Structures of +1 nucleosome-bound PIC-Mediator complex

Science. 2022 Oct 7;378(6615):62-68. doi: 10.1126/science.abn8131. Epub 2022 Oct 6.

Abstract

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.

MeSH terms

  • Chromatin / chemistry
  • Humans
  • Mediator Complex* / chemistry
  • Nucleosomes* / chemistry
  • RNA Polymerase II / chemistry
  • Transcription Initiation Site
  • Transcription Initiation, Genetic*

Substances

  • Chromatin
  • Mediator Complex
  • Nucleosomes
  • RNA Polymerase II