Recognition of the inherently unstable H2A nucleosome by Swc2 is a major determinant for unidirectional H2A.Z exchange
Recognition of the inherently unstable H2A nucleosome by Swc2 is a major determinant for unidirectional H2A.Z exchange
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Swc2 对固有不稳定 H2A 核小体的识别是单向 H2A.Z 交换的主要决定因素
DOI：
10.1016/j.celrep.2021.109183
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发表时间：
2021-05-25
期刊：
影响因子：
8.8
通讯作者：
Zhou, Zheng
中科院分区：
文献类型：
--
作者：
Dai, Linchang;Xiao, Xue;Zhou, Zheng
多亚基染色质重塑器SWR1/SRCAP/p400用自由形式的H2A取代核小体H2A- h2b二聚体。Z-H2B二聚体，但控制h2a - h2a单向的机制。Z交换仍然难以捉摸。在这里，我们使用单分子力谱来剖析H2A核小体和H2A的拆卸/重组过程。Z核小体。我们发现酵母SWR1复合体蛋白2（以前称为Swc2-Z）的n端1-135残基促进含有H2A但不含H2A的核小体的分解。swc2介导的核小体拆卸/重组需要固有不稳定的H2A核小体，其不稳定性由三个H2A α 2-螺旋残基Gly47、Pro49和11e63赋予，因为它们选择性地削弱了H2A- h2b二聚体的结构刚性。它还需要直接锚定在H2A核小体上并在swr1催化的H2A中起作用的Swc2-ZN（残基1-37）。Z置换和酵母H2A。体内Z沉积。我们的发现为SWR1复合体如何区分H2A核小体和H2A提供了机制上的见解。Z核小体，为单向H2A的治理建立了一个简单的范例。Z交换。
The multisubunit chromatin remodeler SWR1/SRCAP/p400 replaces the nucleosomal H2A-H2B dimer with the free-form H2A.Z-H2B dimer, but the mechanism governing the unidirectional H2A-to-H2A.Z exchange remains elusive. Here, we perform single-molecule force spectroscopy to dissect the disassembly/reassembly processes of the H2A nucleosome and H2A.Z nucleosome. We find that the N-terminal 1-135 residues of yeast SWR1 complex protein 2 (previously termed Swc2-Z) facilitate the disassembly of nucleosomes containing H2A but not H2A.Z. The Swc2-mediated nucleosome disassembly/reassembly requires the inherently unstable H2A nucleosome, whose instability is conferred by three H2A alpha 2-helical residues, Gly47, Pro49, and 11e63, as they selectively weaken the structural rigidity of the H2A-H2B dimer, It also requires Swc2-ZN (residues 1-37) that directly anchors to the H2A nucleosome and functions in the SWR1-catalyzed H2A.Z replacement in vitro and yeast H2A.Z deposition in vivo. Our findings provide mechanistic insights into how the SWR1 complex discriminates between the H2A nucleosome and H2A.Z nucleosome, establishing a simple paradigm for the governance of unidirectional H2A.Z exchange.