Climate, Ecology & Environment Group, Los Alamos National Laboratory, Los Alamos, NM, USA.
Genomics & Bioanalytics Group, Los Alamos National Laboratory, Los Alamos, NM, USA.
Commun Biol. 2024 Jun 11;7(1):721. doi: 10.1038/s42003-024-06389-x.
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.
基因组折叠成复杂的构象和结构，据信这些构象和结构会深刻影响其功能。特别是在病毒感染的背景下，这种动态结构-功能关系的复杂性还没有得到很好的理解。为了揭示这种相互作用，我们在这里全面研究了痘苗病毒感染后宿主染色质结构（通过 Hi-C 和 ATAC-seq）和功能变化（通过 RNA-seq）的同时变化。随着时间的推移，感染通过增加长距离染色体内相互作用和 B 区室化，以及降低染色质可及性和染色体间相互作用，显著影响全局和局部染色质结构。局部可及性变化独立于广泛的染色质区室交换（约占基因组的 12%），突出了全局和局部染色质重排的潜在独立机制。虽然感染使宿主基因组结构上浓缩，但几乎存在双向差异基因表达。尽管 TAD 内相互作用整体减弱，但包括下调免疫基因在内的功能变化与局部可及性改变和环域结构重排有关。因此，染色质可及性和局部结构分析为宿主反应提供了有影响力的预测，并可能有助于开发有效的抗病毒对策，包括优化疫苗设计。
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