在SARS-CoV-2感染细胞中的染色质4D组织的多尺度建模
Andrea M Chiariello1, Alex Abraham2, Simona Bianco2
1Dipartimento di Fisica, Università degli Studi di Napoli Federico II, and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, 80126, Naples, Italy. andreamaria.chiariello@na.infn.it.
Nature communications
|May 13, 2024
概括
严重急性呼吸道综合征-冠状病毒-2 (SARS-CoV-2) 感染改变了宿主基因组的染色体组织. 聚合物物理学揭示了弱化的相互作用和改变的动态,影响了基因调节.
科学领域:
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 结构生物学 结构生物学
背景情况:
- 众所周知,SARS-CoV-2感染会改变宿主的表观基因组.
- 驱动SARS-CoV-2诱导的染色质重组的精确机制在很大程度上是未知的.
研究的目的:
- 调查在SARS-CoV-2感染期间宿主基因组染色质重组的物理机制.
- 阐明病毒感染如何影响染色体结构和基因调节.
主要方法:
- 利用聚合物物理原理来建模染色体的行为.
- 分析了A/B区间,拓关联域 (TADs) 和基因关联位置的变化.
- 检查了染色质接触和动态的时间轨迹.
主要成果:
- SARS-CoV-2 感染削弱了 A-A 相互作用,并增强了染色体区内的 A-B 混合.
- TAD重组涉及减少循环挤出和改变相位分离特性,导致相互混合的增加.
- 抗病毒反应基因的染色体结构变得更加可变,表明结构特异性的损失.
- 染色质动态的波动增加有助于改变基因增强剂和更高阶接触.
结论:
- 通过相互作用和动态的物理变化,SARS-CoV-2感染重塑宿主染色体组织.
- 病毒引起的染色体稳定性改变会影响基因调节,特别是针对抗病毒反应途径.
- 了解这些结构变化,可以了解宿主-病原体在表观基因层面的相互作用.
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