The Mediator complex and transcription regulation

Critical Reviews in Biochemistry and Molecular Biology

Volumn 48, Issue 6, 2013, Pages 575-608

  Poss, Zachary C ^a   Ebmeier, Christopher C ^a   Taatjes, Dylan J ^a  

^a UNIVERSITY OF COLORADO   (United States)

Author keywords

CDK8 Mediator; Gdown1; Gene expression; Paused pol II; Review; Super elongation complex; TFIIS

Indexed keywords

CYCLIN DEPENDENT KINASE 8; DNA DIRECTED RNA POLYMERASE; HOST FACTOR; MEDIATOR COMPLEX; MESSENGER RNA; MICRORNA; RNA POLYMERASE II; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR IIA; TRANSCRIPTION FACTOR IIB; TRANSCRIPTION FACTOR IID; TRANSCRIPTION FACTOR IIH; UNTRANSLATED RNA;

BINDING KINETICS; CHROMATIN; CHROMATIN STRUCTURE; DEVELOPMENT; ENZYME ACTIVITY; GENE EXPRESSION REGULATION; HUMAN; MAMMAL; MASS SPECTROMETRY; NONHUMAN; PARALOGY; PLANT; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; PROTEIN QUATERNARY STRUCTURE; PROTEIN STRUCTURE; PROTEIN SUBUNIT; PROTEOMICS; REGULATORY MECHANISM; REVIEW; RNA PROCESSING; TRANSCRIPTION ELONGATION; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION; VIRUS TRANSCRIPTION; YEAST;

ANIMALS; CHROMATIN; CYCLIN-DEPENDENT KINASE 8; GENE EXPRESSION; GENE EXPRESSION REGULATION; MEDIATOR COMPLEX; PROTEIN BIOSYNTHESIS; RNA POLYMERASE II; SACCHAROMYCES CEREVISIAE; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC; TRANSCRIPTIONAL ACTIVATION;

EID: 84888588009     PISSN: 10409238     EISSN: 15497798     Source Type: Journal    
DOI: 10.3109/10409238.2013.840259     Document Type: Review

References (449)

1. Acevedo ML, Kraus WL. (2003). Mediator and p300/CBP-steroid receptor coactivator complexes have distinct roles, but function synergistically, during estrogen receptor alpha-dependent transcription. Mol Cell Biol 23:335-48. (Pubitemid 36008524)
2. Adelman K, Marr MT, Werner J, et al. (2005). Efficient release from promoter-proximal stall sites requires transcript cleavage factor TFIIS. Mol Cell 17:103-12. (Pubitemid 40075369)
3. Adler AS, Mccleland ML, Truong T, et al. (2012). CDK8 maintains tumor dedifferentiation and embryonic stem cell pluripotency. Cancer Res 72:2129-39.
4. Akoulitchev S, Chuikov S, Reinberg D. (2000). TFIIH is negatively regulated by cdk8-containing mediator complexes. Nature 407:102-6.
5. Alarcon C, Zaromytidou A, Xi Q, et al. (2009). Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-b pathways. Cell 139:757-69.
6. Anachkova B, Djeliova V, Russev G. (2005). Nuclear matrix support of DNA replication. J Cell Biochem 96:951-61. (Pubitemid 41688721)
7. Anderson JP, Badruzsaufari E, Schenk PM, et al. (2004). Antagonistic interaction between abscisic acid and jasmonate-ethylene signaling pathways modulates defense gene expression and disease resistance in Arabidopsis. Plant Cell 16:3460-79. (Pubitemid 41096019)
8. Andrau J, van de Pasch L, Lijnzaad P, et al. (2006). Genome-wide location of the coactivator Mediator: binding without activation and transient cdk8 interaction on DNA. Mol Cell 22:179-92.
9. Ansari SA, Ganapathi M, Benschop JJ, et al. (2012). Distinct role of Mediator tail module in regulation of SAGA-dependent, TATA-containing genes in yeast. EMBO J 31:44-57.
10. Ansari SA, He Q, Morse RH. (2009). Mediator complex association with constitutively transcribed genes in yeast. Proc Natl Acad Sci USA 106:16734-9.
11. Ansari AZ, Ogirala A, Ptashne M. (2005). Transcriptional activating regions target attached substrates to a cyclin-dependent kinase. Proc Natl Acad Sci USA 102:2346-9. (Pubitemid 40279378)
12. Asada S, Choi Y, Yamada M, et al. (2002). External control of Her2 expression and cancer cell growth by targeting a Ras-linked coactivator. Proc Natl Acad Sci USA 99:12747-52.
13. Asturias FJ, Jiang YW, Myers LC, et al. (1999). Conserved structures of mediator and RNA polymerase II holoenzyme. Science 283:985-7.
14. Atkins GB, Hu X, Guenther MG, et al. (1999). Coactivators for the orphan nuclear receptor RORalpha. Mol Endocrinol 13:1550-7. (Pubitemid 30650595)
15. Autran D, Jonak C, Belcram K, et al. (2002). Cell numbers and leaf development in Arabidopsis: a functional analysis of the STRUWWELPETER gene. EMBO J 21:6036-49. (Pubitemid 35415322)
16. Backstrom S, Elfving N, Nilsson R, et al. (2007). Purification of a plant mediator from Arabidopsis thaliana identifies PFT1 as the Med25 subunit. Mol Cell 26:717-29. (Pubitemid 46856244)
17. Badi L, Barberis A. (2001). Proteins that genetically interact with the Saccharomyces cerevisiae transcription factor Gal11p emphasize its role in the initiation-elongation transition. Mol Genet Genomics 265: 1076-86. (Pubitemid 32702181)
18. Baek HJ, Kang YK, Roeder RG. (2006). Human Mediator enhances basal transcription by facilitating recruitment of transcription factor IIB during preinitiation complex assembly. J Biol Chem 281: 15172-81. (Pubitemid 43855107)
19. Baek HJ, Malik S, Qin J, Roeder RG. (2002). Requirement of TRAP/mediator for both activator-independent and activator-dependent transcription in conjunction with TFIID-associated TAF(II)s. Mol Cell Biol 22:2842-52. (Pubitemid 34263004)
20. Baidoobonso SM, Guidi BW, Myers LC. (2007). Med19(Rox3) regulates intermodule interactions in the Saccharomyces cerevisiae mediator complex. J Biol Chem 282:5551-9. (Pubitemid 47093718)
21. Baillat D, Hakimi MA, Naar AM, et al. (2005). Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II. Cell 123:265-76. (Pubitemid 41457216)
22. Balamotis MA, Pennella MA, Stevens JL, et al. (2009). Complexity in transcription control at the activation domain-Mediator interface. Sci Signal 2:ra20.
23. Balciunas D, Galman C, Ronne H, Bjorklund S. (1999). The Med1 subunit of the yeast mediator complex is involved in both transcriptional activation and repression. Proc Natl Acad Sci USA 96:376-81. (Pubitemid 29061216)
24. Bancerek J, Poss ZC, Steinparzer I, et al. (2013). CDK8 kinase phosphorylates transcription factor STAT1 to selectively regulate the interferon response. Immunity 38:250-62.
25. Barneche F, Steinmetz F, Echeverria M. (2000). Fibrillarin genes encode both a conserved nucleolar protein and a novel small nucleolar RNA involved in ribosomal RNA methylation in Arabidopsis thaliana. J Biol Chem 275:27212-20.
26. Basehoar AD, Zanton SJ, Pugh BF. (2004). Identification and distinct regulation of yeast TATA box-containing genes. Cell 116:699-709. (Pubitemid 38326728)
27. Baumli S, Hoeppner S, Cramer P. (2005). A conserved mediator hinge revealed in the structure of the MED7.MED21 (Med7.Srb7) hetero-dimer. J Biol Chem 280:18171-8. (Pubitemid 41389062)
28. Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci USA 101:12130-5. (Pubitemid 39145408)
29. Belakavadi M, Fondell JD. (2010). Cyclin-dependent kinase 8 positively cooperates with Mediator to promote thyroid hormone receptor-dependent transcriptional activation. Mol Cell Biol 30: 2437-48.
30. Belakavadi M, Pandey PK, Vijayvargia R, Fondell JD. (2008). MED1 phosphorylation promotes its association with Mediator: implications for nuclear receptor signaling. Mol Cell Biol 28:3932-42. (Pubitemid 351812980)
31. Bernecky C, Grob P, Ebmeier CC, et al. (2011). Molecular architecture of the human Mediator-RNA polymerase II-TFIIF assembly. PLoS Biol 9:e1000603.
32. Bernecky C, Taatjes DJ. (2012). Activator-Mediator binding stabilizes RNA polymerase II orientation within the human Mediator-RNA polymerase II-TFIIF assembly. J Mol Biol 417:387-94.
33. Black JC, Choi JE, Lombardo SR, Carey M. (2006). A mechanism for coordinating chromatin modification and preinitiation complex assembly. Mol Cell 23:809-18. (Pubitemid 44344514)
34. Bonawitz ND, Soltau WL, Blatchley MR, et al. (2012). REF4 and RFR1, subunits of the transcriptional coregulatory complex mediator, are required for phenylpropanoid homeostasis in Arabidopsis. J Biol Chem 287:5434-45.
35. Borggrefe T, Davis R, Erdjument-Bromage H, et al. (2002). A complex of the Srb8,-9,-10, and-11 transcriptional regulatory proteins from yeast. J Biol Chem 277:44202-7. (Pubitemid 36157851)
36. Borggrefe T, Yue X. (2011). Interactions between subunits of the Mediator complex with gene-specific transcription factors. Semin Cell Dev Biol 22:759-68.
37. Boube M, Joulia L, Cribbs DL, Bourbon H. (2002). Evidence for a Mediator of RNA polymerase II transcriptional regulation conserved from yeast to man. Cell 110:143-51. (Pubitemid 34876543)
38. Bourbon HM. (2008). Comparative genomics supports a deep evolutionary origin for the large, four-module transcriptional mediator complex. Nucleic Acids Res 36:3993-4008.
39. Bourbon HM, Aguilera A, Ansari AZ, et al. (2004). A unified nomenclature for protein subunits of mediator complexes linking transcriptional regulators to RNA polymerase II. Mol Cell 14:553-7. (Pubitemid 38739079)
40. Boyer TG, Martin MED, Lees E, et al. (1999). Mammalian Srb/Mediator complex is targeted by adenovirus E1a protein. Nature 399:276-9. (Pubitemid 29246459)
41. Brass AL, Dykxhoorn DM, Benita Y, et al. (2008). Identification of host proteins required for HIV infection through a functional genomic screen. Science 319:921-6. (Pubitemid 351263756)
42. Bray D, Duke T. (2004). Conformational spread: the propagation of allosteric states in large multiprotein complexes. Annu Rev Biophys Biomol Struct 33:53-73. (Pubitemid 38829951)
43. Brower CS, Sato S, Tomomori-Sato C, et al. (2002). 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 USA 99:10353-8.
44. Brzovic PS, Heikaus CC, Kisselev L, et al. (2011). The acidic transcription activator Gcn4 binds the mediator subunit Gal11/Med15 using a simple protein interface forming a fuzzy complex. Mol Cell 44:942-53.
45. Burakov D, Wong CW, Rachez C, et al. (2000). Functional interactions between the estrogen receptor and DRIP205, a subunit of the heteromeric DRIP coactivator complex. J Biol Chem 275:20928-34. (Pubitemid 30457689)
46. Bushman FD, Malani N, Fernandes J, et al. (2009). Host cell factors in HIV replication: meta-analysis of genome-wide studies. PLoS Pathog 5:e1000437.
47. Bushnell DA, Bamdad C, Kornberg RD. (1996). A minimal set of RNA polymerase II transcription protein interactions. J Biol Chem 271: 20170-4. (Pubitemid 26281773)
48. Cai G, Chaban YL, Imasaki T, et al. (2012). Interaction of the mediator head module with RNA polymerase II. Structure 20:899-910.
49. Cai G, Imasaki T, Takagi Y, Asturias FA. (2009). Mediator structural conservation and implications for the regulation mechanism. Structure 17:559-67.
50. Cai G, Imasaki T, Yamada K, et al. (2010). Mediator head module structure and functional interactions. Nat Struct Mol Biol 17:273-9.
51. Cantin GT, Stevens JL, Berk AJ. (2003). Activation domain-mediator interactions promote transcription preinitiation complex assembly on promoter DNA. Proc Natl Acad Sci USA 100:12003-8. (Pubitemid 37271505)
52. Carey M. (1998). The enhanceosome and transcriptional synergy. Cell 92:5-8. (Pubitemid 28053292)
53. Carlson M. (1997). Genetics of transcriptional regulation in yeast: connections with the RNA polymerase II CTD. Annu Rev Cell Dev Biol 13:1-23. (Pubitemid 28034518)
54. Carlsten JO, Szilagyi Z, Liu B, et al. (2012). Mediator promotes CENP-a incorporation at fission yeast centromeres. Mol Cell Biol 32: 4035-43.
55. Carrer M, Liu N, Grueter CE, et al. (2012). Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*. Proc Natl Acad Sci USA 109:15330-5.
56. Carrera I, Janody F, Leeds N, et al. (2008). Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13. Proc Natl Acad Sci USA 105:6644-9. (Pubitemid 351754560)
57. Cee VJ, Chen DYK, Lee MR, Nicolaou KC. (2009). Cortistatin A is a high-affinity ligand of protein kinases Rock, CDK8, and CDK11. Angew Chem Int Ed 48:8952-7.
58. Cerdan PD, Chory J. (2003). Regulation of flowering time by light quality. Nature 423:881-5. (Pubitemid 36781281)
59. Cevik V, Kidd BN, Zhang P, et al. (2012). Mediator25 acts as an integrative hub for the regulation of jasmonate-responsive gene expression in Arabidopsis. Plant Physiol 160:541-55.
60. Chang Y, Howard SC, Herman PK. (2004). The Ras/PKA signaling pathway directly targets the srb9 protein, a component of the general RNA polymerase II transcription apparatus. Mol Cell 15:107-16. (Pubitemid 38850223)
61. Chen J, Ezzeddine N, Waltenspiel B, et al. (2012a). An RNAi screen identifies additional members of the Drosophila Integrator complex and a requirement for cyclin C/Cdk8 in snRNA 3-end formation. RNA 18:2148-56.
62. Chen W, Roeder RG. (2007). The Mediator subunit MED1/TRAP220 is required for optimal glucocorticoid receptor-mediated transcription activation. Nucleic Acids Res 35:6161-9. (Pubitemid 350018578)
63. Chen W, Rogatsky I, Garabedian MJ. (2006). Med14 and Med1 differentially regulate target-specific gene activation by the gluco-corticoid receptor. Mol Endocrinol 20:560-72. (Pubitemid 43291208)
64. Chen W, Zhang X, Birsoy K, Roeder RG. (2010a). A muscle-specific knockout implicates nuclear receptor coactivator MED1 in the regulation of glucose and energy metabolism. Proc Natl Acad Sci USA 107:10196-201.
65. Chen XF, Lehmann L, Lin JJ, et al. (2012b). Mediator and SAGA have distinct roles in Pol II preinitiation complex assembly and function. Cell Rep 2:1061-7.
66. Chen Z, Zhang C, Wu D, et al. (2011). Phospho-MED1-enhanced UBE2C locus looping drives castration-resistant prostate cancer growth. EMBO J 30:2405-19.
67. Chen ZA, Jawhari A, Fischer L, et al. (2010b). Architechture of the RNA polymerase II-TFIIF complex revealed by cross-linking and mass spectrometry. EMBO J 29:717-26.
68. Cheng B, Li T, Rahl PB, et al. (2012). Functional association of Gdown1 with RNA polymerase II poised on human genes. Mol Cell 45:38-50.
69. Cheng JX, Nevado J, Lu Z, Ptashne M. (2002). The TBP-inhibitory domain of TAF145 limits the effects of nonclassical transcriptional activators. Curr Biol 12:934-7. (Pubitemid 34689230)
70. Chi Y, Huddleston MJ, Zhang X, et al. (2001). Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase. Genes Dev 15:1078-92. (Pubitemid 32417301)
71. Choder M, Young RA. (1993). A portion of RNA polymerase II molecules has a component essential for stress responses and stress survival. Mol Cell Biol 13:6984-91. (Pubitemid 23321150)
72. Cianfrocco MA, Kassavetis GA, Grob P, et al. (2013). Human TFIID binds to core promoter DNA in a reorganized structural state. Cell 152:120-31.
73. Clayton AL, Rose S, Barratt MJ, Mahadevan LC. (2000). Phosphoacetylation of histone H3 on c-fos-and c-jun-associated nucleosomes upon gene activation. EMBO J 19:3714-26. (Pubitemid 30462129)
74. Compe E, Egly JM. (2012). TFIIH: when transcription met DNA repair. Nat Rev Mol Cell Biol 13:343-54.
75. Conaway RC, Conaway JW. (2011). Origins and activity of the Mediator complex. Semin Cell Dev Biol 22:729-34.
76. Conaway RC, Conaway JW. (2013). The Mediator complex and transcription elongation. Biochim Biophys Acta 1829:69-75.
77. Core LJ, Lis JT. (2008). Transcription regulation through promoter-proximal pausing of RNA polymerase II. Science 319:1791-2. (Pubitemid 351451556)
78. Core LJ, Waterfall JJ, Lis JT. (2008). Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 322:1845-8.
79. Crawford SE, Qi C, Misra P, et al. (2002). Defects of the heart, eye, and megakaryocytes in peroxisome proliferator activator receptor-binding protein (PBP) null embryos implicate GATA family of transcription factors. J Biol Chem 277:3585-92. (Pubitemid 34953230)
80. D'alessio JA, Ng R, Willenbring H, Tjian R. (2011). Core promoter recognition complex changes accompany liver development. Proc Natl Acad Sci USA 108:3906-11.
81. Dang W, Steffen KK, Perry R, et al. (2009). Histone H4 lysine 16 acetylation regulates cellular lifespan. Nature 459:802-7.
82. Darnell Jr JE. (2002). Transcription factors as targets for cancer therapy. Nat Rev Cancer 2:740-9. (Pubitemid 37328909)
83. Darnell Jr JE. (2013). Reflections on the history of pre-mRNA processing and highlights of current knowledge: a unified picture. RNA 19:443-60.
84. Davis JA, Takagi Y, Kornberg RD, Asturias FA. (2002). Structure of the yeast RNA polymerase II holoenzyme: Mediator conformation and polymerase interaction. Mol Cell 10:409-15. (Pubitemid 35007354)
85. Davis MA, Larimore EA, Fissel BM, et al. (2013). The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator. Genes Dev 27:151-6.
86. Deato MDE, Marr MT, Sottero T, et al. (2008). MyoD targets TAF3/TRF3 to activate Myogenin transcription. Mol Cell 32: 96-105.
87. Ding N, Tomomori-Sato C, Sato S, et al. (2009). MED19 and MED26 are synergistic functional targets of the RE1 silencing transcription factor in epigenetic silencing of neuronal gene expression. J Biol Chem 284:2648-56.
88. Ding N, Zhou H, Esteve P, et al. (2008). Mediator links epigenetic silencing of neuronal gene expression with X-linked mental retardation. Mol Cell 31:347-59.
89. Donner AJ, Ebmeier CC, Taatjes DJ, Espinosa JM. (2010). CDK8 is a positive regulator of transcriptional elongation within the serum response network. Nat Struct Mol Biol 17:194-201.
90. Donner AJ, Szostek S, Hoover JM, Espinosa JM. (2007). CDK8 is a stimulus-specific positive coregulator of p53 target genes. Mol Cell 27:121-33. (Pubitemid 46991381)
91. Drane P, Barel M, Balbo M, Frade R. (1997). Identification of RB18A, a 205 kDa new p53 regulatory protein which shares antigenic and functional properties with p53. Oncogene 15:3013-24. (Pubitemid 28043481)
92. Drogat J, Migeot V, Mommaerts E, et al. (2012). Cdk11-cyclinL controls the assembly of the RNA polymerase II mediator complex. Cell Rep 2:1068-76.
93. Eberhardy SR, Farnham PJ. (2002). Myc recruits P-TEFb to mediate the final step in the transcriptional activation of the cad promoter. J Biol Chem 277:40156-62. (Pubitemid 35191008)
94. Ebert MS, Sharp PA. (2012). Roles for microRNAs in conferring robustness to biological processes. Cell 149:515-24.
95. Ebmeier CC, Taatjes DJ. (2010). Activator-Mediator binding regulates Mediator-cofactor interactions. Proc Natl Acad Sci USA 107: 11283-8.
96. Eichner J, Chen H, Warfield L, Hahn S. (2010). Position of the general transcription factor TFIIF within the RNA polymerase II transcription preinitiation complex. EMBO J 29:706-16.
97. Elfving N, Davoine C, Benlloch R, et al. (2011). The Arabidopsis thaliana Med25 mediator subunit integrates environmental cues to control plant development. Proc Natl Acad Sci USA 108:8245-50.
98. Elmlund H, Baraznenok V, Lindahl M, et al. (2006). The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II. Proc Natl Acad Sci USA 103:15788-93. (Pubitemid 44657545)
99. Esnault C, Ghavi-Helm Y, Brun S, et al. (2008). Mediator-dependent recruitment of TFIIH modules in preinitiation complex. Mol Cell 31: 337-46.
100. Fahey ME, Bennett MJ, Mahon C, et al. (2011). GPS-Prot: a web-based visualization platform for integrating host-pathogen interaction data. BMC Bioinformatics 12:298.
101. Fan X, Struhl K. (2009). Where does mediator bind in vivo? PloS One 4: e5029.
102. Fang L, Stevens JL, Berk AJ, Spindler KR. (2004). Requirement of Sur2 for efficient replication of mouse adenovirus type 1. J Virol 78: 12888-900. (Pubitemid 39507797)
103. Fay A, Misulovin Z, Li J, et al. (2011). Cohesin selectively binds and regulates genes with paused RNA polymerase. Curr Biol 21:1624-34.
104. Firestein R, Bass AJ, Kim SY, et al. (2008). CDK8 is a colorectal cancer oncogene that regulates b-catenin activity. Nature 455:547-51.
105. Firestein R, Shima K, Nosho K, et al. (2010). CDK8 expression in 470 colorectal cancers in relation to beta-catenin activation, other molecular alterations and patient survival. Int J Cancer 126:2863-73.
106. Flanagan PM, Kelleher-III RJ, Sayre MH, et al. (1991). A Mediator required for activation of RNA polymerase II transcription in vitro. Nature 350:436-8. (Pubitemid 21912249)
107. Fondell JD. (2013). The Mediator complex in thyroid hormone receptor action. Biochim Biophys Acta 1830:3867-75.
108. Fondell JD, Ge H, Roeder RG. (1996). Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. Proc Natl Acad Sci USA 93:8329-33. (Pubitemid 26269557)
109. Foulds CE, Feng Q, Ding C, et al. (2013). Proteomic analysis of coregulators bound to ERalpha on DNA and nucleosomes reveals coregulator dynamics. Mol Cell 51:185-99.
110. Frade R, Balbo M, Barel M. (2000). RB18A, whose gene is localized on chromosome 17q12-q21.1, regulates in vivo p53 transactivating activity. Cancer Res 60:6585-9.
111. Friedman RC, Farh KK, Burge CB, Bartel DP. (2009). Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19: 92-105.
112. Fryer CJ, White JB, Jones KA. (2004). Mastermind recruits CycC:Cdk8 to phosphorylate the notch ICD and coordinate activation with turnover. Mol Cell 16:509-20. (Pubitemid 39531875)
113. Fukasawa R, Tsutsui T, Hirose Y, et al. (2012). Mediator CDK subunits are platforms for interactions with various chromatin regulatory complexes. J Biochem 152:241-9.
114. Gaillard H, Tous C, Botet J, et al. (2009). Genome-wide analysis of factors affecting transcription elongation and DNA repair: a new role for PAF and Ccr4-not in transcription-coupled repair. PLoS Genet 5: e1000364.
115. Galbraith MD, Allen MA, Bensard CL, et al. (2013). HIF1A employs CDK8-Mediator to stimulate RNAPII elongation in response to hypoxia. Cell 153:1327-39.
116. Galbraith MD, Donner AJ, Espinosa JM. (2010). CDK8: a positive regulator of transcription. Transcription 1:4-12.
117. Gao S, Alarcon C, Sapkota G, et al. (2009). Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-b signaling. Mol Cell 36: 457-68.
118. Garrett-Engele CM, Siegal ML, Manoli DS, et al. (2002). Intersex, a gene required for female sexual development in Drosophila, is expressed in both sexes and functions together with doublesex to regulate terminal differentiation. Development 129:4661-75. (Pubitemid 35277194)
119. Gaytan De Ayala Alonso A, Gutierrez L, Fritsch C, et al. (2007). A genetic screen identifies novel polycomb group genes in Drosophila. Genetics 176:2099-108. (Pubitemid 47360645)
120. Ge K, Cho YW, Guo H, et al. (2008). Alternative mechanisms by which mediator subunit MED1/TRAP220 regulates peroxisome proliferator-activated receptor gamma-stimulated adipogenesis and target gene expression. Mol Cell Biol 28:1081-91. (Pubitemid 351160064)
121. Ge K, Guermah M, Yuan CX, et al. (2002). Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis. Nature 417:563-7. (Pubitemid 34595925)
122. Geiger JH, Hahn S, Lee S, Sigler PB. (1996). Crystal structure of the yeast TFIIA/TBP/DNA complex. Science 272:830-6. (Pubitemid 26154587)
123. Gerber HP, Hagmann M, Seipel K, et al. (1995). RNA polymerase II C-terminal domain required for enhancer-driven transcription. Nature 374:660-2.
124. Gillmor CS, Park MY, Smith MR, et al. (2010). The MED12-MED13 module of Mediator regulates the timing of embryo patterning in Arabidopsis. Development 137:113-22.
125. Gilmour DS. (2009). Promoter proximal pausing on genes in metazoans. Chromosoma 118:1-10.
126. Gobert V, Osman D, Bras S, et al. (2010). A genome-wide RNA interference screen identifies a differential role of the mediator CDK8 module subunits for GATA/RUNX-activated transcription in Drosophila. Mol Cell Biol 30:2837-48.
127. Goldberg JM, Manning G, Liu A, et al. (2006). The dictyostelium kinome-analysis of the protein kinases from a simple model organism. PLoS Genet 2:e38.
128. Gordon DF, Tucker EA, Tundwal K, et al. (2006). MED220/thyroid receptor-associated protein 220 functions as a transcriptional coacti-vator with Pit-1 and GATA-2 on the thyrotropin-beta promoter in thyrotropes. Mol Endocrinol 20:1073-89.
129. Griffiths SJ, Koegl M, Boutell C, et al. (2013). A systematic analysis of host factors reveals a Med23-interferon-lambda regulatory axis against herpes simplex virus type 1 replication. PLoS Pathog 9:e1003514.
130. Grob P, Cruse MJ, Inouye C, et al. (2006). Cryo-electron microscopy studies of human TFIID: conformational breathing in the integration of gene regulatory cues. Structure 14:511-20. (Pubitemid 43363484)
131. Grontved L, Madsen MS, Boergesen M, et al. (2010). MED14 tethers mediator to the N-terminal domain of peroxisome proliferator-activated receptor gamma and is required for full transcriptional activity and adipogenesis. Mol Cell Biol 30:2155-69.
132. Grueter CE, van Rooij E, Johnson BA, et al. (2012). A cardiac microRNA governs systemic energy homeostasis by regulation of MED13. Cell 149:671-83.
133. Gu W, Malik S, Ito M, et al. (1999). A novel human SRB/MED-containing cofactor complex, Smcc, involved in transcription regulation. Mol Cell 3:97-108. (Pubitemid 29292481)
134. Guenther MG, Levine SS, Boyer LA, et al. (2007). A chromatin landmark and transcription initiation at most promoters in human cells. Cell 130:77-88. (Pubitemid 47031323)
135. Guermah M, Malik S, Roeder RG. (1998). Involvement of TFIID and USA components in transcriptional activation of the human immunodeficiency virus promoter by NF-kappaB and Sp1. Mol Cell Biol 18: 3234-44. (Pubitemid 28240496)
136. Guermah M, Tao Y, Roeder RG. (2001). Positive and negative TAF(II) functions that suggest a dynamic TFIID structure and elicit synergy with traps in activator-induced transcription. Mol Cell Biol 21: 6882-94. (Pubitemid 32911249)
137. Guglielmi B, Soutourina J, Esnault C, Werner M. (2007). TFIIS elongation factor and Mediator act in conjunction during transcription initiation in vivo. Proc Natl Acad Sci USA 104:16062-7. (Pubitemid 350099364)
138. Guidi BW, Bjornsdottir G, Hopkins DC, et al. (2004). Mutual targeting of mediator and the TFIIH kinase Kin28. J Biol Chem 279:29114-20. (Pubitemid 38915783)
139. Guttman M, Rinn JL. (2012). Modular regulatory principles of large non-coding RNAs. Nature 482:339-46.
140. Gwack Y, Baek HJ, Nakamura H, et al. (2003). Principal role of TRAP/mediator and SWI/SNF complexes in Kaposi's sarcoma-associated herpesvirus RTA-mediated lytic reactivation. Mol Cell Biol 23: 2055-67. (Pubitemid 36278816)
141. Hahn S. (2004). Structure and mechanism of the RNA polymerase II transcription machinery. Nat Struct Mol Biol 11:394-403.
142. Hallberg M, Hu GZ, Tronnersjo S, et al. (2006). Functional and physical interactions within the middle domain of the yeast mediator. Mol Genet Genomics 276:197-210. (Pubitemid 44079958)
143. Hallberg M, Polozkov GV, Hu GZ, et al. (2004). Site-specific Srb10-dependent phosphorylation of the yeast Mediator subunit Med2 regulates gene expression from the 2-microm plasmid. Proc Natl Acad Sci USA 101:3370-5. (Pubitemid 38338201)
144. Hasegawa N, Sumitomo A, Fujita A, et al. (2012). Mediator subunits MED1 and MED24 cooperatively contribute to pubertal mammary gland development and growth of breast carcinoma cells. Mol Cell Biol 32:1483-95.
145. He Y, Fang J, Taatjes DJ, Nogales E. (2013). Structural visualization of key steps in human transcription initiation. Nature 495:481-6.
146. Hengartner CJ, Myer VE, Liao S, et al. (1998). Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases. Mol Cell 2:43-53. (Pubitemid 128378965)
147. Hirst M, Kobor MS, Kuriakose N, et al. (1999). GAL4 is regulated by the RNA polymerase II holoenzyme-associated cyclin-dependent protein kinase SRB10/CDK8. Mol Cell 3:673-8.
148. Hittelman AB, Burakov D, Iniguez-Lluhi JA, et al. (1999). Differential regulation of glucocorticoid receptor transcriptional activation via AF-1-associated proteins. EMBO J 18:5380-8. (Pubitemid 29465587)
149. Holstege FC, Jennings EG, Wyrick JJ, et al. (1998). Dissecting the regulatory circuitry of a eukaryotic genome. Cell 95:717-28. (Pubitemid 28544132)
150. Hong S, Haldin CE, Lawson ND, et al. (2005). The zebrafish kohtalo/trap230 gene is required for the development of the brain, neural crest, and pronephric kidney. Proc Natl Acad Sci USA 102: 18473-8. (Pubitemid 43011250)
151. Hu W, Alvarez-Dominguez JR, Lodish HF. (2012). Regulation of mammalian cell differentiation by long non-coding RNAs. EMBO Rep 13:971-83.
152. Hu X, Malik S, Negroiu CC, et al. (2006). A Mediator-responsive form of metazoan RNA polymerase II. Proc Natl Acad Sci USA 103: 9506-11. (Pubitemid 43955855)
153. Hu S, Xie Z, Onishi A, et al. (2009). Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling. Cell 139:610-22.
154. Huang L, Jones AM, Searle I, et al. (2009). An atypical RNA polymerase involved in RNA silencing shares small subunits with RNA polymer-ase II. Nat Struct Mol Biol 16:91-3.
155. Huang S, Holzel M, Knijnenburg T, et al. (2012a). MED12 controls the response to multiple cancer drugs through regulation of TGF-beta receptor signaling. Cell 151:937-50.
156. Huang ZQ, Li J, Sachs LM, et al. (2003). A role for cofactor-cofactor and cofactor-histone interactions in targeting p300, SWI/SNF and Mediator for transcription. EMBO J 22:2146-55. (Pubitemid 36565538)
157. Huang Y, Li W, Yao X, et al. (2012b). Mediator complex regulates alternative mRNA processing via the MED23 subunit. Mol Cell 45: 459-69.
158. Imasaki T, Calero G, Cai G, et al. (2011). Architecture of the Mediator head module. Nature 475:240-3.
159. Imberg-Kazdan K, Ha S, Greenfield A, et al. (2013). A genome-wide RNA interference screen identifies new regulators of androgen receptor function in prostate cancer cells. Genome Res 23:581-91.
160. Ito M, Okano HJ, Darnell RB, Roeder RG. (2002). The TRAP100 component of the TRAP/Mediator complex is essential in broad transcriptional events and development. EMBO J 21:3464-75. (Pubitemid 34760578)
161. Ito J, Sono T, Tasaka M, Furutani M. (2011). MACCHI-BOU 2 is required for early embryo patterning and cotyledon organogenesis in Arabidopsis. Plant Cell Physiol 52:539-52.
162. Ito M, Yuan C, Malik S, et al. (1999). Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators. Mol Cell 3: 361-70. (Pubitemid 29290676)
163. Ito M, Yuan CX, Okano HJ, et al. (2000). Involvement of the TRAP220 component of the TRAP/SMCC coactivator complex in embryonic development and thyroid hormone action. Mol Cell 5:683-93.
164. Janody F, Martirosyan Z, Benlali A, Treisman JE. (2003). Two subunits of the Drosophila mediator complex act together to control cell affinity. Development 130:3691-701. (Pubitemid 37039075)
165. Janody F, Treisman JE. (2011). Requirements for mediator complex subunits distinguish three classes of notch target genes at the Drosophila wing margin. Dev Dyn 240:2051-9.
166. Jiang P, Hu Q, Ito M, et al. (2010). Key roles for MED1 LxxLL motifs in pubertal mammary gland development and luminal-cell differentiation. Proc Natl Acad Sci USA 107:6765-70.
167. Jiang YW, Veschambre P, Erdjument-Bromage H, et al. (1998). Mammalian mediator of transcriptional regulation and its possible role as an end-point of signal transduction pathways. Proc Natl Acad Sci USA 95:8538-43. (Pubitemid 28350523)
168. Jishage M, Malik S, Wagner U, et al. (2012). Transcriptional regulation by Pol II(G) involving mediator and competitive interactions of Gdown1 and TFIIF with Pol II. Mol Cell 45:51-63.
169. Johnson KM, Carey M. (2003). Assembly of a mediator/TFIID/TFIIA complex bypasses the need for an activator. Curr Biol 13:772-7. (Pubitemid 36531027)
170. Johnson LN, Noble ME, Owen DJ. (1996). Active and inactive protein kinases: structural basis for regulation. Cell 85:149-58. (Pubitemid 26118158)
171. Johnson KM, Wang J, Smallwood A, et al. (2002). TFIID and human mediator coactivator complexes assemble cooperatively on promoter DNA. Genes Dev 16:1852-63. (Pubitemid 34803900)
172. Kagey M, Newman J, Bilodeau S, et al. (2010). Mediator and Cohesin connect gene expression and chromatin architecture. Nature 467: 430-5.
173. Kang YK, Guermah M, Yuan CX, Roeder RG. (2002). 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 USA 99:2642-7. (Pubitemid 34240514)
174. Kapanidis AN, Margeat E, Ho SO, et al. (2006). Initial transcription by RNA polymerase proceeds through a DNA-scrunching mechanism. Science 314:1144-7. (Pubitemid 44789044)
175. Kapoor A, Goldberg MS, Cumberland LK, et al. (2010). The histone variant macroH2A suppresses melanoma progression through regulation of CDK8. Nature 468:1105-9.
176. Kato Y, Habas R, Katsuyama Y, et al. (2002). A component of the ARC/Mediator complex required for TGF beta/Nodal signalling. Nature 418:641-6.
177. Keaveney M, Struhl K. (1998). Activator-mediated recruitment of the RNA polymerase II machinery is the predominant mechanism for transcriptional activation in yeast. Mol Cell 1:917-24. (Pubitemid 128379076)
178. Kelleher-III RJ, Flanagan PM, Kornberg RD. (1990). A novel mediator between activator proteins and the RNA polymerase II transcription apparatus. Cell 61:1209-15.
179. Kennison JA, Tamkun JW. (1988). Dosage-dependent modifiers of polycomb and antennapedia mutations in Drosophila. Proc Natl Acad Sci USA 85:8136-40.
180. Kettenberger H, Armache K, Cramer P. (2004). Complete RNA polymerase II elongation complex structure and its interactions with NTP and TFIIS. Mol Cell 16:955-65. (Pubitemid 40018405)
181. Khorosjutina O, Wanrooij PH, Walfridsson J, et al. (2010). A chromatin-remodeling protein is a component of fission yeast mediator. J Biol Chem 285:29729-37.
182. Kidd BN, Cahill DM, Manners JM, et al. (2011). Diverse roles of the Mediator complex in plants. Semin Cell Dev Biol 22:741-8.
183. Kidd BN, Edgar CI, Kumar KK, et al. (2009). The mediator complex subunit PFT1 is a key regulator of jasmonate-dependent defense in Arabidopsis. Plant Cell 21:2237-52.
184. Kim B, Nesvizhskii AI, Rani PG, et al. (2007). The transcription elongation factor TFIIS is a component of RNA polymerase II preinitiation complexes. Proc Natl Acad Sci USA 104:16068-73. (Pubitemid 350099365)
185. Kim JH, Yang CK, Heo K, et al. (2008). CCAR1, a key regulator of Mediator complex recruitment to nuclear receptor transcription complexes. Mol Cell 31:510-19.
186. Kim S, Gross DS. (2013). Mediator recruitment to heat shock genes requires dual Hsf1 activation domains and mediator tail subunits Med15 and Med16. J Biol Chem 288:12197-213.
187. Kim S, Xu X, Hecht A, Boyer TG. (2006a). Mediator is a transducer of Wnt/beta-catenin signaling. J Biol Chem 281:14066-75.
188. Kim TW, Kwon YJ, Kim JM, et al. (2004). MED16 and MED23 of Mediator are coactivators of lipopolysaccharide-and heat-shock-induced transcriptional activators. Proc Natl Acad Sci USA 101: 12153-8. (Pubitemid 39145412)
189. Kim Y, Bjorklund S, Li Y, et al. (1994). A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II. Cell 77:599-608. (Pubitemid 24153999)
190. Kim YJ, Zheng B, Yu Y, et al. (2011). The role of Mediator in small and long noncoding RNA production in Arabidopsis thaliana. EMBO J 30:814-22.
191. Kim YK, Bourgeois CF, Pearson R, et al. (2006b). Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency. EMBO J 25:3596-604. (Pubitemid 44264870)
192. Knuesel MT, Meyer KD, Bernecky C, Taatjes DJ. (2009a). The human CDK8 subcomplex is a molecular switch that controls Mediator co-activator function. Genes Dev 23:439-51.
193. Knuesel MT, Meyer KD, Donner AJ, et al. (2009b). The human CDK8 subcomplex is a histone kinase that requires Med12 for activity and can function independently of Mediator. Mol Cell Biol 29:650-61.
194. Knuesel MT, Taatjes DJ. (2011). Mediator and post-recruitment regulation of RNA polymerase II. Transcription 2:28-31.
195. Kobbe D, Blanck S, Demand K, et al. (2008). AtRECQ2, a RecQ helicase homologue from Arabidopsis thaliana, is able to disrupt various recombinogenic DNA structures in vitro. Plant J 55: 397-405. (Pubitemid 352033350)
196. Koleske AJ, Buratowski S, Nonet M, Young RA. (1992). A novel transcription factor reveals a functional link between the RNA polymerase II CTD and TFIID. Cell 69:883-94.
197. Koleske AJ, Young RA. (1994). An RNA polymerase II holoenzyme responsive to activators. Nature 368:466-9. (Pubitemid 24115355)
198. Konig R, Zhou Y, Elleder D, et al. (2008). Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 135:49-60.
199. Koh SS, Ansari AZ, Ptashne M, Young RA. (1998). An activator target in the RNA polymerase II holoenzyme. Mol Cell 1:895-904. (Pubitemid 128379073)
200. Kornberg RD. (2005). Mediator and the mechanism of transcriptional activation. Trends Biochem Sci 30:235-9. (Pubitemid 40693865)
201. Kornblihtt AR, Schor IE, Allo M, et al. (2013). Alternative splicing: a pivotal step between eukaryotic transcription and translation. Nat Rev Mol Cell Biol 14:153-65.
202. Koschubs T, Lorenzen K, Baumli S, et al. (2010). Preparation and topology of the Mediator middle module. Nucleic Acids Res 38: 3186-95.
203. Koschubs T, Seizl M, Lariviere L, et al. (2009). Identification, structure, and functional requirement of the Mediator submodule Med7N/31. EMBO J 28:69-80.
204. Kostek SA, Grob P, de Carlo S, et al. (2006). Molecular architecture and conformational flexibility of human RNA polymerase II. Structure 14: 1691-700. (Pubitemid 46107277)
205. Krebs AR, Demmers J, Karmodiya K, et al. (2010). ATAC and Mediator coactivators form a stable complex and regulate a set of non-coding RNA genes. EMBO Rep 11:541-7.
206. Kremer SB, Kim S, Jeon JO, et al. (2012). Role of Mediator in regulating Pol II elongation and nucleosome displacement in Saccharomyces cerevisiae. Genetics 191:95-106.
207. Kretzschmar M, Stelzer G, Roeder RG, Meisterernst M. (1994). RNA polymerase II cofactor PC2 facilitates activation of transcription by GAL4-AH in vitro. Mol Cell Biol 14:3927-37. (Pubitemid 24160799)
208. Kuchin S, Treich I, Carlson M. (2000). A regulatory shortcut between the Snf1 protein kinase and RNA polymerase II holoenzyme. Proc Natl Acad Sci USA 97:7916-20. (Pubitemid 30460748)
209. Kuchin S, Yeghiayan P, Carlson M. (1995). Cyclin-dependent protein kinase and cyclin homologs SSN3 and SSN8 contribute to transcriptional control in yeast. Proc Natl Acad Sci USA 92: 4006-10.
210. Lai F, Orom UA, Cesaroni M, et al. (2013). Activating RNAs associate with Mediator to enhance chromatin architecture and transcription. Nature 494:497-501.
211. Lariviere L, Geiger S, Hoeppner S, et al. (2006). Structure and TBP binding of the Mediator head subcomplex Med8-Med18-Med20. Nat Struct Mol Biol 13:895-901. (Pubitemid 44527371)
212. Lariviere L, Plaschka C, Seizl M, et al. (2012). Structure of the Mediator head module. Nature 492:448-51.
213. Larochelle S, Amat R, Glover-Cutter K, et al. (2012). Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA poly-merase II. Nat Struct Mol Biol 19:1108-15.
214. Larschan E, Winston F. (2005). The Saccharomyces cerevisiae Srb8-Srb11 complex functions with the SAGA complex during Gal4-activated transcription. Mol Cell Biol 25:114-23. (Pubitemid 40039804)
215. Lau JF, Nusinzon I, Burakov D, et al. (2003). Role of metazoan mediator proteins in interferon-responsive transcription. Mol Cell Biol 23:620-8. (Pubitemid 36050554)
216. Leclerc V, Tassan JP, O'farrell PH, et al. (1996). Drosophila Cdk8, a kinase partner of cyclin C that interacts with the large subunit of RNA polymerase II. Mol Cell Biol 7:505-13. (Pubitemid 26112559)
217. Lee HK, Park UH, Kim EJ, Um SJ. (2007). MED25 is distinct from TRAP220/MED1 in cooperating with CBP for retinoid receptor activation. EMBO J 26:3545-57.
218. Lee JE, Kim K, Sacchettini JC, et al. (2005a). DRIP150 coactivation of estrogen receptor alpha in ZR-75 breast cancer cells is independent of LXXLL motifs. J Biol Chem 280:8819-30. (Pubitemid 40409571)
219. Lee JH, Cai G, Panigrahi AK, et al. (2010a). A TFIIH-associated mediator head is a basal factor of small nuclear spliced leader RNA gene transcription in early-diverged trypanosomes. Mol Cell Biol 30: 5502-13.
220. Lee KM, Miklos I, Du H, et al. (2005b). Impairment of the TFIIH-associated CDK-activating kinase selectively affects cell cycle-regulated gene expression in fission yeast. Mol Biol Cell 16: 2734-45. (Pubitemid 40741220)
221. Lee SK, Fletcher AG, Zhang L, et al. (2010b). Activation of a poised RNAPII-dependent promoter requires both SAGA and mediator. Genetics 184:659-72.
222. Lee TI, Young RA. (2013). Transcriptional regulation and its misregulation in disease. Cell 152:1237-51.
223. Lehmann L, Ferrari R, Vashisht AA, et al. (2012). Polycomb repressive complex 1 (PRC1) disassembles RNA polymerase II preinitiation complexes. J Biol Chem 287:35784-94.
224. Lehner B, Crombie C, Tischler J, et al. (2006). Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways. Nat Genet 38:896-903. (Pubitemid 44141657)
225. Levine M, Tjian R. (2003). Transcription regulation and animal diversity. Nature 424:147-51. (Pubitemid 36858677)
226. Lewis BA. (2010). Understanding large multiprotein complexes: applying a multiple allosteric networks model to explain the function of the Mediator transcription complex. J Cell Sci 123:159-63.
227. Li H, Gade P, Nallar SC, et al. (2008). The Med1 subunit of transcriptional mediator plays a central role in regulating CCAAT/enhancer- binding protein-beta-driven transcription in response to interferon-gamma. J Biol Chem 283:13077-86.
228. Li XY, Virbasius A, Zhu X, Green MR. (1999). Enhancement of TBP binding by activators and general transcription factors. Nature 399: 605-9.
229. Liao S, Zhang J, Jeffery DA, et al. (1995). A kinase-cyclin pair in the RNA polymerase II holoenzyme. Nature 374:193-6.
230. Lim MK, Tang V, Le Saux A, et al. (2007). Gal11p dosage-compensates transcriptional activator deletions via Taf14p. J Mol Biol 374:9-23. (Pubitemid 47600235)
231. Lin HH, Khosla M, Huang HJ, et al. (2004). A homologue of Cdk8 is required for spore cell differentiation in Dictyostelium. Dev Biol 271: 49-58. (Pubitemid 38757774)
232. Lin JJ, Lehmann LW, Bonora G, et al. (2011). Mediator coordinates PIC assembly with recruitment of CHD1. Genes Dev 25:2198-209.
233. Lin C, Smith ER, Takahashi H, et al. (2010). AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia. Mol Cell 37: 429-37.
234. Linares LK, Kiernan R, Triboulet R, et al. (2007). Intrinsic ubiquitina-tion activity of PCAF controls the stability of the oncoprotein Hdm2. Nat Cell Biol 9:331-8. (Pubitemid 46344613)
235. Linder T, Rasmussen NN, Samuelsen CO, et al. (2008). Two conserved modules of Schizosaccharomyces pombe Mediator regulate distinct cellular pathways. Nucleic Acids Res 36:2489-504. (Pubitemid 351659565)
236. Liu X, Vorontchikhina M, Wang Y, et al. (2008). STAGA recruits Mediator to the MYC oncoprotein to stimulate transcription and cell proliferation. Mol Cell Biol 28:108-21.
237. Liu Y, Kung C, Fishburn J, et al. (2004). Two cyclin-dependent kinases promote RNA polymerase II transcription and formation of the scaffold complex. Mol Cell Biol 24:1721-35. (Pubitemid 38167093)
238. Liu Y, Ranish JA, Aebersold R, Hahn S. (2001). Yeast nuclear extract contains two major forms of RNA polymerase II mediator complexes. J Biol Chem 276:7169-75.
239. Liu Z, Myers LC. (2012). Med5(Nut1) and Med17(Srb4) are direct targets of mediator histone H4 tail interactions. PloS One 7:e38416.
240. Lo WS, Trievel RC, Rojas JR, et al. (2000). Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14. Mol Cell 5:917-26.
241. Loncle N, Boube M, Joulia L, et al. (2007). Distinct roles for Mediator cdk8 module subunits in Drosophila development. EMBO J 26: 1045-54.
242. Lorch Y, Beve J, Gustafsson CM, et al. (2000). Mediator-nucleosome interaction. Mol Cell 6:197-201.
243. Loven J, Hoke HA, Lin CY, et al. (2013). Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 153:320-34.
244. Loyer P, Trembley JH, Katona R, et al. (2005). Role of CDK/cyclin complexes in transcription and RNA splicing. Cell Signal 17: 1033-51. (Pubitemid 40933525)
245. Luo Z, Lin C, Guest E, et al. (2012a). The super elongation complex family of RNA polymerase II elongation factors: gene target specificity and transcriptional output. Mol Cell Biol 32:2608-17.
246. Luo Z, Lin C, Shilatifard A. (2012b). The super elongation complex (SEC) family in transcriptional control. Nat Rev Mol Cell Biol 13: 543-7.
247. Macatee T, Jiang YW, Stillman DJ, Roth SY. (1997). Global alterations in chromatin accessibility associated with loss of SIN4 function. Nucleic Acids Res 25:1240-7. (Pubitemid 27303217)
248. Malagon F, Tong AH, Shafer BK, Strathern JN. (2004). Genetic interactions of DST1 in Saccharomyces cerevisiae suggest a role of TFIIS in the initiation-elongation transition. Genetics 166:1215-27. (Pubitemid 38507042)
249. Malik S, Barrero MJ, Jones T. (2007). Identification of a regulator of transcription elongation as an accessory factor for the human Mediator coactivator. Proc Natl Acad Sci USA 104:6182-7. (Pubitemid 47186069)
250. Malik S, Gu W, Wu W, et al. (2000). The USA-derived transcriptional coactivator PC2 is a submodule of TRAP/SMCC and acts synergis-tically with other PCs. Mol Cell 5:753-60.
251. Malik S, Guermah M, Yuan CX, et al. (2004). Structural and functional organization of TRAP220, the TRAP/mediator subunit that is targeted by nuclear receptors. Mol Cell Biol 24:8244-54. (Pubitemid 39167472)
252. Malik S, Roeder RG. (2010). The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation. Nat Rev Genet 11:761-72.
253. Malik S, Wallberg AE, Kang YK, Roeder RG. (2002). TRAP/SMCC/mediator- dependent transcriptional activation from DNA and chro-matin templates by orphan nuclear receptor hepatocyte nuclear factor 4. Mol Cell Biol 22:5626-37. (Pubitemid 34755771)
254. Malovannaya A, Lanz RB, Jung SY, et al. (2011). Analysis of the human endogenous coregulator complexome. Cell 145:787-99.
255. Malumbres M, Harlow E, Hunt T, et al. (2009). Cyclin-dependent kinases: a family portrait. Nat Cell Biol 11:1275-6.
256. Marr MT, Isogai Y, Wright KJ, Tjian R. (2006). Coactivator cross-talk specifies transcriptional output. Genes Dev 20:1458-69. (Pubitemid 43830653)
257. Mathur S, Vyas S, Kapoor S, Tyagi AK. (2011). The Mediator complex in plants: structure, phylogeny, and expression profiling of representative genes in a dicot (Arabidopsis) and a monocot (rice) during reproduction and abiotic stress. Plant Physiol 157: 1609-27.
258. Max T, Sogaard M, Svejstrup JQ. (2007). Hyperphosphorylation of the C-terminal repeat domain of RNA polymerase II facilitates dissociation of its complex with mediator. J Biol Chem 282:14113-20. (Pubitemid 47100413)
259. Maxon ME, Goodrich JA, Tjian R. (1994). Transcription factor IIE binds preferentially to RNA polymerase IIa and recruits TFIIH: a model for promoter clearance. Genes Dev 8:515-24. (Pubitemid 24086122)
260. Mehta S, Miklos I, Sipiczki M, et al. (2009). The Med8 mediator subunit interacts with the Rpb4 subunit of RNA polymerase II and Ace2 transcriptional activator in Schizosaccharomyces pombe. FEBS Lett 583:3115-20.
261. Meinhart A, Kamenski T, Hoeppner S, et al. (2005). A structural perspective of CTD function. Genes Dev 19:1401-15. (Pubitemid 41003005)
262. Metivier R, Penot G, Hubner MR, et al. (2003). Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115:751-63. (Pubitemid 38030303)
263. Meyer KD, Donner AJ, Knuesel M, et al. (2008). Cooperative activity of CDK8 and GCN5L within Mediator directs tandem phosphoacetyla-tion of histone H3. EMBO J 27:1447-57. (Pubitemid 351733333)
264. Meyer KD, Lin S, Bernecky C, et al. (2010). p53 activates transcription by directing structural shifts in Mediator. Nat Struct Mol Biol 17: 753-60.
265. Milbradt AG, Kulkarni M, Yi T, et al. (2011). Structure of the VP16 transactivator target in the Mediator. Nat Struct Mol Biol 18:410-15.
266. Miller C, Matic I, Maier KC, et al. (2012). Mediator phosphorylation prevents stress response transcription during non-stress conditions. J Biol Chem 287:44017-26.
267. Mittler G, Kremmer E, Timmers HT, Meisterernst M. (2001). Novel critical role of a human mediator complex for basal RNA polymerase II transcription. EMBO Rep 2:808-13. (Pubitemid 32982749)
268. Mittler G, Stühler T, Santolin L, et al. (2003). A novel docking site on Mediator is critical for activation by VP16 in mammalian cells. EMBO J 22:6494-504. (Pubitemid 38009597)
269. Mo X, Kowenz-Leutz E, Xu H, Leutz A. (2004). Ras induces mediator complex exchange on C/EBPb. Mol Cell 13:241-50. (Pubitemid 38183270)
270. Moghai N, Sternberg PW. (2003). A component of the transcriptional mediator complex inhibits RAS-dependent vulval fate specification in C. elegans. Development 130:57-69. (Pubitemid 36113943)
271. Morris EJ, Ji J, Yang F, et al. (2008). E2F1 represses b-catenin transcription and is antagonized by both pRB and CDK8. Nature 455: 552-6.
272. Mouillet JF, Chu T, Nelson DM, et al. (2010). MiR-205 silences MED1 in hypoxic primary human trophoblasts. FASEB J 24:2030-9.
273. Mousley CJ, Yuan P, Gaur NA, et al. (2012). A sterol-binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing. Cell 148:702-15.
274. Mozdy AD, Podell ER, Cech TR. (2008). Multiple yeast genes, including Paf1 complex genes, affect telomere length via telomerase RNA abundance. Mol Cell Biol 28:4152-61. (Pubitemid 351812998)
275. Mukhopadhyay A, Kramer JM, Merkx G, et al. (2010). CDK19 is disrupted in a female patient with bilateral congenital retinal folds, microcephaly and mild mental retardation. Hum Genet 128:281-91.
276. Mukundan B, Ansari A. (2011). Novel role for mediator complex subunit Srb5/Med18 in termination of transcription. J Biol Chem 286: 37053-7.
277. Mukundan B, Ansari A. (2013). Srb5/Med18-mediated termination of transcription is dependent on gene looping. J Biol Chem 288: 11384-94.
278. Mullen AC, Orlando DA, Newman JJ, et al. (2011). Master transcription factors determine cell-type-specific responses to TGF-beta signaling. Cell 147:565-76.
279. Muncke N, Jung C, Rudiger H, et al. (2003). Missense mutations and gene interruption in PROSIT240, a novel TRAP240-like gene, in patients with congenital heart defect (transposition of the great arteries). Circulation 108:2843-50. (Pubitemid 37517810)
280. Muse GW, Gilchrist DA, Nechaev S, et al. (2007). RNA polymerase is poised for activation across the genome. Nat Genet 39:1507-11. (Pubitemid 350191341)
281. Myers LC, Gustafsson CM, Bushnell DA, et al. (1998). The Med proteins of yeast and their function through the RNA polymerase II carboxy-terminal domain. Genes Dev 12:45-54. (Pubitemid 28083657)
282. Naar AM, Beaurang PA, Zhou S, et al. (1999). Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature 398:828-32.
283. Naar AM, Taatjes DJ, Zhai W, et al. (2002). Human CRSP interacts with RNA polymerase II CTD and adopts a specific CTD-bound conformation. Genes Dev 16:1339-44. (Pubitemid 34615087)
284. Nagalingam A, Tighiouart M, Ryden L, et al. (2012). Med1 plays a critical role in the development of tamoxifen resistance. Carcinogenesis 33:918-30.
285. Nair D, Kim Y, Myers LC. (2005). Mediator and TFIIH govern carboxy-terminal domain-dependent transcription in yeast extracts. J Biol Chem 280:33739-48. (Pubitemid 41443092)
286. Nakamura Y, Yamamoto K, He X, et al. (2011). Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25. Nat Commun 2:251.
287. Napoli C, Sessa M, Infante T, Casamassimi A. (2012). Unraveling framework of the ancestral Mediator complex in human diseases. Biochimie 94:579-87.
288. Natarajan K, Jackson BM, Zhou H, et al. (1999). Transcriptional activation by Gcn4p involves independent interactions with the SWI/SNF complex and the SRB/mediator. Mol Cell 4:657-64. (Pubitemid 29531146)
289. Nechaev S, Adelman K. (2011). Pol II waiting in the starting gates: regulating the transition from transcription initiation into productive elongation. Biochim Biophys Acta 1809:34-45.
290. Nelson C, Goto S, Lund K, et al. (2003). Srb10/Cdk8 regulates yeast filamentous growth by phosphorylating the transcription factor Ste12. Nature 421:187-90. (Pubitemid 36090988)
291. Nevado J, Tenbaum SP, Aranda A. (2004). hSrb7, an essential human Mediator component, acts as a coactivator for the thyroid hormone receptor. Mol Cell Endocrinol 222:41-51. (Pubitemid 38900814)
292. Nikolov DB, Chen H, Halay ED, et al. (1995). Crystal structure of a TFIIB-TBP-TATA-element ternary complex. Nature 377:119-28.
293. Nock A, Ascano JM, Barrero MJ, Malik S. (2012). Mediator-regulated transcription through the +1 nucleosome. Mol Cell 48: 837-48.
294. Nonet ML, Young RA. (1989). Intragenic and extragenic suppressors of mutations in the heptapeptide repeat domain of Saccharomyces cerevisiae RNA polymerase II. Genetics 123:715-24. (Pubitemid 20011816)
295. Ohkuma Y, Roeder RG. (1994). Regulation of TFIIH ATPase and kinase activities by TFIIE during active initiation complex formation. Nature 368:160-3. (Pubitemid 24101529)
296. Olsen JV, Blagoev B, Gnad F, et al. (2006). Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127: 635-48. (Pubitemid 44647421)
297. Orom UA, Derrien T, Beringer M, et al. (2010). Long noncoding RNAs with enhancer-like function in human cells. Cell 143:46-58.
298. Pandey PK, Udayakumar TS, Lin X, et al. (2005). Activation of TRAP/Mediator subunit TRAP220/Med1 is regulated by mitogen-activated protein kinase-dependent phosphorylation. Mol Cell Biol 25: 10695-710. (Pubitemid 41747116)
299. Paoletti AC, Parmely TJ, Tomomori-Sato C, et al. (2006). Quantitative proteomic analysis of distinct mammalian Mediator complexes using normalized spectral abundance factors. Proc Natl Acad Sci USA 103: 18928-33. (Pubitemid 350002805)
300. Papantonis A, Larkin JD, Wada Y, et al. (2010). Active RNA polymerases: mobile or immobile molecular machines? PLoS Biol 8:e1000419.
301. Park JM, Gim BS, Kim JM, et al. (2001a). Drosophila Mediator complex is broadly utilized by diverse gene-specific transcription factors at different types of core promoters. Mol Cell Biol 21:2312-23.
302. Park JM, Kim HS, Han SJ, et al. (2000). In vivo requirement of activator-specific binding targets of mediator. Mol Cell Biol 20:8709-19. (Pubitemid 32245904)
303. Park JM, Kim JM, Kim LK, et al. (2003). Signal-induced transcriptional activation by Dif requires the dTRAP80 mediator module. Mol Cell Biol 23:1358-67. (Pubitemid 36177044)
304. Park JM, Werner J, Kim JM, et al. (2001b). Mediator, not holoenzyme, is directly recruited to the heat shock promoter by HSF upon heat shock. Mol Cell 8:9-19. (Pubitemid 32772901)
305. Park SW, Li G, Lin Y, et al. (2005). Thyroid hormone-induced juxtaposition of regulatory elements/factors and chromatin remodeling of Crabp1 dependent on MED1/TRAP220. Mol Cell 19: 643-53. (Pubitemid 41219440)
306. Pavri R, Lewis B, Kim TK, et al. (2005). PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator. Mol Cell 18:83-96. (Pubitemid 40444650)
307. Peng J, Zhou JQ. (2012). The tail-module of yeast Mediator complex is required for telomere heterochromatin maintenance. Nucleic Acids Res 40:581-93.
308. Perales R, Bentley D. (2009). "Cotranscriptionality": the transcription elongation complex as a nexus for nuclear transactions. Mol Cell 36: 178-91.
309. Peterlin BM, Price DH. (2006). Controlling the elongation phase of transcription with P-TEFb. Mol Cell 23:297-305. (Pubitemid 44128850)
310. Phillips AJ, Taatjes DJ. (2013). Small molecule probes to target the human Mediator complex. Isr J Chem 53:588-95.
311. Phillips-Cremins JE, Sauria ME, Sanyal A, et al. (2013). Architectural protein subclasses shape 3D organization of genomes during lineage commitment. Cell 153:1281-95.
312. Pineda Torra I, Freedman LP, Garabedian MJ. (2004). Identification of DRIP205 as a coactivator for the farnesoid X receptor. J Biol Chem 279:36184-91. (Pubitemid 39128953)
313. Pope NJ, Bresnick EH. (2013). Establishment of a cell-type-specific genetic network by the mediator complex component Med1. Mol Cell Biol 33:1938-55.
314. Porter DC, Farmaki E, Altilia S, et al. (2012). Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities. Proc Natl Acad Sci USA 109:13799-804.
315. Ptashne M, Gann A. (1997). Transcriptional activation by recruitment. Nature 386:569-77. (Pubitemid 27175417)
316. Rachez C, Lemon BD, Suldan Z, et al. (1999). Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature 398:824-8.
317. Raithatha S, Su TC, Lourenco P, et al. (2012). Cdk8 regulates stability of the transcription factor Phd1 to control pseudohyphal differentiation of Saccharomyces cerevisiae. Mol Cell Biol 32:664-74.
318. Rana R, Surapureddi S, Kam W, et al. (2011). Med25 is required for RNA polymerase II recruitment to specific promoters, thus regulating xenobiotic and lipid metabolism in human liver. Mol Cell Biol 31: 466-81.
319. Rani PG, Ranish JA, Hahn S. (2004). RNA polymerase II (Pol II)-TFIIF and Pol II-mediator complexes: the major stable Pol II complexes and their activity in transcription initiation and reinitiation. Mol Cell Biol 24:1709-20. (Pubitemid 38167092)
320. Ranish JA, Yudkovsky N, Hahn S. (1999). Intermediates in formation and activity of the RNA polymerase II preinitiation complex: holoenzyme recruitment and a postrecruitment role for the TATA box and TFIIB. Genes Dev 13:49-63. (Pubitemid 29045115)
321. Rau MJ, Fischer S, Neumann CJ. (2006). Zebrafish Trap230/Med12 is required as a coactivator for Sox9-dependent neural crest, cartilage, and ear development. Dev Biol 296:83-93. (Pubitemid 44061756)
322. Reeves WM, Hahn S. (2003). Activator-independent functions of the yeast mediator sin4 complex in preinitiation complex formation and transcription reinitiation. Mol Cell Biol 23:349-58. (Pubitemid 36008525)
323. Reid G, Hubner MR, Metevier R, et al. (2003). Cyclic, proteasome-mediated turnover of unliganded and liganded ERalpha on responsive promoters is an integral feature of estrogen signaling. Mol Cell 11: 695-707. (Pubitemid 36385123)
324. Revyakin A, Liu C, Ebright RH, Strick TR. (2006). Abortive initiation and productive initiation by RNA polymerase involve DNA scrunching. Science 314:1139-43. (Pubitemid 44789043)
325. Risheg H, Graham JM, Clark RD, et al. (2007). A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome. Nat Genet 39:451-3. (Pubitemid 46514774)
326. Robinson PJ, Bushnell DA, Trnka MJ, et al. (2012). Structure of the mediator head module bound to the carboxy-terminal domain of RNA polymerase II. Proc Natl Acad Sci USA 109:17931-5.
327. Rodriguez-Gil A, Garcia-Martinez J, Pelechano V, et al. (2010). The distribution of active RNA polymerase II along the transcribed region is gene-specific and controlled by elongation factors. Nucleic Acids Res 38:4651-64.
328. Ryu S, Zhou S, Ladurner AG, Tjian R. (1999). The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1. Nature 397:446-50.
329. Sakurai H, Fukasawa T. (1997). Yeast Gal11 and transcription factor IIE function through a common pathway in transcriptional regulation. J Biol Chem 272:32663-9.
330. Sakurai H, Fukasawa T. (1998). Functional correlation among Gal 11, transcription factor (TF) Iie, and TFIIH in Saccharomyces cerevisiae. Gal 11 and TFIIE cooperatively enhance TFIIH-mediated phosphor-ylation of RNA polymerase II carboxyl-terminal domain sequences. J Biol Chem 273:9534-8. (Pubitemid 28183038)
331. Sakurai H, Fukasawa T. (2000). Functional connections between mediator components and general transcription factors of Saccharomyces cerevisiae. J Biol Chem 275:37251-6. (Pubitemid 32002147)
332. Sakurai H, Fukasawa T. (2003). Artificial recruitment of certain Mediator components affects requirement of basal transcription factor IIE. Genes Cells 8:41-50. (Pubitemid 36511692)
333. Sakurai H, Kim YJ, Ohishi T, et al. (1996). The yeast GAL11 protein binds to the transcription factor IIE through GAL11 regions essential for its in vivo function. Proc Natl Acad Sci USA 93:9488-92. (Pubitemid 26296635)
334. Sakurai H, Mitsuzawa H, Kimura M, Ishihama A. (1999). The Rpb4 subunit of fission yeast Schizosaccharomyces pombe RNA polymerase II is essential for cell viability and similar in structure to the corresponding subunits of higher eukaryotes. Mol Cell Biol 19:7511-8. (Pubitemid 29493414)
335. Sato S, Tomomori-Sato C, Banks CA, et al. (2003a). A mammalian homolog of Drosophila melanogaster transcriptional coactivator intersex is a subunit of the mammalian Mediator complex. J Biol Chem 278:49671-4. (Pubitemid 37548797)
336. Sato S, Tomomori-Sato C, Banks CA, et al. (2003b). Identification of mammalian Mediator subunits with similarities to yeast Mediator subunits Srb5, Srb6, Med11, and Rox3. J Biol Chem 278:15123-7. (Pubitemid 36799845)
337. Sato S, Tomomori-Sato C, Parmely TJ, et al. (2004). A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology. Mol Cell 14:685-91. (Pubitemid 38739090)
338. Schaaf CA, Kwak H, Koenig A, et al. (2013). Genome-wide control of RNA polymerase II activity by cohesin. PLoS Genet 9:e1003382.
339. Schneider EV, Bottcher J, Blaesse M, et al. (2011). The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder. J Mol Biol 412:251-66.
340. Seila AC, Calabrese JM, Levine SS, et al. (2008). Divergent transcription from active promoters. Science 322:1849-51.
341. Seizl M, Lariviere L, Pfaffeneder T, et al. (2011). Mediator head subcomplex Med11/22 contains a common helix bundle building block with a specific function in transcription initiation complex stabilization. Nucleic Acids Res 39:6291-304.
342. Sela D, Conkright JJ, Chen L, et al. (2013). Role for human mediator subunit MED25 in recruitment of mediator to promoters by endoplasmic reticulum stress-responsive transcription factor ATF6alpha. J Biol Chem 288:26179-87.
343. Serizawa H, Conaway JW, Conaway RC. (1994). An oligomeric form of the large subunit of transcription factor (TF) IIE activates phosphorylation of the RNA polymerase II carboxyl-terminal domain by TFIIH. J Biol Chem 269:20750-6. (Pubitemid 24260491)
344. Shao W, Rosenauer A, Mann K, et al. (2000). Ligand-inducible interaction of the DRIP/TRAP coactivator complex with retinoid receptors in retinoic acid-sensitive and-resistant acute promyelocytic leukemia cells. Blood 96:2233-9.
345. Sharma N, Marguerat S, Mehta S, et al. (2006). The fission yeast Rpb4 subunit of RNA polymerase II plays a specialized role in cell separation. Mol Genet Genomics 276:545-54. (Pubitemid 44691593)
346. Shimogawa H, Kwon Y, Mao Q, et al. (2004). A wrench-shaped synthetic molecule that modulates a transcription factor-coactivator interaction. J Am Chem Soc 126:3461-71. (Pubitemid 38366736)
347. Smallwood A, Black JC, Tanese N, et al. (2008). HP1-mediated silencing targets Pol II coactivator complexes. Nat Struct Mol Biol 15: 318-20. (Pubitemid 351654040)
348. Soloaga A, Thomson S, Wiggin GR, et al. (2003). MSK2 and MSK1 mediate the mitogen-and stress-induced phosphorylation of histone H3 and HMG-14. EMBO J 22:2788-97. (Pubitemid 36712374)
349. Song W, Treich I, Qian N, et al. (1996). SSN genes that affect transcriptional repression in Saccharomyces cerevisiae encode SIN4, ROX3, and SRB proteins associated with RNA polymerase II. Mol Cell Biol 16:115-20. (Pubitemid 126506956)
350. Soutourina J, Wydau S, Ambroise Y, et al. (2011). Direct interaction of RNA polymerase II and mediator required for transcription in vivo. Science 331:1451-4.
351. Spaeth JM, Kim NH, Boyer TG. (2011). Mediator and human disease. Semin Cell Dev Biol 22:776-87.
352. Spahr H, Khorosjutina O, Baraznenok V, et al. (2003). Mediator influences Schizosaccharomyces pombe RNA polymerase II-dependent transcription in vitro. J Biol Chem 278:51301-6. (Pubitemid 38020368)
353. Spahr H, Samuelsen CO, Baraznenok V, et al. (2001). Analysis of Schizosaccharomyces pombe mediator reveals a set of essential subunits conserved between yeast and metazoan cells. Proc Natl Acad Sci USA 98:11985-90. (Pubitemid 32959813)
354. Stevens JL, Cantin GT, Wang G, et al. (2002). Transcription control by E1A and MAP kinase pathway via Sur2 mediator subunit. Science 296:755-8. (Pubitemid 34442008)
355. Stumpf M, Waskow C, Krotschel M, et al. (2006). The mediator complex functions as a coactivator for GATA-1 in erythropoiesis via subunit Med1/TRAP220. Proc Natl Acad Sci USA 103:18504-9. (Pubitemid 44913440)
356. Stumpf M, Yue X, Schmitz S, et al. (2010). Specific erythroid-lineage defect in mice conditionally deficient for Mediator subunit Med1. Proc Natl Acad Sci USA 107:21541-6.
357. Svejstrup JQ, Li Y, Fellows J, et al. (1997). Evidence for a mediator cycle at the initiation of transcription. Proc Natl Acad Sci USA 94: 6075-8. (Pubitemid 27270638)
358. Swanson MJ, Qiu H, Sumibcay L, et al. (2003). A multiplicity of coactivators is required by Gcn4p at individual promoters in vivo. Mol Cell Biol 23:2800-20. (Pubitemid 36403079)
359. Szilagyi Z, Banyai G, Lopez MD, et al. (2012). Cyclin-dependent kinase 8 regulates mitotic commitment in fission yeast. Mol Cell Biol 32: 2099-109.
360. Taatjes DJ, Naar AM, Andel F, et al. (2002). Structure, function, and activator-induced conformations of the CRSP coactivator. Science 295:1058-62. (Pubitemid 34132233)
361. Taatjes DJ, Schneider-Poetsch T, Tjian R. (2004). Distinct conform-ational states of nuclear receptor-bound CRSP-Med complexes. Nat Struct Mol Biol 11:664-71. (Pubitemid 38823534)
362. Taatjes DJ, Tjian R. (2004). Structure and function of CRSP/Med2: a promoter-selective transcriptional co-activator complex. Mol Cell 14:675-83. (Pubitemid 38739089)
363. Takagi Y, Calero G, Komori H, et al. (2006). Head module control of Mediator interactions. Mol Cell 23:355-64. (Pubitemid 44128845)
364. Takagi Y, Kornberg RD. (2006). Mediator as a general transcription factor. J Biol Chem 281:80-9. (Pubitemid 43671165)
365. Takahashi H, Kasahara K, Kokubo T. (2009). Saccharomyces cerevisiae Med9 comprises two functionally distinct domains that play different roles in transcriptional regulation. Genes Cells 14: 53-67.
366. Takahashi H, Parmely TJ, Sato S, et al. (2011). Human Mediator subunit MED26 functions as a docking site for transcription elongation factors. Cell 146:92-104.
367. Takeda K, Saito T, Ochiai H. (2002). A novel Dictyostelium Cdk8 is required for aggregation, but is dispensable for growth. Dev Growth Differ 44:213-23. (Pubitemid 34639367)
368. Tan S, Aso T, Conaway RC, Conaway JW. (1994). Roles for both the RAP30 and RAP74 subunits of transcription factor IIF in transcription initiation and elongation by RNA polymerase II. J Biol Chem 269: 25684-91. (Pubitemid 24336264)
369. Tan S, Hunziker Y, Sargent DF, Richmond TJ. (1996). Crystal structure of a yeast TFIIA/TBP/DNA complex. Nature 381:127-51.
370. Tang Y, Holbert MA, Wurtele H, et al. (2008). Fungal Rtt109 histone acetyltransferase is an unexpected structural homolog of metazoan p300/CBP. Nat Struct Mol Biol 15:998.
371. Taubert S, van Gilst MR, Hansen M, Yamamoto KR. (2006). A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and-independent pathways in C. elegans. Genes Dev 20:1137-49.
372. Thakur JK, Arthanari H, Yang F, et al. (2008). A nuclear receptorlike pathway regulating multidrug resistance in fungi. Nature 452: 604-9. (Pubitemid 351483364)
373. Thakur JK, Arthanari H, Yang F, et al. (2009). Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription factor Oaf1p. J Biol Chem 284:4422-8.
374. Thomas MC, Chiang CM. (2006). The general transcription machinery and general cofactors. Crit Rev Biochem Mol Biol 41:105-78.
375. Thompson CM, Koleske AJ, Chao DM, Young RA. (1993). A multisubunit complex associated with the RNA polymerase II CTD and TATA-binding protein in yeast. Cell 73:1361-75. (Pubitemid 23201149)
376. Thompson CM, Young RA. (1995). General requirement for RNA polymerase II holoenzymes in vivo. Proc Natl Acad Sci USA 92: 4587-90.
377. Thorsen M, Hansen H, Venturi M, et al. (2012). Mediator regulates non-coding RNA transcription at fission yeast centromeres. Epigenetics Chromatin 5:19.
378. Tomomori-Sato C, Sato S, Parmely TJ, et al. (2004). A mammalian mediator subunit that shares properties with Saccharomyces cerevisiae mediator subunit Cse2. J Biol Chem 279:5846-51. (Pubitemid 38220616)
379. Toth JI, Datta S, Athanikar JN, et al. (2004). Selective coactivator interactions in gene activation by SREBP-1a and-1c. Mol Cell Biol 24:8288-300. (Pubitemid 39167476)
380. Toth-Petroczy A, Oldfield CJ, Simon I, et al. (2008). Malleable machines in transcription regulation: the mediator complex. PLoS Comput Biol 4:e1000243.
381. Treisman JE. (2001). Drosophila homologues of the transcriptional coactivation complex subunits TRAP240 and TRAP230 are required for identical processes in eye-antennal disc development. Development 128:603-15. (Pubitemid 32229602)
382. Trompouki E, Bowman TV, Lawton LN, et al. (2011). Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration. Cell 147:577-89.
383. Tsai KL, Sato S, Tomomori-Sato C, et al. (2013). A conserved Mediator-CDK8 kinase module association regulates Mediator-RNA polymer-ase II interaction. Nat Struct Mol Biol 20:611-19.
384. Tsutsui T, Fukasawa R, Tanaka A, et al. (2011). Identification of target genes for the CDK subunits of the Mediator complex. Genes Cells 16: 1208-18.
385. Tsutsui T, Umemura H, Tanaka A, et al. (2008). Human mediator kinase subunit CDK11 plays a negative role in viral activator VP16-dependent transcriptional regulation. Genes Cells 13:817-26.
386. Tudor M, Murray PJ, Onufryk C, et al. (1999). Ubiquitous expression and embryonic requirement for RNA polymerase II coactivator subunit Srb7 in mice. Genes Dev 13:2365-8. (Pubitemid 29453607)
387. Tutter AV, Kowalski MP, Baltus GA, et al. (2009). Role for Med12 in regulation of Nanog and Nanog target genes. J Biol Chem 284:3709-18.
388. Udayakumar TS, Belakavadi M, Choi KH, et al. (2006). Regulation of Aurora-A kinase gene expression via GABP recruitment of TRAP220/MED1. J Biol Chem 281:14691-9. (Pubitemid 43855174)
389. Uwamahoro N, Qu Y, Jelicic B, et al. (2012). The functions of Mediator in Candida albicans support a role in shaping species-specific gene expression. PLoS Genet 8:e1002613.
390. van de Peppel J, Kettelarij N, van Bakel H, et al. (2005). Mediator expression profiling epistasis reveals a signal transduction pathway with antagonistic submodules and highly specific downstream targets. Mol Cell 19:511-22. (Pubitemid 41140008)
391. van Essen D, Engist B, Natoli G, Saccani S. (2009). Two modes of transcriptional activation at native promoters by NF-kappaB p65. PLoS Biol 7:e73.
392. Verger A, Baert JL, Verreman K, et al. (2013). The Mediator complex subunit MED25 is targeted by the N-terminal transactiva-tion domain of the PEA3 group members. Nucleic Acids Res 41: 4847-59.
393. Vijayalingam S, Chinnadurai G. (2013). Adenovirus L-E1A activates transcription through mediator complex-dependent recruitment of the super elongation complex. J Virol 87:3425-34.
394. Vincent O, Kuchin S, Hong SP, et al. (2001). Interaction of the srb10 kinase with sip4, a transcriptional activator of gluconeogenic genes in Saccharomyces cerevisiae. Mol Cell Biol 21:5790-6. (Pubitemid 32737796)
395. Vojnic E, Mourao A, Seizl M, et al. (2011). Structure and VP16 binding of the Mediator Med25 activator interaction domain. Nat Struct Mol Biol 18:404-9.
396. Wada O, Oishi H, Takada I, et al. (2004). BRCA1 function mediates a TRAP/DRIP complex through direct interaction with TRAP220. Oncogene 23:6000-5. (Pubitemid 39093545)
397. Wallberg AE, Yamamura S, Malik S, et al. (2003). Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha. Mol Cell 12:1137-49. (Pubitemid 37487924)
398. Wang D, Garcia-Bassets I, Benner C, et al. (2011). Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature 474:390-4.
399. Wang G, Balamotis MA, Stevens JL, et al. (2005a). Mediator requirement for both recruitment and postrecruitment steps in transcription initiation. Mol Cell 17:683-94. (Pubitemid 40320918)
400. Wang G, Berk AJ. (2002). In vivo association of adenovirus large E1A protein with the human mediator complex in adenovirus-infected and-transformed cells. J Virol 76:9186-93. (Pubitemid 34919877)
401. Wang G, Cantin GT, Stevens JL, Berk AJ. (2001). Characterization of mediator complexes from HeLa cell nuclear extract. Mol Cell Biol 21: 4604-13. (Pubitemid 32588243)
402. Wang J, Walker A, Blackwell TK, Yamamoto KR. (2004a). The Caenorhabditis elegans ortholog of TRAP240, CeTRAP240/let-19, selectively modulates gene expression and is essential for embryo-genesis. J Biol Chem 279:29270-7. (Pubitemid 38915803)
403. Wang KC, Chang HY. (2011). Molecular mechanisms of long noncoding RNAs. Mol Cell 43:904-14.
404. Wang Q, Carroll JS, Brown M. (2005b). Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking. Mol Cell 19:631-42. (Pubitemid 41219439)
405. Wang Q, Sharma D, Ren Y, Fondell JD. (2002). A coregulatory role for the TRAP-mediator complex in androgen receptor-mediated gene expression. J Biol Chem 277:42852-8. (Pubitemid 35285661)
406. Wang S, Ge K, Roeder RG, Hankinson O. (2004b). Role of mediator in transcriptional activation by the aryl hydrocarbon receptor. J Biol Chem 279:13593-600. (Pubitemid 38468885)
407. Wang W, Chen X. (2004). HUA ENHANCER3 reveals a role for a cyclin-dependent protein kinase in the specification of floral organ identity in Arabidopsis. Development 131:3147-56. (Pubitemid 39077438)
408. Wang W, Yao X, Huang Y, et al. (2013). Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb. Transcription 4:39-51.
409. Wang X, Yang N, Uno E, et al. (2006). A subunit of the mediator complex regulates vertebrate neuronal development. Proc Natl Acad Sci USA 103:17284-9. (Pubitemid 44788961)
410. Wang Y, Liu F, Wang W. (2012). Dynamic mechanism for the transcription apparatus orchestrating reliable responses to activators. Sci Rep 2:422.
411. Wansa KD, Muscat GE. (2005). TRAP220 is modulated by the anti-neoplastic agent 6-Mercaptopurine, and mediates the activation of the NR4A subgroup of nuclear receptors. J Mol Endocrinol 34:835-48. (Pubitemid 40903605)
412. Warnmark A, Almlof T, Leers J, et al. (2001). Differential recruitment of the mammalian mediator subunit TRAP220 by estrogen receptors ERalpha and ERbeta. J Biol Chem 276:23397-404.
413. Welcker M, Clurman BE. (2008). FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat Rev Cancer 8:83-93. (Pubitemid 351161321)
414. Wery M, Shematorova E, van Driessche B, et al. (2004). Members of the SAGA and Mediator complexes are partners of the transcription elongation factor TFIIS. EMBO J 23:4232-42. (Pubitemid 39546161)
415. Westerling T, Kuuluvainen E, Makela TP. (2007). Cdk8 is essential for preimplantation mouse development. Mol Cell Biol 27:6177-82. (Pubitemid 47326704)
416. Whyte WA, Orlando DA, Hnisz D, et al. (2013). Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153:307-19.
417. Wiederhold T, Lee MF, James M, et al. (2004). Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2. Oncogene 23:8815-25. (Pubitemid 39593296)
418. Wilusz JE, Sunwoo H, Spector DL. (2009). Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 23:1494-504.
419. Wu PY, Ruhlmann C, Winston F, Schultz P. (2004). Molecular architecture of the S. cerevisiae SAGA complex. Mol Cell 15:199-208. (Pubitemid 38950967)
420. Wu SY, Zhou T, Chiang CM. (2003). Human mediator enhances activator-facilitated recruitment of RNA polymerase II and promoter recognition by TATA-binding protein (TBP) independently of TBP-associated factors. Mol Cell Biol 23:6229-42. (Pubitemid 37013100)
421. Wu YM, Chang JW, Wang CH, et al. (2012). Regulation of mammalian transcription by Gdown1 through a novel steric crosstalk revealed by cryo-EM. EMBO J 31:3575-87.
422. Xu W, Ji JY. (2011). Dysregulation of CDK8 and Cyclin C in tumorigenesis. J Genet Genomics 38:439-52.
423. Xu M, Sharma P, Pan S, et al. (2011a). Core promoter-selective function of HMGA1 and Mediator in Initiator-dependent transcription. Genes Dev 25:2513-24.
424. Xu X, Zhou H, Boyer TG. (2011b). Mediator is a transducer of amyloid-precursor-protein-dependent nuclear signalling. EMBO Rep 12: 216-22.
425. Yang F, Debeaumont R, Zhou S, Näär AM. (2004). The activator-recruited cofactor/Mediator coactivator subunit ARC92 is a functionally important target of the VP16 transcriptional activator. Proc Natl Acad Sci USA 101:2339-44. (Pubitemid 38269313)
426. Yang F, Vought BW, Satterlee JS, et al. (2006). An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeo-stasis. Nature 442:700-04. (Pubitemid 44215326)
427. Yang X, Zhao M, Xia M, et al. (2012). Selective requirement for Mediator MED23 in Ras-active lung cancer. Proc Natl Acad Sci USA 109:E2813-22.
428. Yin JW, Liang Y, Park JY, et al. (2012). Mediator MED23 plays opposing roles in directing smooth muscle cell and adipocyte differentiation. Genes Dev 26:2192-205.
429. Yoda A, Kouike H, Okano H, Sawa H. (2005). Components of the transcriptional Mediator complex are required for asymmetric cell division in C. elegans. Development 132:1885-93. (Pubitemid 40691778)
430. Young ET, Tachibana C, Chang HW, et al. (2008). Artificial recruitment of mediator by the DNA-binding domain of Adr1 overcomes glucose repression of ADH2 expression. Mol Cell Biol 28:2509-16. (Pubitemid 351542353)
431. Yuan CX, Ito M, Fondell JD, et al. (1998). The TRAP220 component of a thyroid hormone receptor-associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion. Proc Natl Acad Sci USA 95:7939-44. (Pubitemid 28326045)
432. Yudkovsky N, Ranish JA, Hahn S. (2000). A transcription reinitiation intermediate that is stabilized by activator. Nature 408:225-9.
433. Zeitlinger J, Stark A, Kellis M, et al. (2007). RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo. Nat Genet 39:1512-6. (Pubitemid 350191345)
434. Zhang X, Krutchinsky A, Fukuda A, et al. (2005). MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription. Mol Cell 19:89-100. (Pubitemid 40884660)
435. Zhang F, Sumibcay L, Hinnebusch AG, Swanson MJ. (2004). A triad of subunits from the Gal11/tail domain of Srb mediator is an in vivo target of transcriptional activator Gcn4p. Mol Cell Biol 24: 6871-86. (Pubitemid 38944364)
436. Zhang X, Yao J, Zhang Y, et al. (2013). The Arabidopsis Mediator complex subunits MED14/SWP and MED16/SFR6/IEN1 differentially regulate defense gene expression in plant immune responses. Plant J 75:484-97.
437. Zhao J, Ramos R, Demma M. (2013). CDK8 regulates E2F1 transcriptional activity through S375 phosphorylation. Oncogene 32: 3520-30.
438. Zhao X, Feng D, Wang Q, et al. (2012). Regulation of lipogenesis by cyclin-dependent kinase 8-mediated control of SREBP-1. J Clin Invest 122:2417-27.
439. Zheng Z, Guan H, Leal F, et al. (2013). Mediator subunit18 controls flowering time and floral organ identity in Arabidopsis. PloS One 8: e53924.
440. Zhou H, Kim S, Ishii S, Boyer TG. (2006). Mediator modulates Gli3-dependent Sonic hedgehog signaling. Mol Cell Biol 26:8667-82. (Pubitemid 44851929)
441. Zhou H, Spaeth JM, Kim NH, et al. (2012a). MED12 mutations link intellectual disability syndromes with dysregulated GLI3-dependent Sonic Hedgehog signaling. Proc Natl Acad Sci USA 109: 19763-8.
442. Zhou H, Xu M, Huang Q, et al. (2008). Genome-scale RNAi screen for host factors required for HIV replication. Cell Host Microbe 4: 495-504.
443. Zhou Q, Li T, Price DH. (2012b). RNA polymerase II elongation control. Annu Rev Biochem 81:119-43.
444. Zhou R, Bonneaud N, Yuan CX, et al. (2002). SOX9 interacts with a component of the human thyroid hormone receptor-associated protein complex. Nucleic Acids Res 30:3245-52. (Pubitemid 34846188)
445. Zhu X, Liu B, Carlsten JO, et al. (2011a). Mediator influences telomeric silencing and cellular life span. Mol Cell Biol 31: 2413-21.
446. Zhu X, Wiren M, Sinha I, et al. (2006). Genome-wide occupancy profile of Mediator and the srb8-11 submodule reveals interactions with coding regions. Mol Cell 22:169-78.
447. Zhu X, Zhang Y, Bjornsdottir G, et al. (2011b). Histone modifications influence mediator interactions with chromatin. Nucleic Acids Res 39: 8342-54.
448. Zhu Y, Qi C, Jain S, et al. (1997). Isolation and characterization of PBP, a protein that interacts with peroxisome proliferator-activated receptor. J Biol Chem 272:25500-6. (Pubitemid 27438856)
449. Zilliacus J, Holter E, Wakui H, et al. (2001). Regulation of glucocortic-oid receptor activity by 14-3-3-dependent intracellular relocalization of the corepressor RIP140. Mol Endocrinol 15:501-11. (Pubitemid 32328128)