Sequence and functional analysis of an upstream regulatory region of human HOXA7 gene.

The Hox genes have been known to be involved in pattern formation during vertebrate development through differential expression along the anteroposterior body axis. Human homologue of position-specific regulatory region of murine Hoxa-7 was cloned from human genomic library. The restriction map of the 18-kb insert was determined, of which a 3.9-kb region was sequenced. Homology plot between the murine and the corresponding human sequence showed high sequence conservation over 70% in several regions. The homologous region has been reduced to about 1.1 kb (HCR: human control region), which contained several putative factor binding sites. The function of HCR was analyzed in transgenic mice and turned out to be a position-specific regulatory element of human, setting the precise anterior boundary of expression in transgenic embryos; at day 12.5 post-coitum a distinct anterior limit of expression was noted at the level of C5 in neural tube and spinal ganglia in transgenic embryos. These results indicate that the regulatory sequences as well as the molecular mechanism for Hox gene expression are highly conserved among vertebrates.