FTZ-F1 IS A COFACTOR IN FTZ ACTIVATION OF THE DROSOPHILA ENGRAILED GENE

The fushi tarazu pair-rule gene is required for the formation of alter nating parasegmental boundaries in the Drosophila embryo, fushi tarazu encodes a homeodomain protein necessary for transcription of the engr ailed gene in even-numbered parasegments, Here we report that, within an engrailed enhancer, adjacent and conserved binding sites for the Fu shi tarazu protein and a cofactor are each necessary, and together suf ficient, for transcriptional activation, Footprinting shows that the c ofactor site can be bound specifically by Ftz-F1, a member of the nucl ear receptor superfamily, Ftz-F1 and the Fushi tarazu homeodomain bind the sites with 4- to 8-fold cooperativity, suggesting that direct con tact between the two proteins may contribute to target recognition, Ev en parasegmental reporter expression is dependent on Fushi tarazu and maternal Ftz-F1, suggesting that these two proteins are indeed the fac tors that act upon the two sites in embryos, The two adjacent binding sites are also required for continued activity of the engrailed enhanc er after Fushi tarazu protein is no longer detectable, including the p eriod when engrailed, and the enhancer, become dependent upon wingless . We also report the existence of a separate negative regulatory eleme nt that apparently responds to odd-skipped.