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The Journal of Immunology, 2003, 170: 3732-3738.
Copyright © 2003 by The American Association of Immunologists

Regulation of the Human Fc{epsilon}RI {alpha}-Chain Distal Promoter1

Masanari Hasegawa*,{dagger}, Chiharu Nishiyama2,*, Makoto Nishiyama{ddagger}, Yushiro Akizawa*,§, Kyoko Takahashi, Tomonobu Ito*, Susumu Furukawa{dagger}, Chisei Ra, Ko Okumura* and Hideoki Ogawa*

* Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan; {dagger} Department of Pediatrics, Yamaguchi University School of Medicine, Ube-shi, Yamaguchi, Japan; {ddagger} 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 {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.


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The JI 2003 170: 3449-3450. [Full Text]  



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