Position effect variegation in Drosophila melanogaster : chemical modification and mutational analysis

Position effect variegation is an event in which the transcriptional fate of a gene is determined long before the product of that gene is required. Thus, it parallels the normal processes of determination and differentiation associated with development in higher organisms. Position effect variegation is thought to result from alterations in chromatin structure at the new heterochromatic-euchromatic boundary. I have found that when fruit flies (Drosophila melanoqaster), bearing a variegating gene, are reared on meduim containing low concentrations of either n-butyrate or n-propionate, the gene inactivation associated with position effect variegation is suppressed. This is true of both X-linked and autosomal variegating genes regardless of the type of heterochromatin with which they are associated. These chemicals are only effective as suppressors of variegation during the embryonic and larval stages suggesting they may only act to modify variegation in dividing cells. Removal of the Y chromosome in males completely abolishes the effects of n-butyrate and n-propionate. I examined the ability of these chemicals to. suppress variegation in flies haploid for the histone gene cluster and found that the combined effect was additive. These results are discussed with respect to current knowledge of chromatin structure and the known effects of n-butyrate and n-propionate. In addition a large scale screen was undertaken to isolate and recover dominant mutations which either suppress or enhance the variegated phenotype. In total, 54 mutations were recovered: 51 suppressors, and 3 enhancers. Preliminary characterization has revealed that the majority of the suppressor mutations are clustered at specific sites in the D. Melanogaster genome. A majority of the suppressors are sensitive to the heterochromatic constitution of the organism but most are insensitive to alterations in developmental temperature. The possibility that' some of these mutations represent lesions in genes coding for structural components of chromatin suggests further characterization, both at the genetic and molecular level, may provide insights not only into position effect variegation but also provide information regarding the basic structure of chromatin.Science, Faculty ofZoology, Department ofGraduat