Homeodomain

DNA binding protein Homeodomain protein segment bound to DNA.

The homeo box is a recurring motif in genes controlling development in insects and vertebrates. Insect bodies are divided into segments that are formed early in the embryonic process. Drosophilia contains three thoracic segments and eight abdominal ones. Cells of different segments usually retain their identity and do not intermix. However, certain mutations, called homeotic mutations, transform one body part into another. The Antennepedia (Antp) mutation, for example, changes an antenna into a leg. It can be inferred that the normal Antp+ gene determines that legs are formed in the right place. In general, homeotic genes control the fundamental architectural plan of the embryo. The two main clusters of homeotic genes are the Antennepedia complex (ANT-C), which regulates the head and anterior thoracic segments, and the bithorax complex (BX-C), which regulates the posterior thoracic segments and abdominal segments.

These large clusters of homeotic genes have been explored using the technique of chromosome walking. ANT-C is longer than 100kb and BX-C is longer than 310 kb. Hybridization studies revealed that many genes in the clusters contain a common sequence. The recurring motif proved to be a sequence, which was called the homeo box. It encodes a 60 residue protein homeodomain. The high content of basic residues suggested that the homeodomain binds to DNA. Indeed, proteins containing the homeodomain are localized in the nucleus and bind to specific DNA sequences. The homeodomain contains the helix-turn-helix motif that is present in procaryotic DNA-binding proteins such as Cro and lambda repressor.