Hatazawa Suguru, Liu Jiuyang, Takizawa Yoshimasa, Zandian Mohamad, Negishi Lumi, Kutateladze Tatiana G, Kurumizaka Hitoshi
Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
iScience. 2022 Jun 9;25(7):104563. doi: 10.1016/j.isci.2022.104563. eCollection 2022 Jul 15.
p300 is a human acetyltransferase that associates with chromatin and mediates vital cellular processes. We now report the cryo-electron microscopy structures of the p300 catalytic core in complex with the nucleosome core particle (NCP). In the most resolved structure, the HAT domain and bromodomain of p300 contact nucleosomal DNA at superhelical locations 2 and 3, and the catalytic site of the HAT domain are positioned near the N-terminal tail of histone H4. Mutations of the p300-DNA interfacial residues of p300 substantially decrease binding to NCP. Three additional classes of p300-NCP complexes show different modes of the p300-NCP complex formation. Our data provide structural details critical to our understanding of the mechanism by which p300 acetylates multiple sites on the nucleosome.
p300是一种与染色质相关联并介导重要细胞过程的人类乙酰转移酶。我们现在报告p300催化核心与核小体核心颗粒（NCP）复合物的冷冻电子显微镜结构。在分辨率最高的结构中，p300的组蛋白乙酰转移酶（HAT）结构域和溴结构域在超螺旋位置2和3处与核小体DNA接触，且HAT结构域的催化位点位于组蛋白H4的N端尾部附近。p300与DNA界面残基的突变会显著降低其与NCP的结合。另外三类p300-NCP复合物显示出不同的p300-NCP复合物形成模式。我们的数据提供了对于理解p300使核小体上多个位点乙酰化机制至关重要的结构细节。
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