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Mediator (coactivator)

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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

  1. ^ Biddick R, Young ET (2005). "Yeast mediator and its role in transcriptional regulation". C. R. Biol. 328 (9): 773–82.  
  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.  
  4. ^ Reeves, Wendy M.; Hahn, Steve (January 2003). "Activator-Independent Functions of the Yeast Mediator Sin4 Complex in Preinitiation Complex Formation and Transcription Reinitiation". Molecular and Cellular Biology 23 (1): 349–358.  
  5. ^ PMID:15175151
  6. ^ Gene-names derived from UniProtKB as of 12 October 2012
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