Chen Xizi, Wang Xinxin, Liu Weida, Ren Yulei, Qu Xuechun, Li Jiabei, Yin Xiaotong, Xu Yanhui
Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Department of Biochemistry and Biophysics, School of Life Sciences, Shanghai Key Laboratory of Radiation Oncology, and Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College of Fudan University, Shanghai 200032, China.
The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, China, Department of Systems Biology for Medicine, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Science. 2022 Oct 7;378(6615):62-68. doi: 10.1126/science.abn8131. Epub 2022 Oct 6.
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.
RNA聚合酶II介导的真核转录起始于前起始复合物（PIC）在核心启动子上的组装。+1核小体位于转录起始位点（TSS）下游约40个碱基对处，位置良好，通常被认为是转录的障碍。与+1核小体结合的PIC-中介体结构表明，PIC-中介体更喜欢与位于TSS下游40个碱基对处的T40N核小体结合，并与T50N接触，但不与T70N核小体接触。核小体通过结合TFIIH亚基p52和中介体亚基MED19及MED26促进PIC-中介体在启动子上的组织，并可能有助于转录起始。PIC-中介体表现出多种核小体结合模式，支持+1核小体在协调PIC-中介体组装中的结构作用。我们的研究揭示了PIC-中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。
