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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The E47 transcription factor negatively regulates CD5 expression during thymocyte development
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The E47 transcription factor negatively regulates CD5 expression during thymocyte development

机译：E47转录因子在胸腺细胞发育过程中负调节CD5表达

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The expression of CD5 increases progressively as thymocytes mature. We have shown that CD5 expression is controlled by a tissue-specific regulatory promoter located upstream of the CD5 translation start sites. Deletion of this regulatory promoter, which contains three potential transcription factor binding sites (CCAAT, kappaE2, and ets) reduces the promoter activity to basal level. Of these sites, only ets proved essential for CD5 expression in T cell lines. Here, we introduce a role for the E47 transcription factor and the CD5 promoter kappaE2 site in regulating CD5 expression during thymocyte development. Using T cell lines, we show that (i) mutation of the kappaE2 site in the CD5 regulatory promoter results in a significant elevation of CD5 promoter activity; (ii) the E47 transcription factor binds to the kappaE2 site; and (iii) overexpression of E47 inhibits CD5 expression. We then show, in high-dimensional fluorescence-activated cell sorting studies with primary thymocytes at successive developmental stages, that (i) intracellular E47 levels decrease as surface CD5 expression increases; (ii) E47 expression is down-regulated and CD5 expression is correspondingly up-regulated in DN3 thymocytes in RAG-2-deficient mice injected with anti-CD3 to mimic pre-T cell receptor stimulation; and (iii) E47 expression is down-regulated and CD5 expression is up-regulated when double positive thymocytes are stimulated in vitro with anti-CD3. Based on these data, we propose that E47 negatively regulates CD5 expression by interacting with the kappaE2 site in the CD5 regulatory promoter and that decreases in E47 in response to developmental signals are critical to the progressive increase in CD5 expression as thymocytes mature. [References: 26]
机译：随着胸腺细胞的成熟，CD5的表达逐渐增加。我们已经表明，CD5表达是由位于CD5翻译起始位点上游的组织特异性调节启动子控制的。删除包含三个潜在的转录因子结合位点（CCAAT，kappaE2和ets）的此调节性启动子可将启动子活性降至基础水平。在这些位点中，只有ets被证明对T细胞系中CD5表达至关重要。在这里，我们介绍了E47转录因子和CD5启动子kappaE2位点在胸腺细胞发育过程中调节CD5表达中的作用。使用T细胞系，我们显示（i）CD5调控启动子中kappaE2位点的突变导致CD5启动子活性显着升高； （ii）E47转录因子与kappaE2位点结合； （iii）E47的过表达抑制CD5表达。然后，我们在连续发展阶段的原代胸腺细胞的高维荧光激活细胞分选研究中显示：（i）细胞内E47水平随着表面CD5表达的增加而降低； （ii）在注射抗CD3以模拟前T细胞受体刺激的RAG-2缺陷小鼠中，DN3胸腺细胞中E47表达下调，而CD5表达上调。 （iii）当用抗CD3体外刺激双阳性胸腺细胞时，E47表达下调而CD5表达上调。根据这些数据，我们提出E47通过与CD5调节启动子中的kappaE2位点相互作用来负调节CD5的表达，并且随着胸腺细胞成熟，E47响应发育信号的降低对于CD5表达的逐步增加至关重要。 [参考：26]

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