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中科院生物物理所科学家Cell Res揭示新型分子伴侣

  1. Anp32e
  2. 分子伴侣
  3. 生物物理所

来源:生物谷 2014-03-17 11:06

中科院生物物理所周政研究组于在高等真核生物发现了一种新的组蛋白伴侣Anp32e。

中科院生物物理所周政研究组于2014年3月11日,《Cell Research》杂志在线发表了"Anp32e, a higher eukaryotic histone chaperone directs preferential recognition for H2A.Z"。该论文在高等真核生物发现了一种新的组蛋白伴侣Anp32e,与常规核小体H2A相比,组蛋白变体H2A.Z与Anp32e具有更高的结合能力。ChIp-Seq表明Anp32e在去除启动子区域的H2A.Z过程中发挥作用,Anp32e与组蛋白复合物的结构揭示了H2A.Z通过构象改变与其伴侣蛋白进行特异识别的分子机制。 研究人员发现并鉴定了一种新的组蛋白伴侣Anp32e。与H2A相比,Anp32e对H2A.Z具有更高的选择性,该蛋白能够抑制H2A.Z-H2B与DNA的多聚现象,具有组蛋白伴侣的功能。H2A.Z-H2B-Anp32e的三元复合物结构显示,与Anp32e结合后,H2A.Z序列中C端的aC螺旋发生构象改变并延伸,伸长的aC螺旋与Anp32e之间形成的疏水作用对H2A.Z和Anp32e复合物结构的稳定起到了至关重要的作用。通过对二者的C端一级序列进行对比,作者发现在aC螺旋所在的区域,H2A序列比H2A.Z序列多出一个关键的甘氨酸。实验证明,H2A序列中这个多出的甘氨酸阻碍了H2AaC螺旋的延伸,从而导致Anp32e对H2A.Z具有更高的选择性。随后的ChIp-Seq分析不但表明H2A.Z和Anp32e在全基因组水平上具有高度相关的染色质定位,而且通过比较敲除Anp32e和过表达Anp32e的ChIp-Seq数据,发现Anp32e在去除启动子区域的H2A.Z过程中发挥作用。(生物谷Bioon.com)

生物谷推荐的英文摘要

Cell Research     doi: 10.1038/cr.2014.30

Anp32e, a higher eukaryotic histone chaperone directs preferential recognition for H2A.Z

Zhuo Mao, Lu Pan, Weixiang Wang, Jian Sun, Shan Shan, Qiang Dong, Xiaoping Liang, Linchang Dai, Xiaojun Ding, She Chen, Zhuqiang Zhang, Bing Zhu and Zheng Zhou

H2A.Z is a highly conserved histone variant in all species. The chromatin deposition of H2A.Z is specifically catalyzed by the yeast chromatin remodeling complex SWR1 and its mammalian counterpart SRCAP. However, the mechanism by which H2A.Z is preferentially recognized by non-histone proteins remains elusive. Here we identified Anp32e, a novel higher eukaryote-specific histone chaperone for H2A.Z. Anp32e preferentially associates with H2A.Z-H2B dimers rather than H2A-H2B dimers in vitro and in vivo and dissociates non-nucleosomal aggregates formed by DNA and H2A-H2B. We determined the crystal structure of the Anp32e chaperone domain (186-232) in complex with the H2A.Z-H2B dimer. In this structure, the region containing Anp32e residues 214-224, which is absent in other Anp32 family proteins, specifically interacts with the extended H2A.Z αC helix, which exhibits an unexpected conformational change. Genome-wide profiling of Anp32e revealed a remarkable co-occupancy between Anp32e and H2A.Z. Cells overexpressing Anp32e displayed a strong global H2A.Z loss at the +1 nucleosomes, whereas cells depleted of Anp32e displayed a moderate global H2A.Z increase at the +1 nucleosomes. This suggests that Anp32e may help to resolve the non-nucleosomal H2A.Z aggregates and also facilitate the removal of H2A.Z at the +1 nucleosomes, and the latter may help RNA polymerase II to pass the first nucleosomal barrier.

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