STRUCTURE OF THE HUMAN HISTAMINE H1 RECEPTOR GENE

Histamine H1 receptor expression has been reported to change in disord ers such as allergic rhinitis, autoimmune myocarditis, rheumatoid arth ritis and atherosclerosis. Here we report the isolation and characteri zation of genomic clones containing the 5' flanking (regulatory) regio n of the human histamine H1 receptor gene. An intron of approx. 5.8 kb was identified in the 5' untranslated region, which suggests that an entire subfamily of G-protein-coupled receptors may contain an intron immediately upstream of the start codon. The transcription initiation site was mapped by 5' rapid amplification of cDNA ends to a region 6.2 kb upstream of the start codon. Immediately upstream of the transcrip tion start site a fragment of 1.85 kb was identified that showed promo ter activity when placed upstream of a luciferase reporter gene and tr ansiently transfected into cells expressing the histamine HI receptor. The promoter sequence shares a number of characteristics with the pro moter sequences of other G-protein-coupled receptor encoding genes, in cluding binding sites for several transcription factors, and the absen ce of TATA and CAAT sequences at the appropriate locations. The promot er sequence described here differs from that reported previously [Fuku i, Fujimoto, Mizuguchi, Sakamoto, Horio, Takai, Yamada and Ito (1994) Biochem. Biophys. Res. Commun. 201, 894-901] because the reported geno mic clone was chimaeric. Furthermore our study provides evidence that the 3' untranslated region of the H1 receptor mRNA is much longer than previously accepted. Together, these findings provide a complete view of the structure of the human histamine H1 receptor gene. Both the co ding region of the H1 receptor gene and its promoter region were indep endently mapped to chromosome 3p25.