A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory
A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory
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DOI：
10.1038/sj.emboj.7601012
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发表时间：
2006-03-08
期刊：
影响因子：
11.4
通讯作者：
Yanagisawa, J
中科院分区：
文献类型：
--
作者：
Murayama, A;Sakura, K;Yanagisawa, J
DNA去甲基化在分化的体细胞中的转录调控中起关键作用。然而，没有实验证据表明基因组小区域中的CpG甲基化限制基因表达。在这里，我们表明，抗CD 3 β/CD 28抗体刺激人CD 4（+）T细胞诱导IL 2表达后的表观遗传变化，包括特定CpG位点的主动去甲基化，招募Oct-1，和组蛋白修饰的变化。当刺激信号被撤回时，Oct-1作为刺激的稳定标记物保留在增强子区域上，导致第二次诱导更快更强。我们的观察结果表明，Oct-1结合后CpG去甲基化是表观遗传调控IL 2表达的关键事件，并可能作为调控事件的记忆。
DNA demethylation plays a critical role in transcriptional regulation in differentiated somatic cells. However, there is no experimental evidence that CpG methylation in a small region of a genome restricts gene expression. Here, we show that the anti-CD3 epsilon/CD28 antibody stimulation of human CD4(+) T cells induces IL2 expression following epigenetic changes, including active demethylation of a specific CpG site, recruitment of Oct-1, and changes in histone modifications. When the stimulatory signal is withdrawn, Oct-1 remains on the enhancer region as a stable marker of the stimulation, causing the second induction to be faster and stronger. Our observations indicate that Oct-1-binding followed by CpG demethylation are key events in the epigenetic regulation of IL2 expression and may act as a memory of the regulatory event.