rojjer 发表于 2016-6-3 10:40 免疫嘛 除了信号通路 还能做啥 |
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Methyltransferase Dnmt3a upregulates HDAC9 to deacetylate the kinase TBK1 for activation of antiviral innate immunity Xia Li, Qian Zhang, Yuanyuan Ding, Yiqi Liu, Dezhi Zhao, Kai Zhao, Qicong Shen, Xingguang Liu, Xuhui Zhu, Nan Li, Zhongyi Cheng, Guoping Fan, Qingqing Wang & Xuetao Cao The DNA methyltransferase Dnmt3a has high expression in terminally differentiated macrophages; however, its role in innate immunity remains unknown. Here we report that deficiency in Dnmt3a selectively impaired the production of type I interferons triggered by pattern-recognition receptors (PRRs), but not that of the proinflammatory cytokines TNF and IL-6. Dnmt3a-deficient mice exhibited enhanced susceptibility to viral challenge. Dnmt3a did not directly regulate the transcription of genes encoding type I interferons; instead, it increased the production of type I interferons through an epigenetic mechanism by maintaining high expression of the histone deacetylase HDAC9. In turn, HDAC9 directly maintained the deacetylation status of the key PRR signaling molecule TBK1 and enhanced its kinase activity. Our data add mechanistic insight into the crosstalk between epigenetic modifications and post-translational modifications in the regulation of PRR signaling and activation of antiviral innate immune responses. http://www.nature.com/ni/journal/vaop/ncurrent/full/ni.3464.html |
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