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

The Fe receptor for IgA (Fc alpha R, CD89), a transmembrane glycoprotein, i s expressed exclusively on human phagocytic cells including monocytes, macr ophages, eosinophils, and neutrophils, and is capable of triggering various effector functions. In the present study, we identified and characterized, for the first time, the FcaR promoter. A 929-bp fragment of Fc alpha R 5'- flanking sequence directed expression of a reporter gene specifically in mo nocytic cell line U937. Deletion analyses localized element(s) directing ti ssue-specific reporter gene expression to the 259 bp proximal to the transl ation initiation site. Within the region; the sequence between 59 and 197 b p downstream of the major transcription start site was shown to be essentia l for promoter activity. This sequence contains multiple potential binding sites for transcription factors which have been reported to function in mye loid-specific gene expression, including three CCAAT enhancer-binding prote in (C/EBP)-binding sites, an NF-kappa B-binding site, an Spl site, an Ets f amily protein consensus-binding site, and a Myb-binding site. In addition, we identified two polymorphisms (C->T transition) at the positions 114 bp u pstream and 56 bp downstream of the major transcription start site, and dem onstrated that the FcaR promoter region carrying both the -114T and +56T al leles had significantly lower promoter activity than that harboring the C a lleles at both sites. Characterization of this promoter will facilitate fur ther analyses of activation stimuli and transcription factors involved in F c alpha R-mediated immune system, and provide new insights into the mechani sm(s) underlying altered FcaR expression associated with diseases such as a llergic diseaes and IgA nephropathy.