Interactions between subunits of Drosophila Mediator and activator proteins.

Mediator was first identified because of its activity in activator-stimulated transcription in vivo and in vitro. Later, biochemical fractionation led to the co-purification of the multi-subunit Mediator complex and RNA polymerase II (pol II). Results of these studies suggested a model whereby transcription-activator proteins, which bind to specific gene regulatory sequences, recruit both Mediator and pol II as a holoenzyme in a one-step mechanism. More recent studies of Drosophila Mediator and additional studies in yeast have demonstrated that different transcription activators can bind and recruit Mediator to promoters in vivo in a step that is independent of pol II recruitment. Moreover, the different activators in Drosophila bind and recruit Mediator via physical interactions with specific subsets of proteins. These features of Mediator function seem to be broadly conserved.

[1]  R. Young,et al.  Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases. , 1998, Molecular cell.

[2]  J. Treisman,et al.  Two subunits of the Drosophila mediator complex act together to control cell affinity , 2003, Development.

[3]  Roger D. Kornberg,et al.  Association of the Mediator complex with enhancers of active genes , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[4]  R. Kornberg,et al.  Mammalian mediator of transcriptional regulation and its possible role as an end-point of signal transduction pathways. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[5]  R. Darnell,et al.  Involvement of the TRAP220 component of the TRAP/SMCC coactivator complex in embryonic development and thyroid hormone action. , 2000, Molecular cell.

[6]  Yang Li,et al.  A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II , 1994, Cell.

[7]  M. Carlson,et al.  Cyclin-dependent protein kinase and cyclin homologs SSN3 and SSN8 contribute to transcriptional control in yeast. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[8]  David M. Chao,et al.  A multisubunit complex associated with the RNA polymerase II CTD and TATA-binding protein in yeast , 1993, Cell.

[9]  J. Lis,et al.  Mediator, not holoenzyme, is directly recruited to the heat shock promoter by HSF upon heat shock. , 2001, Molecular cell.

[10]  William Arbuthnot Sir Lane,et al.  Activator-Specific Requirement of Yeast Mediator Proteins for RNA Polymerase II Transcriptional Activation , 1999, Molecular and Cellular Biology.

[11]  E. Lees,et al.  Mammalian Srb/Mediator complex is targeted by adenovirus E1A protein , 1999, Nature.

[12]  K Nasmyth,et al.  Cdk1 triggers association of RNA polymerase to cell cycle promoters only after recruitment of the mediator by SBF. , 2001, Molecular cell.

[13]  A. Burlingame,et al.  Two distinct coactivators, DRIP/mediator and SRC/p160, are differentially involved in vitamin D receptor transactivation during keratinocyte differentiation. , 2003, Molecular endocrinology.

[14]  A. Shevchenko,et al.  Transcription Control by E1A and MAP Kinase Pathway via Sur2 Mediator Subunit , 2002, Science.

[15]  Min Han,et al.  sur-2, a novel gene, functions late in the let-60 ras-mediated signaling pathway during Caenorhabditis elegans vulval induction. , 1995, Genes & development.

[16]  M. Carlson,et al.  SSN genes that affect transcriptional repression in Saccharomyces cerevisiae encode SIN4, ROX3, and SRB proteins associated with RNA polymerase II , 1996, Molecular and cellular biology.

[17]  Ju-Gyeong Kang,et al.  Drosophila Mediator Complex Is Broadly Utilized by Diverse Gene-Specific Transcription Factors at Different Types of Core Promoters , 2001, Molecular and Cellular Biology.

[18]  D. Stillman,et al.  Yeast global transcriptional regulators Sin4 and Rgr1 are components of mediator complex/RNA polymerase II holoenzyme. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Treisman.  Drosophila homologues of the transcriptional coactivation complex subunits TRAP240 and TRAP230 are required for identical processes in eye-antennal disc development. , 2001, Development.

[20]  C. Horvath,et al.  Role of Metazoan Mediator Proteins in Interferon-Responsive Transcription , 2003, Molecular and Cellular Biology.

[21]  K. Yamamoto,et al.  The Caenorhabditis elegans Ortholog of TRAP240, CeTRAP240/let-19, Selectively Modulates Gene Expression and Is Essential for Embryogenesis* , 2004, Journal of Biological Chemistry.

[22]  J. Qin,et al.  Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators. , 1999, Molecular cell.

[23]  Y. Suzuki,et al.  GAL11 protein, an auxiliary transcription activator for genes encoding galactose-metabolizing enzymes in Saccharomyces cerevisiae , 1988, Molecular and cellular biology.

[24]  Paul Tempst,et al.  Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex , 1999, Nature.

[25]  J. Qin,et al.  A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation. , 1999, Molecular cell.

[26]  M. Boube,et al.  Drosophila homologs of transcriptional mediator complex subunits are required for adult cell and segment identity specification. , 2000, Genes & development.

[27]  Michael R Green,et al.  In vivo target of a transcriptional activator revealed by fluorescence resonance energy transfer. , 2004, Genes & development.

[28]  M. Sundaram,et al.  C. elegans EOR-1/PLZF and EOR-2 positively regulate Ras and Wnt signaling and function redundantly with LIN-25 and the SUR-2 Mediator component. , 2002, Genes & development.

[29]  A. Burlingame,et al.  Two distinct coactivators, DRIP/mediator and SRC/p160, are differentially involved in VDR transactivation during keratinocyte differentiation , 2004, The Journal of Steroid Biochemistry and Molecular Biology.

[30]  Robert Tjian,et al.  The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1 , 1999, Nature.

[31]  Roger D. Kornberg,et al.  A novel mediator between activator proteins and the RNA polymerase II transcription apparatus , 1990, Cell.

[32]  B. Spiegelman,et al.  Transcription coactivator TRAP220 is required for PPARγ2-stimulated adipogenesis , 2002, Nature.

[33]  R. Young,et al.  RNA Polymerase II Holoenzyme Contains SWI/SNF Regulators Involved in Chromatin Remodeling , 1996, Cell.

[34]  P. Sternberg,et al.  A component of the transcriptional mediator complex inhibits RAS-dependent vulval fate specification in C. elegans , 2003, Development.

[35]  Steven Hahn,et al.  A transcription reinitiation intermediate that is stabilized by activator , 2000, Nature.

[36]  R. Tjian,et al.  Composite co-activator ARC mediates chromatin-directed transcriptional activation , 1999, Nature.

[37]  Roger D. Kornberg,et al.  A mediator required for activation of RNA polymerase II transcription in vitro , 1991, Nature.

[38]  S. Han,et al.  An Activator Binding Module of Yeast RNA Polymerase II Holoenzyme , 1999, Molecular and Cellular Biology.

[39]  J. Lis,et al.  Promoter-associated pausing in promoter architecture and postinitiation transcriptional regulation. , 1998, Cold Spring Harbor symposia on quantitative biology.

[40]  Young-Joon Kim,et al.  Drosophila Med6 Is Required for Elevated Expression of a Large but Distinct Set of Developmentally Regulated Genes , 2001, Molecular and Cellular Biology.

[41]  T. Chibazakura,et al.  Structure and molecular analysis of RGR1, a gene required for glucose repression of Saccharomyces cerevisiae , 1990, Molecular and cellular biology.

[42]  Young-Joon Kim,et al.  MED16 and MED23 of Mediator are coactivators of lipopolysaccharide- and heat-shock-induced transcriptional activators. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[43]  M. Meisterernst,et al.  The Mediator of RNA polymerase II , 2005, Chromosoma.

[44]  Involvement of the SIN4 global transcriptional regulator in the chromatin structure of Saccharomyces cerevisiae. , 1992, Molecular and cellular biology.

[45]  Young Chul Lee,et al.  Requirement for a Functional Interaction between Mediator Components Med6 and Srb4 in RNA Polymerase II Transcription , 1998, Molecular and Cellular Biology.

[46]  D. Reinberg,et al.  NAT, a human complex containing Srb polypeptides that functions as a negative regulator of activated transcription. , 1998, Molecular cell.

[47]  Francisco J Asturias,et al.  RNA polymerase II structure, and organization of the preinitiation complex. , 2004, Current opinion in structural biology.

[48]  Young-Joon Kim,et al.  Novel Mediator Proteins of the Small Mediator Complex inDrosophila SL2 Cells , 2002, The Journal of Biological Chemistry.

[49]  R. Darnell,et al.  The TRAP100 component of the TRAP/Mediator complex is essential in broad transcriptional events and development , 2002, The EMBO journal.

[50]  R. Young,et al.  Intragenic and extragenic suppressors of mutations in the heptapeptide repeat domain of Saccharomyces cerevisiae RNA polymerase II. , 1989, Genetics.

[51]  S. W. Emmons,et al.  A C. elegans mediator protein confers regulatory selectivity on lineage-specific expression of a transcription factor gene. , 2000, Genes & development.

[52]  C. Thompson,et al.  Association of an activator with an RNA polymerase II holoenzyme. , 1995, Genes & development.

[53]  R. Kornberg,et al.  Identification of Rox3 as a Component of Mediator and RNA Polymerase II Holoenzyme* , 1997, The Journal of Biological Chemistry.

[54]  Young-Joon Kim,et al.  Signal-Induced Transcriptional Activation by Dif Requires the dTRAP80 Mediator Module , 2003, Molecular and Cellular Biology.

[55]  R. Young,et al.  A kinase–cyclin pair in the RNA polymerase II holoenzyme , 1995, Nature.

[56]  R. Kornberg,et al.  Conserved structures of mediator and RNA polymerase II holoenzyme. , 1999, Science.

[57]  M. Boube,et al.  Evidence for a Mediator of RNA Polymerase II Transcriptional Regulation Conserved from Yeast to Man , 2002, Cell.

[58]  S. Han,et al.  Caenorhabditis elegans mediator complexes are required for developmental-specific transcriptional activation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.