Similar Datasets
Project description:RIP-Seq of EBNA1 from EBV in HEK293T cells
| PRJNA421443 | ENA
Project description:Epstein-Barr virus (EBV) is a ubiquitous human ɣ-herpesvirus implicated in various malignancies, including Burkitt’s lymphoma and gastric carcinomas. In most EBV-associated cancers, the viral genome is maintained as an extrachromosomal episome by the EBV nuclear antigen-1 (EBNA1). EBNA1 is considered to be a highly stable protein that interacts with the ubiquitin-specific protease 7 (USP7), but the precise role of USP7 in controlling EBNA1 stability and function is not fully understood. Here, we show that pharmacological inhibitors and small interfering RNA (siRNA) targeting USP7 reduce EBNA1 protein levels. The USP7 inhibitor GNE6776 altered EBNA1 protein interactions, including disrupting its ability to bind to USP7. GNE6776 also inhibited EBNA1 binding to EBV oriP DNA and reduced viral episome copy number. GNE6776 selectively inhibited EBV+ gastric and lymphoid cell proliferation in cell culture and slowed EBV+ tumor growth in mouse xenograft models. Transcriptomic studies revealed that USP7 inhibition differentially affected EBV+ cancer cells compared to EBV- cells with a significant effect on chromosome segregation and mitotic cell division pathways. Our findings indicate that USP7 inhibition perturbs EBNA1 stability and function and can be exploited to target EBV+ cancer cells selectively.
2025-01-31 | GSE284839 | GEO
Project description:Epstein-Barr virus nuclear antigen 1 (EBNA1) is essential for the replication and stable maintenance of the viral episome in infected cells. Here, we identify the SUMO E3 ligase PIAS1 as a key regulator of EBNA1 through site-specific SUMOylation. Our Chromatin-Immunoprecipitation Sequencing (ChIP-seq) analysis revealed that PIAS1 is enriched at the viral origin of plasmid replication (oriP), where it physically associates with EBNA1 and catalyzes its SUMOylation. Using mutational analysis, we identified three lysine residues on EBNA1 (K17, K75, and K241) as major SUMOylation sites. Disruption of these sites compromises EBNA1’s ability to restrict EBV lytic replication. In addition, both PIAS1 depletion and the disruption of EBNA1 SUMOylation lead to reduced retention of EBNA1-OriP-based EBV mini-replicon, indicating the importance of EBNA1 SUMOylation in viral episome maintenance. Together, these results uncover a conserved post-translational mechanism by which PIAS1-mediated SUMOylation modulates EBNA1 function and EBV episome maintenance and suggests a broader role for SUMOylation in viral latency, lytic replication and persistence.
2025-12-01 | GSE306456 | GEO
Project description:Purpose: To identify the effect of EBV EBNA1 on cellular mRNA alternative splicings Methods: HEK293 cells were transfected with either Flag-EBNA1 vector or empty vector (NC) for 48 hours. Then the cell RNA was sequenced by a PromethION platform (P48-seq, the third generation sequencing). Results: Log-fold changes of up- or down-regulated mRNAs between the control and experiment group were selected with a significance threshold of p<0.05. Conclusions: Our study describes the mRNA alternative splicing changes induced by EBV-EBNA1 in HEK293 cells
2025-12-04 | GSE285484 | GEO
Project description:Epstein-Barr virus (EBV) latent infection is ubiquitously associated with nasopharyngeal carcinoma and gastric cancer, expressing very few viral protein components (EBNA1 and LMP1/2A). We previously showed that EBNA1 inhibitor VK1727 blocked cell cycle progression and growth of EBV+ tumors in vivo. However, the underlying molecular mechanism requires more evidence. In this study, we employed VK1727 to remove EBNA1 binding to viral and cellular genomes in three EBV+ epithelial tumors (PDX C15, C666-1 and SNU719). Then we integrated EBNA1 ChIP-seq and transcriptomic analysis to identify direct gene targets of VK1727, which involve in cell cycle progression and cell proliferation. Our analysis characterized a cell cycle dependent kinase CDC7 and a stem cell transcription factor POU2F1. Further analysis illustrated that EBNA1 binding to CDC7 promoter and POU2F1 intron promotes RNA Pol II-pS5 to initiate transcription of these two genes. Moreover, our results revealed CDC7 inhibitor Simurosertib is epistatic with VK1727 in reduction of EBV copy number, induction of cell cycle arrest, and inhibition of cell proliferation in EBV+ epithelial cancer. While POU2F1 knockdown reduced copy number of EBV, decreased expression of viral genes and inhibited proliferation of SNU719 cells. Our study revealed two functional gene targets of VK1727 in EBV+ epithelial cancers, which provides two potential biomarkers for following therapeutical research.
2026-04-17 | GSE315844 | GEO
Project description:Epstein-Barr virus (EBV) latent infection is ubiquitously associated with nasopharyngeal carcinoma and gastric cancer, expressing very few viral protein components (EBNA1 and LMP1/2A). We previously showed that EBNA1 inhibitor VK1727 blocked cell cycle progression and growth of EBV+ tumors in vivo. However, the underlying molecular mechanism requires more evidence. In this study, we employed VK1727 to remove EBNA1 binding to viral and cellular genomes in three EBV+ epithelial tumors (PDX C15, C666-1 and SNU719). Then we integrated EBNA1 ChIP-seq and transcriptomic analysis to identify direct gene targets of VK1727, which involve in cell cycle progression and cell proliferation. Our analysis characterized a cell cycle dependent kinase CDC7 and a stem cell transcription factor POU2F1. Further analysis illustrated that EBNA1 binding to CDC7 promoter and POU2F1 intron promotes RNA Pol II-pS5 to initiate transcription of these two genes. Moreover, our results revealed CDC7 inhibitor Simurosertib is epistatic with VK1727 in reduction of EBV copy number, induction of cell cycle arrest, and inhibition of cell proliferation in EBV+ epithelial cancer. While POU2F1 knockdown reduced copy number of EBV, decreased expression of viral genes and inhibited proliferation of SNU719 cells. Our study revealed two functional gene targets of VK1727 in EBV+ epithelial cancers, which provides two potential biomarkers for following therapeutical research.
2026-04-27 | GSE315867 | GEO
Project description:EBNA1 is the EBV-encoded nuclear antigen required for viral episome maintenance during latency. EBNA1 is a sequence specific DNA binding protein with high affinity binding sites for the viral genome, especially OriP. EBNA1 can also bind sequence specifically to a large number of sites in the host cellular genome, but the function of these binding sites has remained elusive. EBNA1 is also known to provide a host cell survival function, but the molecular mechanisms accounting for this function are not completely understood. Here, we show by integrating ChIP-Seq and RNA-Seq with experimental validation that MEF2B, IL6R, and EBF1 are high confidence target genes of EBNA1 that are essential for viability of B-lymphocytes latently infected with EBV. We show that EBNA1 binds to ~1000 sites with many, but not all, universally bound in different cell types, including Burkitt lymphoma (BL) and nasopharyngeal carcinoma (NPC). We find that a large subset of EBNA1 binding sites are located proximal to transcription start sites and correlate genome-wide with transcription activity. EBNA1 bound to genes of high significance for B-cell growth and function, including MEF2B, IL6R, EBF1, RNF145, POU2F1, KDM4C, FGR, EGFR, LAIR, CDC7, CD44, and IL17A. EBNA1 depletion from latently infected LCLs results in the loss of cell proliferation, and the loss of gene expression for some EBNA1-bound genes, including MEF2B, EBF1, and IL6R. Depletion of MEF2B, EBF1, or IL6R partially phenocopies EBNA1-depletion by decreasing EBV-positive cell growth and viability. These findings indicate that EBNA1 binds to a large cohort of cellular genes important for cell viability, and implicates EBNA1 as a master coordinator of host cell gene expression important for enhanced survival of latently infected cells. Examination of EBNA1 binding in Raji, MutuI, LCL and C666-1 cells and EBNA1 knockdown effect on mRNA gene expression in LCL
2015-12-16 | E-GEOD-73887 | biostudies-arrayexpress
Project description:EBNA1 is the EBV-encoded nuclear antigen required for viral episome maintenance during latency. EBNA1 is a sequence specific DNA binding protein with high affinity binding sites for the viral genome, especially OriP. EBNA1 can also bind sequence specifically to a large number of sites in the host cellular genome, but the function of these binding sites has remained elusive. EBNA1 is also known to provide a host cell survival function, but the molecular mechanisms accounting for this function are not completely understood. Here, we show by integrating ChIP-Seq and RNA-Seq with experimental validation that MEF2B, IL6R, and EBF1 are high confidence target genes of EBNA1 that are essential for viability of B-lymphocytes latently infected with EBV. We show that EBNA1 binds to ~1000 sites with many, but not all, universally bound in different cell types, including Burkitt lymphoma (BL) and nasopharyngeal carcinoma (NPC). We find that a large subset of EBNA1 binding sites are located proximal to transcription start sites and correlate genome-wide with transcription activity. EBNA1 bound to genes of high significance for B-cell growth and function, including MEF2B, IL6R, EBF1, RNF145, POU2F1, KDM4C, FGR, EGFR, LAIR, CDC7, CD44, and IL17A. EBNA1 depletion from latently infected LCLs results in the loss of cell proliferation, and the loss of gene expression for some EBNA1-bound genes, including MEF2B, EBF1, and IL6R. Depletion of MEF2B, EBF1, or IL6R partially phenocopies EBNA1-depletion by decreasing EBV-positive cell growth and viability. These findings indicate that EBNA1 binds to a large cohort of cellular genes important for cell viability, and implicates EBNA1 as a master coordinator of host cell gene expression important for enhanced survival of latently infected cells.
2015-12-16 | GSE73887 | GEO
Project description:USP7 inhibitors disrupt EBNA1 interactome and EBV tumorigenesis
| PRJNA1200707 | ENA
Project description:Structural Basis for TRF2-RAP1 Recruitment by EBNA1 at the EBV origin of replication.
| MSV000099143 | MassIVE