多个远程cis相互作用在静止的HSV-1基因组中产生CTCF绝缘体依赖的病毒染色质域
bioRxiv : the preprint server for biology
|July 14, 2025
概括
简单疹病毒1 (HSV-1) CTCF绝缘体将病毒DNA组织成染色质环,调节基因表达. 删除CTRL2绝缘体会改变这种组织,从而创建一个更容易访问的病毒基因组.
科学领域:
- * 病毒学 病毒学
- * 分子生物学 * 分子生物学
- * 表观遗传学 是一种表观遗传学.
背景情况:
- * CTCF绝缘体对于细胞系统中的基因组组织和基因调节至关重要.
- *潜伏的简单疹病毒1 (HSV-1) 基因组具有CTCF绝缘体,这些绝缘体会影响邻近的基因转录.
- *以前的研究表明HSV-1 CTCF绝缘体的单维调节作用.
研究的目的:
- * 为了研究HSV-1 CTCF隔离器为三维基因组组织核化染色质循环的假设.
- * 为了确定病毒CTCF绝缘体是否通过3D染色体架构调节遥远基因区域的表达.
- *阐明CTRL2绝缘体在HSV-1染色蛋白循环形成和病毒基因调节中的作用.
主要方法:
- *利用染色体构造捕获碳复制序列 (4C-seq) 来识别HSV-1基因组中的长距离cis相互作用.
- *使用独特的分子标识符4C-seq (UMI-4C-seq) 进行染色体相互作用的定量分析.
- * 在四个视角和在野生型 (wt) 与CTRL2-deleted HSV-1中分析的差异循环中量化了cis相互作用峰值.
主要成果:
- *确定了多个长距离的cis相互作用,形成病毒染色体域,包括CTRL2绝缘体介导的病毒染色体域.
- *删除CTRL2绝缘体破坏了病毒染色体域,并增加了cis相互作用峰值和相互作用长度.
- * 缺少CTRL2的病毒基因组与wtHSV-1相比,表现出一种比wtHSV-1更宽容的转录染色体环境.
结论:
- * HSV-1 CTRL2绝缘体是长距离染色体相互作用的关键调节器.
- * 删除CTRL2会重塑病毒染色体格局,增加可访问性和活力.
- *变化的染色体组织可能会显著影响HSV-1转录程序和延迟关联的染色体状态.
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