tra-1 appears to be a terminal regulator of somatic sex determination, acting to specify female somatic fates. The
tra-1 gene expresses two mRNAs, both encoding zinc finger proteins. TRA-1A has five fingers, and TRA-1B has only the first two fingers. Only TRA-1A binds DNA in vitro. Does TRA-1A have all
tra-1 activity? We used transgenic animals expressing each TRA-1 protein to test their relative contributions to
tra-1 function. TRA-1A rescues most phenotypes of
tra-1 null mutants, while TRA-1B has no effect. Strains expressing TRA-1A from the
tra-1 promoter can be maintained as self-fertile hermaphrodites. These experiments suggest that TRA-1A has most
tra-1 function, though we have not yet seen full rescue. The sex determination pathway resembles other signaling pathways regulating transcription factors. As some of these involve cytoplasmic sequestration, and
tra-1 is regulated post-translationally, we examined the location of TRA-1A protein using an epitope-tagged transgene. We find that hsTRA-1A is predominantly nuclear at all stages in both sexes, suggesting that its down regulation in males occurs in the nucleus. We are interested in how
tra-1 controls the genes that carry out sexual differentiation. We are searching for genes that contain potential
tra-1 binding sites and testing whether those sites mediate regulation by
tra-1. One candidate being tested is
egl-5, which has tandem TRA-1A sites in its promoter region and shows sexually dimorphic phenotypes and transcription. A second candidate is
mab-3, a gene required in males to repress vit gene expression (intestine) and to execute V-ray formation (tail). We are cloning
mab-3, and have obtained phenotypic rescue with a YAC clone from the
mab-3 region.