Mediator (coactivator)
Mediator is a multiprotein complex that functions as a transcriptional coactivator in all eukaryotes. 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 31+ 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]
General structure
The Mediator complex is composed of up to at least 31 subunits in all eukaryotes studied: 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, and CDK8. There are three fungal-specific components, referred to as Med2, Med3 and Med5.[5]
The subunits form at least three structurally distinct submodules. The head and the middle modules interact directly with RNA polymerase II, whereas the elongated tail module interacts with gene-specific regulatory proteins. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation.
- The head module contains: MED6, MED8, MED11, SRB4/MED17, SRB5/MED18, ROX3/MED19, SRB2/MED20 and SRB6/MED22.
- The middle module contains: MED1, MED4, NUT1/MED5, MED7, CSE2/MED9, NUT2/MED10, SRB7/MED21 and SOH1/MED31. CSE2/MED9 interacts directly with MED4.
- The tail module contains: MED2, PGD1/MED3, RGR1/MED14, GAL11/MED15 and SIN4/MED16.
- The CDK8 module contains: MED12, MED13, CCNC and CDK8. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.
Table of Mediator complex subunits present in humans and model organisms[6]
Subunit No. | Human gene | C. elegans gene | D. melanogaster gene | S. cerevisiae gene | Sch. pombe gene | |
---|---|---|---|---|---|---|
MED1 | MED1 | Sop3/mdt-1.1, 1.2 | MED1 | MED1 | med1 | |
Med2 a | MED2 | |||||
Med3 a | PGD1 | |||||
MED4 | MED4 | MED4 | MED4 | med4 | ||
Med5 a | NUT1 | |||||
MED6 | MED6 | MDT-6 | MED6 | MED6 | med6 | |
MED7 | MED7 | MDT-7/let-49 | MED7 | MED7 | med7 | |
MED8 | MED8 | MDT-8 | MED8 | MED8 | med8 | |
Med9 | MED9 | MED9 | CSE2 | |||
Med10 | MED10 | MDT-10 | NUT2 | med10 | ||
Med11 | MED11 | MDT-11 | MED11 | MED11 | med11 | |
MED12 | MED12 | MDT-12/dpy-22 | MED12 | SRB8 | srb8 | |
Med12L | MED12L | |||||
MED13 | MED13 | MDT-13/let-19 | MED13 | SSN2 | srb9 | |
MED14 | MED14 | MDT-14/rgr-1 | MED14 | RGR1 | med14 | |
MED15 | MED15 | mdt-15 | MED15 | GAL11 | YN91_SCHPO b | |
MED16 | MED16 | MED16 | SIN4 | |||
MED17 | MED17 | MDT-17 | MED17 | SRB4 | med17 | |
Med18 | MED18 | MDT-18 | MED18 | SRB5 | med18 | |
Med19 | MED19 | MDT-19 | MED19 | med19 | ||
Med20 | MED20 | MDT-20 | MED20 | SRB2 | med20 | |
MED21 | MED21 | MDT-21 | MED21 | SRB7 | med21 | |
MED22 | MED22 | MDT-22 | MED22 | SRB6 | med22 | |
MED23 | MED23 | MDT-23/sur-2 | MED23 | |||
MED24 | MED24 | MED24 | ||||
MED25 | MED25 | MED25 | ||||
MED26 | MED26 | MED26 | ||||
MED27 | MED27 | MED27 | med27 | |||
MED28 | MED28 | MED28 | ||||
Med29 | MED29 | MDT-19 | MED29 | MED29 | ||
MED30 | MED30 | MED30 | ||||
MED31 | MED31 | MDT-31 | MED31 | SOH1 | med31 | |
CCNC | CCNC | cic-1 | CycC | SSN8 | pch1 | |
CDK8 | CDK8 | cdk-8 | Cdk8 | SSN3 | srb10 | |
- a Fungal-specific
- b Protein-name in Sch. pombe
References
- ↑ Biddick R, Young ET (September 2005). "Yeast mediator and its role in transcriptional regulation". Comptes Rendus Biologies. 328 (9): 773–82. doi:10.1016/j.crvi.2005.03.004. PMID 16168358.
- ↑ Taatjes DJ (2010). "The human Mediator complex: a versatile, genome-wide regulator of transcription". Trends in Biochemical Sciences. 35 (6): 315–22. doi:10.1016/j.tibs.2010.02.004. PMC 2891401. PMID 20299225.
- ↑ Björklund S, Gustafsson CM (May 2005). "The yeast Mediator complex and its regulation". Trends in Biochemical Sciences. 30 (5): 240–4. doi:10.1016/j.tibs.2005.03.008. PMID 15896741.
- ↑ Reeves WM, Hahn S (January 2003). "Activator-independent functions of the yeast mediator sin4 complex in preinitiation complex formation and transcription reinitiation". Molecular and Cellular Biology. 23 (1): 349–58. doi:10.1128/MCB.23.1.349-358.2003. PMC 140685. PMID 12482986.
- ↑ Bourbon HM, Aguilera A, Ansari AZ, Asturias FJ, Berk AJ, Bjorklund S, et al. (2004). "A unified nomenclature for protein subunits of mediator complexes linking transcriptional regulators to RNA polymerase II". Molecular Cell. 14 (5): 553–7. doi:10.1016/j.molcel.2004.05.011. PMID 15175151.
- ↑ Gene-names derived from UniProtKB as of 12 October 2012