Evidence that Runt Acts as a Counter-Repressor of Groucho during Drosophila melanogaster Primary Sex Determination
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abstract
AbstractRunx proteins are bifunctional transcription factors that both repress and activate transcription in animal cells. Typically Runx proteins work in concert with other transcriptional regulators, including co-activators and co-repressors to mediate their biological effects. InDrosophila melanogasterthe archetypal Runx protein, Runt, functions in numerous processes including segmentation, neurogenesis and sex determination. During primary sex determination Runt acts as one of four X-linked signal element (XSE) proteins that direct female-specific activation of the establishmen promoter (Pe) of the master regulatory geneSex-lethal (Sxl). Successful activation ofSxlPerequires that the XSE proteins overcome the repressive effects of maternally deposited Groucho (Gro), a potent co-repressor of the Gro/TLE family. Runx proteins, including Runt, contain a C-terminal peptide, VWRPY, known to bind to Gro/TLE proteins to mediate transcriptional repression. We show that Runts VWRPY co-repressor-interaction domain is needed for Runt to activateSxlPe. Deletion of the Gro-interaction domain eliminates Runt-ability to activateSxlPe, whereas replacement with a higher affinity, VWRPW, sequence promotes Runt-mediated transcription. This suggest that Runt activatesSxlPeby antagonizing Gro function, a conclusion consist with earlier findings that Runt is needed forSxlexpression only in embryonic regions with high Gro activity. Surprisingly we found that Runt is not required for the initial activation activation ofSxlPe. Instead, Runt is needed to keepSxlPeactive during the subsequent period of high-levelSxltranscription suggesting that Runt helps amplfy the difference between female and male XSE signals by counterrepressing Gro in female, but not in male, embryos.
