title: Structure-system correlation identifies a gene regulatory Mediator submodule.
abstract: A combination of crystallography, biochemistry, and gene expression analysis identifies the coactivator subcomplex Med8C/18/20 as a functionally distinct submodule of the Mediator head module. Med8C forms a conserved alpha-helix that tethers Med18/20 to the Mediator. Deletion of Med8C in vivo results in dissociation of Med18/20 from Mediator and in loss of transcription activity of extracts. Deletion of med8C, med18, or med20 causes similar changes in the yeast transcriptome, establishing Med8C/18/20 as a predominantly positive, gene-specific submodule required for low transcription levels of nonactivated genes, including conjugation genes. The presented structure-based system perturbation is superior to gene deletion analysis of gene regulation.
authors.affiliation: Gene Center Munich and Center for Integrated Protein Science CIPSM, Department of Chemistry and Biochemistry, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.
authors.forename: Laurent
authors.initials: L
authors.lastname: Larivière
authors.forename: Martin
authors.initials: M
authors.lastname: Seizl
authors.forename: Sake
authors.initials: S
authors.lastname: van Wageningen
authors.forename: Susanne
authors.initials: S
authors.lastname: Röther
authors.forename: Loes
authors.initials: L
authors.lastname: van de Pasch
authors.forename: Heidi
authors.initials: H
authors.lastname: Feldmann
authors.forename: Katja
authors.initials: K
authors.lastname: Strässer
authors.forename: Steve
authors.initials: S
authors.lastname: Hahn
authors.forename: Frank C P
authors.initials: FC
authors.lastname: Holstege
authors.forename: Patrick
authors.initials: P
authors.lastname: Cramer
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D013058:Mass Spectrometry; D056892:Mediator Complex; D008954:Models, Biological; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C421882:MED8 protein, S cerevisiae; D056892:Mediator Complex; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors