Department of Immunology and Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China.
Protein Cell. 2019 Apr;10(4):285-294. doi: 10.1007/s13238-018-0581-0. Epub 2018 Oct 24.
Polycomb chromobox (CBX) proteins regulate gene transcription by maintaining chromatin states, which guide a variety of biological processes. Now, epigenetic regulation of innate immune response is an emerging field. However, the role of CBX proteins in innate immunity remains unclear. We confirmed that the expression of CBX family proteins, especially Cbx2, was decreased in macrophages upon viral infection, and then we investigated the role of Cbx2 in the antiviral immune response. Silencing or knockdown of Cbx2 in macrophages inhibited virus-induced production of IFN-β. Furthermore, heterozygous Cbx2 knockout were susceptible to VSV challenge. Mechanistically, Cbx2 binds to and recruits Jmjd3 to the Ifnb promoter, leading to demethylation of H3K27me3 and increased transcription of IFN-β. Together, our study reveals a non-traditional function of a Cbx protein and adds new insight into the epigenetic regulation of antiviral innate immunity.
多梳盒（CBX）蛋白通过维持染色质状态来调节基因转录，从而指导多种生物学过程。现在，先天免疫反应的表观遗传调控是一个新兴领域。然而，CBX 蛋白在先天免疫中的作用尚不清楚。我们证实，病毒感染后巨噬细胞中 CBX 家族蛋白的表达，特别是 Cbx2，减少了，然后我们研究了 Cbx2 在抗病毒免疫反应中的作用。沉默或敲低巨噬细胞中的 Cbx2 抑制了病毒诱导的 IFN-β的产生。此外，杂合性 Cbx2 敲除小鼠易受 VSV 挑战。从机制上讲，Cbx2 与 Jmjd3 结合并将其募集到 Ifnb 启动子上，导致 H3K27me3 的去甲基化和 IFN-β 的转录增加。总之，我们的研究揭示了一种 CBX 蛋白的非传统功能，并为抗病毒先天免疫的表观遗传调控提供了新的见解。
