TRANSCRIPTIONAL REGULATION OF THE SEX-LETHAL GENE BY HELIX-LOOP-HELIXPROTEINS

Somatic sex determination in Drosophila depends on the expression of S ex-lethal (Sri), whose level is determined by the relative number of X chromosomes and sets of autosomes (X:A ratio), The first step in regu lation of Sri expression is transcriptional control from its early pro moter and several genes encoding transcription factors of the helix-lo op-helix (HLH) family such as daughterless (de), sisterless-b (sis-b) deadpan (dpn) and extramacrochaetae (emc) have been implicated, By the use of transfection assays and in vitro binding experiments, here we show that da/sis-b heterodimers bind several sites on the Sri early pr omoter with different affinities and consequently tune the level of ac tive transcription from this promoter. Interestingly, our data indicat e that repression by the dpn product of da/sis-b dependent activation results from specific binding of dpn protein to a unique site within t he promoter, This contrasts with the mode of emc repression, which inh ibits the formation of the da/sis-b heterodimers. These results reveal the molecular mechanisms by which Sri gene transcription is positivel y or negatively regulated to control somatic sex determination.