Diverse cell types are formed from a single progenitor cell during development. The phenotype of a differentiated cell results from the expression of a select subset of genes. Molecular analysis of events that regulate cell-specific expression of individual genes is a prerequisite for understanding differentiation and development. In many cases, tissue-specific gene expression results from the interaction of enhancer elements with promoter elements causing activation of transcription. One way to study this process is to characterize mutations in which these interactions are disrupted. In Drosophila, many tissue-specific mutations are caused by the insertion of a transposable element into a gene. In these cases, alteration of gene expression is caused by the modulation of cis-linked regulatory elements in the target gene. Investigation of mechanisms involved in this type of mutagenesis will provide information fundamental to understanding, control of gene expression. The goal of these studies is to analyze the role of several tissue-specific enhancer elements in directing transcription of the yellow gene. This gene is required for proper pigmentation of larval and adult cuticle and derivative structures. The visible phenotype of mutations in this gene has resulted in the identification of a large number of alleles which alter the pattern of pigmentation in the adult fly by disrupting normal enhancer function. These experiments will focus on understanding the molecular basis of the mutation y2. In y2 flies, insertion of a gypsy element 700 bp upstream of the yellow transcription start site causes a tissue-specific alteration of gene expression. This mutagenic effect requires a protein, suppressor of Hairy-wing (su(Hw)), which has characteristics of known transcription factors. This proposal will examine how the su(Hw) protein specifically inactivates enhancer function in body and wing tissues. Experiments will be carried out to examine if the su(Hw) protein can inactivate other enhancer elements within the yellow gene, as well as tissue- specific enhancer elements of the and yolk protein genes. This will determine if the mechanism of su(Hw) mutagenesis is the inactivation of enhancer elements distal to its binding site. Other pattern-specific transposable element-induced mutations of the low gene will be examined to determine if mobile elements share a common mutational mechanism. Lastly, the basis of the inter-allelic complementation which occurs between Y2 and yellow null alleles will be studied. These experiments will elucidate mechanisms by which enhancer elements activate transcription in trans. Studies described herein will contribute to the understanding of mechanisms responsible for controlling gene expression during the development of an organism.
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