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| Status |
Public on May 11, 2024 |
| Title |
Vaccinia virus infection induces concurrent alterations in host chromatin architecture, accessibility, and gene expression [Hi-C] |
| Organism |
Chlorocebus sabaeus |
| Experiment type |
Other
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| Summary |
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.
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| Overall design |
To investigate concurrent alterations in host chromatin accessibility and 3D organization as viralinfection progresses, we infected a susceptible cell line (Vero), derived from African greenmonkey, with Modified Vaccinia virus Ankara strain (MVA). We confirmedsuccessful infection and its gradual progression at 12-, 18-, and 24-hours post infection. At each time point, cells were collected from mock-infected (control) and MVAinfectedcell culture flasks for paired measurement of 3D genomic organization, chromatinaccessibility, and gene expression using Hi-C, ATAC, and RNA sequencing, respectively. We generated and sequenced 12 each Hi-C libraries, RNA-seq libraries, and ATAC libraries inlcuding two biological replcates per condition per timepoint.
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| Contributor(s) |
Venu V, Roth C, Adikari SH, Small EM, Starkenburg SR, Sanbonmatsu KY, Steadman CR |
| Citation(s) |
38862613 |
| BioProject |
PRJNA1037174 |
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| Submission date |
Nov 16, 2023 |
| Last update date |
Jun 28, 2024 |
| Contact name |
Christina Rene Steadman |
| Organization name |
Los Alamos National Laboratory
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| Department |
Earth & Environmental Sciences Division
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| Lab |
Epigenetics Lab
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| Street address |
Bikini Atoll Rd
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| City |
Los Alamos |
| State/province |
New Mexico |
| ZIP/Postal code |
87545 |
| Country |
USA |
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| Platforms (1) |
| GPL30937 |
NextSeq 2000 (Chlorocebus sabaeus) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE248052 |
Vaccinia virus infection induces concurrent alterations in host chromatin architecture, accessibility, and gene expression |
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| Supplementary file |
Size |
Download |
File type/resource |
| GSE248049_UNTR_12hrs_juiced_30.hic |
2.7 Gb |
(ftp)(http) |
HIC |
| GSE248049_UNTR_18hrs_juiced_30.hic |
2.4 Gb |
(ftp)(http) |
HIC |
| GSE248049_UNTR_24hrs_juiced_30.hic |
3.0 Gb |
(ftp)(http) |
HIC |
| GSE248049_VACV_12hrs_juiced_30.hic |
2.5 Gb |
(ftp)(http) |
HIC |
| GSE248049_VACV_18hrs_juiced_30.hic |
2.3 Gb |
(ftp)(http) |
HIC |
| GSE248049_VACV_24hrs_juiced_30.hic |
2.9 Gb |
(ftp)(http) |
HIC |
SRA Run Selector |
| Raw data are available in SRA |
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