Transcriptional regulation of GATA-3 by an intronic regulatory region and fetal liver zinc finger protein 1
Transcriptional regulation of GATA-3 by an intronic regulatory region and fetal liver zinc finger protein 1
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DOI：
10.4049/jimmunol.169.1.248
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发表时间：
2002-07-01
影响因子：
4.4
通讯作者：
Ho, IC
中科院分区：
文献类型：
--
作者：
Hwang, ES;Choi, A;Ho, IC
加塔-3是T细胞特异性转录因子，对T细胞谱系的发育至关重要。然而，加塔-3的转录调控仍然是难以捉摸的。在这项研究中，我们报告了位于第一内含子的小鼠加塔-3基因的调控区的鉴定。内含子调控区包含一个正的和负的顺式作用元件，但作为一个整体，作为一个有效的T细胞特异性增强子，是必要的启动子活性在体外。通过酵母单杂交筛选，我们发现胎肝锌指蛋白1（Fliz 1）可以与小鼠和人加塔-3基因保守的负性顺式作用元件特异性结合。更重要的是，Fliz 1的过表达在体内和体外抑制了加塔-3的表达。我们的数据表明，加塔-3的表达可能部分由内含子调控区和Fliz 1在发育阶段特异性的方式进行调节。
GATA-3 is a T cell-specific transcription factor and is essential for the development of the T cell lineage. The transcriptional regulation of GATA-3, however, remains elusive. In this study, we report the identification of a regulatory region located within the first intron of the murine GATA-3 gene. The intronic regulatory region contains both a positive and a negative cis-acting element but, as a whole, serves as a potent T cell-specific enhancer and is essential for the promoter activity in vitro. By using yeast one-hybrid screening, we discovered that fetal liver zinc finger protein 1 (Fliz1) could bind specifically to the negative cis-acting element, the sequence of which is conserved between the mouse and human GATA-3 genes. More importantly, overexpression of Fliz1 repressed the expression of GATA-3 in vivo and in vitro. Our data suggest that the expression of GATA-3 might be partly regulated by the intronic regulatory region and Fliz1 in a developmental stage-specific fashion.