The Caenorhabditis Gli protein TRA-1 makes a transcriptional activator that promotes spermatogenesis

Gli proteins are conserved transcription factors that regulate development. Caenorhabditis nematodes have a single Gli protein, TRA-1, which controls sex determination. Previously, it was thought that TRA-1 only produced a cleaved product that represses male genes. Here we show that full-length TRA-1 is an activator that promotes spermatogenesis. TRA-1 activator functions at the end of the sex-determination pathway in Caenorhabditis briggsae. The TRRAP homolog TRR-1 also acts at this point to promote spermatogenesis, so we propose that TRA-1 activator works with TRR-1 and the associated Tip60 HAT complex to turn on sperm genes. These results (1) reveal conservation between Gli activation in nematodes and humans, (2) show that Gli activation can occur without Hedgehog signaling, and (3) suggest an ancient role for Gli proteins in spermatogenesis. Finally, since a competition between TRA-1 activator and repressor helps determine germ cell fates, this regulatory flexibility might have facilitated the evolution of self-fertility.