Structure-system correlation identifies a gene regulatory Mediator submodule.

Gene Center Munich and Center for Integrated Protein Science CIPSM, Department of Chemistry and Biochemistry, Ludwig-Maximilians-Universitaet Muenchen, 81377 Munich, Germany.
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.
Mesh Terms:
Electrophoresis, Polyacrylamide Gel, Gene Deletion, Gene Expression Profiling, Gene Expression Regulation, Fungal, Mass Spectrometry, Mediator Complex, Models, Biological, Models, Molecular, Protein Structure, Tertiary, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Structure-Activity Relationship, Transcription Factors, Transcription, Genetic
Genes Dev. Apr. 01, 2008; 22(7);872-7 [PUBMED:18381891]
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