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

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....

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Bibliographic Details
Published in:Genome Research 2006-05, Vol.16 (5), p.627-635
Main Authors: Herrgård, Markus J, Lee, Baek-Seok, Portnoy, Vasiliy, Palsson, Bernhard Ø
Format: Article
Language:English
Subjects:
Chromatin Immunoprecipitation
Computer Simulation
Gene Deletion
Gene Expression Profiling
Gene Expression Regulation, Fungal
Genes, Fungal
Genome, Fungal
Letter
Models, Genetic
Regulatory Elements, Transcriptional
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - growth & development
Saccharomyces cerevisiae - metabolism
Transcription Factors - genetics
Transcription Factors - metabolism
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Summary: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.
ISSN:1088-9051
1549-5469
1549-5477
DOI:10.1101/gr.4083206