中国科学院昆明动物研究所机构知识库

Brd2属于BET家族，通过Bromodomain与H4K12ac结合，继而招募RNApolⅡ，导致下游基因被激活。Brd2是否是I型干扰素反应所必需的还没有确定。我们发现HSV-1感染，LPS和Poly(I:C)刺激细胞后，Brd2的表达水平增加。进一步证明NF-kB和Stat1可以结合Brd2并激活Brd2的表达。而且，在Ifnar1缺失的细胞中，Brd2的表达水平显著减少。结合RNA-seq和ChIP-seq，我们证明Brd2可以直接调控抗病毒基因的表达。与野生型细胞相比较，在Brd2缺失的细胞中VSV病毒滴度和转录水平都是显著增加的。总之，我们的结果揭示，Brd2激活抗病毒基因的表达，并且抑制病毒感染。长链非编码RNA最重要的功能之一是通过顺式和反式机制控制编码蛋白基因的表达。通过分析HSV-1感染诱导的差异表达的长链非编码RNA和预测其功能。我们检测到208个已知的长链非编码RNA和206新的长链非编码RNA。GO和Pathway富集分析揭示潜在的长链非编码RNA的靶基因，包括一些基因参与染色质组装，神经元发育和神经退行性疾病以及免疫反应，比如Toll样受体信号和RIG-I样受体信号。我们发现差异表达的长链非编码RNA参与信号通路从先天免疫反应到神经发育，因此揭示在HSV-1感染中长链非编码RNA调控宿主转录程序的重要作用。寨卡病毒由蚊虫介导的黄病毒，可以引起被感染者小耳畸形和格林-巴利综合征。寨卡病毒感染导致149个差异表达的长链非编码RNA，包括潜在的调控细胞过程的病毒靶基因，比如细胞周期，细胞凋亡和免疫反应。ZIKV感染造成229个基因发生262个可变剪接，这些可变剪接基因主要富集在细胞凋亡，RNA加工，转运和神经元发育过程。在691个差异表达的异构体中，上调的异构体富集在转录调控和氨基酸的生物合成，而下调的异构体富集在细胞周期。这些分析揭示了寨卡病毒诱导的细胞信号通路的变化与宿主转录组变化的特异联系，暗示重要的调控机制。我们的分析揭示了候选的长链非编码RNA，可变剪接和异构体，其有可能在寨卡病毒感染偶倒细胞周期紊乱，细胞凋亡和神经发生的削弱过程中发挥重要的作用。

The BET family member, Brd2, can bind to H4K12ac through its Brodomain and then recruit RNA polⅡ, leading to transcription of genes. Whether Brd2 is required for Type I IFNs responses has not been addressed. Here, we found that the expression level of Brd2 was increased in cell infected by HSV-1 infection, or stimulated with LPS and Poly(I:C). We further demonstrated that NF-kB and Stat1 bound to Brd2 and activated Brd2 expression. What is more, expression level of Brd2 was attenuated in Ifnar1-deficient cells. Combining RNA-seq and ChIP-seq, we demonstrated that Brd2 directly regulated expression of antiviral genes. The titer and transcription level of VSV were significantly increased in Brd2-deficient cells compared with wild-type cells.Taken together, our study reveals that Brd2 activates expression of antiviral genes and inhibites viral infection.One of the most important functions of long noncoding RNAs (LncRNAs) is to control protein coding gene transcription by acting locally in cis, or remotely in trans. Here we analyzed HSV-1 infection induced, differentially expressed LncRNAs and predicted their target genes. We detected 208 annotated and 206 novel differentially expressed LncRNAs. Gene Ontology and Pathway enrichment analyses revealed potential LncRNA targets, including genes in chromatin assembly, genes in neuronal development and neurodegenerative diseases and genes in the immune response, such as Toll-like receptor signaling and RIG-I-like receptor signaling pathways. We found that differentially expressed LncRNAs may regulate the expression of many cellular protein-coding genes involved in pathways from native immunity to neuronal development, thus revealing important roles of LncRNAs in the regulation of host transcriptional programs in HSV-1 infected human cells. The Zika virus (ZIKV) is a mosquito-borne ?avivirus that causes microcephaly and Guillain-Barré syndrome in infected individuals. We obtained 149 differentially expressed LncRNAs, including potential viral targets to modulate cellular processes such as cell cycle, apoptosis and immune response. The infection induced 262 cases of alternative splicing occurring in 229 genes, which were enriched in cell death, RNA processing, transport, and neuron development. Among 691 differentially expressed isoforms, upregulated isoforms were enriched in regulation of transcription, and amino acid biosynthesis, while downregulated isoforms were mostly enriched in cell cycle. Importantly, these analyses revealed specific links between ZIKV induced changes in cellular pathways and the type of changes in the host transcriptome, suggesting important regulatory mechanisms. Our analyses revealed candidate LncRNAs, alternative splicing events and isoforms which may function in ZIKV infection induced cell cycle disruption, apoptosis and attenuation of neurogenesis.