DNA specificity of the bicoid activator protein is determined by homeodomain recognition helix residue 9

Abstract Formation of anterior structures in the Drosophila embryo requires the product of the gene bicoid . The bicoid protein contains a homeodomain and may exert its effects in early development by regulating transcription of the gap gene, hunchback (hb) . Consistent with this view, we have demonstrated that DNA-bound Bicoid fusion proteins stimulate gene expression. We used the gene activation phenotype in yeast to study DNA recognition by the Bicoid homeodomain. We found that a single amino acid replacement at position 9 of the recognition helix was sufficient to switch the DNA specificity of the Bicoid protein. The altered specificity Bicoid mutants recognized DNA sites bound by Ultrabithorax, fushi tarazu , and other related homeodomain proteins. Our results suggest that DNA specificity in Bicoid and Antennapedia class proteins is determined by recognition helix residue 9.