A BZIP PROTEIN, SISTERLESS-A, COLLABORATES WITH BHLH TRANSCRIPTION FACTORS EARLY IN DROSOPHILA DEVELOPMENT TO DETERMINE SEX

Sexual identity in Drosophila is determined by zygotic X-chromosome do se. Two potent indicators of X-chromosome dose are sisterless-a (sis-a ) and sisterless-b (sis-b). Genetic analysis has shown that a diplo-X dose of these genes activates their regulatory target, the feminizing switch gene Sex-lethal (Sxl), whereas a haplo-X dose leaves Sxl inacti ve. sis-b encodes a transcriptional activator of the bHLH family that dimerizes with several other HLH proteins required for the proper asse ssment of X dose. Here, we report that sis-a encodes a bZIP protein ho molog that functions in all somatic nuclei to activate Sxl transcripti on. In contrast with other elements of the sex-determination signal, t he functioning of this transcription factor in somatic cells may be sp ecific to X-chromosome counting. Using in situ hybridization, we deter mined the time course of sis-a, sis-b, and Sxl transcription during th e first few hours after fertilization. The pattern of sis-a RNA accumu lation is very similar to that for sis-b, with a peak in nuclear cycle 12 at about the time of onset of Sxl transcription. Considered in the context of other studies, these results suggest that the ability to d istinguish one X from two is attributable to combinatorial interaction s between bZIP and bHLH proteins and their target, Sxl, as well as to positive and negative interactions with maternally supplied and zygoti cally produced proteins.