Functional interplay between Mediator and RSC chromatin remodeling complex controls nucleosome-depleted region maintenance at promoters

Cell Rep. 2023 May 30;42(5):112465. doi: 10.1016/j.celrep.2023.112465. Epub 2023 May 2.

Abstract

Chromatin organization is crucial for transcriptional regulation in eukaryotes. Mediator is an essential and conserved co-activator thought to act in concert with chromatin regulators. However, it remains largely unknown how their functions are coordinated. Here, we provide evidence in the yeast Saccharomyces cerevisiae that Mediator establishes physical contact with RSC (Remodels the Structure of Chromatin), a conserved and essential chromatin remodeling complex that is crucial for nucleosome-depleted region (NDR) formation. We determine the role of Mediator-RSC interaction in their chromatin binding, nucleosome occupancy, and transcription on a genomic scale. Mediator and RSC co-localize on wide NDRs of promoter regions, and specific Mediator mutations affect nucleosome eviction and TSS-associated +1 nucleosome stability. This work shows that Mediator contributes to RSC remodeling function to shape NDRs and maintain chromatin organization on promoter regions. It will help in our understanding of transcriptional regulation in the chromatin context relevant for severe diseases.

Keywords: CP: Molecular biology; Mediator; RNA polymerase II; RSC; genome-wide distribution; nucleosome-depleted region; transcription; yeast Saccharomyces cerevisiae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Nucleosomes* / metabolism
  • Promoter Regions, Genetic / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Nucleosomes
  • DNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Chromatin