Reexamining the DNA target selectivity of Scalloped.

Selector proteins are transcription factors that coordinate the formation and identity of organs and appendages. The proper formation of these tissues requires the selector proteins to regulate the expression of a large set of genes. Many selector proteins are involved in regulating multiple developmental processes, yet it is not completely clear how they are able to activate different sets of genes in a tissue-specific manner. An association with cofactors is thought to be one method by which enhancer selectivity is achieved. During wing development the selector protein Scalloped (SD) interacts with the cofactor Vestigial (VG). This interaction leads to the activation of a specific set of downstream wing genes. Herein, data are presented indicating that the switch in binding selectivity is likely achieved by VG altering the general affinity that the SD protein has for DNA. The decreased affinity for DNA is compensated for by the fact that the VG protein forms a complex containing two SD proteins. These two properties ensure that the SD-VG complex is able to bind only to enhancers that have two consecutive binding sites. Furthermore, data are presented that indicate that the function of the two terminal domains of the VG protein is not restricted to activating transcription and promoting the recruitment of two SD proteins.