The DNA binding specificity of Ultrabithorax is modulated by cooperative interactions with extradenticle, another homeoprotein.

The Ultrabithorax (Ubx) and Antennapedia (Antp) genes of Drosophila encode homeodomain proteins that have very similar DNA binding specificities in vitro but specify the development of different segmental patterns in vivo. We describe cooperative interactions between Ubx protein and a divergent homeodomain protein, extradenticle (exd), that selectively 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 form of Ubx. Thus, the ability of different homeotic genes to specify distinct segmental patterns may depend on cooperative interactions with proteins such as exd that selectively modulate their otherwise similar DNA binding specificities.