The goal of this research is to elucidate the mechanisms of eucaryotic gene regulation. The system chosen for study is the yeast regulatory pathway defined by the genes CCR4, CRE1, and CRE2. CCR4 is required for the transcription of glucose-repressible alcohol dehydrogenase (ADH2) and other non-fermentative genes. CRE1 and CRE2 are negative effectors that repress CCR4 or some other factor that requires CCR4 for function. The CRE genes are allelic to two members of the SPT gene family, mutations in which suppress promoter insertions at the HIS4 and LYS2 loci. The CCR4 gene is also required for spt-mediated gene expression. Some members of the SPT gene family have been identified as histones and one as the TATA binding protein. The identification of the CRE/SPT genes as regulators of several apparently unrelated systems and as integral components of chromatin and transcription complexes suggests that these regulators, together with CCR4, play key roles in maintaining general transcriptional control of gene expression. The molecular role of the CCR4/CRE genes will be studied by a combination of genetic, biochemical, and recombinant DNA techniques. The functional regions of CCR4 and CRE1 proteins will be identified by deletion and mutation analysis, and the proteins which bind to CCR4 will be identified by immunological and biochemical techniques. The post-transcriptional regulation of CCR4 by the CRE genes will be explored by examining the potential protein-protein interaction of CCR4 with CRE1 and CRE2 and by determining the effect of cre mutations on CCR4 protein abundance. The effects of ccr4 and cre mutations on ADH2 chromatin structure will be determined and the site at ADH2 through which these factors act will be identified. Other genes required for CCR4 function will also be identified by conduction additional mutant hunts, and the potential role of other SPT genes in ADH2 regulation will be examined.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM041215-01A1
Application #
3299250
Study Section
Molecular Biology Study Section (MBY)
Project Start
1990-09-01
Project End
1995-08-31
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of New Hampshire
Department
Type
Schools of Earth Sciences/Natur
DUNS #
111089470
City
Durham
State
NH
Country
United States
Zip Code
03824
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Tucker, M; Valencia-Sanchez, M A; Staples, R R et al. (2001) The transcription factor associated Ccr4 and Caf1 proteins are components of the major cytoplasmic mRNA deadenylase in Saccharomyces cerevisiae. Cell 104:377-86
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Badarinarayana, V; Chiang, Y C; Denis, C L (2000) Functional interaction of CCR4-NOT proteins with TATAA-binding protein (TBP) and its associated factors in yeast. Genetics 155:1045-54

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