Structural Mechanisms of Nucleosome Recognition by Linker Histones.
Structural Mechanisms of Nucleosome Recognition by Linker Histones.
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DOI：
10.1016/j.molcel.2015.06.025
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发表时间：
2015-08-20
期刊：
影响因子：
16
通讯作者：
Bai Y
中科院分区：
文献类型：
--
作者：
Zhou BR;Jiang J;Feng H;Ghirlando R;Xiao TS;Bai Y
连接组蛋白与核小体结合，调节染色质结构和基因表达。尽管经过三十多年的努力，连接组蛋白识别核小体的结构基础仍然是难以捉摸的。在这里，我们报告的球形结构域的鸡连接器组蛋白H5在复杂的核小体在3.5 μ m分辨率，这是使用核磁共振光谱验证的晶体结构。球状结构域位于核小体的二分体上，并与两个DNA接头相互作用。我们的结构整合了突变分析，以前的交联和荧光恢复后的光漂白实验的结果，并有助于解决长期的争论核小体识别的连接组蛋白的结构机制。H5球状结构域的on-dyad结合模式不同于最近报道的果蝇连接体组蛋白H1的off-dyad结合模式。我们证明了具有不同结合模式的连接组蛋白可以折叠染色质，形成不同的高级结构。
Linker histones bind to the nucleosome and regulate the structure of chromatin and gene expression. Despite more than three decades of effort, structural basis of nucleosome recognition by linker histones remains elusive. Here, we report the crystal structure of the globular domain of chicken linker histone H5 in complex with the nucleosome at 3.5 Å resolution, which is validated using nuclear magnetic resonance spectroscopy. The globular domain sits on the dyad of the nucleosome and interacts with both DNA linkers. Our structure integrates results from mutation analyses, previous cross-linking and fluorescence recovery after photobleach experiments, and helps resolve the long debate on structural mechanisms of nucleosome recognition by linker histones. The on-dyad binding mode of the H5 globular domain is different from the recently reported off-dyad binding mode of Drosophila linker histone H1. We demonstrate that linker histones with different binding modes could fold chromatin to form distinct higher-order structures.