The Mediator kinase module: an interface between cell signaling and transcription

Trends Biochem Sci. 2022 Apr;47(4):314-327. doi: 10.1016/j.tibs.2022.01.002.

Olivia Luyties ¹, Dylan J Taatjes ²

Affiliations

1 Department of Biochemistry, University of Colorado, Boulder, CO, USA.
2 Department of Biochemistry, University of Colorado, Boulder, CO, USA. Electronic address: [email protected].

PMID: 35193797 DOI: 10.1016/j.tibs.2022.01.002

Abstract

The Mediator complex controls RNA polymerase II (pol II) activity by coordinating the assembly of pol II regulatory factors at transcription start sites and by mediating interactions between enhancer-bound transcription factors (TFs) and the pol II enzyme. Mediator structure and function is completely altered upon binding the Mediator kinase module, a multi-subunit complex that contains CDK8 or its vertebrate-specific paralog CDK19. Here, we review the mechanisms by which the Mediator kinase module controls pol II transcription, emphasizing its impact on TF activity, pol II elongation, enhancer function, and chromatin architecture. We also highlight how the Mediator kinase module integrates signaling pathways with transcription to enable rapid, stimulus-specific responses, as well as its links to human disease.

Keywords

MED12; MED13; eRNA; enhancer-promoter loops; metabolism; pol II pausing.

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