YEAST HISTONE ACETYLATION GENES AND MUTANTS

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DESCRIPTION: The long term goal of this research is to understand the role of histone acetylation in chromatin structure and function, using the yeast S. cerevisiae to study the process. Since most yeast proteins appear to have human homologs, this project should shed light on human biology and disease. The specific aims are: 1) to determine the function of the yeast histone H4 acetyltransferase, HAT1, whose gene was identified and cloned last year. Since a hat1 null mutant has no obvious phenotypes, other approaches are needed to determine the in vivo function of the HAT1 protein. 2) to characterize the HAT1-interacting proteins, HIF1 and HIF2, identified with the two-hybrid system. The hypothesis that HIF2, and other related proteins, target enzymes such as histone acetyltransferases and histone deacetylases to the histones will be tested. 3) to find other histone acetyltransferase mutants using screening procedures similar to the one used to obtain the hat1-1 mutant. Peptides corresponding to the N-terminal tails of each of the four core histones will be used as substrates for acetyltransferase assays, screening extracts from a collection of yeast temperature-sensitive (ts) mutants to find ones defective in acetyltransferase activity. Once mutants are identified, the corresponding genes will be cloned and the roles of the gene products determined. 4) to examine several other yeast gene products to see if they are histone modifying enzymes.