Structures of+1 nucleosome-bound PIC-Mediator complex

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.

Automated summary

RNA polymerase II-mediated eukaryotic transcription begins with the assembly of the preinitiation complex (PIC) on core promoters. The +1 nucleosome, positioned about 40 base pairs downstream of the transcription start site (TSS), acts as a barrier to transcription. The study shows that the PIC-Mediator prefers binding to the T40N nucleosome located at the 40 base pairs downstream of the TSS and contacts the T50N nucleosome, but not the T70N nucleosome. The nucleosome facilitates the organization of PIC-Mediator on the promoter and may contribute to transcription initiation. The study reveals the molecular mechanism of PIC-Mediator organization on chromatin and emphasizes the significance of the +1 nucleosome in regulating transcription initiation.