An IL-2 response element in the human IL-2 receptor alpha chain promoter is a composite element that binds Stat5, Elf-1, HMG-I(Y) and a GATA family protein

被引:128
|
作者
John, S
Robbins, CM
Leonard, WJ
机构
[1] NHLBI,LAB MOL IMMUNOL,BETHESDA,MD 20892
[2] NATL CTR GENOME RES,GENOME TECHNOL BRANCH,BETHESDA,MD 20892
来源
EMBO JOURNAL | 1996年 / 15卷 / 20期
关键词
Elf-1; GATA; HMG-I(Y); IL-2; receptors; STAT;
D O I
10.1002/j.1460-2075.1996.tb00947.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Expression of the human interleukin-2 (IL-2) receptor alpha chain gene is potently upregulated by its own ligand, IL-2, In this study, we characterize an essential upstream IL-2 response element that contains both consensus and non-consensus GAS motifs, two putative Ets binding sites (EBS), one of which overlaps the consensus GAS moth, and a GATA motif, which overlaps the non-consensus GAS motif, We demonstrate that although the individual components of this element do not respond to IL-2, together they form a composite element capable of conferring IL-2 responsiveness to a heterologous promoter. Multiple factors including Stat5, Elf-1, HMG-I(Y) and GATA family proteins bind to the IL-2 response element and mutation of any one of these binding sites diminishes the activity of this element, An unidentified Ets family protein binds to the EBS overlapping the consensus GAS motif and appears to negatively regulate the human IL-2R alpha promoter, Thus, TL-2-induced IL-2R alpha promoter activity requires a complex upstream element, which appears to contain binding sites for both positive and negative regulatory factors.
引用
收藏
页码:5627 / 5635
页数:9
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