A conserved Mediator-CDK8 kinase module association regulates Mediator-RNA polymerase II interaction.

The CDK8 kinase module (CKM) is a subcomplex that interacts with Mediator and represses transcription. Structural and biochemical analyses now show that interaction of the CKM with Mediator interferes with C-terminal domain–dependent binding of RNA polymerase II to a previously unknown Mediator binding site and with holoenzyme formation, which forms the basis for CKM's repressive effect on transcription.