Abstract
Histamine H1 receptor expression has been reported to change in disorders such as allergic rhinitis, autoimmune myocarditis, rheumatoid arthritis and atherosclerosis. Here we report the isolation and characterization of genomic clones containing the 5' flanking (regulatory) region 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 transcription start site a fragment of 1.85 kb was identified that showed promoter activity when placed upstream of a luciferase reporter gene and transiently transfected into cells expressing the histamine H1 receptor. The promoter sequence shares a number of characteristics with the promoter sequences of other G-protein-coupled receptor encoding genes, including binding sites for several transcription factors, and the absence of TATA and CAAT sequences at the appropriate locations. The promoter sequence described here differs from that reported previously [Fukui, Fujimoto, Mizuguchi, Sakamoto, Horio, Takai, Yamada and Ito (1994) Biochem. Biophys. Res. Commun. 201, 894-901] because the reported genomic 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 coding region of the H1 receptor gene and its promoter region were independently mapped to chromosome 3p25.
Full Text
The Full Text of this article is available as a PDF (759.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adcock I. M. Transcription factors as activators of gene transcription: AP-1 and NF-kappa B. Monaldi Arch Chest Dis. 1997 Apr;52(2):178–186. [PubMed] [Google Scholar]
- Aird W. C., Parvin J. D., Sharp P. A., Rosenberg R. D. The interaction of GATA-binding proteins and basal transcription factors with GATA box-containing core promoters. A model of tissue-specific gene expression. J Biol Chem. 1994 Jan 14;269(2):883–889. [PubMed] [Google Scholar]
- Arias-Montaño J. A., Young J. M. Characteristics of histamine H1 receptors on HeLa cells. Eur J Pharmacol. 1993 May 15;245(3):291–295. doi: 10.1016/0922-4106(93)90110-u. [DOI] [PubMed] [Google Scholar]
- Augustin L. B., Felsheim R. F., Min B. H., Fuchs S. M., Fuchs J. A., Loh H. H. Genomic structure of the mouse delta opioid receptor gene. Biochem Biophys Res Commun. 1995 Feb 6;207(1):111–119. doi: 10.1006/bbrc.1995.1160. [DOI] [PubMed] [Google Scholar]
- Bristow D. R., Zamani M. R. Desensitization of histamine H1 receptor-mediated inositol phosphate production in HeLa cells. Br J Pharmacol. 1993 Jun;109(2):353–359. doi: 10.1111/j.1476-5381.1993.tb13577.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen W. M., Chang A. C., Wang C. M., Lin C. C., Chang N. C. Characterization of the regulatory regions of murine alpha 2C2 adrenoceptor subtype gene. Neurosci Lett. 1996 May 24;210(1):33–36. doi: 10.1016/0304-3940(96)12652-5. [DOI] [PubMed] [Google Scholar]
- De Backer M. D., Gommeren W., Moereels H., Nobels G., Van Gompel P., Leysen J. E., Luyten W. H. Genomic cloning, heterologous expression and pharmacological characterization of a human histamine H1 receptor. Biochem Biophys Res Commun. 1993 Dec 30;197(3):1601–1608. doi: 10.1006/bbrc.1993.2662. [DOI] [PubMed] [Google Scholar]
- Dufau M. L., Tsai-Morris C. H., Hu Z. Z., Buczko E. Structure and regulation of the luteinizing hormone receptor gene. J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):283–291. doi: 10.1016/0960-0760(95)00115-g. [DOI] [PubMed] [Google Scholar]
- Fujimoto K., Horio Y., Sugama K., Ito S., Liu Y. Q., Fukui H. Genomic cloning of the rat histamine H1 receptor. Biochem Biophys Res Commun. 1993 Jan 15;190(1):294–301. doi: 10.1006/bbrc.1993.1045. [DOI] [PubMed] [Google Scholar]
- Fukui H., Fujimoto K., Mizuguchi H., Sakamoto K., Horio Y., Takai S., Yamada K., Ito S. Molecular cloning of the human histamine H1 receptor gene. Biochem Biophys Res Commun. 1994 Jun 15;201(2):894–901. doi: 10.1006/bbrc.1994.1786. [DOI] [PubMed] [Google Scholar]
- Fukui H. [Structure of the histamine H1 receptor gene and transcriptional up-regulation of the H1 receptor]. Nihon Rinsho. 1996 Feb;54(2):389–395. [PubMed] [Google Scholar]
- Goren N., Perez Leiros C., Sterin-Borda L., Borda E. Effect of histamine in autoimmune myocarditis mice. Int J Immunopharmacol. 1994 Sep;16(9):737–745. doi: 10.1016/0192-0561(94)90093-0. [DOI] [PubMed] [Google Scholar]
- Greenwood M. T., Robertson L. A., Patel Y. C. Cloning of the gene encoding human somatostatin receptor 2: sequence analysis of the 5'-flanking promoter region. Gene. 1995 Jul 4;159(2):291–292. doi: 10.1016/0378-1119(95)00059-f. [DOI] [PubMed] [Google Scholar]
- Hahn S., Buratowski S., Sharp P. A., Guarente L. Yeast TATA-binding protein TFIID binds to TATA elements with both consensus and nonconsensus DNA sequences. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5718–5722. doi: 10.1073/pnas.86.15.5718. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamano N., Terada N., Maesako K., Ikeda T., Fukuda S., Wakita J., Yamashita T., Konno A. Expression of histamine receptors in nasal epithelial cells and endothelial cells--the effects of sex hormones. Int Arch Allergy Immunol. 1998 Mar;115(3):220–227. doi: 10.1159/000023904. [DOI] [PubMed] [Google Scholar]
- Hardy E., Farahani M., Hall I. P. Regulation of histamine H1 receptor coupling by dexamethasone in human cultured airway smooth muscle. Br J Pharmacol. 1996 Jun;118(4):1079–1084. doi: 10.1111/j.1476-5381.1996.tb15509.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heng H. H., Squire J., Tsui L. C. High-resolution mapping of mammalian genes by in situ hybridization to free chromatin. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9509–9513. doi: 10.1073/pnas.89.20.9509. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heng H. H., Tsui L. C. Modes of DAPI banding and simultaneous in situ hybridization. Chromosoma. 1993 May;102(5):325–332. doi: 10.1007/BF00661275. [DOI] [PubMed] [Google Scholar]
- Horio Y., Mori Y., Higuchi I., Fujimoto K., Ito S., Fukui H. Molecular cloning of the guinea-pig histamine H1 receptor gene. J Biochem. 1993 Sep;114(3):408–414. doi: 10.1093/oxfordjournals.jbchem.a124190. [DOI] [PubMed] [Google Scholar]
- Huylebroeck D., Maertens G., Verhoeyen M., Lopez C., Raeymakers A., Jou W. M., Fiers W. High-level transient expression of influenza virus proteins from a series of SV40 late and early replacement vectors. Gene. 1988 Jun 30;66(2):163–181. doi: 10.1016/0378-1119(88)90354-x. [DOI] [PubMed] [Google Scholar]
- Ikuyama S., Nawata H. [Structure and function of the promoter region of the TSH receptor gene]. Nihon Rinsho. 1994 Apr;52(4):962–968. [PubMed] [Google Scholar]
- Inoue I., Taniuchi I., Kitamura D., Jenkins N. A., Gilbert D. J., Copeland N. G., Watanabe T. Characteristics of the mouse genomic histamine H1 receptor gene. Genomics. 1996 Aug 15;36(1):178–181. doi: 10.1006/geno.1996.0441. [DOI] [PubMed] [Google Scholar]
- Iriyoshi N., Takeuchi K., Yuta A., Ukai K., Sakakura Y. Increased expression of histamine H1 receptor mRNA in allergic rhinitis. Clin Exp Allergy. 1996 Apr;26(4):379–385. [PubMed] [Google Scholar]
- Javahery R., Khachi A., Lo K., Zenzie-Gregory B., Smale S. T. DNA sequence requirements for transcriptional initiator activity in mammalian cells. Mol Cell Biol. 1994 Jan;14(1):116–127. doi: 10.1128/mcb.14.1.116. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Le Coniat M., Traiffort E., Ruat M., Arrang J. M., Berger R. Chromosomal localization of the human histamine H1-receptor gene. Hum Genet. 1994 Aug;94(2):186–188. doi: 10.1007/BF00202867. [DOI] [PubMed] [Google Scholar]
- Lee S. H., Minowa M. T., Mouradian M. M. Two distinct promoters drive transcription of the human D1A dopamine receptor gene. J Biol Chem. 1996 Oct 11;271(41):25292–25299. doi: 10.1074/jbc.271.41.25292. [DOI] [PubMed] [Google Scholar]
- Leurs R., Traiffort E., Arrang J. M., Tardivel-Lacombe J., Ruat M., Schwartz J. C. Guinea pig histamine H1 receptor. II. Stable expression in Chinese hamster ovary cells reveals the interaction with three major signal transduction pathways. J Neurochem. 1994 Feb;62(2):519–527. doi: 10.1046/j.1471-4159.1994.62020519.x. [DOI] [PubMed] [Google Scholar]
- Liu C. H., Hla T. The mouse gene for the inducible G-protein-coupled receptor edg-1. Genomics. 1997 Jul 1;43(1):15–24. doi: 10.1006/geno.1997.4759. [DOI] [PubMed] [Google Scholar]
- Max S. I., Chowdhury B. A., Fraser C. M. Sequence analysis of the 5'-untranslated region of the human H1 histamine receptor-encoding gene. Gene. 1996 Jun 1;171(2):309–310. doi: 10.1016/0378-1119(96)00036-4. [DOI] [PubMed] [Google Scholar]
- McCuaig K. A., Clarke J. C., White J. H. Molecular cloning of the gene encoding the mouse parathyroid hormone/parathyroid hormone-related peptide receptor. Proc Natl Acad Sci U S A. 1994 May 24;91(11):5051–5055. doi: 10.1073/pnas.91.11.5051. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Minowa M. T., Minowa T., Mouradian M. M. Activator region analysis of the human D1A dopamine receptor gene. J Biol Chem. 1993 Nov 5;268(31):23544–23551. [PubMed] [Google Scholar]
- Minowa T., Minowa M. T., Mouradian M. M. Negative modulator of the rat D2 dopamine receptor gene. J Biol Chem. 1994 Apr 15;269(15):11656–11662. [PubMed] [Google Scholar]
- Mitsuhashi M., Payan D. G. Functional diversity of histamine and histamine receptors. J Invest Dermatol. 1992 Jun;98(6 Suppl):8S–11S. doi: 10.1111/1523-1747.ep12462089. [DOI] [PubMed] [Google Scholar]
- Moguilevsky N., Varsalona F., Guillaume J. P., Noyer M., Gillard M., Daliers J., Henichart J. P., Bollen A. Pharmacological and functional characterisation of the wild-type and site-directed mutants of the human H1 histamine receptor stably expressed in CHO cells. J Recept Signal Transduct Res. 1995 Jan-Mar;15(1-4):91–102. doi: 10.3109/10799899509045210. [DOI] [PubMed] [Google Scholar]
- Murasawa S., Matsubara H., Kijima K., Maruyama K., Mori Y., Inada M. Structure of the rat V1a vasopressin receptor gene and characterization of its promoter region and complete cDNA sequence of the 3'-end. J Biol Chem. 1995 Aug 25;270(34):20042–20050. doi: 10.1074/jbc.270.34.20042. [DOI] [PubMed] [Google Scholar]
- Negro-Alvarez J. M., Funes E., García Cánovas A., Hernández J., García-Sellés F. J., Pagán J. A., López-Sánchez J. D. Antiallergic properties of antihistamines. Allergol Immunopathol (Madr) 1996 Jul-Aug;24(4):177–183. [PubMed] [Google Scholar]
- Padgett R. A., Grabowski P. J., Konarska M. M., Seiler S., Sharp P. A. Splicing of messenger RNA precursors. Annu Rev Biochem. 1986;55:1119–1150. doi: 10.1146/annurev.bi.55.070186.005351. [DOI] [PubMed] [Google Scholar]
- Parks C. L., Shenk T. The serotonin 1a receptor gene contains a TATA-less promoter that responds to MAZ and Sp1. J Biol Chem. 1996 Feb 23;271(8):4417–4430. doi: 10.1074/jbc.271.8.4417. [DOI] [PubMed] [Google Scholar]
- Shiozawa S., Shimizu K., Tanaka K., Hino K. Studies on the contribution of c-fos/AP-1 to arthritic joint destruction. J Clin Invest. 1997 Mar 15;99(6):1210–1216. doi: 10.1172/JCI119277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Singer V. L., Wobbe C. R., Struhl K. A wide variety of DNA sequences can functionally replace a yeast TATA element for transcriptional activation. Genes Dev. 1990 Apr;4(4):636–645. doi: 10.1101/gad.4.4.636. [DOI] [PubMed] [Google Scholar]
- Smale S. T. Transcription initiation from TATA-less promoters within eukaryotic protein-coding genes. Biochim Biophys Acta. 1997 Mar 20;1351(1-2):73–88. doi: 10.1016/s0167-4781(96)00206-0. [DOI] [PubMed] [Google Scholar]
- Takagishi T., Sasaguri Y., Nakano R., Arima N., Tanimoto A., Fukui H., Morimatsu M. Expression of the histamine H1 receptor gene in relation to atherosclerosis. Am J Pathol. 1995 Apr;146(4):981–988. [PMC free article] [PubMed] [Google Scholar]
- Teurich S., Angel P. The glucocorticoid receptor synergizes with Jun homodimers to activate AP-1-regulated promoters lacking GR binding sites. Chem Senses. 1995 Apr;20(2):251–255. doi: 10.1093/chemse/20.2.251. [DOI] [PubMed] [Google Scholar]
- Timmerman H. Cloning of the H1 histamine receptor. Trends Pharmacol Sci. 1992 Jan;13(1):6–7. doi: 10.1016/0165-6147(92)90003-o. [DOI] [PubMed] [Google Scholar]
- Tsai-Morris C. H., Buczko E., Geng Y., Gamboa-Pinto A., Dufau M. L. The genomic structure of the rat corticotropin releasing factor receptor. A member of the class II G protein-coupled receptors. J Biol Chem. 1996 Jun 14;271(24):14519–14525. doi: 10.1074/jbc.271.24.14519. [DOI] [PubMed] [Google Scholar]
- Wood I. C., Roopra A., Buckley N. J. Neural specific expression of the m4 muscarinic acetylcholine receptor gene is mediated by a RE1/NRSE-type silencing element. J Biol Chem. 1996 Jun 14;271(24):14221–14225. doi: 10.1074/jbc.271.24.14221. [DOI] [PubMed] [Google Scholar]
- Wood I. C., Roopra A., Harrington C., Buckley N. J. Structure of the m4 cholinergic muscarinic receptor gene and its promoter. J Biol Chem. 1995 Dec 29;270(52):30933–30940. doi: 10.1074/jbc.270.52.30933. [DOI] [PubMed] [Google Scholar]
- Yamashita M., Fukui H., Sugama K., Horio Y., Ito S., Mizuguchi H., Wada H. Expression cloning of a cDNA encoding the bovine histamine H1 receptor. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11515–11519. doi: 10.1073/pnas.88.24.11515. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Young K. W., Young J. M. Potentiation by 1,4-dithiothreitol of histamine-induced inositol phosphate formation in rat cerebral cortex and human HeLa cells. Eur J Pharmacol. 1994 Nov 15;269(3):283–292. doi: 10.1016/0922-4106(94)90035-3. [DOI] [PubMed] [Google Scholar]
- Zamani R., Bristow D. R. Desensitisation of histamine H1 receptor-mediated calcium mobilisation in HeLa cells: the role of protein kinase C. Biochem Soc Trans. 1993 Nov;21(4):382S–382S. doi: 10.1042/bst021382s. [DOI] [PubMed] [Google Scholar]
- Zenmyo M., Hiraoka K., Sasaguri T., Komiya S., Inoue A., Morimatsu M., Sasaguri Y. Interleukin-4 stimulates rheumatoid synovial fibroblasts to express matrix metalloproteinase-1 (tissue collagenase) and histamine H1 receptor mRNA. Biochem Mol Biol Int. 1996 Dec;40(6):1253–1260. doi: 10.1080/15216549600201903. [DOI] [PubMed] [Google Scholar]