MED17

Summary

Gene Symbol: MED17
Description: mediator complex subunit 17
Alias: CRSP6, CRSP77, DRIP80, SRB4, TRAP80, mediator of RNA polymerase II transcription subunit 17, ARC77, CRSP complex subunit 6, activator-recruited cofactor 77 kDa component, cofactor required for Sp1 transcriptional activation, subunit 6, 77kDa, thyroid hormone receptor-associated protein complex 80 kDa component, transcriptional coactivator CRSP77, vitamin D3 receptor-interacting protein complex 80 kDa component
Species: human
Products:     MED17

Top Publications

  1. Meyer K, Donner A, Knuesel M, York A, Espinosa J, Taatjes D. Cooperative activity of cdk8 and GCN5L within Mediator directs tandem phosphoacetylation of histone H3. EMBO J. 2008;27:1447-57 pubmed publisher
    ..Indeed our results suggest that T/G-Mediator directs early events-such as modification of chromatin templates-in transcriptional activation. ..
  2. Paul E, Zhu Z, Landsman D, Morse R. Genome-wide association of mediator and RNA polymerase II in wild-type and mediator mutant yeast. Mol Cell Biol. 2015;35:331-42 pubmed publisher
    ..of tail module subunits to active gene promoters continues genome-wide when Mediator integrity is compromised in med17 temperature-sensitive (ts) yeast, demonstrating the modular nature of the Mediator complex in vivo...
  3. Jean Jacques H, Poh S, Kuras L. Mediator, known as a coactivator, can act in transcription initiation in an activator-independent manner in vivo. Biochim Biophys Acta Gene Regul Mech. 2018;1861:687-696 pubmed publisher
    ..of Med14 N-terminal half exhibiting widespread transcriptional defects, and existing ts mutants of Kin28 and Med17, we show that, in the absence of activator: (i) Mediator can associate with a promoter as a form devoid of the ..
  4. Figueiredo T, Melo U, Pessoa A, Nóbrega P, Kitajima J, Correa I, et al. Homozygous missense mutation in MED25 segregates with syndromic intellectual disability in a large consanguineous family. J Med Genet. 2015;52:123-7 pubmed publisher
    ..Deleterious mutations in MED12, MED17 and MED23 have already been associated with ID...
  5. Hirabayashi S, Saitsu H, Matsumoto N. Distinct but milder phenotypes with choreiform movements in siblings with compound heterozygous mutations in the transcription preinitiation mediator complex subunit 17 (MED17). Brain Dev. 2016;38:118-23 pubmed publisher
    ..Whole exome sequencing (WES) revealed compound heterozygous mutations in MED17 gene in both siblings: c.1013-5A>G and c...
  6. Aguilo F, Li S, Balasubramaniyan N, Sancho A, Benko S, Zhang F, et al. Deposition of 5-Methylcytosine on Enhancer RNAs Enables the Coactivator Function of PGC-1α. Cell Rep. 2016;14:479-492 pubmed publisher
    ..methylated PGC-1α[K779me] with the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex, the Mediator members MED1 and MED17, and the NOP2/Sun RNA methytransferase 7 (NSUN7) reinforce transcription, and are concomitant with the m(5)C mark ..
  7. Oh G, Yoon J, Lee G, Oh W, Kim S. 20(S)-protopanaxatriol inhibits liver X receptor α-mediated expression of lipogenic genes in hepatocytes. J Pharmacol Sci. 2015;128:71-7 pubmed publisher
    ..Chromatin immunoprecipitation assays revealed that PPT repressed recruitment of the lipogenic coactivator TRAP80 to the SREBP-1c LXRE, but not the ABCA1 LXRE...
  8. Kämpjärvi K, Kim N, Keskitalo S, Clark A, von Nandelstadh P, Turunen M, et al. Somatic MED12 mutations in prostate cancer and uterine leiomyomas promote tumorigenesis through distinct mechanisms. Prostate. 2016;76:22-31 pubmed publisher
    ..was shown to affect interactions between MED12 and other Mediator components (MED1, MED13, MED13L, MED14, MED15, MED17, and MED24)...
  9. Eyboulet F, Wydau Dematteis S, Eychenne T, Alibert O, Neil H, Boschiero C, et al. Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo. Nucleic Acids Res. 2015;43:9214-31 pubmed publisher
    ..However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module...

More Information

Publications44

  1. Nozawa K, Schneider T, Cramer P. Core Mediator structure at 3.4 Å extends model of transcription initiation complex. Nature. 2017;545:248-251 pubmed publisher
    ..16) and Med17 (ref. 17) that tether the middle module...
  2. Vaughan C, Singh S, Grossman S, Windle B, Deb S, Deb S. Gain-of-function p53 activates multiple signaling pathways to induce oncogenicity in lung cancer cells. Mol Oncol. 2017;11:696-711 pubmed publisher
    ..Our analytical data support a model in which GOF p53 complexes with two TFs on the promoter-a mediator protein, Med17, and a histone acetyl transferase, activating histone acetylation-and enhances gene expression to signal cell ..
  3. Montes M, Moreira Ramos S, Rojas D, Urbina F, Käufer N, Maldonado E. RNA polymerase II components and Rrn7 form a preinitiation complex on the HomolD box to promote ribosomal protein gene expression in Schizosaccharomyces pombe. FEBS J. 2017;284:615-633 pubmed publisher
    ..The Mediator complex was required for basal transcription from those promoters in whole cell extract (WCE). The Med17 subunit of Mediator also can be cross-linked to the promoter region of HomolD-containing promoters in vivo, ..
  4. Malik S, Gu W, Wu W, Qin J, Roeder R. The USA-derived transcriptional coactivator PC2 is a submodule of TRAP/SMCC and acts synergistically with other PCs. Mol Cell. 2000;5:753-60 pubmed
  5. Yang F, Vought B, Satterlee J, Walker A, Jim Sun Z, Watts J, et al. An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Nature. 2006;442:700-4 pubmed
    ..Taken together, our findings demonstrate that ARC105 is a key effector of SREBP-dependent gene regulation and control of lipid homeostasis in metazoans. ..
  6. Viscarra J, Wang Y, Hong I, Sul H. Transcriptional activation of lipogenesis by insulin requires phosphorylation of MED17 by CK2. Sci Signal. 2017;10: pubmed publisher
    ..that USF1, a key transcription factor for FASN activation, directly interacted with the Mediator subunit MED17 at the FASN promoter...
  7. Brower C, Sato S, Tomomori Sato C, Kamura T, Pause A, Stearman R, et al. Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase. Proc Natl Acad Sci U S A. 2002;99:10353-8 pubmed
    ..Taken together, our findings are consistent with the model that MED8 could function to recruit ubiquitin ligase activity directly to the RNA polymerase II transcriptional machinery. ..
  8. Ryu S, Zhou S, Ladurner A, Tjian R. The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1. Nature. 1999;397:446-50 pubmed
    ..The presence of common subunits in distinct cofactor complexes suggests a combinatorial mechanism of co-activator assembly during transcriptional activation. ..
  9. Mittler G, Stühler T, Santolin L, Uhlmann T, Kremmer E, Lottspeich F, et al. A novel docking site on Mediator is critical for activation by VP16 in mammalian cells. EMBO J. 2003;22:6494-504 pubmed
    ..Despite many known targets of VP16, ARC92/ACID1 appears to impose a critical control on transcription activation by VP16 in mammalian cells. ..
  10. Ito M, Yuan C, Malik S, Gu W, Fondell J, Yamamura S, et al. Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators. Mol Cell. 1999;3:361-70 pubmed
    ..nuclear receptors with the TRAP220 subunit, p53 and VP16 activation domains interact directly with a newly cloned TRAP80 subunit...
  11. Kaufmann R, Straussberg R, Mandel H, Fattal Valevski A, Ben Zeev B, Naamati A, et al. Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex. Am J Hum Genet. 2010;87:667-70 pubmed publisher
    ..A missense mutation in one of them, MED17, segregated with the disease state in the families and was carried by four of 79 anonymous Caucasus Jews...
  12. Fondell J, Ge H, Roeder R. Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. Proc Natl Acad Sci U S A. 1996;93:8329-33 pubmed
    ..These findings demonstrate the ligand-dependent in vivo formation of a transcriptionally active TR-multisubunit protein complex and suggest a role for TRAPs as positive coactivators for gene-specific transcriptional activation. ..
  13. Donner A, Ebmeier C, Taatjes D, Espinosa J. CDK8 is a positive regulator of transcriptional elongation within the serum response network. Nat Struct Mol Biol. 2010;17:194-201 pubmed publisher
    ..Furthermore, CDK8-Mediator specifically interacts with positive transcription elongation factor b. Thus, we have uncovered a role for CDK8 in transcriptional regulation that may contribute to its oncogenic effects. ..
  14. Zhou H, Xu M, Huang Q, Gates A, Zhang X, Castle J, et al. Genome-scale RNAi screen for host factors required for HIV replication. Cell Host Microbe. 2008;4:495-504 pubmed publisher
    ..This study highlights both the power and shortcomings of large scale loss-of-function screens in discovering host-pathogen interactions. ..
  15. Liu X, Vorontchikhina M, Wang Y, Faiola F, Martinez E. STAGA recruits Mediator to the MYC oncoprotein to stimulate transcription and cell proliferation. Mol Cell Biol. 2008;28:108-21 pubmed
    ..These results suggest a novel STAF65gamma-dependent function of STAGA-type complexes in cell proliferation and transcription activation by MYC postloading of TFIID and RNA polymerase II that involves direct recruitment of core Mediator. ..
  16. Malik S, Wallberg A, Kang Y, Roeder R. TRAP/SMCC/mediator-dependent transcriptional activation from DNA and chromatin templates by orphan nuclear receptor hepatocyte nuclear factor 4. Mol Cell Biol. 2002;22:5626-37 pubmed
    ..Finally, recruitment experiments using immobilized templates strongly suggest that the functional consequences of the physical interaction probably are manifested at a postrecruitment step in the activation pathway. ..
  17. Chiba N, Parvin J. The BRCA1 and BARD1 association with the RNA polymerase II holoenzyme. Cancer Res. 2002;62:4222-8 pubmed
    ..An intact BRCA1 NH(2) terminus is required for the association with holo-pol and for subnuclear localization in S-phase foci. Taken together, these data support a role for BRCA1 regulation of holo-pol function. ..
  18. Stumpf M, Waskow C, Krötschel M, van Essen D, Rodriguez P, Zhang X, et al. The mediator complex functions as a coactivator for GATA-1 in erythropoiesis via subunit Med1/TRAP220. Proc Natl Acad Sci U S A. 2006;103:18504-9 pubmed
    ..In chromatin immunoprecipitation experiments, we find Mediator components at GATA-1-occupied enhancer sites. Thus, we conclude that Mediator subunit Med1 acts as a pivotal coactivator for GATA-1 in erythroid development. ..
  19. Rachez C, Lemon B, Suldan Z, Bromleigh V, Gamble M, Näär A, et al. Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature. 1999;398:824-8 pubmed
    ..The role of nuclear-receptor ligands may, in part, be to recruit such a cofactor complex to the receptor and, in doing so, to enhance transcription of target genes. ..
  20. Fukasawa R, Tsutsui T, Hirose Y, Tanaka A, Ohkuma Y. Mediator CDK subunits are platforms for interactions with various chromatin regulatory complexes. J Biochem. 2012;152:241-9 pubmed publisher
    ..Further studies demonstrated that those could bind not only to CDK19 but also to CDK8. These results help elucidate the functional mechanism for the mutual regulations between transcription and chromatin. ..
  21. Kikuchi Y, Umemura H, Nishitani S, Iida S, Fukasawa R, Hayashi H, et al. Human mediator MED17 subunit plays essential roles in gene regulation by associating with the transcription and DNA repair machineries. Genes Cells. 2015;20:191-202 pubmed publisher
    ..We studied the human head module subunit MED17 (hMED17)...
  22. Näär A, Beaurang P, Zhou S, Abraham S, Solomon W, Tjian R. Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature. 1999;398:828-32 pubmed
    ..Thus, ARC/DRIP is a large composite co-activator that belongs to a family of related cofactors and is targeted by different classes of activator to mediate transcriptional stimulation. ..
  23. Taatjes D, Naar A, Andel F, Nogales E, Tjian R. Structure, function, and activator-induced conformations of the CRSP coactivator. Science. 2002;295:1058-62 pubmed
    ..These results suggest that CRSP may potentiate transcription via specific activator-induced conformational changes. ..
  24. Lau J, Nusinzon I, Burakov D, Freedman L, Horvath C. Role of metazoan mediator proteins in interferon-responsive transcription. Mol Cell Biol. 2003;23:620-8 pubmed
    ..These findings indicate that the IFN-activated ISGF3 transcription factor regulates transcription through contact with DRIP150 and implicate the Mediator coactivator complex in IFN-activated gene regulation. ..
  25. Kim G, Oh G, Yoon J, Lee G, Lee K, Kim S. Hepatic TRAP80 selectively regulates lipogenic activity of liver X receptor. J Clin Invest. 2015;125:183-93 pubmed publisher
    ..effects of LXR by exploiting the specificity of the coactivator thyroid hormone receptor-associated protein 80 (TRAP80)...
  26. Zheng W, Dong X, Yin R, Xu F, Ning H, Zhang M, et al. EDAG positively regulates erythroid differentiation and modifies GATA1 acetylation through recruiting p300. Stem Cells. 2014;32:2278-89 pubmed publisher
    ..Microarray analysis suggested that EDAG knockdown selectively inhibits GATA1-activated target genes. These data provide novel insights into EDAG in regulation of erythroid differentiation. ..
  27. Tsutsui T, Fukasawa R, Shinmyouzu K, Nakagawa R, Tobe K, Tanaka A, et al. Mediator complex recruits epigenetic regulators via its two cyclin-dependent kinase subunits to repress transcription of immune response genes. J Biol Chem. 2013;288:20955-65 pubmed publisher
  28. Knuesel M, Taatjes D. Mediator and post-recruitment regulation of RNA polymerase II. Transcription. 2011;2:28-31 pubmed publisher
    ..These results are discussed together with other recent findings regarding post-recruitment regulation of Pol II. ..
  29. Sato S, Tomomori Sato C, Banks C, Parmely T, Sorokina I, Brower C, et al. A mammalian homolog of Drosophila melanogaster transcriptional coactivator intersex is a subunit of the mammalian Mediator complex. J Biol Chem. 2003;278:49671-4 pubmed
    ..Taken together, our findings identify a new subunit of the mammalian Mediator and shed new light on the architecture of the mammalian Mediator complex. ..
  30. Wang Q, Sharma D, Ren Y, Fondell J. A coregulatory role for the TRAP-mediator complex in androgen receptor-mediated gene expression. J Biol Chem. 2002;277:42852-8 pubmed
    ..Collectively, these data suggest that TRAP-Mediator may play an important coregulatory role in AR-mediated gene expression. ..
  31. Hassa P, Haenni S, Buerki C, Meier N, Lane W, Owen H, et al. Acetylation of poly(ADP-ribose) polymerase-1 by p300/CREB-binding protein regulates coactivation of NF-kappaB-dependent transcription. J Biol Chem. 2005;280:40450-64 pubmed
    ..Thus, acetylation of PARP-1 by p300/CREB-binding protein plays an important regulatory role in NF-kappaB-dependent gene activation by enhancing its functional interaction with p300 and the Mediator complex. ..
  32. Ge K, Guermah M, Yuan C, Ito M, Wallberg A, Spiegelman B, et al. Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis. Nature. 2002;417:563-7 pubmed
    ..These data indicate that TRAP220 acts, via the TRAP complex, as a PPAR gamma(2)-selective coactivator and, accordingly, that it is specific for one fibroblast differentiation pathway (adipogenesis) relative to another (myogenesis). ..
  33. Kang Y, Guermah M, Yuan C, Roeder R. The TRAP/Mediator coactivator complex interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and directly enhances estrogen receptor function in vitro. Proc Natl Acad Sci U S A. 2002;99:2642-7 pubmed
    ..Finally, the complete TRAP/Mediator complex is shown to enhance ER function directly in a highly purified cell-free transcription system. These studies firmly establish a direct role for TRAP/Mediator, through TRAP220, in ER function. ..
  34. Chiba N, Parvin J. Redistribution of BRCA1 among four different protein complexes following replication blockage. J Biol Chem. 2001;276:38549-54 pubmed
    ..These data suggest that BRCA1 participates in multiple cellular processes by multiple protein complexes and that the BRCA1 content of these complexes is dynamically altered after DNA replication blockage. ..
  35. Wallberg A, Yamamura S, Malik S, Spiegelman B, Roeder R. Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha. Mol Cell. 2003;12:1137-49 pubmed