Vaccinia virus infection induces concurrent alterations in host chromatin architecture, accessibility, and gene expression [Hi-C]

ABSTRACT: Genomic DNA folds into complex configurations that produce particular local and globalstructures thought to profoundly impact genome function. To understand the dynamic nature ofthis relationship, we investigated the extent of host chromatin structural and functional changesin response to a viral agent. We performed comprehensive assessments of host architecture (Hi-C), accessibility (ATAC-seq), and gene expression (RNA-seq) in a paired manner in response toattenuated vaccinia (smallpox) virus. Over time, infection significantly increased long-rangeintra-chromosomal interactions and decreased chromatin accessibility. Fine-scale accessibilitychanges were independent of broad-scale chromatin compartment exchange, which increased (upto 12% of the genome) over time, underscoring potential independent mechanisms for global andlocal chromatin reorganization. The majority of differentially expressed genes, including thosedownregulated in immune responses, had concurrent alterations in local accessibility and loopdomain restructuring. Increased B compartmentalization, intra-chromosomal interactions, anddecreased inter-chromosomal interactions and chromatin accessibility together indicate thatinfection converts the host genome into a more condensed state with nearly equal bidirectionaldifferential gene expression. These changes in host chromatin features may have implications fordeveloping efficacious anti-viral countermeasures. Overall, our empirical data provides evidenceof orchestrated concurrent alterations in chromatin architecture, accessibility, and geneexpression in response to infection, further reinforcing the notion of coordinated structurefunctiondynamics of the genome.

ORGANISM(S): Chlorocebus sabaeus

PROVIDER: GSE248049 | GEO | 2024/05/11

REPOSITORIES: GEO