Structure, Expression and Evolutionary Relationships of Murine Homebox Genes in the Hox 2 Cluster
We have characterized the murine homeobox locus, Hox 2, localized on chromosome 11. This gene complex contains at least seven homeoboxes and represents one of the two major mouse clusters, the other being Hox 1. Analysis of two members in the locus, Hox 2.1 and Hox 2.6, shows that the genes are differentially regulated in embryonal carcinoma cells and have both temporally and spatially restricted patterns of expression in mouse embryos. Analysis of RNA isolated from chick embryos reveals that Hox 2.1 related transcripts are expressed in a pattern similar to mouse embryos, suggesting that regulatory regions may be conserved for this gene in the two species. The predicted protein sequences for these Hox 2 genes contain domains, besides the homeodomain, with substantial homology to other vertebrate and Drosophila homeobox proteins. The data suggest that there has been strong selective pressure to conserve other domains, which may functionally interact with or compliment the homeodomain. Comparison of Hox 2.1 and Hox 2.6 to other mouse homeobox genes reveals close sequence identity to specific genes in the Hox 1 cluster, suggesting that these two loci arose by duplication and divergence of an ancestral cluster. Hox 2.6 itself was found to be related to the human gene C13 and the Xenopus XholA gene. This group of genes is also related to the Drosophila Dfd homeotic gene, and appears to represent a ‘Dfd’ class of vertebrate homeobox gene that arose before the divergence between arthropods and vertebrates. The large degree of identity in several domains of mouse homeobox proteins makes it difficult to identify a role for any particular member without a gene-specific probe. To circumvent this problem we have inserted an additional domain into the Hox 2.1 gene that will generate a modified form of the protein. When tissue-culture cells are transfected with the altered Hox 2.1 constructs, an antibody raised against the marker epitope detects the modified Hox 2.1 protein and shows that it is located in the nucleus.
KeywordsChick Embryo Homeobox Gene Embryonal Carcinoma Cell Homeotic Gene Strong Selective Pressure
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