甲基转移酶SETD2介导的STAT1甲基化对干扰素抗病毒活性至关重要
Kun Chen1, Juan Liu2, Shuxun Liu2
1Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China; National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
Cell
|July 29, 2017
概括
通过甲基化STAT1和促进IFN刺激基因 (ISG),表观基因修饰剂SETD2增强了干扰素α (IFNα) 抗病毒免疫力. 失去SETD2会增强乙型肝炎病毒 (HBV) 感染,突出显示SETD2
科学领域:
- 免疫学
- 表观遗传学
- 肝病学
背景情况:
- 通过IFN刺激基因 (ISG) 进行抗病毒防御,干扰素α (IFNα) 信号传递至关重要.
- 虽然IFNα可以抑制乙型肝炎病毒 (HBV) 的复制,但其潜在的表观遗传机制尚未完全理解.
研究的目的:
- 确定调节IFNα介导的抗病毒免疫力对抗HBV的表观遗传修饰剂.
- 阐明SETD2影响IFNα信号传递和HBV复制的分子机制.
主要方法:
- 在IFNα处理的细胞中对711种表观遗传修饰物的高通量RNAi选.
- 在Setd2条件淘汰小鼠中分析HBV复制.
- 生物化学测定以评估STAT1甲基化和H3K36三甲基化.
主要成果:
- SETD2被确定为IFNα抗病毒免疫力的关键增强剂.
- 在小鼠中,肝细胞特异性的Setd2缺失导致HBV感染的增加.
- 在素525中,SETD2直接甲基化STAT1,增强STAT1酸化和抗病毒反应.
- 在ISG促进体中,SETD2催化H3K36的三甲基化,促进基因激活.
结论:
- 通过SETD2进行STAT1甲基化对于IFNα依赖的抗病毒免疫力至关重要.
- 在控制病毒感染,特别是HBV方面,SETD2起着至关重要的作用.
- 在治疗病毒性肝炎方面,SETD2是潜在的治疗点.
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