This project proposes to dissect the molecular mechanisms that determine the pattern of expression of the Drosophila white gene in specific tissues, specific cells and specific developmental stages and modulate it according to the dosage of X chromosome material present in the embryo. The sequence of the different tissue specific determinants in the white regulatory region, their relationship to one another, to the promoter and to the zeste binding sites will be studied using a variety of transposon constructions introduced into the genome by germ line transformation. The transformed lines will be tested for the tissue and cell specificity of expression and for the effects of zeste and zeste mutations both on the functioning of the white promoter and on interchromosomal transvection-like effects. In particular, these experiments will permit the testing of current hypotheses on the role of the zeste product in governing the interaction between regulatory sequences and the promoter. Similar transposon contructions will identify sequences in the white regulatory region that are able to confer X-chromosome dependent dosage compensation on gene expression. This will be done using DNA segments from white placed in front of the xanthine dehydrogenase gene. Affinity chromotography will then be used to isolate a protein factor that binds specifically to the dosage compensation determinant. This work will test basic mechanisms underlying the functional organization of genetic information. These mechanisms could lead to new insights on the control of larger genetic domains such as the globin gene cluster in man.
