Structures of+1 nucleosome-bound PIC-Mediator complex
Structures of+1 nucleosome-bound PIC-Mediator complex
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DOI：
10.1126/science.abn8131
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发表时间：
2022-10-07
期刊：
影响因子：
56.9
通讯作者：
Xu, Yanhui
中科院分区：
文献类型：
--
作者：
Chen, Xizi;Wang, Xinxin;Xu, Yanhui
RNA聚合酶II介导的真核转录起始于核心启动子上的前起始复合物（PIC）的组装。+1核小体位于转录起始位点（TSS）下游约40个碱基对处，通常被称为转录屏障。+1核小体结合的PIC-介体结构表明PIC-介体偏好结合位于TSS下游40个碱基对的T40 N核小体，并且接触T50 N而不接触T70 N核小体。核小体通过结合TFIIH亚基p52和介体亚基MED 19和MED 26促进PIC-介体在启动子上的组织，并且可能有助于转录起始。PIC-介体表现出多种核小体结合模式，支持+1核小体在PIC-介体组装的协调中的结构作用。我们的研究揭示了PIC-介体在染色质上组织的分子机制，并强调了+1核小体在调节转录起始中的重要性。
RNA polymerase II-mediated eukaryotic transcription starts with the assembly of the preinitiation complex (PIC) on core promoters. The +1 nucleosome is well positioned about 40 base pairs downstream of the transcription start site (TSS) and is commonly known as a barrier of transcription. The +1 nucleosome-bound PIC-Mediator structures show that PIC-Mediator prefers binding to T40N nucleosome located 40 base pairs downstream of TSS and contacts T50N but not the T70N nucleosome. The nucleosome facilitates the organization of PIC-Mediator on the promoter by binding TFIIH subunit p52 and Mediator subunits MED19 and MED26 and may contribute to transcription initiation. PIC-Mediator exhibits multiple nucleosome-binding patterns, supporting a structural role of the +1 nucleosome in the coordination of PIC-Mediator assembly. Our study reveals the molecular mechanism of PIC-Mediator organization on chromatin and underscores the significance of the +1 nucleosome in regulating transcription initiation.