The goal of this project is to determine the molecular mechanisms by which gene expression is regulated in a simple eukaryote, the yeast Saccharomyces cerevisiae. In particular, we seek to determine the molecular basis for differentiation of yeast cell type. This proposal is concerned with the following aspects of cell type (mating type) in yeast: (1) The molecular mechanism of action of regulators of gene expression. Our prior work has shown that the yeast mating type locus (MAT) codes for regulator proteins: Alpha2 and al-Alpha2 are negative regulators of gene expression, and Alpha1 is an activator of gene expression. These regulators control expression of a- or Alpha-specific genes at the level of production of RNA. We shall address the following questions: (a) How does the Alpha1 product activate expression of the MFAlpha1 (Alpha-factor) gene? (b) How does the Alpha2 product inhibit expression of the STE6 gene? (c) How does Alpha1-Alpha2 inhibit expression of the HO gene? We shall use a variety of genetic and biochemical methods to address these questions. (2) Mating type interconversion and its regulation. The genetic rearrangement that occurs in mating type interconversion is under a variety of controls. We shall try to determine the molecular basis for several of these controls, some of which concern expression of the HO gene itself. (a) How is expression of the HO gene limited to a specific phase of the cell division cycle? (b) Why do mother cells and not daughter cells express HO? (c) What is responsible for degradation of the HO protein? (d) Why are five genes (SWI1-SWI5) required for expression of HO? (e) Is the HO gene product a component of the HO-dependent endonuclease that appears to be the initiating event in mating type interconversion?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018738-05
Application #
3128144
Study Section
Genetics Study Section (GEN)
Project Start
1981-06-01
Project End
1989-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Maxon, M E; Herskowitz, I (2001) Ash1p is a site-specific DNA-binding protein that actively represses transcription. Proc Natl Acad Sci U S A 98:1495-500
Chu, S; Herskowitz, I (1998) Gametogenesis in yeast is regulated by a transcriptional cascade dependent on Ndt80. Mol Cell 1:685-96
Tabtiang, R K; Herskowitz, I (1998) Nuclear proteins Nut1p and Nut2p cooperate to negatively regulate a Swi4p-dependent lacZ reporter gene in Saccharomyces cerevisiae. Mol Cell Biol 18:4707-18
Chu, S; DeRisi, J; Eisen, M et al. (1998) The transcriptional program of sporulation in budding yeast. Science 282:699-705
Sil, A; Herskowitz, I (1996) Identification of asymmetrically localized determinant, Ash1p, required for lineage-specific transcription of the yeast HO gene. Cell 84:711-22
Banuett, F; Herskowitz, I (1996) Discrete developmental stages during teliospore formation in the corn smut fungus, Ustilago maydis. Development 122:2965-76
Kruger, W; Peterson, C L; Sil, A et al. (1995) Amino acid substitutions in the structured domains of histones H3 and H4 partially relieve the requirement of the yeast SWI/SNF complex for transcription. Genes Dev 9:2770-9
Anna-Arriola, S S; Herskowitz, I (1994) Isolation and DNA sequence of the STE13 gene encoding dipeptidyl aminopeptidase. Yeast 10:801-10
Banuett, F; Herskowitz, I (1994) Identification of fuz7, a Ustilago maydis MEK/MAPKK homolog required for a-locus-dependent and -independent steps in the fungal life cycle. Genes Dev 8:1367-78
Sen, M; Marsh, L (1994) Noncontiguous domains of the alpha-factor receptor of yeasts confer ligand specificity. J Biol Chem 269:968-73

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