|Functional Genomics Section
DOE Human Genome Program Contractor-Grantee Workshop
|121. The Regulatory Network of
Matthew N. Ashby, Tod Flak, and
Darren H. Wong
Eukaryotic cells possess the ability to orchestrate the expression of thousands of genes in response to a changing environment. While numerous genome sequencing projects of eukaryotic model organisms are currently under way, only that of the yeast Saccharomyces cerevisiae has been completed. The modest size of the yeast genome, approximately 6000 hypothetical open reading frames, represents a significant opportunity to study the organization and inter-relationships of the regulation of gene expression on a genomic scale. The Genome Reporter Matrix (GRM) consists of a high density array of yeast colonies each harboring one of over 6000 yeast promoter-reporter fusions. The GRM can measure patterns of gene expression in living cells in response to external stimuli or mutations. The response of yeast exposed to an extensive panel of environmentally important compounds as well as exposure to ionizing radiation will be examined at the level of changes in gene expression. Compensatory changes in gene regulation will also be examined in response to a collection of mutations. Analyses of the 1300 expression profiles of a set of 864 reporters in response to pharmaceutical agents revealed the presence of 26 unique regulons. These analyses will be extended to over 6000 reporters in response to the proposed environmental stimuli. The generality of the regulons identified from these experiments will be assessed by a series of directed experiments in human cells in tissue culture. These experiments will provide a map or framework for the regulatory circuitry within a eukaryote and help determine the extent of the evolutionary conservation between yeast and human cells.
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