Organisms are constantly faced with environmental extremes, involving temperature, starvation, radiation and harmful chemicals. Inducible genes have evolved to respond to these challenges. Organisms are also faced with day-to-day housekeeping tasks, such as synthesizing biomolecules. Recent studies in the budding yeast Saccharomyces cerevisiae suggest that eukaryotes balance housekeeping and stress-response needs through two distinct transcriptional regulatory pathways, represented by two related components of the transcription machinery, TFIID and SAGA, respectively. Knowing whether a gene is primarily regulated by TFIID or SAGA provides enormous predictive insight into its regulation by other transcriptional regulators, and its broader cellular role. Many aspects of this dual pathway remain to be elucidated. The TFIID/SAGA classification has not been conducted under a wide range of conditions that put the genome through its full range of expression, which is necessary for appropriate classification of all genes. While SAGA as been implicated in stress-induced gene expression, it is not known whether its action protects cells from stress. Genes repressed by stress utilize TFIID rather than SAGA, but little is known about what promoter elements control this process. The TATA box has also been implicated in the stress-response. Many TATA-less genes have a conserved TATA box far upstream of its normal location. It's potential involvement in gene regulation remains unknown. To address these problems which are germane to an organism's stress-response and the potential to develop therapeutic agents that heighten the stress response, the following specific aims are proposed: 1) Classify the TFIID/SAGA-dependence of all yeast genes under a wide range of environmental stresses. 2) Determine whether SAGA and/or TFIID provide stress protection. 3) Identify the promoter determinants of stressdirected gene repression. 4) Assess the function of far-upstream TATA boxes. ? ?

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
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Molecular Genetics B Study Section (MGB)
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Balshaw, David M
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Pennsylvania State University
Schools of Arts and Sciences
University Park
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