Integrated analysis of regulatory and metabolic networks reveals novel regulatory mechanisms in Saccharomyces cerevisiae.

TitleIntegrated analysis of regulatory and metabolic networks reveals novel regulatory mechanisms in Saccharomyces cerevisiae.
Publication TypeJournal Article
Year of Publication2006
AuthorsHerrgard MJ, Lee B-S, Portnoy VA, Palsson BØ
JournalGenome research
Volume16
Issue5
Pagination627-35
PubMed Date2006 May
ISSN1088-9051
KeywordsChromatin Immunoprecipitation, Computer Simulation, Gene Deletion, Gene Expression Profiling, Gene Expression Regulation, Fungal, Genes, Fungal, Genome, Fungal, Models, Genetic, Regulatory Elements, Transcriptional, Saccharomyces cerevisiae, Transcription Factors
Abstract

We describe the use of model-driven analysis of multiple data types relevant to transcriptional regulation of metabolism to discover novel regulatory mechanisms in Saccharomyces cerevisiae. We have reconstructed the nutrient-controlled transcriptional regulatory network controlling metabolism in S. cerevisiae consisting of 55 transcription factors regulating 750 metabolic genes, based on information in the primary literature. This reconstructed regulatory network coupled with an existing genome-scale metabolic network model allows in silico prediction of growth phenotypes of regulatory gene deletions as well as gene expression profiles. We compared model predictions of gene expression changes in response to genetic and environmental perturbations to experimental data to identify potential novel targets for transcription factors. We then identified regulatory cascades connecting transcription factors to the potential targets through a systematic model expansion strategy using published genome-wide chromatin immunoprecipitation and binding-site-motif data sets. Finally, we show the ability of an integrated metabolic and regulatory network model to predict growth phenotypes of transcription factor knockout strains. These studies illustrate the potential of model-driven data integration to systematically discover novel components and interactions in regulatory and metabolic networks in eukaryotic cells.

Alternate JournalGenome Res.
PubMed ID16606697

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