Molecular Basis for the PZP Domain of BRPF1 Association with Chromatin
Molecular Basis for the PZP Domain of BRPF1 Association with Chromatin
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DOI：
10.1016/j.str.2019.10.014
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发表时间：
2020-01-07
期刊：
影响因子：
5.7
通讯作者：
Kutateladze, Tatiana G.
中科院分区：
文献类型：
--
作者：
Klein, Brianna J.;Cox, Khan L.;Kutateladze, Tatiana G.
人组蛋白乙酰转移酶MOZ/MORF复合物的组装依赖于支架布罗莫结构域植物同源结构域（PHD）指1（BRPF 1）亚基。BRPF 1（PZP）的PHD-zinc-knuckle-PHD模块已被证明与组蛋白H3尾和DNA相关;然而，识别H3的分子机制以及组蛋白和DNA结合活性之间的关系仍不清楚。在这项研究中，我们报告的晶体结构的BRPF 1（PZP）绑定到H3的尾巴和特征的双向相互作用的BRPF 1（PZP）与核小体核心颗粒（NCP）的接合中的作用。我们发现，尽管BRPF 1（PZP）与H3尾和DNA的相互作用是紧密结合NCP和BRPF 1-MORF-ING 5-MEAF 6复合物的乙酰转移酶功能所必需的，但与H3核小体DNA的结合占主导地位。我们的研究结果表明，功能活跃的BRPF 1（PZP）可能是重要的稳定MOZ/MORF复合物在染色质与可访问的DNA。
The assembly of human histone acetyltransferase MOZ/MORF complexes relies on the scaffolding bromodomain plant homeodomain (PHD) finger 1 (BRPF1) subunit. The PHD-zinc-knuckle-PHD module of BRPF1 (BRPF1(PZP)) has been shown to associate with the histone H3 tail and DNA; however, the molecular mechanism underlying recognition of H3 and the relationship between the histone and DNA-binding activities remain unclear. In this study, we report the crystal structure of BRPF1(PZP) bound to the H3 tail and characterize the role of the bipartite interaction in the engagement of BRPF1(PZP) with the nucleosome core particle (NCP). We find that although both interactions of BRPF1(PZP) with the H3 tail and DNA are required for tight binding to NCP and for acetyltransferase function of the BRPF1-MORF-ING5-MEAF6 complex, binding to extranucleosomal DNA dominates. Our findings suggest that functionally active BRPF1(PZP) might be important in stabilization of the MOZ/MORF complexes at chromatin with accessible DNA.