Several regions of Antennapedia and thyroid transcription factor 1 homeodomains contribute to DNA binding specificity.

The DNA binding specificities of the homeodomains contained in thyroid transcription factor 1 and Antennapedia have been compared. The two homeodomains recognize different DNA sequences, despite the similar amino acid sequences of their recognition helix. Mutations that make the recognition helix of thyroid transcription factor 1 identical to the one contained in Antennapedia have no effects on the binding specificity of thyroid transcription factor 1. The exchange of other segments between these two homeodomains allows the identification of the regions responsible for the observed DNA binding specificities. These results indicate that amino acid residues outside of the recognition helix play an important role in the determination of the DNA binding specificities of these two homeodomains.