A MODEL FOR EXTRADENTICLE FUNCTION AS A SWITCH THAT CHANGES HOX PROTEINS FROM REPRESSORS TO ACTIVATORS

The Drosophila EXD protein and its mammalian counterparts, the PBX pro teins, have been proposed to function in HOX target selectivity, Here we show that exd function is required for the autoactivation phase of Dfd expression in the posterior head, Mutations that change the affini ty of a small autoactivation element for EXD protein result in corresp onding changes in the element's embryonic activity, Our data suggest t hat the EXD and DFD proteins directly activate this element in maxilla ry cells without cooperatively binding to a specialized heterodimer bi nding site. Based on the types of homeotic transformations and changes in gene expression observed in exd mutant embryos, we propose a new m odel for EXD/PBX action in which these proteins are required for HOX p rotein transcriptional activation functions, but dispensable for HOX t ranscriptional repression functions, Although the selection of a speci fic target gene by a HOX protein versus another may be explained in so me cases by the selective modulation of HOX binding specificity by EXD , we favor the idea that EXD interacts in a more general sense with mo st HOX proteins to switch them into a state where they are capable of transcriptional activation.