The goal of the Section on Drosophila Gene Regulation is to understand the regulation of homeotic gene function in Drosophila. The homeotic genes specify segmental identities in Drosophila at both the embryonic and adult stages. They encode homeodomain-containing transcription factors that control cell fates by regulating the transcription of downstream target genes. The homeotic genes are expressed in precise spatial patterns that are crucial for the proper determination of segmental identities. Both loss of expression and ectopic expression in the wrong tissues lead to changes in segmental identities. These changes in identity provide a powerful assay to identify the trans-acting factors that regulate the homeotic genes and the cis-acting sequences through which they act. Both the homeotic genes and the trans-acting factors that regulate them are conserved between Drosophila and man. In addition to many conserved developmental genes, at least half of the disease and cancer-causing genes in man are conserved in Drosophila, making Drosophila a very important model system for the study of human development and disease. Genetic studies have identified the trithorax group of genes that are required for expression or function of the homeotic genes. Reduced function of the trithorax group genes mimics loss of function of the homeotic genes. Many trithorax group proteins are subunits of chromatin-remodeling or transcriptional coactivator complexes. The brahma, moira, and osa genes encode subunits of the Brahma chromatin-remodeling complex, which is conserved from yeast to human. To further understand the function of the Brahma complex, we have been characterizing mutations that interact with mutations in the Brahma complex. As part of these studies, we have recently isolated and characterized mutations in the tonalli and taranis genes in collaboration with Dr. Martha Vazquez and Dr. Mario Zurita of the Universidad Nacional Autonoma de Mexico. One protein isoform encoded by the tonalli gene has an SP-RING finger domain thought to be a SUMO E3 ligase domain. This suggests that sumoylation of one or more subunits of the brahma chomatin remodeling complex could be important for the stability or cellular localization of the complex. Another possibility is that the brahma complex targets sumoylation of other proteins important for transcriptional regulation.
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