Suter U, Texido G, Hofstetter H
Department of Biotechnology, Ciba-Geigy Ltd., Basel, Switzerland.
J Immunol. 1989 Nov 1;143(9):3087-92.
Two species, Fc epsilon RIIa and Fc epsilon RIIb, of the human low-affinity receptor for IgE (Fc epsilon RII/CD23) have recently been described. They differ by only six amino acids in the cytoplasmic N-terminus and are generated by different cell-specific transcriptional start sites that lead to distinct 5'-leader sequences in the corresponding mRNA. In this study, we present the analysis of the promoter which is regulating the expression of the B cell-specific Fc epsilon RIIa. Our data show that this promoter is flanked by several long repetitive elements that are influencing transcription in the Burkitt lymphoma B cell line Jijoye. Serial deletions of the 5'-flanking region of the promoter revealed two major regulatory segments that have either inhibitory or enhancing effects on transcription. In addition, IL-4 caused a two- to four-fold up-regulation of the Fc epsilon RIIa promoter activity and the DNA element responsible was mapped within the first 250 bp of the 5'-flanking region. These results were confirmed by transferring the DNA segment containing the putative IL-4 responsive element to a heterologous thymidine kinase promoter. It was concluded that IL-4 augments the Fc epsilon RIIa expression by transcriptional regulation.
最近已发现人类IgE低亲和力受体(FcεRII/CD23)的两种亚型,即FcεRIIa和FcεRIIb。它们在细胞质N端仅相差6个氨基酸,由不同的细胞特异性转录起始位点产生,导致相应mRNA中5'前导序列不同。在本研究中,我们对调控B细胞特异性FcεRIIa表达的启动子进行了分析。我们的数据表明,该启动子两侧有几个长重复元件,它们影响伯基特淋巴瘤B细胞系Jijoye中的转录。启动子5'侧翼区域的系列缺失揭示了两个主要调控区段,它们对转录具有抑制或增强作用。此外,IL-4使FcεRIIa启动子活性上调2至4倍,负责的DNA元件定位在5'侧翼区域的前250 bp内。通过将包含假定IL-4反应元件的DNA片段转移到异源胸苷激酶启动子上,证实了这些结果。得出的结论是,IL-4通过转录调控增强FcεRIIa的表达。