Liu Zhaolong, Yang Le, Sun Yanxiang, Xie Xiaofeng, Huang Jianping
Department of General Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Department of General Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Mol Immunol. 2016 Oct;78:57-64. doi: 10.1016/j.molimm.2016.08.008. Epub 2016 Sep 5.
ASF1a (anti-silencing function 1a), an evolutionarily conserved protein and a histone chaperone, is required for a variety of chromatin-mediated cellular processes. However, the function of ASF1a in innate immune response remains unclear. Here, we find that ASF1a is induced in Vesicular Stomatitis Virus (VSV)-infected macrophages in a manner that is dependent on IRF3 signal. ASF1a promotes VSV-triggered IFN-β production. Moreover, acetylation of H3K56 increases at the ifnb promoter after VSV infection, which is dependent on ASF1a. Furthermore, we find ASF1a-mediated H3K56ac is dependent on the acetyltransferases activity of CREB binding protein (CBP) and the association between ASF1a and CBP. Therefore, our work provides a new insight into the antiviral mechanism that histone chaperone ASF1a-mediated H3K56ac modification promotes IFN-β production.
ASF1a（抗沉默功能蛋白1a）是一种进化上保守的蛋白质，也是一种组蛋白伴侣，参与多种由染色质介导的细胞过程。然而，ASF1a在先天免疫应答中的功能仍不清楚。在此，我们发现ASF1a在水泡性口炎病毒（VSV）感染的巨噬细胞中被诱导，其诱导方式依赖于IRF3信号。ASF1a促进VSV触发的IFN-β产生。此外，VSV感染后，ifnb启动子处的H3K56乙酰化增加，这依赖于ASF1a。此外，我们发现ASF1a介导的H3K56ac依赖于CREB结合蛋白（CBP）的乙酰转移酶活性以及ASF1a与CBP之间的关联。因此，我们的工作为组蛋白伴侣ASF1a介导的H3K56ac修饰促进IFN-β产生的抗病毒机制提供了新的见解。
