The Role of Zinc Finger Proteins During Target Gene Activation by HOM-C Proteins.

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0090040MahaffeyHox genes encode homeodomain-containing transcription factors that specify body pattern during embryogenesis in all metazoans. In the fruit fly, Drosophila melanogaster these genes are located in the Antennapedia- and Bithorax-Complexes. Each individual hox gene is expressed in a specific anterior/posterior domain wherein the encoded protein specifies regional identity through activation of a specific set of target genes. However, the DNA binding properties of the different hox proteins are quite similar This has lead to the hypothesis that interactions with cofactors play an important role in target gene selection by the hox proteins, though few cofactors are known. Recent results from the Mahaffey lab indicate that regionally-expressed zinc finger transcription factors are likely cofactors for the Deformed (Dfd) and Sex combs reduced (Scr) hox proteins. Loss of the two, redundant zinc finger genes, disconnected (disco) and disco-related (disco-r) causes a phenotype similar to loss of Dfd and Scr. Dr. Mahaffey proposed that an interaction between the hox and zinc finger proteins supplies the additional specificity that is required for selection and activation of hox target genes. Further, he proposes that this may be a conserved mechanism that governs body plan specification in other regions of the embryo and in other animals. This hypothesis leads to several predictions that Dr. Mahaffey will test. Dr. Mahaffey will ectopically co-express Disco and Dfd in Drosophila to determine whether both proteins will cause a broader transformation than that of Dfd alone. He will investigate the possibility of molecular interactions between Disco and Dfd, including protein-protein and protein-DNA binding studies. He will also search for Disco/Disco-r response elements at known Dfd target genes, and, if found, he will undertake molecular characterizations of these response elements. To examine the possibility that this is a conserved mechanism, he will use RNAi to eliminate the disco/disco-r function(s) from beetle Tribolium to test whether this causes a homeotic transformation similar to that observed due to loss of Tc-Dfd and Tc-Scr.