PDF(Pubmed)
Abstract：
The genome folds into complex configurations and structures thought to profoundly impact its function. The intricacies of this dynamic structure-function relationship are not well understood particularly in the context of viral infection. To unravel this interplay, here we provide a comprehensive investigation of simultaneous host chromatin structural (via Hi-C and ATAC-seq) and functional changes (via RNA-seq) in response to vaccinia virus infection. Over time, infection significantly impacts global and local chromatin structure by increasing long-range intra-chromosomal interactions and B compartmentalization and by decreasing chromatin accessibility and inter-chromosomal interactions. Local accessibility changes are independent of broad-scale chromatin compartment exchange (~12% of the genome), underscoring potential independent mechanisms for global and local chromatin reorganization. While infection structurally condenses the host genome, there is nearly equal bidirectional differential gene expression. Despite global weakening of intra-TAD interactions, functional changes including downregulated immunity genes are associated with alterations in local accessibility and loop domain restructuring. Therefore, chromatin accessibility and local structure profiling provide impactful predictions for host responses and may improve development of efficacious anti-viral counter measures including the optimization of vaccine design.
摘要：
基因组折叠成复杂的构型和结构，被认为会深刻影响其功能。这种动态结构-功能关系的复杂性尚未得到很好的理解，特别是在病毒感染的背景下。为了解开这种相互作用，在这里，我们提供了对痘苗病毒感染的同时宿主染色质结构（通过Hi-C和ATAC-seq）和功能变化（通过RNA-seq）的全面调查。随着时间的推移,感染通过增加长期染色体内相互作用和B区划分以及降低染色质可及性和染色体间相互作用来显着影响全局和局部染色质结构。局部可达性变化与广泛的染色质区室交换无关（约占基因组的12％），强调全球和局部染色质重组的潜在独立机制。虽然感染在结构上浓缩了宿主基因组，双向差异基因表达几乎相等。尽管TAD内部相互作用在全球范围内减弱，包括下调免疫基因在内的功能变化与局部可达性和环域重组的改变有关。因此,染色质可及性和局部结构分析为宿主反应提供了有效的预测，并可能改善有效的抗病毒对策的发展，包括疫苗设计的优化。
