We have recently discovered that position effect occurs near telomeres in Saccharomyces cerevisiae. The position effect is manifested as transcriptional repression, which, unexpectedly, is metastable in its mitotic inheritance. The long term goal of this research is to understand the mechanism of position effect at telomeres, with the intent: 1. to dissect the chromosomal structure of telomeres and learn its relationship to telomere function, and, 2. that the conclusions will serve as a paradigm for position effect at other chromosomal locations, and in all eukaryotes. Dissecting position effect and telomere function will elucidate a critical area of chromosome biology, which is fundamental to understanding proper cellular function. The proposed research will develop a firm understanding of position effect at S. cerevisiae telomeres by pursuing the following specific aims: 1) To identify and construct additional genes that are susceptible to telomere-specific position effect. Specifically, genes that have a phenotypic selection or screen for determining transcriptional repression or metastable variegation will be examined/constructed. These genes will be used in aims 2-3. In addition, the classification of such genes as to their susceptibility to position effect may provide insights into the mechanism of repression. 2) To determine how the specific location of genes near a telomere affects the ability of the genes to be repressed. This includes determining the distance over which position effect occurs from a telomere, and whether two genes either on the same telomere or different telomeres are coordinately regulated in the same cell. This information will be used in aim 3. 3) To identify genes or conditions that modify telomere-specific position effect. Genes that modify position effect are hypothesized to be part of the telomeric chromatin structure, or be involved in its assembly.
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