Identification and characterization of the promoter for the gene encoding the human myeloid IgA Fc receptor (FcalphaR, CD89).
The Fc receptor for IgA (FcalphaR, CD89), a transmembrane glycoprotein, is expressed exclusively on human phagocytic cells including monocytes, macrophages, eosinophils, and neutrophils, and is capable of triggering various effector functions. In the present study, we identified and characterized, for the first time, the FcalphaR promoter. A 929-bp fragment of FcalphaR 5'-flanking sequence directed expression of a reporter gene specifically in monocytic cell line U937. Deletion analyses localized element(s) directing tissue-specific reporter gene expression to the 259 bp proximal to the translation initiation site. Within the region, the sequence between 59 and 197 bp downstream of the major transcription start site was shown to be essential for promoter activity. This sequence contains multiple potential binding sites for transcription factors which have been reported to function in myeloid-specific gene expression, including three CCAAT enhancer-binding protein (C/EBP)-binding sites, an NF-kappaB-binding site, an Spl site, an Ets family protein consensus-binding site, and a Myb-binding site. In addition, we identified two polymorphisms (C-->T transition) at the positions 114 bp upstream and 56 bp downstream of the major transcription start site, and demonstrated that the FcalphaR promoter region carrying both the -114T and +56T alleles had significantly lower promoter activity than that harboring the C alleles at both sites. Characterization of this promoter will facilitate further analyses of activation stimuli and transcription factors involved in FcalphaR-mediated immune system, and provide new insights into the mechanism(s) underlying altered FcalphaR expression associated with diseases such as allergic diseaes and IgA nephropathy.
Shimokawa
T
T
Allergy Research Center, Juntendo University School of Medicine, Tokyo, Japan.
Tsuge
T
T
Okumura
K
K
Ra
C
C
D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D006367:HeLa Cells; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011401:Promoter Regions, Genetic; D011961:Receptors, Fc / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D017384:Sequence Deletion; D020079:Terminal Repeat Sequences; D020298:U937 Cells
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc