SWITCHING THE IN-VIVO SPECIFICITY OF A MINIMAL HOX-RESPONSIVE ELEMENT

The homeodomain proteins encoded by the Hox complex genes do not bind DNA with high specificity, In vitro, Hox specificity can be increased by binding to DNA cooperatively with the homeodomain protein extradent icle or its vertebrate homologs, the pbx proteins (together, the PBC f amily), Here we show that a two basepair change in a Hox-PBC binding s ite switches the Hox-dependent expression pattern generated in vivo, f rom labial to Deformed. The change in vivo correlates with an altered Hox binding specificity in vitro, Further, we identify similar Deforme d-PBC binding sites in the Deformed and Hoxb-4 genes and show that the y generate Deformed or Hoxb-4 expression patterns in Drosophila and mo use embryos, respectively, These results suggest a model in which Hox- PBC binding sites play an instructive role in Hox specificity by promo ting the formation of different Hox-PBC heterodimers in vivo. Thus, th e choice of Hox partner, and therefore Hox target genes, depends on su btle differences between Hox-PBC binding sites.