REGULATION OF SEGMENTATION AND SEGMENTAL IDENTITY BY DROSOPHILA HOMEOPROTEINS - THE ROLE OF DNA-BINDING IN FUNCTIONAL-ACTIVITY AND SPECIFICITY

Recent advances have shed new light on how the Q50 homeoproteins act i n Drosophila. These transcription factors hare remarkably similar and promiscuous DNA-binding specificities in vitro; Set they each specify distinct developmental fates in vivo, One current model suggests that, because the Q50 homeoproteins have distinct biological functions, the y must each regulate different target genes, According to this 'co-sel ective binding' model, significant binding of Q50 homeoproteins to fun ctional DNA elements in vivo would be dependent upon cooperative inter actions with other transcription factors (cofactors), If the Q50 homeo proteins each interact differently with cofactors, they could be selec tively targeted to unique, limited subsets of their in vitro recogniti on sites and thus control different genes, However, a variety of exper iments question this model, Molecular and genetic experiments suggest that the Q50 homeoproteins do not regulate very distinct sets of genes , Instead, they mostly control the expression of a large number of sha red targets, The distinct morphogenic properties of the various Q50 ho meoproteins may principally result from the different manners in which they either activate or repress these common targets, Further, in viv o binding studies indicate that at least two Q50 homeoproteins have ve ry broad and similar DNA-binding specificities in embryos, a result th at is inconsistent with the 'co-selective binding' model, Based on the se and other data, we suggest that Q50 homeoproteins bind many of thei r recognition sites without the aid of cofactors, In this 'widespread binding' model, cofactors act mainly by helping to distinguish the way in which homeoproteins regulate targets to which they are already bou nd.