Mediator as a General Transcription Factor*

Others have shown that yeast strains bearing a ts mutation in the Srb4 subunit of Mediator cease transcription of all mRNA at the restrictive temperature, in a manner virtually indistinguishable from a strain bearing a ts mutation in the largest subunit of RNA polymerase II. We find that srb4ts Mediator is defective for the stimulation of basal RNA polymerase II transcription at the restrictive temperature in vitro. Taken together, these findings lead to the suggestion that Mediator is required for basal RNA polymerase II transcription in vivo. On this basis, Mediator is identified as a general transcription factor, comparable in importance to RNA polymerase II and other general factors for the initiation of transcription. The possibility that Mediator serves as an anti-inhibitor, opposing the effects of global negative regulators, is largely excluded.

[1]  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.

[2]  R. Young,et al.  General requirement for RNA polymerase II holoenzymes in vivo. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[3]  M. Carey,et al.  Assembly of a Mediator/TFIID/TFIIA Complex Bypasses the Need for an Activator , 2003, Current Biology.

[4]  John J. Wyrick,et al.  Interplay of Positive and Negative Regulators in Transcription Initiation by RNA Polymerase II Holoenzyme , 1998, Molecular and Cellular Biology.

[5]  A. Hinnebusch,et al.  Interdependent Recruitment of SAGA and Srb Mediator by Transcriptional Activator Gcn4p , 2005, Molecular and Cellular Biology.

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

[7]  R. Roeder,et al.  Activation of class II gene transcription by regulatory factors is potentiated by a novel activity , 1991, Cell.

[8]  M Ptashne,et al.  An activator target in the RNA polymerase II holoenzyme. , 1998, Molecular cell.

[9]  J. Park,et al.  In Vivo Requirement of Activator-Specific Binding Targets of Mediator , 2000, Molecular and Cellular Biology.

[10]  P. Wade,et al.  Transcriptional activation in an improved whole-cell extract from Saccharomyces cerevisiae , 1991, Molecular and cellular biology.

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

[12]  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.

[13]  R. Roeder,et al.  Dynamic regulation of pol II transcription by the mammalian Mediator complex. , 2005, Trends in biochemical sciences.

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

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

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

[17]  J. Qin,et al.  Requirement of TRAP/Mediator for Both Activator-Independent and Activator-Dependent Transcription in Conjunction with TFIID-Associated TAFIIs , 2002, Molecular and Cellular Biology.

[18]  Joan W Conaway,et al.  The mammalian Mediator complex and its role in transcriptional regulation. , 2005, Trends in biochemical sciences.

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

[20]  R. Young,et al.  Functional antagonism between RNA polymerase II holoenzyme and global negative regulator NC2 in vivo. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[21]  M. Meisterernst,et al.  A single point mutation in TFIIA suppresses NC2 requirement in vivo , 2000, The EMBO journal.

[22]  Roger D Kornberg,et al.  Structure of the yeast RNA polymerase II holoenzyme: Mediator conformation and polymerase interaction. , 2002, Molecular cell.

[23]  M. Meisterernst,et al.  Characterization of the basal inhibitor of class II transcription NC2 from Saccharomyces cerevisiae. , 1996, Nucleic acids research.

[24]  Robert Tjian,et al.  Mechanism of transcriptional activation by Sp1: Evidence for coactivators , 1990, Cell.

[25]  E. Kremmer,et al.  Novel critical role of a human Mediator complex for basal RNA polymerase II transcription , 2001, EMBO reports.

[26]  Young-Joon Kim,et al.  Interactions between subunits of Drosophila Mediator and activator proteins. , 2005, Trends in biochemical sciences.

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

[28]  G. Berben,et al.  The YDp plasmids: A uniform set of vectors bearing versatile gene disruption cassettes for Saccharomyces cerevisiae , 1991, Yeast.

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

[30]  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.

[31]  R. Roeder,et al.  Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

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

[33]  Roger D Kornberg,et al.  Mediator and the mechanism of transcriptional activation. , 2005, Trends in biochemical sciences.

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

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

[36]  Francisco J Asturias,et al.  Structure of eukaryotic Mediator complexes. , 2005, Trends in biochemical sciences.

[37]  D. Bushnell,et al.  The Med proteins of yeast and their function through the RNA polymerase II carboxy-terminal domain. , 1998, Genes & development.

[38]  R. Kornberg,et al.  Revised Subunit Structure of Yeast Transcription Factor IIH (TFIIH) and Reconciliation with Human TFIIH* , 2003, Journal of Biological Chemistry.

[39]  A. Antoni,et al.  A novel multi-purpose cassette for repeated integrative epitope tagging of genes in Saccharomyces cerevisiae. , 2000, Gene.

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

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

[42]  J. Svejstrup,et al.  The multiple roles of transcription/repair factor TFIIH. , 1996, Trends in biochemical sciences.

[43]  J. Ranish,et al.  Intermediates in formation and activity of the RNA polymerase II preinitiation complex: holoenzyme recruitment and a postrecruitment role for the TATA box and TFIIB. , 1999, Genes & development.

[44]  B. Séraphin,et al.  A generic protein purification method for protein complex characterization and proteome exploration , 1999, Nature Biotechnology.