C/EBP alpha and Ets protein family members regulate the human myeloid IgA Fc receptor (Fc alpha R, CD89) promoter.
Fc alpha R (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 Fc alpha R 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/EBP alpha acts as a major activator of the Fc alpha R promoter at least in immature myeloid cells. In addition, we found two additional functional targets of C/EBP alpha at -139 and -127. On the other hand, the Fc alpha R 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 Fc alpha R promoter activity, suggesting some functional interaction between these factors. As the in vivo role of Fc alpha R is still incompletely defined, these findings reveal the features controlling the Fc alpha R promoter in myeloid lineage and provide a foundation for clarifying regulatory mechanisms of Fc alpha R gene expression associated with its potential roles.
Shimokawa
Toshibumi
T
Allergy Research Center and Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Ra
Chisei
C
D020121:5' Untranslated Regions / Q000737:chemistry / Q000276:immunology; D020816:Amino Acid Motifs / Q000235:genetics / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018387:Codon, Initiator / Q000737:chemistry / Q000276:immunology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D036383:Ephrin-A2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000276:immunology*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050783:Proto-Oncogene Proteins c-ets; D011961:Receptors, Fc / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation / Q000276:immunology; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D020121:5' Untranslated Regions; D015703:Antigens, CD; D022763:CCAAT-Enhancer-Binding Protein-alpha; D018387:Codon, Initiator; D004268:DNA-Binding Proteins; D036383:Ephrin-A2; C036832:Fc(alpha) receptor; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011961:Receptors, Fc; D015534:Trans-Activators; D014157:Transcription Factors