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Mapping pathways and phenotypes by systematic gene overexpression.

Molecular cell | Feb 3, 2006

http://www.ncbi.nlm.nih.gov/pubmed/16455487

Many disease states result from gene overexpression, often in a specific genetic context. To explore gene overexpression phenotypes systematically, we assembled an array of 5280 yeast strains, each containing an inducible copy of an S. cerevisiae gene, covering >80% of the genome. Approximately 15% of the overexpressed genes (769) reduced growth rate. This gene set was enriched for cell cycle-regulated genes, signaling molecules, and transcription factors. Overexpression of most toxic genes resulted in phenotypes different from known deletion mutant phenotypes, suggesting that overexpression phenotypes usually reflect a specific regulatory imbalance rather than disruption of protein complex stoichiometry. Global overexpression effects were also assayed in the context of a cyclin-dependent kinase mutant (pho85Delta). The resultant gene set was enriched for Pho85p targets and identified the yeast calcineurin-responsive transcription factor Crz1p as a substrate. Large-scale application of this approach should provide a strategy for identifying target molecules regulated by specific signaling pathways.

Pubmed ID: 16455487 RIS Download

Mesh terms: Gene Expression Profiling | Gene Expression Regulation, Fungal | Genes, Fungal | Oligonucleotide Array Sequence Analysis | Phenotype | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins | Signal Transduction

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Associated grants

  • Agency: Biotechnology and Biological Sciences Research Council, Id: BB/C505140/1

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