Structure-system correlation identifies a gene regulatory Mediator submodule.

Publication Type:

Journal Article

Source:

Genes & development, Volume 22, Issue 7, p.872-7 (2008)

Keywords:

2008, Basic Sciences Division, Center-Authored Paper, Electrophoresis, Polyacrylamide Gel, Gene Deletion, Gene Expression Profiling, Gene Expression Regulation, Fungal, Genomics Core Facility, mass spectrometry, Mediator Complex, Models, Biological, Models, Molecular, Protein Structure, Tertiary, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Scientific Imaging Core Facility, Shared Resources, Structure-Activity Relationship, TRANSCRIPTION FACTORS, Transcription, Genetic

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.