Inhibition of EZH2 Causes Retrotransposon Derepression and Immune Activation in Porcine Lung Alveolar Macrophages.
Inhibition of EZH2 Causes Retrotransposon Derepression and Immune Activation in Porcine Lung Alveolar Macrophages.
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抑制 EZH2 导致猪肺泡巨噬细胞逆转录转座子去抑制和免疫激活
DOI：
10.3390/ijms24032394
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发表时间：
2023-01-25
影响因子：
5.6
通讯作者：
Sun, Ming-an
中科院分区：
文献类型：
--
作者：
Zhang, Liangliang;Jin, Jian;Qin, Weiyun;Jiang, Jing;Bao, Wenbin;Sun, Ming-an
肺泡巨噬细胞（Alveolar macrophages, AMs）是抵御各种呼吸道病原体的第一道防线，其免疫应答对呼吸道感染的结局有着深远的影响。zeste homolog 2增强子（Enhancer of zeste homolog 2, EZH2）催化H3K27的三甲基化实现表观遗传抑制，其免疫调节功能越来越受到关注，但其在AMs中的确切功能在很大程度上仍不清楚。以猪3D4/21 AM细胞为模型，研究了EZH2抑制后转录组学和表观基因组学的变化。我们发现，抑制EZH2可引起许多免疫基因的转录激活，并抑制随后的甲型流感病毒感染。有趣的是，转座因子的特定家族，特别是内源性逆转录病毒因子（erv）和属于逆转录转座子的LINEs，也会被抑制。虽然一些抑制的ERV家族是猪特有的，但已知少数祖先家族在人类中受到ezh2介导的抑制。鉴于erv的抑制可以通过“病毒模仿”促进先天免疫激活，我们推测erv也可能参与了EZH2抑制后AMs的同步免疫激活。总的来说，本研究提高了对am中ezh2相关免疫调控的理解，并为猪反转录转座子的表观遗传调控提供了新的见解。
Alveolar macrophages (AMs) form the first defense line against various respiratory pathogens, and their immune response has a profound impact on the outcome of respiratory infection. Enhancer of zeste homolog 2 (EZH2), which catalyzes the trimethylation of H3K27 for epigenetic repression, has gained increasing attention for its immune regulation function, yet its exact function in AMs remains largely obscure. Using porcine 3D4/21 AM cells as a model, we characterized the transcriptomic and epigenomic alterations after the inhibition of EZH2. We found that the inhibition of EZH2 causes transcriptional activation of numerous immune genes and inhibits the subsequent infection by influenza A virus. Interestingly, specific families of transposable elements, particularly endogenous retrovirus elements (ERVs) and LINEs which belong to retrotransposons, also become derepressed. While some of the derepressed ERV families are pig-specific, a few ancestral families are known to be under EZH2-mediated repression in humans. Given that derepression of ERVs can promote innate immune activation through “viral mimicry”, we speculate that ERVs may also contribute to the coinciding immune activation in AMs after the inhibition of EZH2. Overall, this study improves the understanding of the EZH2-related immune regulation in AMs and provides novel insights into the epigenetic regulation of retrotransposons in pigs.
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影响因子：
32.4
作者：
Aegerter, Helena;Lambrecht, Bart N.;Jakubzick, Claudia, V
通讯作者：
Jakubzick, Claudia, V
影响因子：
4.3
作者：
Joshi, Nikita;Walter, James M.;Misharin, Alexander V.
通讯作者：
Misharin, Alexander V.
影响因子：
8.7
作者：
Buttler CA;Chuong EB
通讯作者：
Chuong EB
影响因子：
7
作者：
Kelly, Conor J.;Chitko-McKown, Carol G.;Chuong, Edward B.
通讯作者：
Chuong, Edward B.
DOI：
10.1126/science.aad5497
发表时间：
2016-03-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chuong EB;Elde NC;Feschotte C
通讯作者：
Feschotte C