Human CD94 gene expression: Dual promoters differing in responsiveness to IL-2 or IL-15
Human CD94 gene expression: Dual promoters differing in responsiveness to IL-2 or IL-15
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DOI：
10.4049/jimmunol.171.10.5277
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发表时间：
2003-11-15
影响因子：
4.4
通讯作者：
Coligan, JE
中科院分区：
文献类型：
--
作者：
Lieto, LD;Borrego, F;Coligan, JE
CD 94是CD 94/NKG 2受体家族二聚化所需的C型凝集素，其在NK细胞和T细胞亚群上表达。关于CD 94基因表达和调节CD 94转录的元件知之甚少。在这项研究中，我们报告CD 94基因表达受到远端和近端启动子的调节，这些启动子转录每个启动子特有的独特初始外显子。这导致两种转录物;先前描述的CD 94 mRNA和新的CD 94 C mRNA。所有NK细胞和CD 94（+）、CD 8（+）α T细胞均转录CD 94 mRNA。用IL-2或IL-15刺激NK和CD 8（+）α T细胞可诱导CD 94 C mRNA的转录。远端和近端启动子都含有具有IFN-γ激活和Ets结合位点的元件，称为GAS/EBS。此外，一个未知的元素，称为网站A，被确定在近端启动子。EMSA分析表明，组成因子可以结合到含有每个元素的寡核苷酸探针。用IL-2或IL-15处理原代NK细胞后，可以用含有近端或远端GAS/EBS元件的寡核苷酸探针检测单独的诱导型复合物。这些元件在小鼠和人类之间是高度保守的，这表明两个物种都通过早于其进化分歧的机制来调节CD 94基因表达。
CD94 is a C-type lectin required for the dimerization of the CD94/NKG2 family of receptors, which are expressed on NK cells and T cell subsets. Little is known about CD94 gene expression and the elements that regulate CD94 transcription. In this study, we report that CD94 gene expression is regulated by distal and proximal promoters that transcribe unique initial exons specific to each promoter. This results in two species of transcripts; the previously described CD94 mRNA and a novel CD94C mRNA. All NK cells and CD94(+), CD8(+) alphabeta T cells transcribe CD94 mRNA. Stimulation of NK and CD8(+) alphabeta T cells with IL-2 or IL-15 induced the transcription of CD94C mRNA. The distal and proximal promoters both contain elements with IFN-gamma-activated and Ets binding sites, known as GAS/EBS. Additionally, an unknown element, termed site A, was identified in the proximal promoter. EMSA analyses showed that constitutive factors could bind to oligonucleotide probes containing each element. After treatment of primary NK cells with IL-2 or IL-15, separate inducible complexes could be detected with oligonucleotide probes containing either the proximal or distal GAS/EBS elements. These elements are highly conserved between mice and humans, which suggests that both species regulate CD94 gene expression via mechanisms that predate their evolutionary divergence.