The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
11 Dec 2023
11 Dec 2023
Historique:
accepted:
10
10
2023
revised:
04
10
2023
received:
04
08
2023
pubmed:
27
10
2023
medline:
27
10
2023
entrez:
27
10
2023
Statut:
ppublish
Résumé
Epstein-Barr virus (EBV) establishes lifelong asymptomatic infection by replication of its chromatinized episomes with the host genome. EBV exhibits different latency-associated transcriptional repertoires, each with distinct three-dimensional structures. CTCF, Cohesin and PARP1 are involved in maintaining viral latency and establishing episome architecture. Epstein-Barr virus-associated gastric cancer (EBVaGC) represents 1.3-30.9% of all gastric cancers globally. EBV-positive gastric cancers exhibit an intermediate viral transcription profile known as 'Latency II', expressing specific viral genes and noncoding RNAs. In this study, we investigated the impact of PARP1 inhibition on CTCF/Cohesin binding in Type II latency. We observed destabilization of the binding of both factors, leading to a disrupted three-dimensional architecture of the episomes and an altered viral gene expression. Despite sharing the same CTCF binding profile, Type I, II and III latencies exhibit different 3D structures that correlate with variations in viral gene expression. Additionally, our analysis of H3K27ac-enriched interactions revealed differences between Type II latency episomes and a link to cellular transformation through docking of the EBV genome at specific sites of the Human genome, thus promoting oncogene expression. Overall, this work provides insights into the role of PARP1 in maintaining active latency and novel mechanisms of EBV-induced cellular transformation.
Identifiants
pubmed: 37889078
pii: 7331012
doi: 10.1093/nar/gkad936
pmc: PMC10711448
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
12092-12110Subventions
Organisme : NIAID NIH HHS
ID : R01 AI130209
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA269043
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM124449
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009171
Pays : United States
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.
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