CLONING OF THE GENE CODING FOR A HUMAN RECEPTOR FOR FORMYL PEPTIDES - CHARACTERIZATION OF A PROMOTER REGION AND EVIDENCE FOR POLYMORPHIC EXPRESSION

被引:24
作者
PEREZ, HD [1 ]
HOLMES, R [1 ]
KELLY, E [1 ]
MCCLARY, J [1 ]
CHOU, Q [1 ]
ANDREWS, WH [1 ]
机构
[1] BERLEX BIOSCI,DEPT MOLEC BIOL,S SAN FRANCISCO,CA 94080
关键词
D O I
10.1021/bi00161a044
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recently we reported that, in HL-60 cells, transcription of the formyl peptide receptor (FPR) gene can be up- and downregulated by agents that induce differentiation of HL-60 cells into neutrophils. To begin studying the mechanisms involved in regulation of FPR gene expression, we cloned two human cDNAs and the gene coding for FPR. The genomic clone (pINF14) contained a 14.5-kb insert. A 2.7-kb EcoRI fragment was obtained from pINF14 that hybridized with an FPR open reading frame probe. The EcoRI fragment was sequenced and found to contain an intronless FPR open reading frame. Sequence alignment of the EcoRI genomic fragment with the FPR cDNA revealed that the first 31 bases of 5' untranslated FPR cDNA were not represented in the genomic fragment. Furthermore, a splicing consensus sequence was present in the genomic fragment at the site of divergence with the cDNA sequence. Restriction mapping and Southern blot analysis identified a 121-bp fragment that contained the sequence corresponding to the first 31 bases of 5' untranslated FPR cDNA. An additional (previously undescribed) 15-bp cDNA sequence in the 5' end of FPR were identified using an anchored polymerase chain reaction. This sequence was also contained in the genomic 121-bp fragment. This 121-bp fragment was located 5.2 kb (intron) upstream of the FPR open reading frame. It contained an unusual TATA box and displayed transcriptional activity in vitro and in vivo. Potential binding sites for AP-1 and glucocorticoid receptor were identified upstream of the putative TATA box. This genomic organization has not been reported previously in a gene coding for a seven transmembrane domain receptor. Furthermore, comparison of human FPR cDNAs with the FPR gene suggests that FPR is expressed as allelic forms of a polymorphic gene.
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页码:11595 / 11599
页数:5
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