PH-DEPENDENT ENCHANCEMENT OF DNA-BINDING BY THE ULTRABITHORAX HOMEODOMAIN

Ultrabithorax (Ubx) and Deformed (Dfd) proteins of Drosophila melanoga ster contain homeodomains (HD) that are structurally similar and recog nize similar DNA sequences, despite functionally distinct genetic regu latory roles for Ubx and Dfd. We report in the present study that Ubx- HD binding to a single optimal target site displayed significantly inc reased affinity and higher salt concentration dependence at lower pH, while Dfd-HD binding to DNA was unaffected by pH. Results from studies of chimeric Ubx-Dfd homeodomains showed that the N- and C-terminal re gions of the Ubx-HD are required Tor this pH dependence. The increase in binding affinity at lower pH was greater for the Ubx optimal bindin g site than for other DNA binding sites, indicating that subtle sequen ce alterations in DNA binding sites may influence pH-dependent behavio r. These data demonstrate enhanced DNA binding affinity at lower pH fo r the Ubx-HD in vitro and suggest the potential for significant discri mination of DNA binding sites in vivo.