Structure and expression of the human histamine H4-receptor gene.
We report the characterization by genomics-based approach of the human H4-receptor gene structure. The H4-receptor gene have been mapped by radiation hybrid experiments (Gene Bridge 4) on chromosome 18q11.2, between the AFMBB11WH5 and CHLC.GATA85D10 markers. The H4-receptor gene spans more than 21 kbp and contains three exons separated by two large introns (>7 kbp). RT-PCR analysis showed that the H4-receptor gene encoded a 3.7 kb mRNA which did not seem to be alternatively spliced within its coding region. The H4-receptor transcripts were found to be highly expressed in peripheral tissues implicated in inflammatory responses such as leukocytes, spleen, lung, and liver. In addition, low expression level of the H4-receptor mRNA was also detected in several human brain regions. Analysis of the 5'-flanking region of the H4-receptor gene did not reveal the existence of canonical TATA or CAAT-box. However, several putative regulatory elements mediating TNFalpha or IL-6-stimulated transcriptional activation were detected. The uteroglobin promoter binding factor, known to mediate anti-inflammatory response of uteroglobin, in the lung, was also found in this region. Thus, the description of the H4-receptor gene promoter region will facilitate the elucidation of its transcriptional control by factors secreted during inflammatory responses.
Cogé
F
F
Division de Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, 125 chemin de Ronde, Croissy sur Seine, 78 290, France.
Guénin
S P
SP
Rique
H
H
Boutin
J A
JA
Galizzi
J P
JP
D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D015139:Blotting, Southern; D001921:Brain / Q000378:metabolism; D015698:Genomic Library; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008969:Molecular Sequence Data; D009928:Organ Specificity; D020161:Physical Chromosome Mapping; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D021101:Radiation Hybrid Mapping; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine / Q000235:genetics*; D000074040:Receptors, Histamine H4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013154:Spleen / Q000378:metabolism
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; C418607:HRH4 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4