Histone H3 lysine 9 di-methylation as an epigenetic signature of the interferon response.
Histone H3 lysine 9 di-methylation as an epigenetic signature of the interferon response.
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DOI：
10.1084/jem.20112343
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发表时间：
2012-04-09
期刊：
影响因子：
--
通讯作者：
Tarakhovsky A
中科院分区：
文献类型：
--
作者：
Fang TC;Schaefer U;Mecklenbrauker I;Stienen A;Dewell S;Chen MS;Rioja I;Parravicini V;Prinjha RK;Chandwani R;MacDonald MR;Lee K;Rice CM;Tarakhovsky A
组蛋白H3赖氨酸9(H3K9me2)的双甲基化抑制干扰素基因的表达，赖氨酸甲基转移酶G9a的缺失或失活将成纤维细胞转化为对RNA病毒具有抵抗力的干扰素产生细胞。有效的抗病毒免疫依赖于感染细胞或由病毒衍生核酸触发的细胞产生I型干扰素的能力，I型干扰素可激活许多抗病毒基因的转录。然而，不成比例的强表达或慢性干扰素是炎症性和自身免疫性疾病的常见原因。我们描述了一种表观遗传学机制，它决定了干扰素和干扰素刺激基因(ISG)在细胞类型上的差异，以响应外部信号。我们发现组蛋白H3赖氨酸9(H3K9me2)的二甲基化是干扰素和干扰素诱导的抗病毒基因表达的抑制因子。我们发现H3K9me2在干扰素和ISG中的水平与成纤维细胞和树突状细胞中干扰素和ISG表达的范围和幅度呈负相关。因此，基因消融或药物灭活赖氨酸甲基转移酶G9a是产生H3K9me2所必需的，导致成纤维细胞表型转化为高效产生干扰素的细胞，并使这些细胞对致病RNA病毒产生抗药性。综上所述，我们的研究表明，H3K9me2和控制其丰度的酶是天然抗病毒免疫的关键调节因子。
Di-methylation of histone H3 at lysine 9 (H3K9me2) suppresses expression of interferon genes, and deletion or inactivation of the lysine methyltransferase G9a converts fibroblasts into interferon-producing cells resistant to RNA viruses. Effective antiviral immunity depends on the ability of infected cells or cells triggered with virus-derived nucleic acids to produce type I interferon (IFN), which activates transcription of numerous antiviral genes. However, disproportionately strong or chronic IFN expression is a common cause of inflammatory and autoimmune diseases. We describe an epigenetic mechanism that determines cell type–specific differences in IFN and IFN-stimulated gene (ISG) expression in response to exogenous signals. We identify di-methylation of histone H3 at lysine 9 (H3K9me2) as a suppressor of IFN and IFN-inducible antiviral gene expression. We show that levels of H3K9me2 at IFN and ISG correlate inversely with the scope and amplitude of IFN and ISG expression in fibroblasts and dendritic cells. Accordingly, genetic ablation or pharmacological inactivation of lysine methyltransferase G9a, which is essential for the generation of H3K9me2, resulted in phenotypic conversion of fibroblasts into highly potent IFN-producing cells and rendered these cells resistant to pathogenic RNA viruses. In summary, our studies implicate H3K9me2 and enzymes controlling its abundance as key regulators of innate antiviral immunity.
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影响因子：
56.9
作者：
Nakayam, J;Rice, JC;Grewal, SIS
通讯作者：
Grewal, SIS
DOI：
10.1084/jem.20061469
发表时间：
2006-10-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kolossov E;Bostani T;Roell W;Breitbach M;Pillekamp F;Nygren JM;Sasse P;Rubenchik O;Fries JW;Wenzel D;Geisen C;Xia Y;Lu Z;Duan Y;Kettenhofen R;Jovinge S;Bloch W;Bohlen H;Welz A;Hescheler J;Jacobsen SE;Fleischmann BK
通讯作者：
Fleischmann BK
影响因子：
16
作者：
Kubicek, Stefan;O'Sullivan, Roderick J.;Jenuwein, Thomas
通讯作者：
Jenuwein, Thomas
影响因子：
14.8
作者：
Lee, Tong Ihn;Johnstone, Sarah E.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
64.5
作者：
Agalioti, T;Chen, GY;Thanos, D
通讯作者：
Thanos, D