Mediator (coactivator)

Mediator is a multiprotein complex that functions as a transcriptional coactivator. It was discovered by Roger D. Kornberg, winner of the 2006 Nobel Prize in Chemistry. It is also referred to in scientific literature as the Vitamin D Receptor Interacting Protein (DRIP) coactivator complex and the Thyroid Hormone Receptor-associated Proteins (TRAP).

The Mediator complex is required for the successful transcription of nearly all class II gene promoters in yeast.^[1] It works in the same manner in mammals. The human Mediator complex has 26 subunits and is 1.2 MDa in size. Its large surface area provides great potential for protein–protein interaction, even though its sequences do not contain many predicted functional domains. Mediator has been shown to associate with general transcription factors, as well as RNA polymerase II, and is essential for activator-dependent transcription. It has also been demonstrated that the Mediator complex is involved in activator-independent transcription, implying that it may provide a fundamental control of the formation of the initiation complex.^[2] Mediator functions as a coactivator and binds to the C-terminal domain of RNA polymerase II holoenzyme, acting as a bridge between this enzyme and transcription factors.^[3][4]

Component proteins

Human genes which encoded component proteins of the mediator complex include:

• MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11
• MED12, MED13, MED13L, MED14, MED15, MED16, MED17
• MED18, MED19, MED20, MED21, MED22, MED23, MED24
• MED25, MED26, MED27, MED28, MED29, MED30, MED31
• CCNC, CDK8, CDK19

References

1. ^ Biddick R, Young ET (2005). "Yeast mediator and its role in transcriptional regulation". C. R. Biol. 328 (9): 773–82. doi:10.1016/j.crvi.2005.03.004. PMID 16168358. 
2. ^ Taatjes, D.J. (2010) The human Mediator complex: a versatile, genome-wide regulator of transcription. Trends Biochem. Sci. 35 (6): 315–322
3. ^ Björklund S, Gustafsson CM (2005). "The yeast Mediator complex and its regulation". Trends Biochem. Sci. 30 (5): 240–4. doi:10.1016/j.tibs.2005.03.008. PMID 15896741. 
4. ^ Reeves, Wendy M.; Hahn, Steve (January 2003). "Activator-Independent Functions of the Yeast Mediator Sin4 Complex in Preinitiation Complex Formation and Transcription Reinitiation" (^{[dead link]}). Molecular and Cellular Biology 23 (1): 349–358. doi:10.1128/MCB.23.1.349-358.2003. PMC 140685. PMID 12482986. http://biosupport.licor.com./docs/odyssey/pubs/activator_independent_function_of_sin4.pdf