Lecture 11 and 12
Basis for Hox specificity
Introduction: The homeotic (Hox) genes are a highly conserved set of genes that encode transcription factors that are important in specifying cell fate along the anterior-posterior body axis. Hox gene expression is spatially regulated, and it is their unique expression patterns that is responsible for bringing about the formation of appropriate structures in appropriate segments. Homeotic genes were first identified as dominant mutations that changed the identity of structures. One of the best studied examples of these is the gene Antennapedia (Antp), which as the name suggests, causes the transformation of antennal structures to the corresponding (homologous) leg structures.
There are eight Hox genes in Drosophila, all of which bind DNA through their homeodomain (see lecture 9). The eight genes are located within two clusters, the Antennepedia complex (ANT-C) which regulates the formation of head and anterior thoracic segments, and the bithorax complex (BX-C), which regulates the formation of posterior thoracic segments and abdominal segments. Hox genes show colinearity; more 3' genes on the clusters have more anterior boundaries of expression in the developing embryo.
Although HOX proteins, which all contain a homeodomain, bind to DNA in a sequence-specific manner, their DNA binding specificities usually overlap. For example, the HOX proteins Antennapedia (ANTP) and Ultrabithorax (UBX) have indistinguishable DNA binding specificities in vitro yet generate very different identities in vivo. The paper we are discussing today attempts to explain this problem. The major finding is that HOX specificity, albeit UBX specificity, is controlled, at least in part, by cofactors that cooperatively bind with it to DNA. This cofactor is the homeodomain protein encoded by the gene extradenticle (exd).
The DNA binding specificity of Ultrabithorax is modulated by cooperative interactions with extradenticle, another homeoprotein.
Chan SK, Jaffe L, Capovilla M, Botas J, Mann RS.
Department of Biochemistry and Molecular Biophysics, Columbia
University, New York, New York 10032.
Cell. 1994 Aug 26;78(4):603-15.