A T cell-specific enhancer in the interleukin-3 locus is activated cooperatively by Oct and NFAT elements within a DNase I-hypersensitive site

A T cell-specific enhancer in the interleukin-3 locus is activated cooperatively by Oct and NFAT elements within a DNase I-hypersensitive site
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DOI:
10.1016/s1074-7613(00)80424-0
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发表时间:
1997-02-01
期刊:
影响因子:
32.4
通讯作者:
Cockerill, PN
Cockerill, PN
中科院分区:
医学1区
文献类型:
--
作者:
Duncliffe, KN;Bert, AG;Cockerill, PN

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白细胞介素-3(IL-3)是主要在活化的T细胞中表达的细胞因子。在这里,我们确定了一个可诱导的T细胞特异性增强子14 kb的IL-3基因的上游,响应T细胞受体信号通路的激活。IL-3增强子跨越了仅在T细胞中发现的可诱导的环孢菌素A敏感的DNA酶I超敏位点。增强子中存在四个NFAT样元件。两个最活跃的NFAT样元件位于DNase I超敏位点的中心。这些NFAT样元件之一包括重叠的Oct-和NFATp/c-结合位点,其以高度协同的方式发挥作用。我们认为IL-3基因的T细胞特异性表达部分是通过Oct和NFAT家族蛋白之间的合作通过增强子控制的。
Interleukin-3 (IL-3) is a cytokine that is expressed primarily in activated T cells. Here we identified an inducible T cell-specific enhancer 14 kb upstream of the IL-3 gene that responded to activation of T cell receptor signaling pathways. The IL-3 enhancer spanned an inducible cyclosporin A-sensitive DNase I-hypersensitive site found only in T cells. Four NFAT-like elements exist within the enhancer. The two most active NFAT-like elements were located at the center of the DNase I-hypersensitive site. One of these NFAT-like elements encompassed overlapping Oct- and NFATp/c-binding sites, which functioned in a highly synergistic manner. We suggest that the T cell-specific expression of the IL-3 gene is partly controlled through the enhancer by cooperation between Oct and NFAT family proteins.