- EBV Type II latency relies on PARP1 activity and is essential for gastric epithelial cell transformation in EBV-associated Gastric Cancer (EBVaGC)
- Maestri, Davide <1995>
Subject
- BIO/11 Biologia molecolare
Description
- Epstein-Barr virus (EBV) establishes a lifelong asymptomatic infection by replicating its chromatinized genome, called episome, together with the host genome. EBV exhibits different latency-associated transcriptional repertoires that mirror its three-dimensional structures of the genome. CTCF, Cohesin and PARP1 are involved in maintaining viral latency and establishing episome architecture. Epstein-Barr virus-associated gastric cancer (EBVaGC) represents almost 10% of all gastric cancers globally. EBVaGC exhibit an intermediate viral transcription profile known as "Latency II", expressing specific viral genes and non-coding RNAs. In this study, we investigated the impact of PARP1 inhibition on CTCF/Cohesin binding in Type II latency. We observed a destabilization of the binding of both factors, leading to a disrupted three-dimensional architecture of the episomes and consequently, an altered viral gene expression. Despite sharing the same CTCF binding profile, Type I, II, and III latencies display different 3D episomal structures that correlate with variations in viral gene expression. Additionally, our analysis of H3K27ac-enriched chromatin interactions revealed differences between Type II latency episomes and a link to cellular transformation through docking of the EBV episomes 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.
Date
- 2024-04-08
Type
- Doctoral Thesis
- PeerReviewed
Format
- application/pdf
Identifier
urn:nbn:it:unibo-29995
Maestri, Davide (2024) EBV Type II latency relies on PARP1 activity and is essential for gastric epithelial cell transformation in EBV-associated Gastric Cancer (EBVaGC), [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Biologia cellulare e molecolare