|
| Status |
Public on Oct 11, 2023 |
| Title |
The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC [RNA-seq] |
| Organisms |
Homo sapiens; human gammaherpesvirus 4 |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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% to 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.
|
| |
|
| Overall design |
RNA sequencing of Human and EBV transcriptome in YCCEL1 and SNU719 cell lines
|
| |
|
| Contributor(s) |
Maestri D, Napoletani G, Kossenkov A, Preston-Alp S, Caruso LB, Tempera I |
| Citation(s) |
37889078 |
| |
| Submission date |
Aug 03, 2023 |
| Last update date |
Dec 22, 2023 |
| Contact name |
Italo Tempera |
| E-mail(s) |
itempera@wistar.org
|
| Organization name |
The Wistar Institute
|
| Street address |
3601 Spruce Street
|
| City |
Philadelphia |
| ZIP/Postal code |
10194 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL23185 |
Illumina HiSeq 2500 (Homo sapiens; Human gammaherpesvirus 4) |
|
| Samples (3) |
|
| This SubSeries is part of SuperSeries: |
| GSE239995 |
The three-dimensional structure of the EBV genome plays a crucial role in regulating viral gene expression in EBVaGC |
|
| Relations |
| BioProject |
PRJNA1001894 |
