A universal target sequence is bound in vitro by diverse homeodomains.

To determine the number of DNA binding proteins capable of binding a consensus Engrailed binding site, this consensus sequence was used to screen a library of Drosophila cDNA clones in a bacteriophage expression vector. We retrieved clones encoding 20 distinct DNA binding domains, 17 of which are homeodomains. Binding to a variety of oligonucleotides confirms the related sequence specificity of the retrieved binding domains. Nonetheless, the homeodomains have remarkably diverse amino acid sequences. We conclude that during the evolutionary divergence of homeodomains, the specificity of DNA binding has been much more highly conserved than the amino acid sequence.