Tail and Kinase Modules Differently Regulate Core Mediator Recruitment and Function In Vivo

Mol Cell. 2016 Nov 3;64(3):455-466. doi: 10.1016/j.molcel.2016.09.002. Epub 2016 Oct 20.


Mediator is a highly conserved transcriptional coactivator organized into four modules, namely Tail, Middle, Head, and Kinase (CKM). Previous work suggests regulatory roles for Tail and CKM, but an integrated model for these activities is lacking. Here, we analyzed the genome-wide distribution of Mediator subunits in wild-type and mutant yeast cells in which RNA polymerase II promoter escape is blocked, allowing detection of transient Mediator forms. We found that although all modules are recruited to upstream activated regions (UAS), assembly of Mediator within the pre-initiation complex is accompanied by the release of CKM. Interestingly, our data show that CKM regulates Mediator-UAS interaction rather than Mediator-promoter association. In addition, although Tail is required for Mediator recruitment to UAS, Tailless Mediator nevertheless interacts with core promoters. Collectively, our data suggest that the essential function of Mediator is mediated by Head and Middle at core promoters, while Tail and CKM play regulatory roles.

Keywords: Cdk8/Srb10; TFIIH/Kin28; kinase module; mediator; tail module.

MeSH terms

  • Binding Sites
  • Gene Expression Regulation, Fungal*
  • Mediator Complex / genetics*
  • Mediator Complex / metabolism
  • Models, Molecular
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • RNA Polymerase II / genetics*
  • RNA Polymerase II / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Factor TFIIB / genetics*
  • Transcription Factor TFIIB / metabolism
  • Transcription Initiation, Genetic
  • Transcriptional Activation


  • Mediator Complex
  • Protein Subunits
  • SUA7 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factor TFIIB
  • RNA Polymerase II