Sex-specific transcriptional regulation by the male and female doublesex proteins of Drosophila.

The somatic sexual phenotype of Drosophila is regulated by the sexual differentiation pathway. Male (DSXM) and female (DSXF) proteins encoded by doublesex (dsx), a gene at the end of this pathway, bind to three sites within a 127-bp enhancer that directs sex- and tissue-specific transcription of Yolk protein genes. We describe mutagenesis of these binding sites and the resulting effects on DSXM and DSXF binding in vitro and on gene regulation in wild-type and dsx mutant flies. The results demonstrate that DSXM represses and DSXF activates transcription from the two strongest binding sites. Thus, the pathway regulates sex-specific transcription through the male and female dsx proteins that act directly on the target gene, but with opposite effects.