Structure-system correlation identifies a gene regulatory Mediator submodule

• Published in: Genes & development Vol. 22; no. 7; pp. 872 - 877
• Main Authors: Larivière, Laurent, Seizl, Martin, van Wageningen, Sake, Röther, Susanne, van de Pasch, Loes, Feldmann, Heidi, Strässer, Katja, Hahn, Steve, Holstege, Frank C P, Cramer, Patrick
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.04.2008
• Subjects: Electrophoresis, Polyacrylamide Gel; Gene Deletion; Gene Expression Profiling; Gene Expression Regulation, Fungal; Mass Spectrometry; Mediator Complex; Models, Biological; Models, Molecular; Protein Structure, Tertiary; Research Communication; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Structure-Activity Relationship; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.465108

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.