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首页> 外文期刊>Journal of interferon and cytokine research: The official journal of the International Society for Interferon and Cytokine Research >Interferon-alpha induces reversible DNA demethylation of the interferon-induced transmembrane protein-3 core promoter in human melanoma cells.
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Interferon-alpha induces reversible DNA demethylation of the interferon-induced transmembrane protein-3 core promoter in human melanoma cells.

机译：干扰素-α诱导人黑素瘤细胞中干扰素诱导的跨膜蛋白3核心启动子的可逆DNA脱甲基。

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摘要

The interferon (IFN)-alpha response gene interferon-induced transmembrane protein 3 (IFITM3) has antiproliferative properties in a number of biological systems. In the human melanoma cell line D10, IFITM3 is constitutively expressed and we show that the core promoter is significantly hypomethylated compared to ME15 cells, where IFITM3 is tightly controlled. We demonstrate that treatment of ME15 cells with the demethylating agent 5'-aza-2'-deoxycytidine enhances IFITM3 expression after IFN-alpha treatment. In a time-course experiment, we show that IFN-alpha induces demethylation of specific CpG sites of the IFITM3 core promoter 6 h after stimulation and that promoter methylation is precisely re-set to the naive state 24 h after stimulation. This cyclable modification of methylation requires costimulation with tumor growth factor-beta or expression of the calcium binding protein S100A2, which are known cofactors for enhancement of antiproliferative activity in ME15 cells. Thus, the transcriptional response to IFN-alpha can be enhanced by promoter demethylation of a subset of inducible genes such as IFITM3. This epigenetic modulation might be crucial to augment the immune response under critical conditions in vivo.
机译：干扰素（IFN）-α反应基因干扰素诱导的跨膜蛋白3（IFITM3）在许多生物系统中均具有抗增殖特性。在人黑素瘤细胞系D10中，IFITM3组成型表达，并且我们显示，与严格控制IFITM3的ME15细胞相比，核心启动子甲基化程度显着降低。我们证明用脱甲基剂5'-氮杂-2'-脱氧胞苷处理ME15细胞可增强IFN-α处理后的IFITM3表达。在一个时程实验中，我们显示了刺激后6小时，IFN-α会诱导IFITM3核心启动子的特定CpG位点脱甲基，并且刺激后24小时，启动子的甲基化精确地重置为幼稚状态。这种甲基化的可循环修饰需要与肿瘤生长因子-β或钙结合蛋白S100A2的表达共同刺激，而钙结合蛋白S100A2是已知的增强ME15细胞抗增殖活性的辅因子。因此，可以通过诸如IFITM3的可诱导基因子集的启动子去甲基化来增强对IFN-α的转录反应。这种表观遗传调控对于在体内关键条件下增强免疫应答可能至关重要。

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