Abstract
The alpha-chain of the high affinity receptor for IgE (Fc epsilon RI) is essential for cell surface expression of Fc epsilon RI and binding of the IgE Ab. The human alpha-chain gene possesses two promoters: the proximal promoter, which is highly conserved with that of rodent; and the distal promoter, the structure and role of which are largely unknown. Transcriptional regulation of the alpha-chain distal promoter was investigated in this study. Transient reporter assay revealed critical region for transcription activity located within -27/-17. EMSA identified Elf-1, YY1, and PU.1 as transcription factors binding to this region. In contrast to the proximal promoter, which was trans-activated by YY1 and PU.1, these transcription factors exhibited repressive function on this promoter. Addition of IL-4 caused a marked increase in transcription from the distal promoter and subsequently increased the intracellular production of the alpha-chain. These results indicate that IL-4-dependent up-regulation of the human alpha-chain was due to enhancement of distal promoter activity and suggests that the two promoters have different regulatory mechanisms for alpha-chain expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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DNA-Binding Proteins / isolation & purification
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DNA-Binding Proteins / metabolism
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Down-Regulation / genetics
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Down-Regulation / immunology
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Erythroid-Specific DNA-Binding Factors
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Gene Expression Regulation, Neoplastic / immunology*
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Humans
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Interleukin-4 / pharmacology
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Molecular Sequence Data
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Promoter Regions, Genetic / immunology*
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Proto-Oncogene Proteins / isolation & purification
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Proto-Oncogene Proteins / metabolism
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Receptors, IgE / antagonists & inhibitors
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Receptors, IgE / genetics*
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Receptors, IgE / metabolism*
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Regulatory Sequences, Nucleic Acid / immunology
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Repressor Proteins / isolation & purification
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Repressor Proteins / metabolism
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Repressor Proteins / physiology
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Trans-Activators / isolation & purification
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Trans-Activators / metabolism
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Transcription Factors / isolation & purification
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Transcription Factors / metabolism
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Transcription Initiation Site
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Tumor Cells, Cultured
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YY1 Transcription Factor
Substances
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DNA-Binding Proteins
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Erythroid-Specific DNA-Binding Factors
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Proto-Oncogene Proteins
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Receptors, IgE
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Repressor Proteins
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Trans-Activators
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Transcription Factors
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YY1 Transcription Factor
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YY1 protein, human
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proto-oncogene protein Spi-1
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Interleukin-4