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Cited by 922Genomics and Chromatin DynamicsChromatin Remodeling and CancerNuclear Structure and Function

The Mediator complex: a central integrator of transcription

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Allen, Benjamin L., Taatjes, Dylan J.·2015·Nature Reviews Molecular Cell Biology
DOI 10.1038/nrm3951PMC PMC4963239
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Abstract

The RNA polymerase II (Pol II) enzyme transcribes all protein-coding and most non-coding RNA genes and is globally regulated by Mediator - a large, conformationally flexible protein complex with a variable subunit composition (for example, a four-subunit cyclin-dependent kinase 8 module can reversibly associate with it). These biochemical characteristics are fundamentally important for Mediator's ability to control various processes that are important for transcription, including the organization of chromatin architecture and the regulation of Pol II pre-initiation, initiation, re-initiation, pausing and elongation. Although Mediator exists in all eukaryotes, a variety of Mediator functions seem to be specific to metazoans, which is indicative of more diverse regulatory requirements.

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  • At active enhancers, BRD4 co-localises with the Mediator complex, which assembles the pre-initiation complex and RNAP to initiate transcription.

    “At active enhancers, the BRD4 protein co-localises with the Mediator complex, which in turn assembles the pre-initiation complex (PIC) and RNAP to initiate transcription [66–68].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [66]

    The “Mediator roles in pol II transcription” and “PIC assembly” sections say that Mediator is generally required for PIC assembly and enables RNA polymerase II recruitment. The “DNA looping” section links Mediator to enhancer activity, but the passages retrieved for BRD4 do not establish that BRD4 co-localises with Mediator at active enhancers. Page numbers are not available in our copy. (LLM, conf=0.88)

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  1. [1]Plank JL Dean A Enhancer Function: Mechanistic and Genome-Wide Insights Come Together Mol Cell 55 5 14 2014 24996062 PMC8441652
  2. [4]Xu W Ji JY Dysregulation of CDK8 and Cyclin C in tumorigenesis J Genet Genomics 38 439 52 2011 22035865 PMC9792140
  3. [5]Spaeth JM Kim NH Boyer TG Mediator and human disease Semin Cell Dev Biol 22 776 87 2011 21840410 PMC4100472
  4. [6]Schiano C Casamassimi A Vietri MT Rienzo M Napoli C The roles of mediator complex in cardiovascular diseases Biochim Biophys Acta 1839 444 51 2014 24751643
  5. [8]Malik S Structural and functional organization of TRAP220, the TRAP/mediator subunit that is targeted by nuclear receptors Mol Cell Biol 24 8244 54 2004 15340084 PMC515042
  6. [9]Taatjes DJ Tjian R Structure and Function of CRSP/Med2: a promoter-selective transcriptional co-activator complex Mol Cell 14 675 683 2004 15175162
  7. [10]Fondell JD Ge H Roeder RG Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex Proc Natl Acad Sci USA 93 8329 8333 1996 The first biochemical purification of a human Mediator complex 8710870 PMC38670
  8. [11]Stevens JL Transcription control by E1A and MAP kinase pathway via Sur2 mediator subunit Science 296 755 758 2002 11934987
  9. [12]Ito M Yuan CX Okano HJ Darnell RB Roeder RG Involvement of the TRAP220 component of the TRAP/SMCC coactivator complex in embryonic development and thyroid hormone action Mol Cell 5 683 93 2000 10882104
  10. [13]D'Alessio JA Ng R Willenbring H Tjian R Core promoter recognition complex changes accompany liver development Proc Natl Acad Sci U S A 108 3906 11 2011 21368148 PMC3054039
  11. [14]Deato MDE MyoD targets TAF3/TRF3 to activate Myogenin transcription Mol Cell 32 96 105 2008 18851836 PMC2629732
  12. [15]Herrera FJ Yamaguchi T Roelink H Tjian R Core promoter factor TAF9B regulates neuronal gene expression Elife 3 e02559 2014 25006164 PMC4083437
  13. [16]Liu Y Ranish JA Aebersold R Hahn S Yeast nuclear extract contains two major forms of RNA polymerase II mediator complexes J Biol Chem 276 7169 7175 2001 11383511
  14. [17]Taatjes DJ Naar AM Andel F Nogales E Tjian R Structure, function, and activator-induced conformations of the CRSP coactivator Science 295 1058 1062 2002 Showed that the structural state of human Mediator changes upon binding the activation domains of transcription factors 11834832
  15. [18]Knuesel MT Meyer KD Bernecky C Taatjes DJ The human CDK8 subcomplex is a molecular switch that controls Mediator co-activator function Genes Dev 23 439 451 2009 19240132 PMC2648653
  16. [19]Tsai KL A conserved Mediator-CDK8 kinase module association regulates Mediator-RNA polymerase II interaction Nat Struct Mol Biol 20 611 9 2013 23563140 PMC3648612
  17. [20]Davis MA The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator Genes Dev 27 151 6 2013 23322298 PMC3566307
  18. [21]Barbieri CE Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer Nat Genet 44 685 9 2012 22610119 PMC3673022
  19. [22]Li N Cyclin C is a haploinsufficient tumour suppressor Nat Cell Biol 16 1080 91 2014 25344755 PMC4235773
  20. [23]Makinen N MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas Science 334 252 5 2011 21868628
  21. [24]Risheg H A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome Nat Genet 39 451 453 2007 17334363
  22. [25]Ding N Mediator links epigenetic silencing of neuronal gene expression with X-linked mental retardation Mol Cell 31 347 359 2008 18691967 PMC2583939
  23. [26]Turunen M Uterine leiomyoma-linked MED12 mutations disrupt mediator-associated CDK activity Cell Rep 7 654 60 2014 24746821 PMC4041330
  24. [27]Donner AJ Ebmeier CC Taatjes DJ Espinosa JM CDK8 is a positive regulator of transcriptional elongation within the serum response network Nat Struct Mol Biol 17 194 201 2010 20098423 PMC2920286
  25. [28]Galbraith MD HIF1A Employs CDK8-Mediator to Stimulate RNAPII Elongation in Response to Hypoxia Cell 153 1327 39 2013 23746844 PMC3681429
  26. [29]Alarcon C Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-β pathways Cell 139 757 769 2009 19914168 PMC2818353
  27. [31]Hirst M Kobor MS Kuriakose N Greenblatt J Sadowski I GAL4 is regulated by the RNA polymerase II holoenzyme-associated cyclin-dependent protein kinase SRB10/CDK8 Mol Cell 3 673 8 1999 10360183
  28. [32]Vincent O Interaction of the srb10 kinase with sip4, a transcriptional activator of gluconeogenic genes in saccharomyces cerevisiae Mol Cell Biol 21 5790 5796 2001 11486018 PMC87298
  29. [33]Morris EJ E2F1 represses β-catenin transcription and is antagonized by both pRB and CDK8 Nature 455 552 556 2008 Together with Ref. 165, identified CDK8 as a colon cancer oncogene 18794899 PMC3148807
  30. [34]Zhao X Regulation of lipogenesis by cyclin-dependent kinase 8-mediated control of SREBP-1 J Clin Invest 122 2417 27 2012 22684109 PMC3386818
  31. [36]Muncke N 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 2850 2003 14638541
  32. [37]Mukhopadhyay A CDK19 is disrupted in a female patient with bilateral congenital retinal folds, microcephaly and mild mental retardation Hum Genet 128 281 291 2010 20563892 PMC2921488
  33. [38]Toth-Petroczy A Malleable machines in transcription regulation: the mediator complex PLoS Comput Biol 4 e1000243 2008 Revealed that yeast and human Mediator contain a preponderance of predicted intrinsically disordered sequence domains 19096501 PMC2588115
  34. [39]Asturias FJ Jiang YW Myers LC Gustafsson CM Kornberg RD Conserved structures of mediator and RNA polymerase II holoenzyme Science 283 985 7 1999 The first insights regarding Mediator structure and the nature of the Mediator–pol II interaction 9974391
  35. [40]Cai G Imasaki T Takagi Y Asturias FA Mediator structural conservation and implications for the regulation mechanism Structure 17 559 567 2009 19368889 PMC2673807
  36. [41]Meyer KD Lin S Bernecky C Gao Y Taatjes DJ p53 activates transcription by directing structural shifts in Mediator Nat Struct Mol Biol 17 753 760 2010 Structural and functional evidence for transcription factor-induced structural shifts in Mediator being required for activation of transcription 20453859 PMC2932482
  37. [42]Naar AM Taatjes DJ Zhai W Nogales E Tjian R Human CRSP interacts with RNA polymerase II CTD and adopts a specific CTD-bound conformation Genes Dev 16 1339 1344 2002 12050112 PMC186316
  38. [43]Ebmeier CC Taatjes DJ Activator-Mediator binding regulates Mediator-cofactor interactions Proc Natl Acad Sci U S A 107 11283 11288 2010 20534441 PMC2895140
  39. [45]Wang X Redefining the modular organization of the core Mediator complex Cell Res 24 796 808 2014 Together with Ref. 44, this study redefined previous models of yeast Mediator subunit architecture 24810298 PMC4085763
  40. [46]Dotson MR Structural organization of yeast and mammalian mediator complexes Proc Natl Acad Sci USA 97 14307 14310 2000 11114191 PMC18914
  41. [47]Reeves WM Hahn S Activator-independent functions of the yeast mediator sin4 complex in preinitiation complex formation and transcription reinitiation Mol Cell Biol 23 349 358 2003 12482986 PMC140685
  42. [48]Sakurai H Fukasawa T Functional connections between mediator components and general transcription factors of Saccharomyces cerevisiae J Biol Chem 275 37251 6 2000 10973956
  43. [49]Sakurai H Kim YJ Ohishi T Kornberg RD Fukasawa T The yeast GAL11 protein binds to the transcription factor IIE through GAL11 regions essential for its in vivo function Proc Natl Acad Sci U S A 93 9488 92 1996 8790357 PMC38455
  44. [50]Ansari SA Distinct role of Mediator tail module in regulation of SAGA-dependent, TATA-containing genes in yeast EMBO J 31 44 57 2012 21971086 PMC3252575
  45. [51]Lim MK Gal11p dosage-compensates transcriptional activator deletions via Taf14p J Mol Biol 374 9 23 2007 17919657
  46. [52]Guglielmi B A high resolution protein interaction map of the yeast Mediator complex Nucleic Acids Research 32 5379 91 2004 15477388 PMC524289
  47. [53]Cevher MA Reconstitution of active human core Mediator complex reveals a critical role of the MED14 subunit Nat Struct Mol Biol 2014 Demonstrated that an active, partial Mediator complex can be reconstituted from recombinant expression of individual subunits; revealed key roles for MED14 and MED26 PMC4259101 25383669
  48. [54]Imasaki T Architecture of the Mediator head module Nature 475 240 3 2011 21725323 PMC4109712
  49. [55]Lariviere L Model of the Mediator middle module based on protein cross-linking Nucleic Acids Res 41 9266 73 2013 23939621 PMC3814369
  50. [56]Lariviere L Structure of the Mediator head module Nature 492 448 51 2012 23123849
  51. [57]Robinson PJ Bushnell DA Trnka MJ Burlingame AL Kornberg RD Structure of the mediator head module bound to the carboxy-terminal domain of RNA polymerase II Proc Natl Acad Sci U S A 109 17931 5 2012 23071300 PMC3497735
  52. [58]Bernecky C Grob P Ebmeier CC Nogales E Taatjes DJ Molecular architecture of the human Mediator-RNA polymerase II-TFIIF assembly PLoS Biol 9 e1000603 2011 21468301 PMC3066130
  53. [59]Davis JA Takagi Y Kornberg RD Asturias FA Structure of the yeast RNA polymerase II holoenzyme: Mediator conformation and polymerase interaction Mol Cell 10 409 415 2002 12191485
  54. [60]Holstege FC Dissecting the regulatory circuitry of a eukaryotic genome Cell 95 717 28 1998 An important study that demonstrated a global requirement for Mediator and TFIIH for pol II transcription in yeast 9845373
  55. [61]Myers LC Gustafsson CM Hayashibara KC Brown PO Kornberg RD Mediator protein mutations that selectively abolish activated transcription Proc Natl Acad Sci USA 96 67 72 1999 9874773 PMC15094
  56. [62]Kim Y Bjorklund S Li Y Sayre MH Kornberg RD A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II Cell 77 599 608 1994 8187178
  57. [63]Myers LC The Med proteins of yeast and their function through the RNA polymerase II carboxy-terminal domain Genes Dev 12 45 54 1998 9420330 PMC316402
  58. [64]Thompson CM Koleske AJ Chao DM Young RA A multisubunit complex associated with the RNA polymerase II CTD and TATA-binding protein in yeast Cell 73 1361 75 1993 8324825
  59. [65]Guermah M Tao Y Roeder RG 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 2001 11564872 PMC99865
  60. [66]Johnson KM Wang J Smallwood A Arayata C Carey M TFIID and human mediator coactivator complexes assemble cooperatively on promoter DNA Genes Dev 16 1852 1863 2002 12130544 PMC186393
  61. [67]Marr MT Isogai Y Wright KJ Tjian R Coactivator cross-talk specifies transcriptional output Genes Dev 20 1458 1469 2006 16751183 PMC1475759
  62. [68]Takahashi H Human Mediator subunit MED26 functions as a docking site for transcription elongation factors Cell 146 92 104 2011 Direct role for MED26 in binding the SEC and affecting transcription elongation in human cells 21729782 PMC3145325
  63. [69]Xu M Core promoter-selective function of HMGA1 and Mediator in Initiator-dependent transcription Genes Dev 25 2513 24 2011 22156211 PMC3243061
  64. [70]Baek HJ Kang YK Roeder RG Human Mediator enhances basal transcription by facilitating recruitment of transcription factor IIB during preinitiation complex assembly J Biol Chem 281 15172 15181 2006 16595664
  65. [71]Johnson KM Carey M Assembly of a mediator/TFIID/TFIIA complex bypasses the need for an activator Curr Biol 13 772 777 2003 12725737
  66. [72]Jishage M Transcriptional regulation by Pol II(G) involving mediator and competitive interactions of Gdown1 and TFIIF with Pol II Mol Cell 45 51 63 2012 22244332 PMC3259531
  67. [73]Esnault C Mediator-dependent recruitment of TFIIH modules in Preinitiation Complex Mol Cell 31 337 346 2008 18691966
  68. [74]Seizl M Lariviere L Pfaffeneder T Wenzeck L Cramer P 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 2011 21498544 PMC3152362
  69. [75]Hu X A Mediator-responsive form of metazoan RNA polymerase II Proc Natl Acad Sci U S A 103 9506 11 2006 16769904 PMC1480437
  70. [76]Cheng B Functional association of Gdown1 with RNA polymerase II poised on human genes Mol Cell 45 38 50 2012 22244331 PMC3259526
  71. [77]Wu YM Regulation of mammalian transcription by Gdown1 through a novel steric crosstalk revealed by cryo-EM EMBO J 31 3575 87 2012 22850672 PMC3433857
  72. [78]Svejstrup JQ Evidence for a mediator cycle at the initiation of transcription Proc Natl Acad Sci U S A 94 6075 8 1997 9177171 PMC21003
  73. [79]Corden JL RNA polymerase II C-terminal domain: Tethering transcription to transcript and template Chem Rev 113 8423 55 2013 24040939 PMC3988834
  74. [80]Eick D Geyer M The RNA polymerase II carboxy-terminal domain (CTD) code Chem Rev 113 8456 90 2013 23952966
  75. [81]Boeing S Rigault C Heidemann M Eick D Meisterernst M RNA polymerase II C-terminal heptarepeat domain Ser-7 phosphorylation is established in a mediator-dependent fashion Journal of Biological Chemistry 285 188 96 2010 19901026 PMC2804165
  76. [82]Nair D Kim Y Myers LC Mediator and TFIIH govern carboxy-terminal domain-dependent transcription in yeast extracts J Biol Chem 280 33739 33748 2005 16076843
  77. [83]Jeronimo C Robert F Kin28 regulates the transient association of Mediator with core promoters Nat Struct Mol Biol 21 449 55 2014 24704787 PMC3997488
  78. [84]Wong KH Jin Y Struhl K TFIIH phosphorylation of the Pol II CTD stimulates mediator dissociation from the preinitiation complex and promoter escape Mol Cell 54 601 12 2014 24746699 PMC4035452
  79. [85]Rhee HS Pugh BF Genome-wide structure and organization of eukaryotic pre-initiation complexes Nature 483 295 301 2012 22258509 PMC3306527
  80. [86]Lee SK Chen X Huang L Stargell LA The head module of Mediator directs activation of preloaded RNAPII in vivo Nucleic Acids Res 41 10124 34 2013 24005039 PMC3905900
  81. [87]Core LJ Waterfall JJ Lis JT Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters Science 322 1845 1848 2008 19056941 PMC2833333
  82. [88]Seila AC Divergent transcription from active promoters Science 322 1849 1851 2008 19056940 PMC2692996
  83. [89]Guenther MG Levine SS Boyer LA Jaenisch R Young RA A chromatin landmark and transcription initiation at most promoters in human cells Cell 130 77 88 2007 17632057 PMC3200295
  84. [90]Muse GW RNA polymerase is poised for activation across the genome Nat Genet 39 1507 1511 2007 17994021 PMC2365887
  85. [91]Zeitlinger J RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo Nat Genet 39 1512 1516 2007 17994019 PMC2824921
  86. [92]Kremer SB Role of Mediator in regulating Pol II elongation and nucleosome displacement in Saccharomyces cerevisiae Genetics 191 95 106 2012 22377631 PMC3338273
  87. [93]Malik S Wallberg AE Kang YK Roeder RG TRAP/SMCC/mediator-dependent transcriptional activation from DNA and chromatin templates by orphan nuclear receptor hepatocyte nuclear factor 4 Mol Cell Biol 22 5626 5637 2002 12101254 PMC133960
  88. [94]Wang G Mediator requirement for both recruitment and postrecruitment steps in transcription initiation Mol Cell 17 683 694 2005 15749018
  89. [95]Adelman K Lis JT Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans Nat Rev Genet 13 720 31 2012 22986266 PMC3552498
  90. [96]Lin C 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 37 429 437 2010 20159561 PMC2872029
  91. [97]Luo Z Lin C Shilatifard A The super elongation complex (SEC) family in transcriptional control Nat Rev Mol Cell Biol 13 543 7 2012 22895430
  92. [98]Paoletti AC Quantitative proteomic analysis of distinct mammalian Mediator complexes using normalized spectral abundance factors Proc Natl Acad Sci U S A 103 18928 33 2006 17138671 PMC1672612
  93. [99]Balamotis MA Complexity in transcription control at the activation domain-Mediator interface Sci Signal 2 ra20 2009 19417216 PMC2774526
  94. [100]Park JM Werner J Kim JM Lis JT Kim YJ Mediator, not holoenzyme, is directly recruited to the heat shock promoter by HSF upon heat shock Mol Cell 8 9 19 2001 One of the first studies that suggested a role for Mediator in regulating paused or “post-initiated” pol II enzymes 11511356
  95. [101]Schaaf CA Genome-wide control of RNA polymerase II activity by cohesin PLoS Genet 9 e1003382 2013 23555293 PMC3605059
  96. [103]Lin C Garruss AS Luo Z Guo F Shilatifard A The RNA Pol II elongation factor Ell3 marks enhancers in ES cells and primes future gene activation Cell 152 144 56 2013 23273992 PMC3556173
  97. [104]Guglielmi B Soutourina J Esnault C Werner M TFIIS elongation factor and Mediator act in conjunction during transcription initiation in vivo Proc Natl Acad Sci U S A 104 16062 7 2007 17901206 PMC2042162
  98. [105]Kim B The transcription elongation factor TFIIS is a component of RNA polymerase II preinitiation complexes Proc Natl Acad Sci U S A 104 16068 73 2007 17913884 PMC2042163
  99. [106]Nock A Ascano JM Barrero MJ Malik S Mediator-regulated transcription through the +1 nucleosome Mol Cell 48 837 48 2012 23159738 PMC3534924
  100. [107]Malik S Barrero MJ Jones T Identification of a regulator of transcription elongation as an accessory factor for the human Mediator coactivator Proc Natl Acad Sci U S A 104 6182 7 2007 17404243 PMC1851085
  101. [108]Larson DR Direct observation of frequency modulated transcription in single cells using light activation Elife (Cambridge) 2 e00750 2013 PMC3780543 24069527
  102. [109]Sandaltzopoulos R Becker PB Heat shock factor increases the reinitiation rate from potentiated chromatin templates Mol Cell Biol 18 361 367 1998 9418883 PMC121506
  103. [110]Yudkovsky N Ranish JA Hahn S A transcription reinitiation intermediate that is stabilized by activator Nature 408 225 229 2000 Provided evidence for a re-initiation “scaffold” PIC that contains most PIC factors, including Mediator 11089979
  104. [111]Reid G Cyclic, proteasome-mediated turnover of unliganded and liganded ERalpha on responsive promoters is an integral feature of estrogen signaling Mol Cell 11 695 707 2003 12667452
  105. [112]Andrau J Genome-wide location of the coactivator Mediator: binding without activation and transient cdk8 interaction on DNA Mol Cell 22 179 192 2006 One of the first studies to reveal co-localization of Cdk8 with Mediator across the yeast genome 16630888
  106. [113]Mo X Kowenz-Leutz E Xu H Leutz A Ras induces mediator complex exchange on C/EBPb Mol Cell 13 241 250 2004 14759369
  107. [114]Kim YK Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency EMBO J 25 3596 604 2006 16874302 PMC1538560
  108. [115]Pavri R PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator Mol Cell 18 83 96 2005 The first study to reveal a potential means by which CDK8 module–Mediator interactions are regulated in mammalian cells 15808511
  109. [116]Ansari SA Mediator, TATA-binding Protein, and RNA Polymerase II Contribute to Low Histone Occupancy at Active Gene Promoters in Yeast J Biol Chem 289 14981 14995 2014 24727477 PMC4031549
  110. [117]Gilchrist DA Pausing of RNA polymerase II disrupts DNA-specified nucleosome organization to enable precise gene regulation Cell 143 540 551 2010 21074046 PMC2991113
  111. [118]Sharma VM Li B Reese JC SWI/SNF-dependent chromatin remodeling of RNR3 requires TAF(II)s and the general transcription machinery Genes Dev 17 502 15 2003 12600943 PMC195993
  112. [119]Lin JJ Mediator coordinates PIC assembly with recruitment of CHD1 Genes Dev 25 2198 209 2011 21979373 PMC3205589
  113. [120]Lemieux K Gaudreau L Targeting of Swi/Snf to the yeast GAL1 UAS G requires the Mediator, TAF IIs, and RNA polymerase II EMBO J 23 4040 50 2004 15385957 PMC524348
  114. [121]Vilar JM Saiz L DNA looping in gene regulation: from the assembly of macromolecular complexes to the control of transcriptional noise Curr Opin Genet Dev 15 136 44 2005 15797196
  115. [122]Levine M Cattoglio C Tjian R Looping back to leap forward: transcription enters a new era Cell 157 13 25 2014 24679523 PMC4059561
  116. [123]Fanucchi S Shibayama Y Burd S Weinberg MS Mhlanga MM Chromosomal contact permits transcription between coregulated genes Cell 155 606 20 2013 24243018
  117. [124]Li G Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation Cell 148 84 98 2012 22265404 PMC3339270
  118. [126]Kieffer-Kwon KR Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation Cell 155 1507 20 2013 24360274 PMC3905448
  119. [128]Phillips-Cremins JE Architectural Protein Subclasses Shape 3D Organization of Genomes during Lineage Commitment Cell 153 1281 95 2013 23706625 PMC3712340
  120. [130]Muto A Nipbl and mediator cooperatively regulate gene expression to control limb development PLoS Genet 10 e1004671 2014 25255084 PMC4177752
  121. [131]Dobi KC Winston F Analysis of transcriptional activation at a distance in Saccharomyces cerevisiae Mol Cell Biol 27 5575 86 2007 17526727 PMC1952096
  122. [132]Mukundan B Ansari A Srb5/Med18-mediated termination of transcription is dependent on gene looping J Biol Chem 288 11384 94 2013 23476016 PMC3630880
  123. [133]Orom UA Long noncoding RNAs with enhancer-like function in human cells Cell 143 46 58 2010 20887892 PMC4108080
  124. [134]Lai F Activating RNAs associate with Mediator to enhance chromatin architecture and transcription Nature 494 497 501 2013 Demonstrated that non-coding RNAs transcribed from distal sequence elements can interact with Mediator to regulate gene looping to the promoter and transcription activation 23417068 PMC4109059
  125. [135]Wang D Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA Nature 474 390 394 2011 21572438 PMC3117022
  126. [136]Hah N Murakami S Nagari A Danko CG Kraus WL Enhancer transcripts mark active estrogen receptor binding sites Genome Res 23 1210 23 2013 23636943 PMC3730096
  127. [137]Lam MT Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription Nature 498 511 5 2013 23728303 PMC3839578
  128. [138]Li W Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation Nature 498 516 20 2013 23728302 PMC3718886
  129. [139]Hsieh CL Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation Proc Natl Acad Sci U S A 111 7319 24 2014 24778216 PMC4034202
  130. [140]Step SE Anti-diabetic rosiglitazone remodels the adipocyte transcriptome by redistributing transcription to PPARgamma-driven enhancers Genes Dev 28 1018 28 2014 24788520 PMC4018489
  131. [141]Bartolomei MS Halden NF Cullen CR Corden JL Genetic analysis of the repetitive carboxyl-terminal domain of the largest subunit of mouse RNA polymerase II Mol Cell Biol 8 330 9 1988 3275873 PMC363128
  132. [142]Gerber HP RNA polymerase II C-terminal domain required for enhancer-driven transcription Nature 374 660 2 1995 7715709
  133. [143]Oya E Mediator directs co-transcriptional heterochromatin assembly by RNA interference-dependent and -independent pathways PLoS Genet 9 e1003677 2013 23966866 PMC3744440
  134. [144]Carlsten JO Mediator promotes CENP-a incorporation at fission yeast centromeres Mol Cell Biol 32 4035 43 2012 22851695 PMC3457525
  135. [145]Thorsen M Hansen H Venturi M Holmberg S Thon G Mediator regulates non-coding RNA transcription at fission yeast centromeres Epigenetics Chromatin 5 19 2012 23171760 PMC3541127
  136. [146]Lenstra TL The specificity and topology of chromatin interaction pathways in yeast Mol Cell 42 536 49 2011 21596317 PMC4435841
  137. [147]Peng J Zhou JQ The tail-module of yeast Mediator complex is required for telomere heterochromatin maintenance Nucleic Acids Res 40 581 93 2012 21930512 PMC3258146
  138. [148]Suzuki Y Nishizawa M The yeast GAL11 protein is involved in regulation of the structure and the position effect of telomeres Mol Cell Biol 14 3791 9 1994 8196622 PMC358746
  139. [149]Zhu X Mediator influences telomeric silencing and cellular life span Mol Cell Biol 31 2413 21 2011 21482672 PMC3133415
  140. [150]Marr SK Lis JT Treisman JE Marr MT The Metazoan-Specific Mediator Subunit 26 (Med26) Is Essential For Viability And Is Found At Both Active Genes And Pericentric Heterochromatin In Drosophila Mol Cell Biol 34 2710 2720 2014 24820420 PMC4097656
  141. [151]Smallwood A Black JC Tanese N Pradhan S Carey M HP1-mediated silencing targets Pol II coactivator complexes Nat Struct Mol Biol 15 318 20 2008 18264112
  142. [152]Jiang YW 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 1998 9671713 PMC21111
  143. [153]Gaarenstroom T Hill CS TGF-beta signaling to chromatin: How Smads regulate transcription during self-renewal and differentiation Semin Cell Dev Biol 32C 107 118 2014 24503509
  144. [154]Kato Y Habas R Katsuyama Y Naar A He X A component of the ARC/Mediator complex required for TGF beta/Nodal signalling Nature 418 641 646 2002 12167862
  145. [155]Zhao M Mediator MED15 modulates transforming growth factor beta (TGFbeta)/Smad signaling and breast cancer cell metastasis J Mol Cell Biol 5 57 60 2013 23014762
  146. [156]Huang S MED12 controls the response to multiple cancer drugs through regulation of TGF-beta receptor signaling Cell 151 937 50 2012 23178117 PMC3672971
  147. [157]Knuesel MT Meyer KD Donner AJ Espinosa JM Taatjes DJ The human CDK8 subcomplex is a histone kinase that requires Med12 for activity and can function independently of Mediator Mol Cell Biol 29 650 661 2009 19047373 PMC2630685
  148. [158]Gao S Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-b signaling Mol Cell 36 457 468 2009 19917253 PMC2796330
  149. [159]Kahn M Can we safely target the WNT pathway? Nat Rev Drug Discov 13 513 32 2014 24981364 PMC4426976
  150. [160]Carrera I Janody F Leeds N Duveau F Treisman JE Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13 Proc Natl Acad Sci U S A 105 6644 9 2008 18451032 PMC2373359
  151. [161]Rocha PP Scholze M Bleiss W Schrewe H Med12 is essential for early mouse development and for canonical Wnt and Wnt/PCP signaling Development 137 2723 31 2010 20630950
  152. [162]Kim S Xu X Hecht A Boyer TG Mediator is a transducer of Wnt/beta-catenin signaling J Biol Chem 281 14066 14075 2006 16565090
  153. [163]Zhang H Emmons SW A C. elegans mediator protein confers regulatory selectivity on lineage-specific expression of a transcription factor gene Genes & Development 14 2161 2172 2000 10970880 PMC316889
  154. [164]Zhao J Ramos R Demma M CDK8 regulates E2F1 transcriptional activity through S375 phosphorylation Oncogene 2012 22945643
  155. [165]Firestein R CDK8 is a colorectal cancer oncogene that regulates β-catenin activity Nature 455 547 551 2008 Together with Ref. 33, identified CDK8 as a colon cancer oncogene 18794900 PMC2587138
  156. [166]Kasza A Signal-dependent Elk-1 target genes involved in transcript processing and cell migration Biochim Biophys Acta 1829 1026 33 2013 23711433
  157. [167]Wang W Mediator MED23 links insulin signaling to the adipogenesis transcription cascade Dev Cell 16 764 771 2009 19460352 PMC2835773
  158. [168]Yin JW Mediator MED23 plays opposing roles in directing smooth muscle cell and adipocyte differentiation Genes Dev 26 2192 205 2012 22972934 PMC3465740
  159. [169]Belakavadi M Pandey PK Vijayvargia R Fondell JD MED1 phosphorylation promotes its association with Mediator: implications for nuclear receptor signaling Mol Cell Biol 28 3932 3942 2008 18391015 PMC2423130
  160. [170]Pandey PK Activation of TRAP/Mediator subunit TRAP220/Med1 is regulated by mitogen-activated protein kinase-dependent phosphorylation Mol Cell Biol 25 10695 10710 2005 16314496 PMC1316958
  161. [171]Papantonis A Cook PR Transcription factories: genome organization and gene regulation Chem Rev 113 8683 705 2013 23597155
  162. [172]Han TW Cell-free formation of RNA granules: bound RNAs identify features and components of cellular assemblies Cell 149 768 79 2012 22579282
  163. [174]Tompa P Hydrogel formation by multivalent IDPs Intrinsically Disordered Proteins 1 e24068 2013 PMC5424804 28516006
  164. [175]Takagi Y Kornberg RD Mediator as a general transcription factor J Biol Chem 281 80 89 2006 16263706
  165. [176]Bourbon HM Comparative genomics supports a deep evolutionary origin for the large, four-module transcriptional mediator complex Nucleic Acids Res 36 3993 4008 2008 18515835 PMC2475620
  166. [177]van der Lee R Classification of intrinsically disordered regions and proteins Chem Rev 114 6589 631 2014 24773235 PMC4095912
  167. [178]Madhani HD The frustrated gene: origins of eukaryotic gene expression Cell 155 744 9 2013 24209615 PMC4163148
  168. [179]Kuuluvainen E Cyclin-dependent Kinase 8 Module Expression Profiling Reveals Requirement of Mediator Subunits 12 and 13 for Transcription of Serpent-dependent Innate Immunity Genes in Drosophila J Biol Chem 289 16252 16261 2014 24778181 PMC4047394
  169. [180]Napoli C Sessa M Infante T Casamassimi A Unraveling framework of the ancestral Mediator complex in human diseases Biochimie 94 579 87 2012 21983542
  170. [181]Phillips AJ Taatjes DJ Small molecule probes to target the human Mediator complex Isr J Chem 53 588 595 2013 25705053 PMC4334163
  171. [182]Milbradt AG Structure of the VP16 transactivator target in the Mediator Nat Struct Mol Biol 18 410 415 2011 21378963 PMC3076674
  172. [183]Vojnic E Structure and VP16 binding of the Mediator Med25 activator interaction domain Nat Struct Mol Biol 18 404 409 2011 21378965
  173. [184]Yang F An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis Nature 442 700 704 2006 16799563
  174. [186]Whyte WA Master transcription factors and mediator establish super-enhancers at key cell identity genes Cell 153 307 19 2013 23582322 PMC3653129
  175. [187]Gerstein MB Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project Science 330 1775 87 2010 21177976 PMC3142569
  176. [188]mod EC Identification of functional elements and regulatory circuits by Drosophila modENCODE Science 330 1787 97 2010 21177974 PMC3192495
  177. [189]Li Q Peterson KR Fang X Stamatoyannopoulos G Locus control regions Blood 100 3077 86 2002 12384402 PMC2811695
  178. [190]Darnell JE Jr Reflections on the history of pre-mRNA processing and highlights of current knowledge: a unified picture RNA 19 443 60 2013 23440351 PMC3677254
  179. [191]Grunberg S Hahn S Structural insights into transcription initiation by RNA polymerase II Trends Biochem Sci 38 603 11 2013 24120742 PMC3843768
  180. [192]Thomas MC Chiang CM The general transcription machinery and general cofactors Crit Rev Biochem Mol Biol 41 105 178 2006 16858867
  181. [193]He Y Fang J Taatjes DJ Nogales E Structural visualization of key steps in human transcription initiation Nature 495 481 6 2013 23446344 PMC3612373
  182. [194]Murakami K Architecture of an RNA polymerase II transcription pre-initiation complex Science 342 1238724 2013 24072820 PMC4039082
  183. [195]Muhlbacher W Conserved architecture of the core RNA polymerase II initiation complex Nat Commun 5 4310 2014 25007739
  184. [196]Bieniossek C The architecture of human general transcription factor TFIID core complex Nature 493 699 702 2013 23292512
  185. [197]Bernecky C Taatjes DJ Activator–Mediator binding stabilizes RNA polymerase II orientation within the human Mediator–RNA polymerase II–TFIIF assembly J Mol Biol 417 387 394 2012 22343046 PMC4582759

Cited by

Sorted by citations

Authors
Allen, B. L., & Taatjes, D. J.
Affiliations
University of Colorado Boulder (US)
Corresponding author
Taatjes, Dylan J.
ORCID
Venue
Nature Reviews Molecular Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2015-02-18
Volume
16
Issue
3
Pages
155-166
ISSN
  • 1471-0072 (ISSN-L)
  • 1471-0080
DOI
10.1038/nrm3951
PMC
PMC4963239
OpenAlex
W1986156026
Cited by
922
References
12
Citations by year
2026: 62 · 2025: 74 · 2024: 83 · 2023: 72 · 2022: 73 · 2021: 84 · 2020: 104 · 2019: 77 · 2018: 101 · 2017: 88 · 2016: 82 · 2015: 20 · 2013: 1
FWCI
9.49
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Molecular Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (CA175849, CA175448, R21CA175849, CA1707041, R21CA175448, R01CA170741)
  • National Institute of General Medical Sciences (T32-GM08759, T32GM008759, T32GM142607)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
Mediator complex, RNA polymerase II, transcriptional regulation, chromatin structure, transcription initiation, reinitiation, transcriptional pausing, transcription elongation
MeSH terms
Animals, Chromatin, Female, Gene Expression Regulation, Histones, Humans, Leiomyoma, RNA Polymerase II, Transcription Factors, Transcription, Genetic, Uterine Neoplasms, Signal Transduction, RNA, Untranslated, Mediator Complex

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