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RI
-Chain Distal Promoter1




* Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan;
Department of Pediatrics, Yamaguchi University School of Medicine, Ube-shi, Yamaguchi, Japan;
Biotechnology Research Center, University of Tokyo, Tokyo, Japan;
Pharmacobioregulation Research Laboratory, Hanno Research Center, Taiho Pharmaceutical Co., Ltd., Saitama, Japan;
¶ Department of Molecular Cell Immunology and Allergology, Advanced Medical Research, Nihon University School of Medicine, Tokyo, Japan
The
-chain of the high affinity receptor for IgE (Fc
RI) is essential for cell surface expression of Fc
RI and binding of the IgE Ab. The human
-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
-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
-chain. These results indicate that IL-4-dependent up-regulation of the human
-chain was due to enhancement of distal promoter activity and suggests that the two promoters have different regulatory mechanisms for
-chain expression.
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