THE DROSOPHILA-DORSAL MORPHOGEN REPRESSES THE TOLLOID GENE BY INTERACTING WITH A SILENCER ELEMENT

The dorsal protein (DL) regulates the transcriptional activity of seve ral genes that determine cell fate along the dorsoventral axis of the Drosophila melanogaster embryo. DL is present at high levels in ventra l nuclei, where it activates some genes (twi and sna) and represses ot hers (zen, dpp, and tld). DL shows homology to the Rel family of prote ins and interacts with specific DNA sequences in the regulatory region s of its target genes. The distal portion of the zen gene acts as a si lencer that can mediate the repression of a heterologous promoter in v entral regions of the embryo. It contains four DL binding sites which alone are sufficient for activation but not repression. Here we analyz e the interaction of DL with another one of its repressed targets, the tolloid (tld) ene. Approximately 800 bp of 5'-flanking sequences upst ream of the tld coding region were shown to drive an expression patter n indistinguishable from the wild-type pattern. A 423-bp fragment loca ted within these sequences contains two DL binding sites and was shown to act as a silencer to mediate ventral repression. Point mutations i n the sites abolish not only DNA binding but also ventral repression. We discuss a comparison of the DNA sequences from the zen and tld prom oters and the possible mechanisms of transcriptional silencing.