 是假定的 H2A.Z 组蛋白交换复合物 p400/TIP60 的成员。ANP32E 通过一个新的称为 H2A.Z 相互作用结构域（ZID）与 H2A.Z docking 结构域的短区域相互作用。复合物形成的 1.48Å 分辨率晶体结构，以及生化数据支持了一种潜在的分子机制，即通过 H2A.Z 羧基末端α-螺旋的特定延伸，从核小体中驱逐 H2A.Z/H2B，并通过 ANP32E 稳定 H2A.Z/H2B。最后，通过染色质免疫沉淀测序分析 ANP32E(-/-)细胞中的 H2A.Z 定位，显示 H2A.Z 在整个基因组范围内富集、重新分布和积累在特定的染色质调控区域，特别是在增强子和绝缘子上。
Zotero 插件