生物
ISG15
甲基转移酶
甲基化
表观遗传学
STAT1
干扰素
组蛋白甲基转移酶
干扰素刺激基因
癌症研究
遗传学
免疫系统
先天免疫系统
基因
泛素
作者
Kun Chen,Juan Liu,Shuxun Liu,Meng Xia,Xiaomin Zhang,Dan Han,Yingming Jiang,Chunmei Wang,Xuetao Cao
出处
期刊:Cell
[Elsevier]
日期:2017-07-01
卷期号:170 (3): 492-506.e14
被引量:202
标识
DOI:10.1016/j.cell.2017.06.042
摘要
Interferon-α (IFNα) signaling is essential for antiviral response via induction of IFN-stimulated genes (ISGs). Through a non-biased high-throughput RNAi screening of 711 known epigenetic modifiers in cellular models of IFNα-mediated inhibition of HBV replication, we identified methyltransferase SETD2 as a critical amplifier of IFNα-mediated antiviral immunity. Conditional knockout mice with hepatocyte-specific deletion of Setd2 exhibit enhanced HBV infection. Mechanistically, SETD2 directly mediates STAT1 methylation on lysine 525 via its methyltransferase activity, which reinforces IFN-activated STAT1 phosphorylation and antiviral cellular response. In addition, SETD2 selectively catalyzes the tri-methylation of H3K36 on promoters of some ISGs such as ISG15, leading to gene activation. Our study identifies STAT1 methylation on K525 catalyzed by the methyltransferase SETD2 as an essential signaling event for IFNα-dependent antiviral immunity and indicates potential of SETD2 in controlling viral infections.
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