Comparative structural and functional analysis of the olfactory receptor genes flanking the human and mouse beta-globin gene clusters

By sequencing regions flanking the beta -globin gene complex in mouse (Hbbc ) and human (HBBC), we have shown that the beta -globin gene cluster is sur rounded by a larger duster of olfactory receptor genes (ORGs). To facilitat e sequence comparisons and to investigate the regulation of ORC expression, we have mapped 5' sequences of mRNA from olfactory epithelium encoding bet a -globin-proximal ORGs. We have found that several of these genes contain multiple noncoding exons that can be alternatively spliced. Surprisingly, t he only common motifs found in the promoters of these genes are a "TATA" bo x and a purine-rich motif. Sequence comparisons between human and mouse rev eal that most of the conserved regions are confined to the coding regions a nd transcription units of the genes themselves, but a few blocks of conserv ed sequence also are found outside of ORG transcription units. The possible influence of beta -globin regulatory sequences on ORG expression in olfact ory epithelium was tested in mice containing a deletion of the endogenous b eta -globin locus control region, but no change in expression of the neighb oring ORGs was detected. We evaluate the implications of these results for possible mechanisms of regulation of ORG transcription.