Structural basis of H2A.Z recognition by SRCAP chromatin-remodeling subunit YL1
Structural basis of H2A.Z recognition by SRCAP chromatin-remodeling subunit YL1
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DOI：
10.1038/nsmb.3190
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发表时间：
2016-04-01
影响因子：
16.8
通讯作者：
Zhou, Zheng
中科院分区：
文献类型：
--
作者：
Liang, Xiaoping;Shan, Shan;Zhou, Zheng
组蛋白变异体H2A.Z是基因启动子和增强子两侧动态核小体的通用标记，通过SRCAP(SWR1)整合到染色质中，SRCAP(SWR1)是一种依赖于ATP的多组分染色质重塑复合体。SRCAP(SWR1)的YL1(Swc2)亚基在H_2A.Z识别中起着至关重要的作用，但它是如何实现这一点的尚不清楚。在这里，我们报道了果蝇黑腹果蝇YL1(dYL1-Z)与H_2A_Z-H_2B二聚体以1.9埃分辨率形成的H_2A_Z结合区的晶体结构。DYL1-Z结构域采用一种新的鞭状结构，包裹在H_2A.Z-H_2B上，优先识别主要是由环2中的三个残基、H_2A_Z的超酸性斑块和延伸的αC螺旋授予的。重要的是，该结构域对于体内萌芽酵母H_2A.Z的沉积和SRCAP(SWR1)催化的组蛋白H_2A.Z体外置换是必不可少的。我们的研究将YL1-Z与已知的H2A.Z伴侣区分开来，并提出了一种基于增加结合亲和力的分级机制，促进了H2A.Z从SRCAP(SWR1)向核小体的转移。
Histone variant H2A.Z, a universal mark of dynamic nucleosomes flanking gene promoters and enhancers, is incorporated into chromatin by SRCAP (SWR1), an ATP-dependent, multicomponent chromatin-remodeling complex. The YL1 (Swc2) subunit of SRCAP (SWR1) plays an essential role in H2A.Z recognition, but how it achieves this has been unclear. Here, we report the crystal structure of the H2A.Z-binding domain of Drosophila melanogaster YL1 (dYL1-Z) in complex with an H2A.Z-H2B dimer at 1.9-angstrom resolution. The dYL1-Z domain adopts a new whip-like structure that wraps over H2A.Z-H2B, and preferential recognition is largely conferred by three residues in loop 2, the hyperacidic patch and the extended alpha C helix of H2A.Z. Importantly, this domain is essential for deposition of budding yeast H2A.Z in vivo and SRCAP (SWR1)-catalyzed histone H2A.Z replacement in vitro. Our studies distinguish YL1-Z from known H2A.Z chaperones and suggest a hierarchical mechanism based on increasing binding affinity facilitating H2A.Z transfer from SRCAP (SWR1) to the nucleosome.