C/EBPα and Ets Protein Family Members Regulate the Human Myeloid IgA Fc Receptor (FcαR, CD89) Promoter

摘要

FcαR (CD89), the FcR for IgA, is expressed exclusively in myeloid cells, including monocytes/macrophages, neutrophils, and eosinophils, and is thought to mediate IgA-triggered cellular functions in immunity. Here we demonstrate that the FcαR 5′-flanking region from ?102 to ?64 relative to the ATG translation initiation codon is essential for promoter activity and contains two functional binding motifs for C/EBP and Ets family members at ?74 and ?92, respectively. EMSAs and cotransfection experiments show that C/EBPα acts as a major activator of the FcαR promoter at least in immature myeloid cells. In addition, we found two additional functional targets of C/EBPα at ?139 and ?127. On the other hand, the FcαR Ets binding motif could bind Elf-1 and mediate the trans -activation by cotransfected Elf-1, but a major component of the complex forming on this site appears to be an unidentified Ets-like nuclear protein that is preferentially detected in cells of hemopoietic origin. Furthermore, separation of the C/EBP and Ets binding sites reduces FcαR promoter activity, suggesting some functional interaction between these factors. As the in vivo role of FcαR is still incompletely defined, these findings reveal the features controlling the FcαR promoter in myeloid lineage and provide a foundation for clarifying regulatory mechanisms of FcαR gene expression associated with its potential roles.