Nitrogen metabolism in the yeast S. cerevisiae is an excellent model system in which to study eucaryotic transcriptional regulation and regulatory networks. This yeast is able to selectively utilize good nitrogen sources in preference to poor ones. This selectivity (designated nitrogen catabolite repression, NCR) is accomplished through regulated operation of four GATA-transcription factors (Gln3p, Gat1p/Nil1p, Dal80p/Uga43p, Deh1p/ GZF3p) that bind to GATA-containing sequences in the promoters of NCR-sensitive genes. Aggregate work from several laboratories, including our own, has shown that when nitrogen is in excess, Gln3p and Gat1p are phosphorylated and excluded from the nucleus. When nitrogen is limiting, these proteins are no longer phosphorylated, become localized to the nucleus, and mediate NCR-sensitive transcription. We propose to continue our studies of the GATA-family regulon, performing experiments that will elucidate the steps and proteins involved in the regulation of Gln3p, Gat1p and Ure2p activities and intracellular localization. We will also investigate the mechanisms by which Mks1p influences operation of the GATA regulon. We have established genome-wide transcription analysis in our lab and propose to identify: new members of the GATA-factor regulon, the ways in which the member genes are regulated, and how they in turn regulate GATA-factor gene expression and activity. Three new GATA-factors, Gat2p, Gat3p and Gat4p, were discovered in our pilot experiment. We propose to identify the functions of Gat2p, which is the GATA-factor most structurally homologous to Gat1p. We will also determine how Gat2p itself is regulated. We are especially interested in the interface between and integration of GATA-factor regulon components with other regulatory systems in the cell. The complexity of even this simple system is daunting, but will yield highly useful information and experience for developing and interpreting studies of far more complicated yeast and mammalian regulatory cascades.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Microbial Physiology and Genetics Subcommittee 2 (MBC)
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Anderson, James J
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University of Tennessee Health Science Center
Other Basic Sciences
Schools of Medicine
United States
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Tate, Jennifer J; Rai, Rajendra; Cooper, Terrance G (2018) More than One Way in: Three Gln3 Sequences Required To Relieve Negative Ure2 Regulation and Support Nuclear Gln3 Import in Saccharomyces cerevisiae. Genetics 208:207-227
Cooper, Terrance G (2017) Editorial: Saccharomyces riding the waves of technology and transition. FEMS Yeast Res 17:
Cooper, Terrance G (2017) What do the pictures say-snapshots of a career. FEMS Yeast Res 17:
Tate, Jennifer J; Buford, David; Rai, Rajendra et al. (2017) General Amino Acid Control and 14-3-3 Proteins Bmh1/2 Are Required for Nitrogen Catabolite Repression-Sensitive Regulation of Gln3 and Gat1 Localization. Genetics 205:633-655
Cooper, Terrance G (2016) Editorial: Retrospectives - lives behind the science. FEMS Yeast Res 16:fow005
Slonimski, Piotr P; Cooper, Terrance G; von Borstel, Robert C Jack (2016) Piotr P. Slonimski - The Warrior Pope: The discovery of mitochondrial (petite) mutants and split genes. FEMS Yeast Res 16:fow004
Rai, Rajendra; Tate, Jennifer J; Cooper, Terrance G (2016) Multiple Targets on the Gln3 Transcription Activator Are Cumulatively Required for Control of Its Cytoplasmic Sequestration. G3 (Bethesda) 6:1391-408
Rai, Rajendra; Tate, Jennifer J; Shanmuganatham, Karthik et al. (2015) Nuclear Gln3 Import Is Regulated by Nitrogen Catabolite Repression Whereas Export Is Specifically Regulated by Glutamine. Genetics 201:989-1016
Georis, Isabelle; Isabelle, Georis; Tate, Jennifer J et al. (2015) Premature termination of GAT1 transcription explains paradoxical negative correlation between nitrogen-responsive mRNA, but constitutive low-level protein production. RNA Biol 12:824-37
Tate, Jennifer J; Georis, Isabelle; Rai, Rajendra et al. (2015) GATA Factor Regulation in Excess Nitrogen Occurs Independently of Gtr-Ego Complex-Dependent TorC1 Activation. G3 (Bethesda) 5:1625-38

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