biostudies-literatureLuyties ONIAID NIH HHSNCI NIH HHSNIGMS NIH HHS314-327https://www.ebi.ac.uk/biostudies/studies/S-EPMC8939868biostudies-literatureUnknown47(4)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.Trends in biochemical sciencesThe Mediator kinase module: an interface between cell signaling and transcription.PMC8939868F31 CA254478R35 GM139550R01 AI156739Luyties OTaatjes DJfalseThe Mediator kinase module: an interface between cell signaling and transcription.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.2022-01-01T00:00:00Z2022 Apr2024-11-15T17:55:52.062Z2024-11-15T17:55:52.062ZS-EPMC89398683519379710.1016/j.tibs.2022.01.002