Mediator Undergoes a Compositional Change during Transcriptional Activation

Abstract

Mediator is a transcriptional co-activator recruited toenhancers by DNA-binding activators, and it also interacts with RNA polymerase (Pol) II as part of thepreinitiation complex (PIC). We demonstrate that a single Mediator complex associates with the enhancer and core promoter invivo, indicating that it can physically bridge these transcriptional elements. However, the Mediator kinase module associates strongly with the enhancer, but not with the core promoter, and it dissociates from the enhancer upon depletion of the TFIIH kinase. Severing the kinase module from Mediator by removing the connecting subunit Med13 does not affect Mediator association at the core promoter but increases occupancy at enhancers. Thus, Mediator undergoes a compositional change in which the kinase module, recruited via Mediator to the enhancer, dissociates from Mediator to permit association with Pol II and the PIC. As such,Mediator acts as a dynamic bridge between the enhancer and core promoter.