Resarch progress of transcription mediator complex

doi:10.14088/j.cnki.issn0439-8114.2020.03.001

Abstract

Abstract: The mediator complex, a highly conserved large complex with modular tissue, is widely distributed in eukaryotes and is involved in the transmission of information between transcription factors and RNA polymerase II. The main function of the mediator complex is to regulate the expression of downstream genes by interacting with transcription factors stimulated by different signaling pathways. In addition, the mediator complex interacts with various cofactors to participate in processes such as transcriptional elongation, mRNA export, and selective splicing, thereby controlling various physiological functions of the cell. The close relationship between mediator complexes and disease makes it possible to study the treatment of disease with mediator as a target. Based on the structure of the mediator complex, the molecular mechanism and function of the mediator complex in the regulation of gene expression were introduced, in order to provide reference for the following research.

Key words: mediator complex, structure, molecular mechanism, function

CLC Number:

WANG Wen, LIU Kun. Resarch progress of transcription mediator complex[J]. HUBEI AGRICULTURAL SCIENCES, 2020, 59(3): 5-8.

References

[1] BOUBE M,FAUCHER C,JOULIA L,et al.Drosophila homologs of transcriptional mediator complex subunits are required for adult cell and segment identity specification[J].Genes Dev,2000, 14(22):2906-2917.
[2] JIANG Y W,VESCHAMBRE P,ERDJUMENT-BROMAGE H,et al.Mammalian mediator of transcriptional regulation and its possible role as an end-point of signal transduction pathways[J].Proc Natl Acad Sci USA,1998,95(15):8538-8543.
[3] SIERECKI E.The Mediator complex and the role of protein-protein interactions in the gene regulation machinery[J].Semin Cell Dev Biol,2018,(in press).
[4] CEVHER M A,SHI Y,LI D,et al.Reconstitution of active human core Mediator complex reveals a critical role of the MED14 subunit[J].Nature structural & molecular biology,2014,21(12):1028-1034.
[5] NOZAWA K,SCHNEIDER T R,CRAMER P.Core Mediator structure at 3.4 Å extends model of transcription initiation complex[J].Nature,2017,545(7653):248-251.
[6] WANG X,SUN Q,DING Z,et al.Redefining the modular organization of the core Mediator complex[J].Cell Res,2014,24(7):796-808.
[7] TSAI K L,SATO C T,SATO S,et al.Subunit architecture and functional modular rearrangements of the transcriptional mediator complex[J].Cell,2014,157(2):1430-1444.
[8] SOUTOURINA J.Transcription regulation by the Mediator complex[J].Nature reviews molecular cell biology,2017,19(4):262-274.
[9] PLASCHKA C,LARIVIÈRE L,WENZECK L, et al. Architecture of the RNA polymerase II-Mediator core initiation complex[J].Nature,2015,518(7539):376-380.
[10] SOUTOURINA J.Transcription regulation by the Mediator complex[J].Nature reviews molecular cell biology,2017,19(4):262-274.
[11] TSAI K,YU X,GOPALAN S,et al.Mediator structure and rearrangements required for holoenzyme formation[J].Nature,2017,544(7649):196-201.
[12] ROBINSON P J,TRNKA M J,PELLARIN R,et al.Molecular architecture of the yeast Mediator complex[J].eLife,2015,4.e08719.
[13] ROBINSON P J,TRNKA M J,BUSHNELL D A,et al.Structure of a complete Mediator-RNA polymerase II Pre-Initiation complex[J].Cell,2016,166(6):1411-1422.
[14] LARIVIERE L,SEIZL M,CRAMER P.A structural perspective on Mediator function[J].Curr Opin Cell Biol,2012,24(3):305-313.
[15] MEYER K D,LIN S C,BERNECKY C,et al.p53 activates transcription by directing structural shifts in Mediator[J].Nat Struct Mol Biol,2010,17(6):753-760.
[16] LIN J J,LEHMANN L W,BONORA G,et al.Mediator coordinates PIC assembly with recruitment of CHD1[J].Genes Dev,2011,25(20):2198-2209.
[17] POSS Z C,EBMEIER C C,TAATJES D J.The Mediator complex and transcription regulation[J].Crit Rev Biochem Mol Biol,2013,48(6):575-608.
[18] VAN ESSEN D,ENGIST B,NATOLI G,et al.Two modes of transcriptional activation at native promoters by NF-kappaB p65[J].PLoS Biol,2009,7(3):e73.
[19] ITO M,YUAN C X,MALIK S,et al.Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators[J].Mol Cell,1999,3(3):361-370.
[20] STEVENS J L,CANTIN G T,WANG G,et al.Transcription control by E1A and MAP kinase pathway via Sur2 mediator subunit[J].Science,2002,296(5568):755-758.
[21] FONDELL J D,GE H,ROEDER R G.Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex[J].Proc Natl Acad Sci USA,1996,93(16):8329-8333.
[22] RACHEZ C,LEMON B D,SULDAN Z,et al.Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex[J].Nature,1999,398-824.
[23] GE K,CHO Y W,GUO H,et al.Alternative mechanisms by which mediator subunit MED1/TRAP220 regulates peroxisome proliferator-activated receptor gamma-stimulated adipogenesis and target gene expression[J].Mol Cell Biol,2008,28(3):1081-1091.
[24] GE K,GUERMAH M,YUAN C,et al.Transcription coactivator TRAP220 is required for PPARγ2-stimulated adipogenesis[J]. Nature,2002,417-563.
[25] MALIK S,WALLBERG A E,KANG Y K,et al.TRAP/SMCC/mediator-dependent transcriptional activation from DNA and chromatin templates by orphan nuclear receptor hepatocyte nuclear factor 4[J].Mol Cell Biol,2002,22(15):5626-5637.
[26] HITTELMAN A B,BURAKOV D,INIGUEZ-LLUHI J A,et al. Differential regulation of glucocorticoid receptor transcriptional activation via AF-1-associated proteins[J].EMBO J,1999,18(19):5380-5388.
[27] KANG Y K,GUERMAH M,YUAN C X,et al.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[J].Proc Natl Acad Sci USA,2002,99(5):2642-2647.
[28] YUAN C X,ITO M,FONDELL J D,et al.The TRAP220 component of a thyroid hormone receptor-associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion[J].Proc Natl Acad Sci USA,1998, 95(14):7939-7944.
[29] ZHU Y,QI C,JAIN S,et al.Isolation and characterization of PBP,a protein that interacts with peroxisome proliferator-activated receptor[J].J Biol Chem,1997,272(41):25500-25506.
[30] MEYER K D,LIN S C,BERNECKY C,et al.p53 activates transcription by directing structural shifts in Mediator[J].Nat Struct Mol Biol,2010,17(6):753-760.
[31] WADA O,OISHI H,TAKADA I,et al.BRCA1 function mediates a TRAP/DRIP complex through direct interaction with TRAP220[J].Oncogene,2004,23(35):6000-6005.
[32] WANSA K D,MUSCAT G E.TRAP220 is modulated by the antineoplastic agent 6-Mercaptopurine,and mediates the activation of the NR4A subgroup of nuclear receptors[J].J Mol Endocrinol,2005,34(3):835-848.
[33] PINEDA T I,FREEDMAN L P,GARABEDIAN M J.Identification of DRIP205 as a coactivator for the Farnesoid X receptor[J].J Biol Chem,2004,279(35):36184-36191.
[34] ATKINS G B,HU X,GUENTHER M G,et al.Coactivators for the orphan nuclear receptor RORalpha[J].Mol Endocrinol,1999, 13(9):1550-1557.
[35] WANG S,GE K,ROEDER R G,et al.Role of mediator in transcriptional activation by the aryl hydrocarbon receptor[J].J Biol Chem,2004,279(14):13593-13600.
[36] STUMPF M,WASKOW C,KROTSCHEL M,et al.The mediator complex functions as a coactivator for GATA-1 in erythropoiesis via subunit Med1/TRAP220[J].Proc Natl Acad Sci USA,2006,103(49):18504-18509.
[37] GORDON D F,TUCKER E A,TUNDWAL K,et al.MED220/thyroid receptor-associated protein 220 functions as a transcriptional coactivator with Pit-1 and GATA-2 on the thyrotropin-beta promoter in thyrotropes[J].Mol Endocrinol,2006, 20(5):1073-1089.
[38] UDAYAKUMAR T S,BELAKAVADI M,CHOI K H,et al.Regulation of Aurora-A kinase gene expression via GABP recruitment of TRAP220/MED1[J].J Biol Chem,2006,281(21):14691-14699.
[39] LIU X,VORONTCHIKHINA M,WANG Y L,et al.STAGA recruits Mediator to the MYC oncoprotein to stimulate transcription and cell proliferation[J].Mol Cell Biol,2008,28(1):108-121.
[40] ZILLIACUS J,HOLTER E,WAKUI H,et al.Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140[J].Mol Endocrinol,2001, 15(4):501-511.
[41] WALLBERG A E,YAMAMURA S,MALIK S,et al.Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha[J].Mol Cell,2003, 12(5):1137-1149.
[42] LI H,GADE P,NALLAR S C,et al.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].J Biol Chem,2008,283(19):13077-13086.
[43] JIA Y,VISWAKARMA N,REDDY J K.Med1 subunit of the mediator complex in nuclear receptor-regulated energy metabolism,liver regeneration,and hepatocarcinogenesis[J].Gene Expr,2014,16(2):63-75.
[44] NATARAJAN K,JACKSON B M,ZHOU H,et al.Transcriptional activation by Gcn4p involves independent interactions with the SWI/SNF complex and the SRB/mediator[J].Mol Cell,1999,4(4):657-664.
[45] ZHANG F,SUMIBCAY L,HINNEBUSCH A G,et al.A triad of subunits from the Gal11/tail domain of Srb mediator is an in vivo target of transcriptional activator Gcn4p[J].Mol Cell Biol,2004,24(15):6871-6886.
[46] MEHTA S,MIKLOS I,SIPICZKI M,et al.The Med8 mediator subunit interacts with the Rpb4 subunit of RNA polymerase II and Ace2 transcriptional activator in Schizosaccharomyces pombe[J].FEBS Lett,2009,583(19):3115-3120.
[47] LI X,YANG R,CHEN H.The Arabidopsis thaliana Mediator subunit MED8 regulates plant immunity to Botrytis Cinerea through interacting with the basic helix-loop-helix (bHLH) transcription factor FAMA[J].PLoS One,2018,13(3):e193458.
[48] WANG F,WEI H,TONG Z,et al.Knockdown of NtMed8, a Med8-like gene,causes abnormal development of vegetative and floral organs in tobacco (Nicotiana tabacum L.)[J].Plant Cell Rep,2011,30(11):2117-2129.
[49] GWACK Y,BAEK H J,NAKAMURA H,et al.Principal role of TRAP/mediator and SWI/SNF complexes in Kaposi's sarcoma-associated herpesvirus RTA-mediated lytic reactivation[J].Mol Cell Biol,2003,23(6):2055-2067.
[50] RAU M J,FISCHER S,NEUMANN C J.Zebrafish Trap230/Med12 is required as a coactivator for Sox9-dependent neural crest,cartilage and ear development[J].Dev Biol,2006,296(1):83-93.
[51] TUTTER A V,KOWALSKI M P,BALTUS G A,et al.Role for Med12 in Regulation of Nanog and Nanog Target Genes[J].Journal of biological chemistry,2009,284(6):3709-3718.
[52] KIM S,XU X,HECHT A,et al.Mediator is a transducer of Wnt/beta-catenin signaling[J].J Biol Chem,2006,281(20):14066-14075.
[53] DING N,ZHOU H,ESTEVE P,et al.Mediator Links Epigenetic Silencing of Neuronal Gene Expression with X-Linked Mental Retardation[J].Molecular cell,2008,31(3):347-359.
[54] DING N,ZHOU H,ESTEVE P O,et al.Mediator links epigenetic silencing of neuronal gene expression with x-linked mental retardation[J].Mol Cell,2008,31(3):347-359.
[55] ZHOU H,KIM S,ISHII S,et al.Mediator modulates Gli3-dependent Sonic hedgehog signaling[J].Mol Cell Biol,2006,26(23):8667-8682.
[56] CARRERA I,JANODY F,LEEDS N,et al.Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13[J].Proc Natl Acad Sci USA,2008,105(18):6644-6649.
[57] XU X,ZHOU H,BOYER T G.Mediator is a transducer of amyloid-precursor-protein-dependent nuclear signalling[J].EMBO Rep,2011,12(3):216-222.
[58] CHEN W,ROGATSKY I,GARABEDIAN M J.MED14 and MED1 differentially regulate target-specific gene activation by the glucocorticoid receptor[J].Mol Endocrinol,2006,20(3):560-572.
[59] LAU J F,NUSINZON I,BURAKOV D,et al.Role of metazoan mediator proteins in interferon-responsive transcription[J].Mol Cell Biol,2003,23(2):620-628.
[60] LEE J E,KIM K,SACCHETTINI J C,et al.DRIP150 coactivation of estrogen receptor alpha in ZR-75 breast cancer cells is independent of LXXLL motifs[J].J Biol Chem,2005,280(10):8819-8830.
[61] GRONTVED L,MADSEN M S,BOERGESEN M,et al.MED14 tethers mediator to the N-terminal domain of peroxisome proliferator-activated receptor gamma and is required for full transcriptional activity and adipogenesis[J].Mol Cell Biol,2010,30(9):2155-2169.
[62] TOTH J I,DATTA S,ATHANIKAR J N,et al.Selective coactivator interactions in gene activation by SREBP-1a and -1c[J].Mol Cell Biol,2004,24(18):8288-8300.
[63] WANG C,DU X,MOU Z.The Mediator Complex Subunits MED14,MED15,and MED16 Are Involved in Defense Signaling Crosstalk in Arabidopsis[J].Front Plant Sci,2016,7:1947.
[64] LIN X,RINALDO L,FAZLY A F,et al.Depletion of Med10 enhances Wnt and suppresses Nodal signaling during zebrafish embryogenesis[J].Dev Biol,2007,303(2):536-548.
[65] KATO Y,HABAS R,KATSUYAMA Y,et al.A component of the ARC/Mediator complex required for TGF beta/Nodal signalling[J].Nature,2002,418(6898):641-646.
[66] TAUBERT S,VAN GILST M R,HANSEN M,et al. A Mediator subunit,MDT-15,integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways in C. elegans[J].Genes Dev,2006,20(9):1137-1149.
[67] THAKUR J K,ARTHANARI H,YANG F,et al.Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription factor Oaf1p[J].J Biol Chem,2009,284(7):4422-4428.
[68] PARK J M,KIM H S,HAN S J,et al.In vivo requirement of activator-specific binding targets of mediator[J].Mol Cell Biol,2000,20(23):8709-8719.
[69] YANG F,VOUGHT B W,SATTERLEE J S,et al.An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis[J].Nature,2006,442:700.
[70] ZHAO M,YANG X,FU Y,et al.Mediator MED15 modulates transforming growth factor beta (TGFbeta)/Smad signaling and breast cancer cell metastasis[J].J Mol Cell Biol,2013,5(1):57-60.
[71] SYRING I,WEITEN R,MULLER T,et al.The knockdown of the Mediator complex subunit MED15 restrains urothelial bladder cancer cells' malignancy[J].Oncol Lett,2018,16(3):3013-3021.
[72] KIM T W,KWON Y J,KIM J M,et al.MED16 and MED23 of Mediator are coactivators of lipopolysaccharide-and heat-shock-induced transcriptional activators[J].Proc Natl Acad Sci USA,2004,101(33):12153-12158.
[73] SWANSON M J,QIU H,SUMIBCAY L,et al.A multiplicity of coactivators is required by Gcn4p at individual promoters in vivo[J].Mol Cell Biol,2003,23(8):2800-2820.
[74] BURAKOV D,WONG C W,RACHEZ C,et al.Functional interactions between the estrogen receptor and DRIP205,a subunit of the heteromeric DRIP coactivator complex[J].J Biol Chem,2000,275(27):20928-20934.
[75] PARK J M,WERNER J,KIM J M,et al.Mediator,Not Holoenzyme,Is Directly Recruited to the Heat Shock Promoter by HSF upon Heat Shock[J].2001,8(1):9-19.
[76] KOH S S,ANSARI A Z,PTASHNE M,et al.An activator target in the RNA polymerase II holoenzyme[J].Mol Cell,1998,1(6):895-904.
[77] PARK J M,KIM J M,KIM L K,et al.Signal-induced transcriptional activation by Dif requires the dTRAP80 mediator module[J].Mol Cell Biol,2003,23(4):1358-1367.
[78] VISCARRA J A,WANG Y,HONG I H, et al. Transcriptional activation of lipogenesis by insulin requires phosphorylation of MED17 by CK2[J].Sci Signal,2017,10(467):eaai8596.
[79] KIKUCHI Y,UMEMURA H,NISHITANI S,et al.Human mediator MED17 subunit plays essential roles in gene regulation by associating with the transcription and DNA repair machineries[J].Genes Cells,2015,20(3):191-202.
[80] DING N,TOMOMORI-SATO C,SATO S,et al.MED19 and MED26 are synergistic functional targets of the RE1 silencing transcription factor in epigenetic silencing of neuronal gene expression[J].J Biol Chem,2009,284(5):2648-2656.
[81] ZHAO Y,MENG Q,GAO X,et al.Down-regulation of mediator complex subunit 19 (Med19) induces apoptosis in human laryngocarcinoma HEp2 cells in an Apaf-1-dependent pathway[J].Am J Transl Res,2017,9(2):755-761.
[82] ZHANG X,FAN Y,LIU B,et al.Med19 promotes breast cancer cell proliferation by regulating CBFA2T3/HEB expression[J].Breast Cancer,2017,24(3):433-441.
[83] NEVADO J,TENBAUM S P,ARANDA A. hSrb7,an essential human Mediator component,acts as a coactivator for the thyroid hormone receptor[J].Mol Cell Endocrinol,2004,222(1-2):41-51.
[84] HALLBERG M,HU G Z,TRONNERSJO S,et al.Functional and physical interactions within the middle domain of the yeast mediator[J].Mol Genet Genomics,2006,276(2):197-210.
[85] SATO S,TOMOMORI-SATO C,TSAI K L,et al.Role for the MED21-MED7 Hinge in Assembly of the Mediator-RNA Polymerase II Holoenzyme[J].J Biol Chem,2016,291(52):26886-26898.
[86] MO X,KOWENZ-LEUTZ E,XU H,et al.Ras induces mediator complex exchange on C/EBP beta[J].Mol Cell,2004,13(2):241-250.
[87] SHIMOGAWA H,KWON Y,MAO Q,et al.A wrench-shaped synthetic molecule that modulates a transcription factor-coactivator interaction[J].J Am Chem Soc,2004,126(11):3461-3471.
[88] WANG G,BALAMOTIS M A,STEVENS J L,et al.Mediator Requirement for Both Recruitment and Postrecruitment Steps in Transcription Initiation[J].Molecular Cell,2005,17(5):683-694.
[89] GRIFFITHS S J,KOEGL M,BOUTELL C,et al.A systematic analysis of host factors reveals a Med23-interferon-lambda regulatory axis against herpes simplex virus type 1 replication[J].PLoS Pathog,2013,9(8):e1003514.
[90] LIU Z,YAO X,YAN G,et al.Mediator MED23 cooperates with RUNX2 to drive osteoblast differentiation and bone development[J].Nat Commun,2016,7:11149.
[91] CHU Y,GOMEZ R L,HUANG P,et al.Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity[J].Cell Res,2014,24(10):1250-1265.
[92] HASEGAWA N,SUMITOMO A,FUJITA A,et al.Mediator subunits MED1 and MED24 cooperatively contribute to pubertal mammary gland development and growth of breast carcinoma cells[J].Mol Cell Biol,2012,32(8):1483-1495.
[93] LEE H K,PARK U H,KIM E J,et al.MED25 is distinct from TRAP220/MED1 in cooperating with CBP for retinoid receptor activation[J].EMBO J,2007,26(15):3545-3557.
[94] RANA R,SURAPUREDDI S,KAM W,et al.Med25 is required for RNA polymerase II recruitment to specific promoters,thus regulating xenobiotic and lipid metabolism in human liver[J].Mol Cell Biol,2011,31(3):466-481.
[95] VERGER A,BAERT J L,VERREMAN K,et al.The Mediator complex subunit MED25 is targeted by the N-terminal transactivation domain of the PEA3 group members[J].Nucleic Acids Res,2013,41(9):4847-4859.
[96] NAKAMURA Y,YAMAMOTO K,HE X,et al.Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25[J].Nat Commun,2011,2:251.
[97] SELA D,CONKRIGHT J J,CHEN L,et al.Role for human mediator subunit MED25 in recruitment of mediator to promoters by endoplasmic reticulum stress-responsive transcription factor ATF6alpha[J].J Biol Chem,2013,288(36):26179-26187.
[98] WIEDERHOLD T,LEE M F,JAMES M,et al.Magicin,a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2[J].Oncogene,2004,23(54):8815-8825.
[99] GARRETT-ENGELE C M,SIEGAL M L,MANOLI D S,et al. intersex,a gene required for female sexual development in Drosophila,is expressed in both sexes and functions together with doublesex to regulate terminal differentiation[J].Development,2002,129(20):4661-4675.
[100] SATO S,TOMOMORI-SATO C,BANKS C A,et al.A mammalian homolog of Drosophila melanogaster transcriptional coactivator intersex is a subunit of the mammalian Mediator complex[J].J Biol Chem,2003,278(50):49671-49674.
[101] KUUSELO R,SAVINAINEN K,SANDSTROM S,et al.MED29,a component of the mediator complex,possesses both oncogenic and tumor suppressive characteristics in pancreatic cancer[J].Int J Cancer,2011,129(11):2553-2565.
[102] BEADLE E P,STRAUB J A,BUNNELL B A,et al.MED31 involved in regulating self-renewal and adipogenesis of human mesenchymal stem cells[J].Mol Biol Rep,2018.45(5):1545-1550.
[103] ZHANG X,ZHOU W,CHEN Q,et al.Mediator subunit MED31 is required for radial patterning of Arabidopsis roots[J].Proc Natl Acad Sci USA,2018,115(24):E5624-E5633.
[104] EBERHARDY S R,FARNHAM P J.Myc recruits P-TEFb to mediate the final step in the transcriptional activation of the cad promoter[J].J Biol Chem,2002,277(42):40156-40162.
[105] PARK J M,WERNER J,KIM J M,et al.Mediator, not holoenzyme,is directly recruited to the heat shock promoter by HSF upon heat shock[J].Mol Cell,2001,8(1):9-19.
[106] YERGIYEV O,GARIB G,SCHOEDEL K,et al.CDK8 Expression in Extrauterine Leiomyosarcoma Correlates With Tumor Stage and Progression[J].Appl Immunohistochem Mol Morphol,2018,26(3):161-164.
[107] KOLESKE A J,BURATOWSKI S,NONET M, et al.A novel transcription factor reveals a functional link between the RNA polymerase II CTD and TFIID[J].Cell,1992,69(5):883-894.
[108] RANISH J A,YUDKOVSKY N,HAHN S.Intermediates in formation and activity of the RNA polymerase II preinitiation complex:holoenzyme recruitment and a postrecruitment role for the TATA box and TFIIB[J].Genes Dev,1999,13(1):49-63.
[109] EYCHENNE T,NOVIKOVA E,BARRAULT M B,et al.Functional interplay between Mediator and TFIIB in preinitiation complex assembly in relation to promoter architecture[J].Genes Dev,2016,30(18):2119-2132.
[110] AKOULITCHEV S,CHUIKOV S,REINBERG D.TFIIH is negatively regulated by cdk8-containing mediator complexes[J].Nature,2000,407(6800):102-106.
[111] JANG M K,MOCHIZUKI K,ZHOU M,et al.The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription[J].Molecular cell,2005,19(4):523-534.
[112] YANG Z,YIK J H N,CHEN R,et al. Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4[J].Molecular cell,2005,19(4):535-545.
[113] DONNER A J,EBMEIER C C,TAATJES D J,et al.CDK8 is a positive regulator of transcriptional elongation within the serum response network[J].Nat Struct Mol Biol,2010,17(2):194-201.
[114] GUGLIELMI B,SOUTOURINA J,ESNAULT C,et al.TFIIS elongation factor and Mediator act in conjunction during transcription initiation in vivo[J].Proc Natl Acad Sci USA,2007, 104(41):16062-16067.
[115] BENTLEY D L.Coupling mRNA processing with transcription in time and space[J].Nat Rev Genet,2014,15(3):163-175.
[116] BEN-YISHAY R,ASHKENAZY A J,SHAV-TAL Y.Dynamic encounters of genes and transcripts with the nuclear pore[J].Trends genet,2016,32(7):419-431.
[117] SCHNEIDER M,HELLERSCHMIED D,SCHUBERT T,et al.The nuclear pore-associated TREX-2 complex employs mediator to regulate gene expression[J].Cell,2015,162(5):1016-1028.
[118] SOUTOURINA J.Transcription regulation by the Mediator complex[J].Nature reviews molecular cell biology,2017,19(4):262-274.
[119] 汪炜,尹景雯,刘艾洁,等.中介体复合物——真核转录调控中的中央控制器[J].中国细胞生物学学报,2011(6):597-607.
[120] KLUMPER N,SYRING I,OFFERMANN A,et al.Differential expression of Mediator complex subunit MED15 in testicular germ cell tumors[J].Diagn Pathol,2015,10:165.
[121] siRNA-mediated silencing of CDK8 inhibits proliferation and growth in breast cancer cells[Retraction][J].Int J Clin Exp Pathol,2018,11(3):1836.