Evidence for multiple promoter elements orchestrating male-specific regulation of the her-1 gene in Caenorhabditis elegans.

The sex-determining gene her-1 is required for male development in Caenorhabditis elegans. In XO males, two her-1 mRNAs, her-1a and her-1b, are transcribed from two separate promoters: P1, located in the 5'-flanking region, and P2, located in the large second intron. In XX hermaphrodites, accumulation of both her-1 transcripts is repressed by the sdc genes, which in turn are negatively regulated by the xol-1 gene. When introduced into a xol-1(y9) background, transgenic arrays, including 3.4 kb of her-1 intron 2 sequence (P2), result in phenotypes that mimic those of sdc(lf) mutants, including suppression of XO lethality and masculinization of both XX and XO animals. The masculinization, but not the suppression of XO lethality, is dependent on endogenous her-1 activity. These effects could therefore result from sequestration (titration) of sdc gene products by sequences in the arrays, causing derepression of her-1 (masculinizing effect) and disruption of the dosage compensation machinery (allowing survival of XO animals). We used these effects as an assay in a deletion analysis of the two her-1 promoter regions to define potential cis-regulatory sites required for the putative titration. Several regions in P2 contributed to these effects. P1 was effective only in combination with certain P2 sequences and only if a particular P1 site previously implicated in her-1 repression was intact. These results suggest that normal repression of transcription from P1 in XX animals may involve cooperative interaction with sequences in the P2 region. In experiments to test for a possible role of the her-1b transcript in regulation of sdc genes, no significant effects could be demonstrated.