The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation

Roeder, R. G. Transcriptional regulation and the role of diverse coactivators in animal cells. FEBS Lett. 579, 909–915 (2005).

Kornberg, R. D. Mediator and the mechanism of transcriptional activation. Trends Biochem. Sci. 30, 235–239 (2005).

Malik, S. & Roeder, R. G. Dynamic regulation of Pol II transcription by the mammalian Mediator complex. Trends Biochem. Sci. 30, 256–263 (2005).

Malik, S. & Roeder, R. G. Transcriptional regulation through Mediator-like coactivators in yeast and metazoan cells. Trends Biochem. Sci. 25, 277–283 (2000).

Lee, T. I. & Young, R. A. Transcription of eukaryotic protein-coding genes. Annu. Rev. Genet. 34, 77–137 (2000).

Myers, L. C. & Kornberg, R. D. Mediator of transcriptional regulation. Annu. Rev. Biochem. 69, 729–749 (2000). References 5 and 6 review seminal studies in yeast that identified the Mediator complex in this organism.

Bourbon, H. M. Comparative genomics supports a deep evolutionary origin for the large, four-module transcriptional mediator complex. Nucleic Acids Res. 36, 3993–4008 (2008).

Sato, S. et al. A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology. Mol. Cell 14, 685–691 (2004). This paper helped to resolve the problem of compositional heterogeneity that accompanied early studies reporting Mediator isolation. It also helped establish the near-final subunit composition of the mammalian Mediator complex.

Backstrom, S., Elfving, N., Nilsson, R., Wingsle, G. & Bjorklund, S. Purification of a plant mediator from Arabidopsis thaliana identifies PFT1 as the Med25 subunit. Mol. Cell 26, 717–729 (2007).

Guglielmi, B. et al. A high resolution protein interaction map of the yeast Mediator complex. Nucleic Acids Res. 32, 5379–5391 (2004).

Cai, G., Imasaki, T., Takagi, Y. & Asturias, F. J. Mediator structural conservation and implications for the regulation mechanism. Structure 17, 559–567 (2009).

Takagi, Y. et al. Head module control of Mediator interactions. Mol. Cell 23, 355–364 (2006).

Fondell, J. D., Ge, H. & Roeder, R. G. Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. Proc. Natl Acad. Sci. USA 93, 8329–8333 (1996). This paper first identified the human Mediator complex in association with ligand-bound thyroid hormone receptor and helped establish the paradigm of the Mediator as an interface between transcriptional activators and the Pol II machinery.

Malik, S., Gu, W., Wu, W., Qin, J. & Roeder, R. G. The USA-derived transcriptional coactivator PC2 is a submodule of TRAP/SMCC and acts synergistically with other PCs. Mol. Cell 5, 753–760 (2000).

Malik, S., Baek, H. J., Wu, W. & Roeder, R. G. Structural and functional characterization of PC2 and RNA polymerase II-associated subpopulations of metazoan Mediator. Mol. Cell. Biol. 25, 2117–2129 (2005).

Elmlund, H. et al. The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II. Proc. Natl Acad. Sci. USA 103, 15788–15793 (2006).

Knuesel, M. T., Meyer, K. D., Bernecky, C. & Taatjes, D. J. The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function. Genes Dev. 23, 439–451 (2009).

Tsutsui, T. et al. Human mediator kinase subunit CDK11 plays a negative role in viral activator VP16-dependent transcriptional regulation. Genes Cells 13, 817–826 (2008).

Zhang, X. et al. MED1/TRAP220 exists predominantly in a TRAP/ Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription. Mol. Cell 19, 89–100 (2005).

Jiang, P. et al. Key roles for MED1 LxxLL motifs in pubertal mammary gland development and luminal-cell differentiation. Proc. Natl Acad. Sci. USA 107, 6765–6770 (2010).

Toth-Petroczy, A. et al. Malleable machines in transcription regulation: the Mediator complex. PLoS Comput. Biol. 4, e1000243 (2008).

Ryu, S., Zhou, S., Ladurner, A. G. & Tjian, R. The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1. Nature 397, 446–450 (1999).

Blazek, E., Mittler, G. & Meisterernst, M. The Mediator of RNA polymerase II. Chromosoma 113, 399–408 (2005).

Mangelsdorf, D. J. et al. The nuclear receptor superfamily: the second decade. Cell 83, 835–839 (1995).

Glass, C. K. & Rosenfeld, M. G. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev. 14, 121–141 (2000).

Rachez, C. et al. Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature 398, 824–828 (1999).

Ge, K. et al. Transcription coactivator TRAP220 is required for PPAR γ 2-stimulated adipogenesis. Nature 417, 563–567 (2002). This physiological study showed how distinct subunits in the Mediator complex can control specific developmental and signalling pathways.

Ge, K. et al. Alternative mechanisms by which Mediator subunit MED1/TRAP220 regulates peroxisome proliferator-activated receptor γ-stimulated adipogenesis and target gene expression. Mol. Cell. Biol. 28, 1081–1091 (2008).

Malik, S., Wallberg, A. E., Kang, Y. K. & Roeder, R. G. 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).

Hittelman, A. B., Burakov, D., Iniguez-Lluhi, J. A., Freedman, L. P. & Garabedian, M. J. Differential regulation of glucocorticoid receptor transcriptional activation via AF-1-associated proteins. EMBO J. 18, 5380–5388 (1999).

Kang, Y. K., Guermah, M., Yuan, C. X. & Roeder, R. G. The TRAP/Mediator coactivator complex interacts directly with estrogen receptors α and β through the TRAP220 subunit and directly enhances estrogen receptor function in vitro. Proc. Natl Acad. Sci. USA 99, 2642–2647 (2002).

Malik, S. et al. Structural and functional organization of TRAP220, the TRAP/Mediator subunit that is targeted by nuclear receptors. Mol. Cell. Biol. 24, 8244–8254 (2004).

Ito, M., Yuan, C. X., Okano, H. J., Darnell, R. B. & Roeder, R. G. Involvement of the TRAP220 component of the TRAP/SMCC coactivator complex in embryonic development and thyroid hormone action. Mol. Cell 5, 683–693 (2000). This mouse knockout study showed how distinct subunits in the Mediator complex can control specific developmental and signalling pathways.

Grontved, L., Madsen, M. S., Boergesen, M., Roeder, R. G. & Mandrup, S. MED14 tethers Mediator to the N-terminal domain of peroxisome proliferator-activated receptor γ and is required for full transcriptional activity and adipogenesis. Mol. Cell. Biol. 30, 2155–2169 (2010).

Stumpf, M. et al. The Mediator complex functions as a coactivator for GATA-1 in erythropoiesis via subunit Med1/TRAP220. Proc. Natl Acad. Sci. USA 103, 18504–18509 (2006).

Boyer, T. G., Martin, M. E., Lees, E., Ricciardi, R. P. & Berk, A. J. Mammalian Srb/Mediator complex is targeted by adenovirus E1A protein. Nature 399, 276–279 (1999).

Wang, G. et al. Mediator requirement for both recruitment and postrecruitment steps in transcription initiation. Mol. Cell 17, 683–694 (2005).

Wang, W. et al. Mediator MED23 links insulin signaling to the adipogenesis transcription cascade. Dev. Cell 16, 764–771 (2009).

Yang, F. et al. An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Nature 442, 700–704 (2006).

Taubert, S., Van Gilst, M. R., Hansen, M. & Yamamoto, K. R. A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways in C. elegans. Genes Dev. 20, 1137–1149 (2006).

Thakur, J. K. et al. Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription factor Oaf1p. J. Biol. Chem. 284, 4422–4428 (2009).

Kato, Y., Habas, R., Katsuyama, Y., Naar, A. M. & He, X. A component of the ARC/Mediator complex required for TGF β/Nodal signalling. Nature 418, 641–646 (2002).

Ito, M., Okano, H. J., Darnell, R. B. & Roeder, R. G. The TRAP100 component of the TRAP/Mediator complex is essential in broad transcriptional events and development. EMBO J. 21, 3464–3475 (2002).

Stevens, J. L., Cantin, G. T., Wang, G., Shevchenko, A. & Berk, A. J. Transcription control by E1A and MAP kinase pathway via Sur2 Mediator subunit. Science 296, 755–758 (2002). This knockout study showed how distinct subunits in the Mediator complex can control specific developmental and signalling pathways.

Carlson, M. Genetics of transcriptional regulation in yeast: connections to the RNA polymerase II CTD. Annu. Rev. Cell Dev. Biol. 13, 1–23 (1997).

Ito, M. et al. Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators. Mol. Cell 3, 361–370 (1999).

Park, J. M., Werner, J., Kim, J. M., Lis, J. T. & Kim, Y. J. Mediator, not holoenzyme, is directly recruited to the heat shock promoter by HSF upon heat shock. Mol. Cell 8, 9–19 (2001).

Meyer, K. D., Lin, S. C., Bernecky, C., Gao, Y. & Taatjes, D. J. p53 activates transcription by directing structural shifts in Mediator. Nature Struct. Mol. Biol. 17, 753–760 (2010).

Mittler, G. et al. A novel docking site on Mediator is critical for activation by VP16 in mammalian cells. EMBO J. 22, 6494–6504 (2003).

Yang, F., DeBeaumont, R., Zhou, S. & Naar, A. M. The activator-recruited cofactor/Mediator coactivator subunit ARC92 is a functionally important target of the VP16 transcriptional activator. Proc. Natl Acad. Sci. USA 101, 2339–2344 (2004).

Kim, T. W. et al. MED16 and MED23 of Mediator are coactivators of lipopolysaccharide- and heat-shock-induced transcriptional activators. Proc. Natl Acad. Sci. USA 101, 12153–12158 (2004).

Belakavadi, M., Pandey, P. K., Vijayvargia, R. & Fondell, J. D. MED1 phosphorylation promotes its association with mediator: implications for nuclear receptor signaling. Mol. Cell. Biol. 28, 3932–3942 (2008).

Lehner, B., Crombie, C., Tischler, J., Fortunato, A. & Fraser, A. G. Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways. Nature Genet. 38, 896–903 (2006).

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

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

Wang, X., Yang, N., Uno, E., Roeder, R. G. & Guo, S. A subunit of the mediator complex regulates vertebrate neuronal development. Proc. Natl Acad. Sci. USA 103, 17284–17289 (2006).

Ding, N. et al. Mediator links epigenetic silencing of neuronal gene expression with x-linked mental retardation. Mol. Cell 31, 347–359 (2008). This study extended the repressive functions of the kinase module of the Mediator to a role in establishing an epigenetically silenced state in differentiated neurons. It also provided insights into how defects in Mediator function can lead to human disease.

Loncle, N. et al. Distinct roles for Mediator Cdk8 module subunits in Drosophila development. EMBO J. 26, 1045–1054 (2007).

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

Belakavadi, M. & Fondell, J. D. Cyclin-dependent kinase 8 positively cooperates with Mediator to promote thyroid hormone receptor-dependent transcriptional activation. Mol. Cell. Biol. 30, 2437–2448 (2010).

Taatjes, D. J., Naar, A. M., Andel, F., Nogales, E. & Tjian, R. Structure, function, and activator-induced conformations of the CRSP coactivator. Science 295, 1058–1062 (2002).

Benoff, B. et al. Structural basis of transcription activation: the CAP-α CTD–DNA complex. Science 297, 1562–1566 (2002).

Taatjes, D. J., Schneider-Poetsch, T. & Tjian, R. Distinct conformational states of nuclear receptor-bound CRSP–Med complexes. Nature Struct. Mol. Biol. 11, 664–671 (2004).

Baek, H. J., Kang, Y. K. & Roeder, R. G. Human Mediator enhances basal transcription by facilitating recruitment of transcription factor IIB during preinitiation complex assembly. J. Biol. Chem. 281, 15172–15181 (2006).

Pavri, R. et al. PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of Mediator. Mol. Cell 18, 83–96 (2005).

Esnault, C. et al. Mediator-dependent recruitment of TFIIH modules in preinitiation complex. Mol. Cell 31, 337–346 (2008).

Kim, Y. J., Bjorklund, S., Li, Y., Sayre, M. H. & Kornberg, R. D. A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II. Cell 77, 599–608 (1994).

Akoulitchev, S., Chuikov, S. & Reinberg, D. TFIIH is negatively regulated by cdk8-containing Mediator complexes. Nature 407, 102–106 (2000).

Hengartner, C. J. et al. Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases. Mol. Cell 2, 43–53 (1998).

Furumoto, T. et al. A kinase subunit of the human Mediator complex, CDK8, positively regulates transcriptional activation. Genes Cells 12, 119–132 (2007).

Donner, A. J., Szostek, S., Hoover, J. M. & Espinosa, J. M. CDK8 is a stimulus-specific positive coregulator of p53 target genes. Mol. Cell 27, 121–133 (2007).

Li, B., Carey, M. & Workman, J. L. The role of chromatin during transcription. Cell 128, 707–719 (2007).

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

Black, J. C., Choi, J. E., Lombardo, S. R. & Carey, M. A mechanism for coordinating chromatin modification and preinitiation complex assembly. Mol. Cell 23, 809–818 (2006). This paper exemplifies biochemical studies that have revealed how Mediator can work with chromatin co-activators.

Fondell, J. D., Guermah, M., Malik, S. & Roeder, R. G. Thyroid hormone receptor-associated proteins and general positive cofactors mediate thyroid hormone receptor function in the absence of the TATA box-binding protein-associated factors of TFIID. Proc. Natl Acad. Sci. USA 96, 1959–1964 (1999).

Sharma, D. & Fondell, J. D. Ordered recruitment of histone acetyltransferases and the TRAP/Mediator complex to thyroid hormone-responsive promoters in vivo. Proc. Natl Acad. Sci. USA 99, 7934–7939 (2002).

Wallberg, A. E., Yamamura, S., Malik, S., Spiegelman, B. M. & Roeder, R. G. Coordination of p300-mediated chromatin remodeling and TRAP/Mediator function through coactivator PGC-1α. Mol. Cell 12, 1137–1149 (2003).

Chen, W., Yang, Q. & Roeder, R. G. Dynamic interactions and cooperative functions of PGC-1α and MED1 in TRα-mediated activation of the brown-fat-specific UCP-1 gene. Mol. Cell 35, 755–768 (2009).

Rodriguez-Navarro, S. Insights into SAGA function during gene expression. EMBO Rep. 10, 843–850 (2009).

Qiu, H. et al. Interdependent recruitment of SAGA and Srb mediator by transcriptional activator Gcn4p. Mol. Cell. Biol. 25, 3461–3474 (2005).

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

Meyer, K. D. et al. Cooperative activity of cdk8 and GCN5L within Mediator directs tandem phosphoacetylation of histone H3. EMBO J. 27, 1447–1457 (2008).

Krebs, A. R. et al. ATAC and Mediator coactivators form a stable complex and regulate a set of non-coding RNA genes. EMBO Rep. 11, 541–547 (2010).

Kouzarides, T. Chromatin modifications and their function. Cell 128, 693–705 (2007).

Ooi, L. & Wood, I. C. Chromatin crosstalk in development and disease: lessons from REST. Nature Rev. Genet. 8, 544–554 (2007).

Kuchin, S. & Carlson, M. Functional relationships of Srb10-Srb11 kinase, carboxy-terminal domain kinase CTDK-I, and transcriptional corepressor Ssn6-Tup1. Mol. Cell. Biol. 18, 1163–1171 (1998).

Bernstein, B. E. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315–326 (2006).

Tutter, A. V. et al. Role for Med12 in regulation of Nanog and Nanog target genes. J. Biol. Chem. 284, 3709–3718 (2009).

Boyer, L. A. et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122, 947–956 (2005).

Venters, B. J. & Pugh, B. F. A canonical promoter organization of the transcription machinery and its regulators in the Saccharomyces genome. Genome Res. 19, 360–371 (2009).

Saunders, A., Core, L. J. & Lis, J. T. Breaking barriers to transcription elongation. Nature Rev. Mol. Cell Biol. 7, 557–567 (2006).

Guenther, M. G., Levine, S. S., Boyer, L. A., Jaenisch, R. & Young, R. A. A chromatin landmark and transcription initiation at most promoters in human cells. Cell 130, 77–88 (2007).

Margaritis, T. & Holstege, F. C. Poised RNA polymerase II gives pause for thought. Cell 133, 581–584 (2008).

Malik, S., Barrero, M. J. & Jones, T. Identification of a regulator of transcription elongation as an accessory factor for the human Mediator coactivator. Proc. Natl Acad. Sci. USA 104, 6182–6187 (2007).

Yang, Z. et al. Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Mol. Cell 19, 535–545 (2005).

Malagon, F., Tong, A. H., Shafer, B. K. & Strathern, J. N. Genetic interactions of DST1 in Saccharomyces cerevisiae suggest a role of TFIIS in the initiation–elongation transition. Genetics 166, 1215–1227 (2004).

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. USA 104, 16062–16067 (2007).

Palangat, M., Renner, D. B., Price, D. H. & Landick, R. A negative elongation factor for human RNA polymerase II inhibits the anti-arrest transcript-cleavage factor TFIIS. Proc. Natl Acad. Sci. USA 102, 15036–15041 (2005).

Krogan, N. J. et al. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Mol. Cell. Biol. 23, 4207–4218 (2003).

Yudkovsky, N., Ranish, J. A. & Hahn, S. A transcription reinitiation intermediate that is stabilized by activator. Nature 408, 225–229 (2000).

Kuras, L., Borggrefe, T. & Kornberg, R. D. Association of the Mediator complex with enhancers of active genes. Proc. Natl Acad. Sci. USA 100, 13887–13891 (2003).

Park, S. W. et al. Thyroid hormone-induced juxtaposition of regulatory elements/factors and chromatin remodeling of Crabp1 dependent on MED1/TRAP220. Mol. Cell 19, 643–653 (2005).

Kagey, M. H. et al. Mediator and cohesin connect gene expression and chromatin architecture. Nature 18 Aug 2010 (doi:10.1038/nature09380). This recent study extends the role of the Mediator to enhancer–promoter communication, which is emerging as an important aspect of transcriptional control.

Hatzis, P. & Talianidis, I. Dynamics of enhancer–promoter communication during differentiation-induced gene activation. Mol. Cell 10, 1467–1477 (2002).

Szutorisz, H., Dillon, N. & Tora, L. The role of enhancers as centres for general transcription factor recruitment. Trends Biochem. Sci. 30, 593–599 (2005).

Butler, J. E. & Kadonaga, J. T. The RNA polymerase II core promoter: a key component in the regulation of gene expression. Genes Dev. 16, 2583–2592 (2002).

Muncke, N. et al. 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).

Philibert, R. A. & Madan, A. Role of MED12 in transcription and human behavior. Pharmacogenomics 8, 909–916 (2007).

Firestein, R. et al. CDK8 is a colorectal cancer oncogene that regulates β-catenin activity. Nature 455, 547–551 (2008).

Morris, E. J. et al. E2F1 represses β-catenin transcription and is antagonized by both pRB and CDK8. Nature 455, 552–556 (2008).

Zhu, Y. et al. Amplification and overexpression of peroxisome proliferator-activated receptor binding protein (PBP/PPARBP) gene in breast cancer. Proc. Natl Acad. Sci. USA 96, 10848–10853 (1999).

Nonet, M. L. & Young, R. A. Intragenic and extragenic suppressors of mutations in the heptapeptide repeat domain of Saccharomyces cerevisiae RNA polymerase II. Genetics 123, 715–724 (1989).

Gu, W. et al. A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation. Mol. Cell 3, 97–108 (1999).

Holstege, F. C. et al. Dissecting the regulatory circuitry of a eukaryotic genome. Cell 95, 717–728 (1998).

Andrau, J. C. et al. Genome-wide location of the coactivator Mediator: binding without activation and transient Cdk8 interaction on DNA. Mol. Cell 22, 179–192 (2006).

Zhu, X. et al. Genome-wide occupancy profile of Mediator and the Srb8–11 module reveals interactions with coding regions. Mol. Cell 22, 169–178 (2006).

Fan, X., Chou, D. M. & Struhl, K. Activator-specific recruitment of Mediator in vivo. Nature Struct. Mol. Biol. 13, 117–120 (2006).

Ansari, S. A., He, Q. & Morse, R. H. Mediator complex association with constitutively transcribed genes in yeast. Proc. Natl Acad. Sci. USA 106, 16734–16739 (2009).

Mittler, G., Kremmer, E., Timmers, H. T. & Meisterernst, M. Novel critical role of a human Mediator complex for basal RNA polymerase II transcription. EMBO Rep. 2, 808–813 (2001).

Baek, H. J., Malik, S., Qin, J. & Roeder, R. G. Requirement of TRAP/Mediator for both activator-independent and activator-dependent transcription in conjunction with TFIID-associated TAFIIs. Mol. Cell. Biol. 22, 2842–2852 (2002).

Takagi, Y. & Kornberg, R. D. Mediator as a general transcription factor. J. Biol. Chem. 281, 80–89 (2006).

Hu, X. et al. A Mediator-responsive form of metazoan RNA polymerase II. Proc. Natl Acad. Sci. USA 103, 9506–9511 (2006).

Gazdag, E. et al. TBP2 is essential for germ cell development by regulating transcription and chromatin condensation in the oocyte. Genes Dev. 23, 2210–2223 (2009).

Deato, M. D. et al. MyoD targets TAF3/TRF3 to activate myogenin transcription. Mol. Cell 32, 96–105 (2008).

Baumli, S., Hoeppner, S. & Cramer, P. A conserved Mediator hinge revealed in the structure of the MED7.MED21 (Med7.Srb7) heterodimer. J. Biol. Chem. 280, 18171–18178 (2005).

Lariviere, L. et al. Structure and TBP binding of the Mediator head subcomplex Med8–Med18–Med20. Nature Struct. Mol. Biol. 13, 895–901 (2006).

Bourbon, H. M. et al. A unified nomenclature for protein subunits of ediator complexes linking transcriptional regulators to RNA polymerase II. Mol. Cell 14, 553–557 (2004).