HSV-1 感染诱导了 +1 核酶体的下游转移
Elena Weiß1, Adam W Whisnant2,3, Thomas Hennig2,3
1Institute of Informatics, Ludwig-Maximilians-Universität München, Munich, Germany.
Journal of virology
|March 25, 2025
概括
简单疹病毒1感染通过耗尽RNA聚合酶II (Pol II) 导致宿主转录关闭. 这导致核细胞在宿主促进体的定位下游转移,扩大可访问的染色体区域.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 简单疹病毒1 (HSV-1) 感染导致宿主细胞转录的显著破坏.
- 感染HSV-1导致宿主转录活动的丧失和转录终止的中断.
- 之前在酵母中进行的研究表明,RNA聚合酶II (Pol II) 枯竭导致核细胞的定位变化.
研究的目的:
- 为了研究性HSV-1感染对宿主染色质可访问性和核细胞定位的影响.
- 确定Pol II耗尽在HSV-1诱导的染色质变化中的作用.
- 为了识别涉及改变染色质结构的HSV-1特定蛋白质.
主要方法:
- CHIPmentation用于绘制基因组变异H2A.Z.分布的地图.
- 可访问的染色质的测序,以确定开放的染色质区域.
- 使用α-amanitin抑制Pol II活动,并分析核细胞定位.
- 对HSV-1蛋白质 (ICP4,ICP27,ICP22) 和病毒DNA复制的基因操纵.
主要成果:
- 炎症性HSV-1感染扩展了促进者的染色质可访问性到下游区域,特别是高度表达的基因.
- HSV-1 感染会导致 +1 核细胞的下游转移,这与 H2A.Z 分布变化有关.
- 由α-amanitin或HSV-1感染引起的Pol II耗尽,导致类似的下游转移+1核细胞.
- 防止病毒DNA复制 (酸,ICP4淘汰) 在很大程度上消除了这些染色质变化.
结论:
- 从宿主基因组中,HSV-1诱导的Pol II的耗尽是下游+1核细胞转移的主要驱动因素.
- 在HSV-1感染期间观察到宿主促进体的染色质结构变化是Pol II损失的结果.
- 这些发现提供了病毒感染,Pol II调节和宿主表观基因组变化之间的机制联系.
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