Skip to main content
SpringerLink
Log in

Structure and Functions of the Mediator Complex

  • Review
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Mediator is a key factor in the regulation of expression of RNA polymerase II-transcribed genes. Recent studies have shown that Mediator acts as a coordinator of transcription activation and participates in maintaining chromatin architecture in the cell nucleus. In this review, we present current concepts on the structure and functions of Mediator.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CKM:

Cdk8 kinase module

CTD:

C-terminal domain of RNA polymerase II Rpb1 subunit

IDR:

intrinsically disordered protein regions

ncRNA:

noncoding RNA

PIC:

preinitiation complex

Pol I, II, III:

DNA-dependent RNA polymerase I, II, and III,respectively

UAS:

upstream activating sequence

References

  1. Allen, B. L., and Taatjes, D. J. (2015) The Mediator complex: a central integrator of transcription, Nat. Rev. Mol. Cell Biol., 16, 155–166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Borggrefe, T., and Yue, X. (2011) Interactions between sub-units of the Mediator complex with gene-specific transcription factors, Semin. Cell Devel. Biol., 22, 759–768.

    Article  CAS  Google Scholar 

  3. Youn, D. Y., Xiaoli, A. M., Pessin, J. E., and Yang, F. (2016) Regulation of metabolism by the Mediator complex, Biophys. Rep., 2, 69–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Clark, A. D., Oldenbroek, M., and Boyer, T. G. (2015) Mediator kinase module and human tumorigenesis, Crit. Rev. Biochem. Mol. Biol., 5BB0, 393–426.

    Google Scholar 

  5. Jeronimo, C., and Robert, F. (2017) The Mediator complex: at the nexus of RNA polymerase II transcription, Trends Cell Biol., 27, 765–783.

    Article  CAS  PubMed  Google Scholar 

  6. Tsai, K. L., Tomomori-Sato, C., Sato, S., Conaway, R. C., Conaway, J. W., and Asturias, F. J. (2014) Subunit architecture and functional modular rearrangements of the transcriptional mediator complex, Cell, 158, 463.

    Article  CAS  PubMed  Google Scholar 

  7. Wang, X., Sun, Q., Ding, Z., Ji, J., Wang, J., Kong, X., Yang, J., and Cai, G. (2014) Redefining the modular organization of the core Mediator complex, Cell Res., 24, 796–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tsai, K. L., Yu, X., Gopalan, S., Chao, T. C., Zhang, Y., Florens, L., Washburn, M. P., Murakami, K., Conaway, R. C., Conaway, J. W., and Asturias, F. J. (2017) Mediator structure and rearrangements required for holoenzyme formation, Nature, 544, 196–201.

    Article  CAS  PubMed  Google Scholar 

  9. Harper, T. M., and Taatjes, D. J. (2017) The complex structure and function of Mediator, J. Biol. Chem., in press.

    Google Scholar 

  10. Cevher, M. A., Shi, Y., Li, D., Chait, B. T., Malik, S., and Roeder, R. G. (2014) Reconstitution of active human core Mediator complex reveals a critical role of the MED14 sub-unit, Nat. Struct. Mol. Biol., 21, 1028–1034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tsai, K. L., Tomomori-Sato, C., Sato, S., Conaway, R. C., Conaway, J. W., and Asturias, F. J. (2014) Subunit architecture and functional modular rearrangements of the transcriptional mediator complex, Cell, 157, 1430–1444.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Plaschka, C., Lariviere, L., Wenzeck, L., Seizl, M., Hemann, M., Tegunov, D., Petrotchenko, E. V., Borchers, C. H., Baumeister, W., Herzog, F., Villa, E., and Cramer, P. (2015) Architecture of the RNA polymerase II–Mediator core initiation complex, Nature, 518, 376–380.

    Article  CAS  PubMed  Google Scholar 

  13. Robinson, P. J., Trnka, M. J., Bushnell, D. A., Davis, R. E., Mattei, P. J., Burlingame, A. L., and Kornberg, R. D. (2016) Structure of a complete Mediator–RNA polymerase II pre-initiation complex, Cell, 166, 1411–1422.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Nozawa, K., Schneider, T. R., and Cramer, P. (2017) Core Mediator structure at 3.4 Å extends model of transcription initiation complex, Nature, 545, 248–251.

    Article  CAS  PubMed  Google Scholar 

  15. D’Alessio, J. A., Ng, R., Willenbring, H., and Tjian, R. (2011) Core promoter recognition complex changes accompany liver development, Proc. Natl. Acad. Sci. USA, 108, 3906–3911.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Marr, S. K., Lis, J. T., Treisman, J. E., and Marr, M. T., 2nd (2014) The metazoan-specific mediator subunit 26 (Med26) is essential for viability and is found at both active genes and pericentric heterochromatin in Drosophila melanogaster, Mol. Cell. Biol., 34, 2710–2720.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Zhu, X., Chen, L., Carlsten, J. O., Liu, Q., Yang, J., Liu, B., and Gustafsson, C. M. (2015) Mediator tail subunits can form amyloid-like aggregates in vivo and affect stress response in yeast, Nucleic Acids Res., 43, 7306–7314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Nagulapalli, M., Maji, S., Dwivedi, N., Dahiya, P., and Thakur, J. K. (2016) Evolution of disorder in Mediator complex and its functional relevance, Nucleic Acids Res., 44, 1591–1612.

    Article  PubMed  Google Scholar 

  19. Daniels, D., Ford, M., Schwinn, M., Benink, H., Galbraith, M., Amunugama, R., Jones, R., Allen, D., Okazaki, N., Yamakawa, H., Miki, F., Nagase, T., Espinosa, J., and Urh, M. (2013) Mutual exclusivity of MED12/MED12L, MED13/13L, and CDK8/19 paralogs revealed within the CDK–Mediator kinase module, J. Proteom. Bioinform., S2, 004.

    Google Scholar 

  20. Tsai, K. L., Sato, S., Tomomori-Sato, C., Conaway, R. C., Conaway, J. W., and Asturias, F. J. (2013) A conserved Mediator–CDK8 kinase module association regulates Mediator–RNA polymerase II interaction, Nat. Struct. Mol. Biol., 20, 611–619.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang, X., Wang, J., Ding, Z., Ji, J., Sun, Q., and Cai, G. (2013) Structural flexibility and functional interaction of Mediator Cdk8 module, Protein Cell, 4, 911–920.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Carrera, I., Janody, F., Leeds, N., Duveau, F., and Treisman, J. E. (2008) Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13, Proc. Natl. Acad. Sci. USA, 105, 6644–6649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ito, J., Fukaki, H., Onoda, M., Li, L., Li, C., Tasaka, M., and Furutani, M. (2016) Auxin-dependent compositional change in Mediator in ARF7-and ARF19-mediated transcription, Proc. Natl. Acad. Sci. USA, 113, 6562–6567.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kim, S., Xu, X., Hecht, A., and Boyer, T. G. (2006) Mediator is a transducer of Wnt/beta-catenin signaling, J. Biol. Chem., 281, 14066–14075.

    Article  CAS  PubMed  Google Scholar 

  25. Tutter, A. V., Kowalski, M. P., Baltus, G. A., Iourgenko, V., Labow, M., Li, E., and Kadam, S. (2009) Role for Med12 in regulation of Nanog and Nanog target genes, J. Biol. Chem., 284, 3709–3718.

    Article  CAS  PubMed  Google Scholar 

  26. Zhu, Y., Schluttenhoffer, C. M., Wang, P., Fu, F., Thimmapuram, J., Zhu, J. K., Lee, S. Y., Yun, D. J., and Mengiste, T. (2014) Cyclin-dependent kinases differentially regulates plant immunity to fungal pathogens through kinase-dependent and -independent functions in Arabidopsis, Plant Cell, 26, 4149–4170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Anandhakumar, J., Moustafa, Y. W., Chowdhary, S., Kainth, A. S., and Gross, D. S. (2016) Evidence for multiple Mediator complexes in yeast independently recruited by activated heat shock factor, Mol. Cell. Biol., 36, 1943–1960.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Thomas-Claudepierre, A. S., Robert, I., Rocha, P. P., Raviram, R., Schiavo, E., Heyer, V., Bonneau, R., Luo, V. M., Reddy, J. K., Borggrefe, T., Skok, J. A., and Reina-San-Martin, B. (2016) Mediator facilitates transcriptional activation and dynamic long-range contacts at the IgH locus during class switch recombination, J. Exp. Med., 213, 303–312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Drogat, J., Migeot, V., Mommaerts, E., Mullier, C., Dieu, M., Van Bakel, H., and Hermand, D. (2012) Cdk11-cyclinL controls the assembly of the RNA polymerase II mediator complex, Cell Rep., 2, 1068–1076.

    Article  CAS  PubMed  Google Scholar 

  30. Davis, M. A., Larimore, E. A., Fissel, B. M., Swanger, J., Taatjes, D. J., and Clurman, B. E. (2013) The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator, Genes Dev., 27, 151–156.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pavri, R., Lewis, B., Kim, T. K., Dilworth, F. J., Erdjument-Bromage, H., Tempst, P., De Murcia, G., Evans, R., Chambon, P., and Reinberg, D. (2005) PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator, Mol. Cell, 18, 83–96.

    Article  CAS  PubMed  Google Scholar 

  32. Alarcon, C., Zaromytidou, A. I., Xi, Q., Gao, S., Yu, J., Fujisawa, S., Barlas, A., Miller, A. N., Manova-Todorova, K., Macias, M. J., Sapkota, G., Pan, D., and Massague, J. (2009) Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways, Cell, 139, 757–769.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Fryer, C. J., White, J. B., and Jones, K. A. (2004) Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover, Mol. Cell, 16, 509–520.

    Article  CAS  PubMed  Google Scholar 

  34. Zhao, X., Feng, D., Wang, Q., Abdulla, A., Xie, X. J., Zhou, J., Sun, Y., Yang, E. S., Liu, L. P., Vaitheesvaran, B., Bridges, L., Kurland, I. J., Strich, R., Ni, J. Q., Wang, C., Ericsson, J., Pessin, J. E., Ji, J. Y., and Yang, F. (2012) Regulation of lipogenesis by cyclin-dependent kinase 8-mediated control of SREBP-1, J. Clin. Invest., 122, 2417–2427.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhao, J., Ramos, R., and Demma, M. (2013) CDK8 regulates E2F1 transcriptional activity through S375 phosphorylation, Oncogene, 32, 3520–3530.

    Article  CAS  PubMed  Google Scholar 

  36. Bancerek, J., Poss, Z. C., Steinparzer, I., Sedlyarov, V., Pfaffenwimmer, T., Mikulic, I., Dolken, L., Strobl, B., Muller, M., Taatjes, D. J., and Kovarik, P. (2013) CDK8 kinase phosphorylates transcription factor STAT1 to selectively regulate the interferon response, Immunity, 38, 250–262.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Knuesel, M. T., Meyer, K. D., Donner, A. J., Espinosa, J. M., and Taatjes, D. J. (2009) 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.

    Article  CAS  PubMed  Google Scholar 

  38. Chen, M., Liang, J., Ji, H., Yang, Z., Altilia, S., Hu, B., Schronce, A., McDermott, M. S. J., Schools, G. P., Lim, C. U., Oliver, D., Shtutman, M. S., Lu, T., Stark, G. R., Porter, D. C., Broude, E. V., and Roninson, I. B. (2017) CDK8/19 Mediator kinases potentiate induction of transcription by NFkappaB, Proc. Natl. Acad. Sci. USA, 114, 10208–10213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Poss, Z. C., Ebmeier, C. C., Odell, A. T., Tangpeerachaikul, A., Lee, T., Pelish, H. E., Shair, M. D., Dowell, R. D., Old, W. M., and Taatjes, D. J. (2016) Identification of Mediator kinase substrates in human cells using cortistatin A and quantitative phosphoproteomics, Cell Rep., 15, 436–450.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Law, M. J., and Finger, M. A. (2017) The Saccharomyces cerevisiae Cdk8 Mediator represses AQY1 transcription by inhibiting Set1p-dependent histone methylation, G3 (Bethesda), 7, 1001–1010.

    Article  CAS  Google Scholar 

  41. Donner, A. J., Ebmeier, C. C., Taatjes, D. J., and Espinosa, J. M. (2010) CDK8 is a positive regulator of transcriptional elongation within the serum response network, Nat. Struct. Mol. Biol., 17, 194–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Galbraith, M. D., Allen, M. A., Bensard, C. L., Wang, X., Schwinn, M. K., Qin, B., Long, H. W., Daniels, D. L., Hahn, W. C., Dowell, R. D., and Espinosa, J. M. (2013) HIF1A employs CDK8-mediator to stimulate RNAPII elongation in response to hypoxia, Cell, 153, 1327–1339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Van de Peppel, J., Kettelarij, N., Van Bakel, H., Kockelkorn, T. T., Van Leenen, D., and Holstege, F. C. (2005) Mediator expression profiling epistasis reveals a signal transduction pathway with antagonistic submodules and highly specific downstream targets, Mol. Cell, 19, 511–522.

    Article  PubMed  CAS  Google Scholar 

  44. Adler, A. S., McCleland, M. L., Truong, T., Lau, S., Modrusan, Z., Soukup, T. M., Roose-Girma, M., Blackwood, E. M., and Firestein, R. (2012) CDK8 maintains tumor dedifferentiation and embryonic stem cell pluripotency, Cancer Res., 72, 2129–2139.

    Article  CAS  PubMed  Google Scholar 

  45. Vogl, M. R., Reiprich, S., Kuspert, M., Kosian, T., Schrewe, H., Nave, K. A., and Wegner, M. (2013) Sox10 cooperates with the mediator subunit 12 during terminal differentiation of myelinating glia, J. Neurosci., 33, 6679–6690.

    Article  CAS  PubMed  Google Scholar 

  46. Zhou, H., Spaeth, J. M., Kim, N. H., Xu, X., Friez, M. J., Schwartz, C. E., and Boyer, T. G. (2012) MED12 mutations link intellectual disability syndromes with dysregulated GLI3-dependent Sonic Hedgehog signaling, Proc. Natl. Acad. Sci. USA, 109, 19763–19768.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kuuluvainen, E., Hakala, H., Havula, E., Sahal Estime, M., Ramet, M., Hietakangas, V., and Makela, T. P. (2014) 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kagey, M. H., Newman, J. J., Bilodeau, S., Zhan, Y., Orlando, D. A., Van Berkum, N. L., Ebmeier, C. C., Goossens, J., Rahl, P. B., Levine, S. S., Taatjes, D. J., Dekker, J., and Young, R. A. (2010) Mediator and cohesin connect gene expression and chromatin architecture, Nature, 467, 430–435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Whyte, W. A., Orlando, D. A., Hnisz, D., Abraham, B. J., Lin, C. Y., Kagey, M. H., Rahl, P. B., Lee, T. I., and Young, R. A. (2013) Master transcription factors and mediator establish super-enhancers at key cell identity genes, Cell, 153, 307–319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Grunberg, S., Henikoff, S., Hahn, S., and Zentner, G. E. (2016) Mediator binding to UASs is broadly uncoupled from transcription and cooperative with TFIID recruitment to promoters, EMBO J., 35, 2435–2446.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Poss, Z. C., Ebmeier, C. C., and Taatjes, D. J. (2013) The Mediator complex and transcription regulation, Crit. Rev. Biochem. Mol. Biol., 48, 575–608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Yin, J. W., and Wang, G. (2014) The Mediator complex: a master coordinator of transcription and cell lineage development, Development, 141, 977–987.

    Article  CAS  PubMed  Google Scholar 

  53. Jeronimo, C., Langelier, M. F., Bataille, A. R., Pascal, J. M., Pugh, B. F., and Robert, F. (2016) Tail and kinase modules differently regulate core Mediator recruitment and function in vivo, Mol. Cell, 64, 455–466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Petrenko, N., Jin, Y., Wong, K. H., and Struhl, K. (2016) Mediator undergoes a compositional change during transcriptional activation, Mol. Cell, 64, 443–454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Grants, J. M., Ying, L. T., Yoda, A., You, C. C., Okano, H., Sawa, H., and Taubert, S. (2016) The Mediator kinase module restrains epidermal growth factor receptor signaling and represses vulval cell fate specification in Caenorhabditis elegans, Genetics, 202, 583–599.

    Article  CAS  PubMed  Google Scholar 

  56. McDermott, M. S., Chumanevich, A. A., Lim, C. U., Liang, J., Chen, M., Altilia, S., Oliver, D., Rae, J. M., Shtutman, M., Kiaris, H., Gyorffy, B., Roninson, I. B., and Broude, E. V. (2017) Inhibition of CDK8 mediator kinase suppresses estrogen dependent transcription and the growth of estrogen receptor positive breast cancer, Oncotarget, 8, 12558–12575.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Yamamoto, S., Hagihara, T., Horiuchi, Y., Okui, A., Wani, S., Yoshida, T., Inoue, T., Tanaka, A., Ito, T., Hirose, Y., and Ohkuma, Y. (2017) Mediator cyclin-dependent kinases upregulate transcription of inflammatory genes in cooperation with NF-kappaB and C/EBPbeta on stimulation of Toll-like receptor 9, Genes Cells, 22, 265–276.

    Article  CAS  PubMed  Google Scholar 

  58. Xie, X. J., Hsu, F. N., Gao, X., Xu, W., Ni, J. Q., Xing, Y., Huang, L., Hsiao, H. C., Zheng, H., Wang, C., Zheng, Y., Xiaoli, A. M., Yang, F., Bondos, S. E., and Ji, J. Y. (2015) CDK8-cyclin C mediates nutritional regulation of developmental transitions through the ecdysone receptor in Drosophila, PLoS Biol., 13, e1002207.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Malik, S., and Roeder, R. G. (2016) Mediator: a draw-bridge across the enhancer–promoter divide, Mol. Cell, 64, 433–434.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Wong, K. H., Jin, Y., and Struhl, K. (2014) TFIIH phosphorylation of the Pol II CTD stimulates mediator dissociation from the preinitiation complex and promoter escape, Mol. Cell, 54, 601–612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lacombe, T., Poh, S. L., Barbey, R., and Kuras, L. (2013) Mediator is an intrinsic component of the basal RNA polymerase II machinery in vivo, Nucleic Acids Res., 41, 9651–9662.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Harlen, K. M., and Churchman, L. S. (2017) The code and beyond: transcription regulation by the RNA polymerase II carboxy-terminal domain, Nature Rev. Mol. Cell Biol., 18, 263–273.

    Article  CAS  Google Scholar 

  63. Eychenne, T., Novikova, E., Barrault, M. B., Alibert, O., Boschiero, C., Peixeiro, N., Cornu, D., Redeker, V., Kuras, L., Nicolas, P., Werner, M., and Soutourina, J. (2016) Functional interplay between Mediator and TFIIB in preinitiation complex assembly in relation to promoter architecture, Genes Dev., 30, 2119–2132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Jishage, M., Malik, S., Wagner, U., Uberheide, B., Ishihama, Y., Hu, X., Chait, B. T., Gnatt, A., Ren, B., and Roeder, R. G. (2012) Transcriptional regulation by Pol II(G) involving mediator and competitive interactions of Gdown1 and TFIIF with Pol II, Mol. Cell, 45, 51–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Johnson, K. M., and Carey, M. (2003) Assembly of a mediator/TFIID/TFIIA complex bypasses the need for an activator, Curr. Biol., 13, 772–777.

    Article  CAS  PubMed  Google Scholar 

  66. Esnault, C., Ghavi-Helm, Y., Brun, S., Soutourina, J., Van Berkum, N., Boschiero, C., Holstege, F., and Werner, M. (2008) Mediator-dependent recruitment of TFIIH modules in preinitiation complex, Mol. Cell, 31, 337–346.

    Article  CAS  PubMed  Google Scholar 

  67. Seizl, M., Lariviere, L., Pfaffeneder, T., Wenzeck, L., and Cramer, P. (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, 6291–6304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Eyboulet, F., Wydau-Dematteis, S., Eychenne, T., Alibert, O., Neil, H., Boschiero, C., Nevers, M. C., Volland, H., Cornu, D., Redeker, V., Werner, M., and Soutourina, J. (2015) Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo, Nucleic Acids Res., 43, 9214–9231.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Malik, S., Molina, H., and Xue, Z. (2017) PIC activation through functional interplay between Mediator and TFIIH, J. Mol. Biol., 429, 48–63.

    Article  CAS  PubMed  Google Scholar 

  70. Petrenko, N., Jin, Y., Wong, K. H., and Struhl, K. (2017) Evidence that Mediator is essential for Pol II transcription, but is not a required component of the preinitiation complex in vivo, eLife, 6.

    Google Scholar 

  71. Boeing, S., Rigault, C., Heidemann, M., Eick, D., and Meisterernst, M. (2010) RNA polymerase II C-terminal heptarepeat domain Ser-7 phosphorylation is established in a mediator-dependent fashion, J. Biol. Chem., 285, 188–196.

    Article  CAS  PubMed  Google Scholar 

  72. Jeronimo, C., and Robert, F. (2014) Kin28 regulates the transient association of Mediator with core promoters, Nat. Struct. Mol. Biol., 21, 449–455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Tantale, K., Mueller, F., Kozulic-Pirher, A., Lesne, A., Victor, J. M., Robert, M. C., Capozi, S., Chouaib, R., Backer, V., Mateos-Langerak, J., Darzacq, X., Zimmer, C., Basyuk, E., and Bertrand, E. (2016) A single-molecule view of transcription reveals convoys of RNA polymerases and multi-scale bursting, Nat. Commun., 7, 12248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kremer, S. B., Kim, S., Jeon, J. O., Moustafa, Y. W., Chen, A., Zhao, J., and Gross, D. S. (2012) Role of Mediator in regulating Pol II elongation and nucleosome displacement in Saccharomyces cerevisiae, Genetics, 191, 95–106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Scheidegger, A., and Nechaev, S. (2016) RNA polymerase II pausing as a context-dependent reader of the genome, Biochem. Cell Biol., 94, 82–92.

    Article  CAS  PubMed  Google Scholar 

  76. Malik, S., Barrero, M. J., and 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, 6182–6187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Guglielmi, B., Soutourina, J., Esnault, C., and Werner, M. (2007) TFIIS elongation factor and Mediator act in conjunction during transcription initiation in vivo, Proc. Natl. Acad. Sci. USA, 104, 16062–16067.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Wery, M., Shematorova, E., Van Driessche, B., Vandenhaute, J., Thuriaux, P., and Van Mullem, V. (2004) Members of the SAGA and Mediator complexes are partners of the transcription elongation factor TFIIS, EMBO J., 23, 4232–4242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Nock, A., Ascano, J. M., Barrero, M. J., and Malik, S. (2012) Mediator-regulated transcription through the +1 nucleosome, Mol. Cell, 48, 837–848.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Hu, X., Malik, S., Negroiu, C. C., Hubbard, K., Velalar, C. N., Hampton, B., Grosu, D., Catalano, J., Roeder, R. G., and Gnatt, A. (2006) A Mediator-responsive form of metazoan RNA polymerase II, Proc. Natl. Acad. Sci. USA, 103, 9506–9511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. DeLaney, E., and Luse, D. S. (2016) Gdown1 associates efficiently with RNA polymerase II after promoter clearance and displaces TFIIF during transcript elongation, PLoS One, 11, e0163649.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Wang, W., Yao, X., Huang, Y., Hu, X., Liu, R., Hou, D., Chen, R., and Wang, G. (2013) Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb, Transcription, 4, 39–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Conaway, R. C., and Conaway, J. W. (2013) The Mediator complex and transcription elongation, Biochim. Biophys. Acta, 1829, 69–75.

    Article  CAS  PubMed  Google Scholar 

  84. Hertweck, A., Evans, C. M., Eskandarpour, M., Lau, J. C., Oleinika, K., Jackson, I., Kelly, A., Ambrose, J., Adamson, P., Cousins, D. J., Lavender, P., Calder, V. L., Lord, G. M., and Jenner, R. G. (2016) T-bet activates Th1 genes through Mediator and the super elongation complex, Cell Rep., 15, 2756–2770.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Galli, G. G., Carrara, M., Yuan, W. C., Valdes-Quezada, C., Gurung, B., Pepe-Mooney, B., Zhang, T., Geeven, G., Gray, N. S., De Laat, W., Calogero, R. A., and Camargo, F. D. (2015) YAP drives growth by controlling transcriptional pause release from dynamic enhancers, Mol. Cell, 60, 328–337.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Bhagwat, A. S., Roe, J. S., Mok, B. Y. L., Hohmann, A. F., Shi, J., and Vakoc, C. R. (2016) BET bromodomain inhibition releases the Mediator complex from select cis-regulatory elements, Cell Rep., 15, 519–530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Takahashi, H., Parmely, T. J., Sato, S., Tomomori-Sato, C., Banks, C. A., Kong, S. E., Szutorisz, H., Swanson, S. K., Martin-Brown, S., Washburn, M. P., Florens, L., Seidel, C. W., Lin, C., Smith, E. R., Shilatifard, A., Conaway, R. C., and Conaway, J. W. (2011) Human mediator subunit MED26 functions as a docking site for transcription elongation factors, Cell, 146, 92–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Lens, Z., Cantrelle, F. X., Peruzzini, R., Hanoulle, X., Dewitte, F., Ferreira, E., Baert, J. L., Monte, D., Aumercier, M., Villeret, V., Verger, A., and Landrieu, I. (2017) Solution structure of the N-terminal domain of Mediator subunit MED26 and molecular characterization of its interaction with EAF1 and TAF7, J. Mol. Biol., 429, 3043–3055.

    Article  CAS  PubMed  Google Scholar 

  89. Takahashi, H., Takigawa, I., Watanabe, M., Anwar, D., Shibata, M., Tomomori-Sato, C., Sato, S., Ranjan, A., Seidel, C. W., Tsukiyama, T., Mizushima, W., Hayashi, M., Ohkawa, Y., Conaway, J. W., Conaway, R. C., and Hatakeyama, S. (2015) MED26 regulates the transcription of snRNA genes through the recruitment of little elongation complex, Nat. Commun., 6, 5941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Dahlberg, O., Shilkova, O., Tang, M., Holmqvist, P. H., and Mannervik, M. (2015) P-TEFb, the super elongation complex and mediator regulate a subset of non-paused genes during early Drosophila embryo development, PLoS Genet., 11, e1004971.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Uthe, H., Vanselow, J. T., and Schlosser, A. (2017) Proteomic analysis of the Mediator complex interactome in Saccharomyces cerevisiae, Sci. Rep., 7, 43584.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Huang, Y., Li, W., Yao, X., Lin, Q. J., Yin, J. W., Liang, Y., Heiner, M., Tian, B., Hui, J., and Wang, G. (2012) Mediator complex regulates alternative mRNA processing via the MED23 subunit, Mol. Cell, 45, 459–469.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Chereji, R. V., Bharatula, V., Elfving, N., Blomberg, J., Larsson, M., Morozov, A. V., Broach, J. R., and Bjorklund, S. (2017) Mediator binds to boundaries of chromosomal interaction domains and to proteins involved in DNA looping, RNA metabolism, chromatin remodeling, and actin assembly, Nucleic Acids Res., 45, 8806–8821.

    CAS  PubMed  Google Scholar 

  94. Schneider, M., Hellerschmied, D., Schubert, T., Amlacher, S., Vinayachandran, V., Reja, R., Pugh, B. F., Clausen, T., and Kohler, A. (2015) The nuclear pore-associated TREX-2 complex employs Mediator to regulate gene expression, Cell, 162, 1016–1028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Liu, Z., and Myers, L. C. (2012) Med5(Nut1) and Med17(Srb4) are direct targets of mediator histone H4 tail interactions, PLoS One, 7, e38416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Zhu, X., Zhang, Y., Bjornsdottir, G., Liu, Z., Quan, A., Costanzo, M., Davila Lopez, M., Westholm, J. O., Ronne, H., Boone, C., Gustafsson, C. M., and Myers, L. C. (2011) Histone modifications influence mediator interactions with chromatin, Nucleic Acids Res., 39, 8342–8354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Lemieux, K., and Gaudreau, L. (2004) Targeting of Swi/Snf to the yeast GAL1 UAS G requires the Mediator, TAF IIs, and RNA polymerase II, EMBO J., 23, 4040–4050.

    CAS  PubMed  Google Scholar 

  98. Sharma, V. M., Li, B., and Reese, J. C. (2003) SWI/SNF-dependent chromatin remodeling of RNR3 requires TAF(II)s and the general transcription machinery, Genes Dev., 17, 502–515.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Fukasawa, R., Tsutsui, T., Hirose, Y., Tanaka, A., and Ohkuma, Y. (2012) Mediator CDK subunits are platforms for interactions with various chromatin regulatory complexes, J. Biochem., 152, 241–249.

    Article  CAS  PubMed  Google Scholar 

  100. Khorosjutina, O., Wanrooij, P. H., Walfridsson, J., Szilagyi, Z., Zhu, X., Baraznenok, V., Ekwall, K., and Gustafsson, C. M. (2010) A chromatin-remodeling protein is a component of fission yeast mediator, J. Biol. Chem., 285, 29729–29737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Lin, J. J., Lehmann, L. W., Bonora, G., Sridharan, R., Vashisht, A. A., Tran, N., Plath, K., Wohlschlegel, J. A., and Carey, M. (2011) Mediator coordinates PIC assembly with recruitment of CHD1, Genes Dev., 25, 2198–2209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Bhoite, L. T., Yu, Y., and Stillman, D. J. (2001) The Swi5 activator recruits the Mediator complex to the HO promoter without RNA polymerase II, Genes Dev., 15, 2457–2469.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Yoon, S., Qiu, H., Swanson, M. J., and Hinnebusch, A. G. (2003) Recruitment of SWI/SNF by Gcn4p does not require Snf2p or Gcn5p but depends strongly on SWI/SNF integrity, SRB mediator, and SAGA, Mol. Cell. Biol., 23, 8829–8845.

    CAS  PubMed  Google Scholar 

  104. Ansari, S. A., Paul, E., Sommer, S., Lieleg, C., He, Q., Daly, A. Z., Rode, K. A., Barber, W. T., Ellis, L. C., LaPorta, E., Orzechowski, A. M., Taylor, E., Reeb, T., Wong, J., Korber, P., and Morse, R. H. (2014) 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.

    CAS  PubMed  Google Scholar 

  105. Acevedo, M. L., and Kraus, W. L. (2003) Mediator and p300/CBP-steroid receptor coactivator complexes have distinct roles, but function synergistically, during estrogen receptor alpha-dependent transcription with chromatin templates, Mol. Cell. Biol., 23, 335–348.

    CAS  PubMed  Google Scholar 

  106. Aranda-Orgilles, B., Saldana-Meyer, R., Wang, E., Trompouki, E., Fassl, A., Lau, S., Mullenders, J., Rocha, P. P., Raviram, R., Guillamot, M., Sanchez-Diaz, M., Wang, K., Kayembe, C., Zhang, N., Amoasii, L., Choudhuri, A., Skok, J. A., Schober, M., Reinberg, D., Sicinski, P., Schrewe, H., Tsirigos, A., Zon, L. I., and Aifantis, I. (2016) MED12 regulates HSC-specific enhancers independently of mediator kinase activity to control hematopoiesis, Cell Stem Cell, 19, 784–799.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Huang, Z. Q., Li, J., Sachs, L. M., Cole, P. A., and Wong, J. (2003) A role for cofactor–cofactor and cofactor–histone interactions in targeting p300, SWI/SNF and Mediator for transcription, EMBO J., 22, 2146–2155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Ebmeier, C. C., and Taatjes, D. J. (2010) Activator–Mediator binding regulates Mediator–cofactor interactions, Proc. Natl. Acad. Sci. USA, 107, 11283–11288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Meyer, K. D., Donner, A. J., Knuesel, M. T., York, A. G., Espinosa, J. M., and Taatjes, D. J. (2008) Cooperative activity of cdk8 and GCN5L within Mediator directs tandem phosphoacetylation of histone H3, EMBO J., 27, 1447–1457.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Bhaumik, S. R., and Green, M. R. (2001) SAGA is an essential in vivo target of the yeast acidic activator Gal4p, Genes Dev., 15, 1935–1945.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Larschan, E., and Winston, F. (2005) The Saccharomyces cerevisiae Srb8–Srb11 complex functions with the SAGA complex during Gal4-activated transcription, Mol. Cell. Biol., 25, 114–123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Bryant, G. O., and Ptashne, M. (2003) Independent recruitment in vivo by Gal4 of two complexes required for transcription, Mol. Cell, 11, 1301–1309.

    Article  CAS  PubMed  Google Scholar 

  113. Leroy, C., Cormier, L., and Kuras, L. (2006) Independent recruitment of mediator and SAGA by the activator Met4, Mol. Cell. Biol., 26, 3149–3163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Liu, X., Vorontchikhina, M., Wang, Y. L., Faiola, F., and Martinez, E. (2008) STAGA recruits Mediator to the MYC oncoprotein to stimulate transcription and cell proliferation, Mol. Cell. Biol., 28, 108–121.

    Article  PubMed  CAS  Google Scholar 

  115. Malik, S., Wallberg, A. E., Kang, Y. K., and Roeder, R. G. (2002) 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Krebs, A. R., Demmers, J., Karmodiya, K., Chang, N. C., Chang, A. C., and Tora, L. (2010) ATAC and Mediator coactivators form a stable complex and regulate a set of non-coding RNA genes, EMBO Rep., 11, 541–547.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Yao, X., Tang, Z., Fu, X., Yin, J., Liang, Y., Li, C., Li, H., Tian, Q., Roeder, R. G., and Wang, G. (2015) The Mediator subunit MED23 couples H2B mono-ubiquitination to transcriptional control and cell fate determination, EMBO J., 34, 2885–2902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Law, M. J., and Ciccaglione, K. (2015) Fine-tuning of histone H3 Lys4 methylation during pseudohyphal differentiation by the CDK submodule of RNA polymerase II, Genetics, 199, 435–453.

    Article  PubMed  CAS  Google Scholar 

  119. Ding, N., Zhou, H., Esteve, P. O., Chin, H. G., Kim, S., Xu, X., Joseph, S. M., Friez, M. J., Schwartz, C. E., Pradhan, S., and Boyer, T. G. (2008) Mediator links epigenetic silencing of neuronal gene expression with x-linked mental retardation, Mol. Cell, 31, 347–359.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Tsutsui, T., Fukasawa, R., Shinmyouzu, K., Nakagawa, R., Tobe, K., Tanaka, A., and Ohkuma, Y. (2013) Mediator complex recruits epigenetic regulators via its two cyclin-dependent kinase subunits to repress transcription of immune response genes, J. Biol. Chem., 288, 20955–20965.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. D’Urso, A., Takahashi, Y. H., Xiong, B., Marone, J., Coukos, R., Randise-Hinchliff, C., Wang, J. P., Shilatifard, A., and Brickner, J. H. (2016) Set1/COM-PASS and Mediator are repurposed to promote epigenetic transcriptional memory, eLife, 5.

    Google Scholar 

  122. McCleland, M. L., Soukup, T. M., Liu, S. D., Esensten, J. H., De Sousa e Melo, F., Yaylaoglu, M., Warming, S., Roose-Girma, M., and Firestein, R. (2015) Cdk8 deletion in the Apc(Min) murine tumour model represses EZH2 activity and accelerates tumourigenesis, J. Pathol., 237, 508–519.

    Article  CAS  PubMed  Google Scholar 

  123. Fukasawa, R., Iida, S., Tsutsui, T., Hirose, Y., and Ohkuma, Y. (2015) Mediator complex cooperatively regulates transcription of retinoic acid target genes with Polycomb Repressive Complex 2 during neuronal differentiation, J. Biochem., 158, 373–384.

    Article  CAS  PubMed  Google Scholar 

  124. Papadopoulou, T., Kaymak, A., Sayols, S., and Richly, H. (2016) Dual role of Med12 in PRC1-dependent gene repression and ncRNA-mediated transcriptional activation, Cell Cycle, 15, 1479–1493.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Englert, N. A., Luo, G., Goldstein, J. A., and Surapureddi, S. (2015) Epigenetic modification of histone 3 lysine 27: mediator subunit MED25 is required for the dissociation of polycomb repressive complex 2 from the promoter of cytochrome P450 2C9, J. Biol. Chem., 290, 2264–2278.

    Article  CAS  PubMed  Google Scholar 

  126. Zhu, X., Liu, B., Carlsten, J. O., Beve, J., Nystrom, T., Myers, L. C., and Gustafsson, C. M. (2011) Mediator influences telomeric silencing and cellular life span, Mol. Cell. Biol., 31, 2413–2421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Kim, Y. J., Zheng, B., Yu, Y., Won, S. Y., Mo, B., and Chen, X. (2011) The role of Mediator in small and long noncoding RNA production in Arabidopsis thaliana, EMBO J., 30, 814–822.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Oya, E., Kato, H., Chikashige, Y., Tsutsumi, C., Hiraoka, Y., and Murakami, Y. (2013) Mediator directs co-transcriptional heterochromatin assembly by RNA interference-dependent and -independent pathways, PLoS Genet., 9, e1003677.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Thorsen, M., Hansen, H., Venturi, M., Holmberg, S., and Thon, G. (2012) Mediator regulates non-coding RNA transcription at fission yeast centromeres, Epigenetics Chromatin, 5, 19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Peng, J., and Zhou, J. Q. (2012) The tail-module of yeast Mediator complex is required for telomere heterochromatin maintenance, Nucleic Acids Res., 40, 581–593.

    Article  CAS  PubMed  Google Scholar 

  131. Chen, Z., Zhang, C., Wu, D., Chen, H., Rorick, A., Zhang, X., and Wang, Q. (2011) Phospho-MED1-enhanced UBE2C locus looping drives castration-resistant prostate cancer growth, EMBO J., 30, 2405–2419.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Park, S. W., Li, G., Lin, Y. P., Barrero, M. J., Ge, K., Roeder, R. G., and Wei, L. N. (2005) Thyroid hormone-induced juxtaposition of regulatory elements/factors and chromatin remodeling of Crabp1 dependent on MED1/TRAP220, Mol. Cell, 19, 643–653.

    Article  CAS  PubMed  Google Scholar 

  133. Saramaki, A., Diermeier, S., Kellner, R., Laitinen, H., Vaisanen, S., and Carlberg, C. (2009) Cyclical chromatin looping and transcription factor association on the regulatory regions of the p21 (CDKN1A) gene in response to 1alpha,25-dihydroxyvitamin D3, J. Biol. Chem., 284, 8073–8082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Wang, Q., Carroll, J. S., and Brown, M. (2005) Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking, Mol. Cell, 19, 631–642.

    Article  CAS  PubMed  Google Scholar 

  135. Muto, A., Ikeda, S., Lopez-Burks, M. E., Kikuchi, Y., Calof, A. L., Lander, A. D., and Schilling, T. F. (2014) Nipbl and mediator cooperatively regulate gene expression to control limb development, PLoS Genet., 10, e1004671.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Fournier, M., Bourriquen, G., Lamaze, F. C., Cote, M. C., Fournier, E., Joly-Beauparlant, C., Caron, V., Gobeil, S., Droit, A., and Bilodeau, S. (2016) FOXA and master transcription factors recruit Mediator and Cohesin to the core transcriptional regulatory circuitry of cancer cells, Sci. Rep., 6, 34962.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Phillips-Cremins, J. E., Sauria, M. E., Sanyal, A., Gerasimova, T. I., Lajoie, B. R., Bell, J. S., Ong, C. T., Hookway, T. A., Guo, C., Sun, Y., Bland, M. J., Wagstaff, W., Dalton, S., McDevitt, T. C., Sen, R., Dekker, J., Taylor, J., and Corces, V. G. (2013) Architectural protein subclasses shape 3D organization of genomes during lineage commitment, Cell, 153, 1281–1295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Krivega, I., and Dean, A. (2017) LDB1-mediated enhancer looping can be established independent of mediator and cohesin, Nucleic Acids Res., 45, 8255–8268.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Levine, M., Cattoglio, C., and Tjian, R. (2014) Looping back to leap forward: transcription enters a new era, Cell, 157, 13–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Dobi, K. C., and Winston, F. (2007) Analysis of transcriptional activation at a distance in Saccharomyces cerevisiae, Mol. Cell. Biol., 27, 5575–5586.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Mukundan, B., and Ansari, A. (2013) Srb5/Med18-mediated termination of transcription is dependent on gene looping, J. Biol. Chem., 288, 11384–11394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Hsieh, T. H., Weiner, A., Lajoie, B., Dekker, J., Friedman, N., and Rando, O. J. (2015) Mapping nucleosome resolution chromosome folding in yeast by micro-C, Cell, 162, 108–119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Lai, F., Orom, U. A., Cesaroni, M., Beringer, M., Taatjes, D. J., Blobel, G. A., and Shiekhattar, R. (2013) Activating RNAs associate with Mediator to enhance chromatin architecture and transcription, Nature, 494, 497–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Hsieh, C. L., Fei, T., Chen, Y., Li, T., Gao, Y., Wang, X., Sun, T., Sweeney, C. J., Lee, G. S., Chen, S., Balk, S. P., Liu, X. S., Brown, M., and Kantoff, P. W. (2014) Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation, Proc. Natl. Acad. Sci. USA, 111, 7319–7324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Step, S. E., Lim, H. W., Marinis, J. M., Prokesch, A., Steger, D. J., You, S. H., Won, K. J., and Lazar, M. A. (2014) Anti-diabetic rosiglitazone remodels the adipocyte transcriptome by redistributing transcription to PPARgamma-driven enhancers, Genes Dev., 28, 1018–1028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Siersbaek, R., Madsen, J. G. S., Javierre, B. M., Nielsen, R., Bagge, E. K., Cairns, J., Wingett, S. W., Traynor, S., Spivakov, M., Fraser, P., and Mandrup, S. (2017) Dynamic rewiring of promoter-anchored chromatin loops during adipocyte differentiation, Mol. Cell, 66, 420–435.

    Article  CAS  PubMed  Google Scholar 

  147. Liu, J., Perumal, N. B., Oldfield, C. J., Su, E. W., Uversky, V. N., and Dunker, A. K. (2006) Intrinsic disorder in transcription factors, Biochemistry, 45, 6873–6888.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Wright, P. E., and Dyson, H. J. (2015) Intrinsically disordered proteins in cellular signalling and regulation, Nat. Rev. Mol. Cell Biol., 16, 18–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Larson, A. G., Elnatan, D., Keenen, M. M., Trnka, M. J., Johnston, J. B., Burlingame, A. L., Agard, D. A., Redding, S., and Narlikar, G. J. (2017) Liquid droplet formation by HP1alpha suggests a role for phase separation in heterochromatin, Nature, 547, 236–240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., Shindyalov, I. N., and Bourne, P. E. (2000) The protein data bank, Nucleic Acids Res., 28, 235–242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Lawson, C. L., Baker, M. L., Best, C., Bi, C., Dougherty, M., Feng, P., Van Ginkel, G., Devkota, B., Lagerstedt, I., Ludtke, S. J., Newman, R. H., Oldfield, T. J., Rees, I., Sahni, G., Sala, R., Velankar, S., Warren, J., Westbrook, J. D., Henrick, K., Kleywegt, G. J., Berman, H. M., and Chiu, W. (2011) EMDataBank.org: unified data resource for CryoEM, Nucleic Acids Res., 39, 456–464.

    Article  CAS  Google Scholar 

  152. Schneider, E. V., Bottcher, J., Blaesse, M., Neumann, L., Huber, R., and Maskos, K. (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, 251–266.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Gene Biology, Russian Academy of Sciences, 119334, Moscow, Russia

    E. V. Putlyaev, A. N. Ibragimov, L. A. Lebedeva, P. G. Georgiev & Y. V. Shidlovskii

  2. Sechenov First Moscow State Medical University, 119048, Moscow, Russia

    Y. V. Shidlovskii

Authors
  1. E. V. Putlyaev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. N. Ibragimov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. A. Lebedeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. G. Georgiev
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y. V. Shidlovskii
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. V. Shidlovskii.

Additional information

Original Russian Text © E. V. Putlyaev, A. N. Ibragimov, L. A. Lebedeva, P. G. Georgiev, Y. V. Shidlovskii, 2018, published in Biokhimiya, 2018, Vol. 83, No. 4, pp. 577–591.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Putlyaev, E.V., Ibragimov, A.N., Lebedeva, L.A. et al. Structure and Functions of the Mediator Complex. Biochemistry Moscow 83, 423–436 (2018). https://doi.org/10.1134/S0006297918040132

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297918040132

Keywords

Search

Navigation