Format

Send to

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

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

Author information

1
Institut de recherches cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, QC H2W 1R7, Canada.
2
Département de Biochimie et Médecine Moléculaire, Faculté de Médecine, Université de Montréal, 2900 Boulevard Edouard-Montpetit, Montréal, QC H3T 1J4, Canada.
3
Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, 456A North Frear Laboratory, University Park, PA 16802, USA.
4
Institut de recherches cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, QC H2W 1R7, Canada; Département de Médecine, Faculté de Médecine, Université de Montréal, 2900 Boulevard Edouard-Montpetit, Montréal, QC H3T 1J4, Canada. Electronic address: francois.robert@ircm.qc.ca.

Abstract

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

PMID:
27773677
PMCID:
PMC5824718
DOI:
10.1016/j.molcel.2016.09.002
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center