Structures of +1 nucleosome–bound PIC-Mediator complex

• Published in: Science (American Association for the Advancement of Science) 2022-10, Vol.378 (6615), p.62-68
• Main Authors: Chen, Xizi, Wang, Xinxin, Liu, Weida, Ren, Yulei, Qu, Xuechun, Li, Jiabei, Yin, Xiaotong, Xu, Yanhui
• Format: Article
• Language: English
• Subjects: Base pairs; Epigenetics; Transcription initiation
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.abn8131

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. Eukaryotic transcription initiation starts with the assembly of a preinitiation complex (PIC) on core promoters covering transcription start sites (TSS). The +1 nucleosome, the first downstream nucleosome from a TSS, consists of characteristic epigenetic marks and is commonly thought to be a barrier of early transcription. Chen et al . determined the structures of nucleosome-bound PIC-Mediator. Structural and biochemical analyses show that the nucleosome makes multiple contacts with PIC-Mediator and may enhance transcription activity if the nucleosome is positioned 40 or 50 base pairs (but not 70 base pairs) downstream of TSS. This study provides a structural basis for understanding the regulatory function of the +1 nucleosome in transcription initiation. —DJ Structural analysis reveals molecular mechanism of preinitiation complex–Mediator organization on chromatin RNA polymerase II–mediated eukaryotic transcription initiation.