THE DNA-BINDING SPECIFICITY OF ULTRABITHORAX IS MODULATED BY COOPERATIVE INTERACTIONS WITH EXTRADENTICLE, ANOTHER HOMEOPROTEIN

The Ultrabithorax (Ubx) and Antennapedia (Antp) genes of Drosophila en code homeodomain proteins that have very similar DNA binding specifici ties in vitro but specify the development of different segmental patte rns in vivo. We describe cooperative interactions between Ubx protein and a divergent homeodomain protein, extradenticle (exd), that selecti vely increases the affinity of Ubx, but not Antp, for a particular DNA target. We also provide evidence that Ubx and exd bind to neighboring sites on this DNA and interact directly to stabilize the DNA-bound fo rm of Ubx. Thus, the ability of different homeotic genes to specify di stinct segmental patterns may depend on cooperative interactions with proteins such as exd that selectively modulate their otherwise similar DNA binding specificities.