T-helper type 2 cell-specific expression of the ST2 gene is regulated by transcription factor GATA-3

T-helper type 2 cell-specific expression of the ST2 gene is regulated by transcription factor GATA-3
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DOI:
10.1016/j.bbaexp.2005.01.012
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发表时间:
2005-04-05
期刊:
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子:
--
通讯作者:
Tominaga, S
Tominaga, S
中科院分区:
其他
文献类型:
--
作者:
Hayakawa, M;Yanagisawa, K;Tominaga, S

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ST 2是白细胞介素-1受体家族的成员,并且在2型T辅助(Th 2)细胞中表达。在这里,我们已经研究了负责在Th 2细胞中的ST 2基因的转录调控的分子机制,使用小鼠胸腺瘤。细胞系EL-4。ST 2基因具有远端和近端启动子。用佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)和双丁酰cAMP(Bt(2)cAMP)刺激EL-4细胞,ST 2 mRNA由远端启动子产生。转录起始位点上游约100 bp的区域含有两个加塔共有位点,是报告基因分析中远端启动子激活所必需的。电泳迁移率变动分析表明,转录因子加塔-3与PMA + Bt(2)cAMP刺激的EL-4细胞核提取物的加塔共有位点之一(-84至-79)结合。加塔-3的过表达增强了远端启动子的活性。另一方面,加塔共有位点的突变抵消了加塔-3的增强作用。这些数据表明,加塔-3是一个重要的转录因子的表达ST 2基因在Th 2细胞。(c)2005 Elsevier B. V.保留所有权利。
ST2 is a member of the interleukin-l receptor family and is expressed in type-2 T helper (Th2) cells. Here, we have studied the molecular mechanism responsible for the transcriptional regulation of the ST2 gene in Th2 cells using a mouse thymoma. cell line, EL-4. The ST2 gene has distal and proximal promoters. ST2 mRNA was produced from the distal promoter in EL-4 cells stimulated with both phorbol 12-myristate 13-acetate (PMA) and dibutyryl cAMP (Bt(2)cAMP). The region of approximately 100 bp upstream of transcription start site, containing two GATA consensus sites, was indispensable for the activation of the distal promoter in reporter gene analysis. An electrophoretic mobility shift assay showed that transcription factor GATA-3 bound one of the GATA consensus sites (from -84 to -79) with nuclear extracts from PMA plus Bt(2)cAMP-stimulated EL-4 cells. The overexpression of GATA-3 enhanced the activity of the distal promoter. On the other hand, mutations of the GATA consensus site canceled out the enhancement by GATA-3. These data suggest that GATA-3 is an important transcription factor for the expression of the ST2 gene in Th2 cells. (c) 2005 Elsevier B.V. All rights reserved.