CONVERSION OF A DORSAL-DEPENDENT SILENCER INTO AN ENHANCER - EVIDENCEFOR DORSAL COREPRESSORS

In Drosophila, the dorsal (dl) morphogen gradient initiates the differ entiation of the embryonic mesoderm and neuroectoderm by activating th e expression of regulatory genes (e.g. twist and snail) in a concentra tion-dependent manner. dl also functions as a repressor that establish es the dorsal epidermis and amnioserosa by restricting regulatory gene s such as dpp and zen to dorsal regions of the embryo. The ability of dl to function as both an activator and repressor distinguishes it fro m the bicoid morphogen, which appears to function solely as an activat or. In an effort to determine how dl functions as a repressor we have performed a detailed characterization of a zen silencer element, calle d the VRE, which mediates ventral repression in response to the dl gra dient. A minimal 110 bp VRE sequence is identified, which is able to s ilence the ventral expression of a heterologous promoter. This sequenc e contains two dl binding sites as well as binding sites for additiona l nuclear factors present in early embryos. Mutations in the latter bi nding sites convert the minimal VRE into an enhancer, which mediates t ranscriptional activation in ventral regions in response to dl. These results suggest that dl is intrinsically an activator, but is converte d into a potent silencer when it interacts with neighboring corepresso rs.