| Structural highlights
Function
[MED20_YEAST] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.[1] [2] [3] [4] [MED22_YEAST] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.[5] [6] [7] [MED11_YEAST] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex (PIC) with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. The essential MED11/22 heterodimer specifically functions in promoting stable PIC formation.[8] [9] [10] [11] [MED8_YEAST] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. MED8 binds to the consensus sequence 5'-[AC][AG]GAAAT-3' in both the UAS of SUC2 and the DRS2 of HXK2.[12] [13] [14] [15] [16] [17] [MED6_YEAST] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.[18] [19] [20] [21] [22] [MED17_YEAST] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.[23] [24] [25] [26] [27] [MED18_YEAST] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.[28] [29] [30] [31] [32] [33]
Publication Abstract from PubMed
The X-ray crystal structure of the Head module, one-third of the Mediator of transcriptional regulation, has been determined as a complex with the C-terminal domain (CTD) of RNA polymerase II. The structure reveals multiple points of interaction with an extended conformation of the CTD; it suggests a basis for regulation by phosphorylation of the CTD. Biochemical studies show a requirement for Mediator-CTD interaction for transcription.
Structure of the Mediator Head module bound to the carboxy-terminal domain of RNA polymerase II.,Robinson PJ, Bushnell DA, Trnka MJ, Burlingame AL, Kornberg RD Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):17931-5. doi:, 10.1073/pnas.1215241109. Epub 2012 Oct 15. PMID:23071300[34]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nair D, Kim Y, Myers LC. Mediator and TFIIH govern carboxyl-terminal domain-dependent transcription in yeast extracts. J Biol Chem. 2005 Oct 7;280(40):33739-48. Epub 2005 Aug 2. PMID:16076843 doi:http://dx.doi.org/M506067200
- ↑ van de Peppel J, Kettelarij N, van Bakel H, Kockelkorn TT, van Leenen D, Holstege FC. Mediator expression profiling epistasis reveals a signal transduction pathway with antagonistic submodules and highly specific downstream targets. Mol Cell. 2005 Aug 19;19(4):511-22. PMID:16109375 doi:http://dx.doi.org/10.1016/j.molcel.2005.06.033
- ↑ Takagi Y, Kornberg RD. Mediator as a general transcription factor. J Biol Chem. 2006 Jan 6;281(1):80-9. Epub 2005 Nov 1. PMID:16263706 doi:http://dx.doi.org/M508253200
- ↑ Takagi Y, Calero G, Komori H, Brown JA, Ehrensberger AH, Hudmon A, Asturias F, Kornberg RD. Head module control of mediator interactions. Mol Cell. 2006 Aug 4;23(3):355-64. PMID:16885025 doi:http://dx.doi.org/S1097-2765(06)00412-6
- ↑ Nair D, Kim Y, Myers LC. Mediator and TFIIH govern carboxyl-terminal domain-dependent transcription in yeast extracts. J Biol Chem. 2005 Oct 7;280(40):33739-48. Epub 2005 Aug 2. PMID:16076843 doi:http://dx.doi.org/M506067200
- ↑ Takagi Y, Kornberg RD. Mediator as a general transcription factor. J Biol Chem. 2006 Jan 6;281(1):80-9. Epub 2005 Nov 1. PMID:16263706 doi:http://dx.doi.org/M508253200
- ↑ Takagi Y, Calero G, Komori H, Brown JA, Ehrensberger AH, Hudmon A, Asturias F, Kornberg RD. Head module control of mediator interactions. Mol Cell. 2006 Aug 4;23(3):355-64. PMID:16885025 doi:http://dx.doi.org/S1097-2765(06)00412-6
- ↑ Nair D, Kim Y, Myers LC. Mediator and TFIIH govern carboxyl-terminal domain-dependent transcription in yeast extracts. J Biol Chem. 2005 Oct 7;280(40):33739-48. Epub 2005 Aug 2. PMID:16076843 doi:http://dx.doi.org/M506067200
- ↑ Takagi Y, Kornberg RD. Mediator as a general transcription factor. J Biol Chem. 2006 Jan 6;281(1):80-9. Epub 2005 Nov 1. PMID:16263706 doi:http://dx.doi.org/M508253200
- ↑ Takagi Y, Calero G, Komori H, Brown JA, Ehrensberger AH, Hudmon A, Asturias F, Kornberg RD. Head module control of mediator interactions. Mol Cell. 2006 Aug 4;23(3):355-64. PMID:16885025 doi:http://dx.doi.org/S1097-2765(06)00412-6
- ↑ Esnault C, Ghavi-Helm Y, Brun S, Soutourina J, Van Berkum N, Boschiero C, Holstege F, Werner M. Mediator-dependent recruitment of TFIIH modules in preinitiation complex. Mol Cell. 2008 Aug 8;31(3):337-46. doi: 10.1016/j.molcel.2008.06.021. PMID:18691966 doi:http://dx.doi.org/10.1016/j.molcel.2008.06.021
- ↑ Chaves RS, Herrero P, Moreno F. Med8, a subunit of the mediator CTD complex of RNA polymerase II, directly binds to regulatory elements of SUC2 and HXK2 genes. Biochem Biophys Res Commun. 1999 Jan 19;254(2):345-50. PMID:9918841 doi:http://dx.doi.org/10.1006/bbrc.1998.9954
- ↑ Moreno-Herrero F, Herrero P, Colchero J, Baro AM, Moreno F. Analysis by atomic force microscopy of Med8 binding to cis-acting regulatory elements of the SUC2 and HXK2 genes of saccharomyces cerevisiae. FEBS Lett. 1999 Oct 15;459(3):427-32. PMID:10526178
- ↑ Kang JS, Kim SH, Hwang MS, Han SJ, Lee YC, Kim YJ. The structural and functional organization of the yeast mediator complex. J Biol Chem. 2001 Nov 9;276(45):42003-10. Epub 2001 Sep 12. PMID:11555651 doi:http://dx.doi.org/10.1074/jbc.M105961200
- ↑ Nair D, Kim Y, Myers LC. Mediator and TFIIH govern carboxyl-terminal domain-dependent transcription in yeast extracts. J Biol Chem. 2005 Oct 7;280(40):33739-48. Epub 2005 Aug 2. PMID:16076843 doi:http://dx.doi.org/M506067200
- ↑ Takagi Y, Kornberg RD. Mediator as a general transcription factor. J Biol Chem. 2006 Jan 6;281(1):80-9. Epub 2005 Nov 1. PMID:16263706 doi:http://dx.doi.org/M508253200
- ↑ Takagi Y, Calero G, Komori H, Brown JA, Ehrensberger AH, Hudmon A, Asturias F, Kornberg RD. Head module control of mediator interactions. Mol Cell. 2006 Aug 4;23(3):355-64. PMID:16885025 doi:http://dx.doi.org/S1097-2765(06)00412-6
- ↑ Nair D, Kim Y, Myers LC. Mediator and TFIIH govern carboxyl-terminal domain-dependent transcription in yeast extracts. J Biol Chem. 2005 Oct 7;280(40):33739-48. Epub 2005 Aug 2. PMID:16076843 doi:http://dx.doi.org/M506067200
- ↑ Takagi Y, Kornberg RD. Mediator as a general transcription factor. J Biol Chem. 2006 Jan 6;281(1):80-9. Epub 2005 Nov 1. PMID:16263706 doi:http://dx.doi.org/M508253200
- ↑ Takagi Y, Calero G, Komori H, Brown JA, Ehrensberger AH, Hudmon A, Asturias F, Kornberg RD. Head module control of mediator interactions. Mol Cell. 2006 Aug 4;23(3):355-64. PMID:16885025 doi:http://dx.doi.org/S1097-2765(06)00412-6
- ↑ Lee YC, Min S, Gim BS, Kim YJ. A transcriptional mediator protein that is required for activation of many RNA polymerase II promoters and is conserved from yeast to humans. Mol Cell Biol. 1997 Aug;17(8):4622-32. PMID:9234719
- ↑ Holstege FC, Jennings EG, Wyrick JJ, Lee TI, Hengartner CJ, Green MR, Golub TR, Lander ES, Young RA. Dissecting the regulatory circuitry of a eukaryotic genome. Cell. 1998 Nov 25;95(5):717-28. PMID:9845373
- ↑ Kang JS, Kim SH, Hwang MS, Han SJ, Lee YC, Kim YJ. The structural and functional organization of the yeast mediator complex. J Biol Chem. 2001 Nov 9;276(45):42003-10. Epub 2001 Sep 12. PMID:11555651 doi:http://dx.doi.org/10.1074/jbc.M105961200
- ↑ Nair D, Kim Y, Myers LC. Mediator and TFIIH govern carboxyl-terminal domain-dependent transcription in yeast extracts. J Biol Chem. 2005 Oct 7;280(40):33739-48. Epub 2005 Aug 2. PMID:16076843 doi:http://dx.doi.org/M506067200
- ↑ Takagi Y, Kornberg RD. Mediator as a general transcription factor. J Biol Chem. 2006 Jan 6;281(1):80-9. Epub 2005 Nov 1. PMID:16263706 doi:http://dx.doi.org/M508253200
- ↑ Takagi Y, Calero G, Komori H, Brown JA, Ehrensberger AH, Hudmon A, Asturias F, Kornberg RD. Head module control of mediator interactions. Mol Cell. 2006 Aug 4;23(3):355-64. PMID:16885025 doi:http://dx.doi.org/S1097-2765(06)00412-6
- ↑ Holstege FC, Jennings EG, Wyrick JJ, Lee TI, Hengartner CJ, Green MR, Golub TR, Lander ES, Young RA. Dissecting the regulatory circuitry of a eukaryotic genome. Cell. 1998 Nov 25;95(5):717-28. PMID:9845373
- ↑ Holstege FC, Jennings EG, Wyrick JJ, Lee TI, Hengartner CJ, Green MR, Golub TR, Lander ES, Young RA. Dissecting the regulatory circuitry of a eukaryotic genome. Cell. 1998 Nov 25;95(5):717-28. PMID:9845373
- ↑ Kang JS, Kim SH, Hwang MS, Han SJ, Lee YC, Kim YJ. The structural and functional organization of the yeast mediator complex. J Biol Chem. 2001 Nov 9;276(45):42003-10. Epub 2001 Sep 12. PMID:11555651 doi:http://dx.doi.org/10.1074/jbc.M105961200
- ↑ Nair D, Kim Y, Myers LC. Mediator and TFIIH govern carboxyl-terminal domain-dependent transcription in yeast extracts. J Biol Chem. 2005 Oct 7;280(40):33739-48. Epub 2005 Aug 2. PMID:16076843 doi:http://dx.doi.org/M506067200
- ↑ van de Peppel J, Kettelarij N, van Bakel H, Kockelkorn TT, van Leenen D, Holstege FC. Mediator expression profiling epistasis reveals a signal transduction pathway with antagonistic submodules and highly specific downstream targets. Mol Cell. 2005 Aug 19;19(4):511-22. PMID:16109375 doi:http://dx.doi.org/10.1016/j.molcel.2005.06.033
- ↑ Takagi Y, Kornberg RD. Mediator as a general transcription factor. J Biol Chem. 2006 Jan 6;281(1):80-9. Epub 2005 Nov 1. PMID:16263706 doi:http://dx.doi.org/M508253200
- ↑ Takagi Y, Calero G, Komori H, Brown JA, Ehrensberger AH, Hudmon A, Asturias F, Kornberg RD. Head module control of mediator interactions. Mol Cell. 2006 Aug 4;23(3):355-64. PMID:16885025 doi:http://dx.doi.org/S1097-2765(06)00412-6
- ↑ Robinson PJ, Bushnell DA, Trnka MJ, Burlingame AL, Kornberg RD. Structure of the Mediator Head module bound to the carboxy-terminal domain of RNA polymerase II. Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):17931-5. doi:, 10.1073/pnas.1215241109. Epub 2012 Oct 15. PMID:23071300 doi:http://dx.doi.org/10.1073/pnas.1215241109
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