Cohesin promotes HSV-1 lytic transcription by facilitating the binding of RNA Pol II on viral genes.
Cohesin promotes HSV-1 lytic transcription by facilitating the binding of RNA Pol II on viral genes.
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Cohesin 通过促进 RNA Pol II 与病毒基因的结合来促进 HSV-1 裂解转录
DOI：
10.1186/s12985-021-01495-2
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发表时间：
2021-01-23
期刊：
影响因子：
4.8
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Li X;Yu Y;Lang F;Chen G;Wang E;Li L;Li Z;Yang L;Cao X;Fraser NW;Zhou J
单纯疱疹病毒I型(HSV-1)是一种大的双链DNA病毒，它进入上皮细胞进行生产性感染并重组宿主细胞核。粘附素是间期和有丝分裂染色体的主要组成部分，由SMC1、SMC3和SCC1(Mcd1/Rad21)、SCC3(Sa1/Sa2)组成，具有多种功能，包括姐妹染色单体凝聚、DNA双链断裂修复和转录调控。我们利用RNAi技术检测粘附素对HSV-1转录、基因组拷贝数和病毒滴度的影响，然后通过免疫荧光、定量聚合酶链式反应和芯片实验了解粘附素在HSV-1转录和复制中的作用。结果我们报道了凝聚素亚单位SMC1和Rad21被招募到HSV-1裂解性复制区段。基因敲除导致病毒转录、蛋白表达和病毒复制间隔的成熟减少。SMc1和Rad21基因敲除导致总的RNA polII占位水平降低，但增加了RNA polII ser5与病毒基因的磷酸化结合。结论粘附素通过促进RNA POL II转录活性和防止染色质在病毒基因组上的沉默而促进HSV-1裂解转录。
BackgroundHerpes Simplex Virus type I (HSV-1) is a large double-stranded DNA virus that enters productive infection in epithelial cells and reorganizes the host nucleus. Cohesin, a major constituent of interphase and mitotic chromosomes comprised of SMC1, SMC3, and SCC1 (Mcd1/Rad21), SCC3 (SA1/SA2), have diverse functions, including sister chromatid cohesion, DNA double-stranded breaks repair, and transcriptional control. Little is known about the role of cohesin in HSV-1 lytic infection.MethodsWe measured the effect on HSV-1 transcription, genome copy number, and viral titer by depleting cohesin components SMC1 or Rad21 using RNAi, followed by immunofluorescence, qPCR, and ChIP experiments to gain insight into cohesin's function in HSV-1 transcription and replication.ResultsHere, we report that cohesion subunits SMC1 and Rad21 are recruited to the lytic HSV-1 replication compartment. The knockdown results in decreased viral transcription, protein expression, and maturation of viral replication compartments. SMC1 and Rad21 knockdown leads to the reduced overall RNA pol II occupancy level but increased RNA pol II ser5 phosphorylation binding on viral genes. Consistent with this, the knockdown increased H3K27me3 modification on these genes.ConclusionsThese results suggest that cohesin facilitates HSV-1 lytic transcription by promoting RNA Pol II transcription activity and preventing chromatin's silencing on the viral genome.
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