GA结合蛋白调节T细胞中白细胞介素7受体α链基因的表达。

GA binding protein regulates interleukin 7 receptor alpha-chain gene expression in T cells.

作者信息

Xue Hai-Hui, Bollenbacher Julie, Rovella Valentina, Tripuraneni Radhika, Du Yu-Bin, Liu Cheng-Yu, Williams Ann, McCoy J Philip, Leonard Warren J

机构信息

Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7N252, Bethesda, Maryland 20892-1674, USA.

出版信息

Nat Immunol. 2004 Oct;5(10):1036-44. doi: 10.1038/ni1117. Epub 2004 Sep 7.

DOI:10.1038/ni1117

PMID:15361867

Abstract

The interleukin 7 receptor alpha-chain (IL-7Ralpha) is essential for T cell development in both humans and mice and for B cell development in mice. Whereas the transcription factor PU.1 regulates IL-7Ralpha expression in mouse pro-B cells via a GGAA motif, we demonstrate here that GA binding protein (GABP) bound to this site and was essential in the regulation of IL-7Ralpha expression in T cells, where PU.1 is not expressed. Moreover, IL-7Ralpha expression was diminished substantially in thymocytes but was normal on B220(+) fetal liver cells from mouse embryos with diminished expression of GABPalpha. Thus, GABP is essential for the regulation of IL-7Ralpha expression in T cells, and the differential regulation of IL-7Ralpha in distinct lymphoid lineages is achieved at least in part by differential recruitment of factors to the same GGAA motif.

摘要

白细胞介素7受体α链（IL-7Rα）对人类和小鼠的T细胞发育以及小鼠的B细胞发育至关重要。转录因子PU.1通过GGAA基序调节小鼠前B细胞中的IL-7Rα表达，而我们在此证明，GA结合蛋白（GABP）结合到该位点，并且在T细胞中IL-7Rα表达的调节中必不可少，因为T细胞中不表达PU.1。此外，在胸腺细胞中IL-7Rα表达大幅减少，但在GABPα表达减少的小鼠胚胎的B220(+)胎肝细胞上表达正常。因此，GABP对T细胞中IL-7Rα表达的调节至关重要，并且至少部分地通过将不同因子募集到相同的GGAA基序来实现不同淋巴谱系中IL-7Rα的差异调节。