Mapping pathways and phenotypes by systematic gene overexpression

Richelle Sopko, Dongqing Huang, Nicolle Preston, Gordon Chua, Balázs Papp, Kimberly Kafadar, Mike Snyder, Stephen G. Oliver, Martha Cyert, Timothy R. Hughes, Charles Boone, Brenda Andrews

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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 (pho85Δ). 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. ©2006 Elsevier Inc.
    Original languageEnglish
    Pages (from-to)319-330
    Number of pages11
    JournalMolecular Cell
    Volume21
    Issue number3
    DOIs
    Publication statusPublished - 3 Feb 2006

    Research Beacons, Institutes and Platforms

    • Manchester Institute of Biotechnology

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