The TRA‐1 transcription factor binds TRA‐2 to regulate sexual fates in Caenorhabditis elegans

The tra‐1 and tra‐2 sex‐determining genes promote female fates in Caenorhabditis elegans . Classical genetic studies placed tra‐1 as the terminal regulator of the pathway with tra‐2 acting upstream as a regulator of regulators of tra‐1 . Here we report the surprising result that the TRA‐1 transcription factor binds the intracellular domain of the TRA‐2 membrane protein. This binding is dependent on the MX regulatory domain, a region of the TRA‐2 intracellular domain shown previously to be critical for the onset of hermaphrodite spermatogenesis. The functional importance of the TRA‐1–TRA‐2 physical interaction is supported by genetic interactions between tra‐1(0) and tra‐2(mx) mutations: a reduction of tra‐1 gene dose from two copies to one copy enhances the tra‐2(mx) feminization phenotype, but has no apparent somatic effect. In Caenorhabditis briggsae , we also find an MX‐dependent interaction between Cb‐TRA‐1 and Cb‐TRA‐2, but intriguingly, no cross‐species interactions are seen. The conservation of the TRA‐1–TRA‐2 interaction underscores its importance in sex determination.