Identification and characterization of the promoter for the gene encoding the human myeloid IgA Fc receptor (FcαR, CD89)

The Fc receptor for IgA (FcαR, 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 FcαR promoter. A 929-bp fragment of FcαR 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-κB-binding site, an Sp1 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 FcαR 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 FcαR-mediated immune system, and provide new insights into the mechanism(s) underlying altered FcαR expression associated with diseases such as allergic diseaes and IgA nephropathy.