Regulation of the human FcεRI α-chain distal promoter
Regulation of the human FcεRI α-chain distal promoter
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DOI：
10.4049/jimmunol.170.7.3732
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发表时间：
2003-04-01
影响因子：
4.4
通讯作者：
Ogawa, H
中科院分区：
文献类型：
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作者：
Hasegawa, M;Nishiyama, C;Ogawa, H
IgE高亲和力受体（Fc ε RI）的α链对于Fc ε RI的细胞表面表达和IgE Ab的结合至关重要。人类α链基因具有两个启动子：近端启动子，其与啮齿动物的启动子高度保守;和远端启动子，其结构和作用在很大程度上是未知的。在这项研究中，α-链远端启动子的转录调控进行了研究。瞬时报告基因分析显示转录活性的关键区域位于-27/-17范围内。EMSA鉴定Elf-1、YY 1和PU. 1为与该区域结合的转录因子。与被YY 1和PU.1反式激活的近端启动子相反，这些转录因子在该启动子上表现出抑制功能。IL-4的添加引起从远端启动子的转录的显著增加，并且随后增加α链的细胞内产生。这些结果表明，IL-4依赖性上调的人α链是由于远端启动子活性的增强，并表明这两个启动子有不同的α链表达的调节机制。
The alpha-chain of the high affinity receptor for IgE (FcepsilonRI) is essential for cell surface expression of FcepsilonRI 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.