PDF(Pubmed)
Abstract：
Proper transcription regulation by key transcription factors, such as IRF3, is critical for anti-viral defense. Dynamics of enhancer activity play important roles in many biological processes, and epigenomic analysis is used to determine the involved enhancers and transcription factors. To determine new transcription factors in anti-DNA-virus response, we have performed H3K27ac ChIP-Seq and identified three transcription factors, NR2F6, MEF2D and MAFF, in promoting HSV-1 replication. NR2F6 promotes HSV-1 replication and gene expression in vitro and in vivo, but not dependent on cGAS/STING pathway. NR2F6 binds to the promoter of MAP3K5 and activates AP-1/c-Jun pathway, which is critical for DNA virus replication. On the other hand, NR2F6 is transcriptionally repressed by c-Jun and forms a negative feedback loop. Meanwhile, cGAS/STING innate immunity signaling represses NR2F6 through STAT3. Taken together, we have identified new transcription factors and revealed the underlying mechanisms involved in the network between DNA viruses and host cells.
摘要：
通过关键转录因子进行适当的转录调节，例如IRF3，对于抗病毒防御至关重要。增强子活性的动力学在许多生物过程中起着重要作用,和表观基因组分析用于确定所涉及的增强子和转录因子。为了确定抗DNA病毒反应中的新转录因子，我们进行了H3K27acChIP-Seq，并鉴定了三种转录因子，NR2F6，MEF2D和MAFF，促进HSV-1复制。NR2F6在体外和体内促进HSV-1的复制和基因表达，但不依赖于cGAS/STING途径。NR2F6与MAP3K5的启动子结合并激活AP-1/c-Jun通路,这对DNA病毒复制至关重要。另一方面,NR2F6被c-Jun转录抑制并形成负反馈回路。同时,cGAS/STING先天免疫信号通过STAT3抑制NR2F6。一起来看,我们已经确定了新的转录因子，并揭示了DNA病毒和宿主细胞之间网络的潜在机制。
