Binding of the Vestigial co-factor switches the DNA-target selectivity of the Scalloped selector protein

The formation and identity of organs and appendages are regulated by specif ic selector genes that encode transcription factors that regulate potential ly large sets of target genes. The DNA-binding domains of selector proteins often exhibit relatively low DNA-binding specificity in vitro. It is not u nderstood how the target selectivity of most selector proteins is determine d in vivo. The Scalloped selector protein controls wing development in Dros ophila by regulating the expression of numerous target genes and forming a complex with the Vestigial protein. We show that binding of Vestigial to Sc alloped switches the DNA-binding selectivity of Scalloped. Two conserved do mains of the Vestigial protein that are not required for Scalloped binding in solution are required for the formation of the heterotetrameric Vestigia l-Scalloped complex on DNA. We suggest that Vestigial affects the conformat ion of Scalloped to create a wing cell-specific DNA-binding selectivity. Th e modification of selector protein DNA-binding specificity by co-factors ap pears to be a general mechanism for regulating their target selectivity in vivo.