Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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5' Untranslated Regions / chemistry
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5' Untranslated Regions / immunology
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Amino Acid Motifs / genetics
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Amino Acid Motifs / immunology
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Antigens, CD / genetics*
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Antigens, CD / metabolism*
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Base Sequence
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Binding Sites / genetics
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Binding Sites / immunology
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CCAAT-Enhancer-Binding Protein-alpha / genetics
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CCAAT-Enhancer-Binding Protein-alpha / metabolism
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CCAAT-Enhancer-Binding Protein-alpha / physiology*
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Codon, Initiator / chemistry
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Codon, Initiator / immunology
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / metabolism
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Ephrin-A2 / genetics
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Ephrin-A2 / metabolism
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Gene Expression Regulation / immunology*
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HeLa Cells
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Humans
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Jurkat Cells
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Molecular Sequence Data
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Multigene Family / immunology
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Myeloid Cells / immunology*
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Myeloid Cells / metabolism*
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Promoter Regions, Genetic / immunology*
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Protein Binding / genetics
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Protein Binding / immunology
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-ets
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Receptors, Fc / antagonists & inhibitors
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Receptors, Fc / genetics*
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Receptors, Fc / metabolism*
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Trans-Activators / physiology
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / physiology*
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Transcriptional Activation / immunology
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Tumor Cells, Cultured
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U937 Cells
Substances
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5' Untranslated Regions
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Antigens, CD
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CCAAT-Enhancer-Binding Protein-alpha
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Codon, Initiator
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DNA-Binding Proteins
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Ephrin-A2
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Fc(alpha) receptor
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-ets
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Receptors, Fc
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Trans-Activators
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Transcription Factors