MediatorKomplex

MediatorKomplex, commonly referred to as the Mediator complex, is a large multi-subunit transcriptional coactivator found in eukaryotic cells. It functions as an adaptor that conveys regulatory information from sequence-specific transcription factors bound at enhancers and promoters to RNA polymerase II, enabling proper transcription initiation and regulation.

The Mediator is organized into functional modules. In many eukaryotes, core Mediator comprises the head, middle, and tail modules, while an additional kinase module can reversibly associate with the complex. The kinase module includes CDK8 or CDK19, Cyclin C, and subunits MED12 and MED13; the remaining subunits form the core Mediator that interfaces with RNA Pol II. Subunit composition is species-specific but the modular architecture is conserved.

Functionally, Mediator does not bind DNA directly but is recruited by transcription factors and chromatin context. It facilitates assembly of the RNA Pol II preinitiation complex at gene promoters, stabilizes promoter–enhancer communication, and can influence transcription initiation and promoter escape. The kinase module can modulate activity by phosphorylating transcription factors and components of the Pol II machinery, thereby enabling context-dependent activation or repression of gene expression and affecting promoter-proximal pausing.

Evolutionarily, Mediator is conserved from yeast to humans and is essential for many developmental programs and cellular responses to signaling pathways. Experimental studies, including structural analyses, have illuminated its modular organization and dynamic interactions with transcription factors and Pol II. Dysregulation or mutation of Mediator subunits has been linked to developmental disorders and cancer, underscoring its central role in transcriptional regulation.