Epigenetic Code of Host Chromosome Docking Sites for Epstein-Barr Virus (EBV) Latent Episomes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA532536 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Epstein-Barr virus (EBV) genomes persist in latently infected cells as extrachromosomal plasmids that attach to host chromosomes through the tethering functions of EBNA1, a viral encoded sequence-specific DNA binding protein. Here we employed circular chromosome conformation capture (4C) analysis to identify genomewide associations between EBV episomes and host chromosomes. We found that EBV episomes in Burkitt lymphoma (BL) cells preferentially associate with EBNA1 sequence-specific DNA binding sites in the cellular genome that are also enriched for B-cell factors EBF1 and RBP-jK, the repressive histone mark H3K9me3, and surrounded by AT-rich sequence. These attachment sites corresponded to transcriptionally silenced genes with enrichment in neuronal function. Depletion of EBNA1 from EBV latently infected BL cells led to a transcriptional de-repression of these silenced genes. EBV attachment sites in lymphoblastoid cells (LCLs) showed different correlations, suggesting that latency types are functionally linked to the epigenetic environment of host chromosome attachment sites.
2019-11-14 | GSE129703 | GEO
Project description:Comprehensive Profiling of Epstein-Barr Virus-Encoded miRNAome Associated with Specific Latent Type in Tumor Cells Epstein-Barr virus (EBV) is an etiological cause of many human lymphocytic and epithelial malignancies. EBV expressed different genes associated with three latent types. So far as many as 44 EBV-encoded miRNA species have been found but their comprehensive and comparative profiling is not well documented in three latent infection states linked to various tumor cells. In this study, we utilized the polyA-tailed quantitative real time RT-PCR procedure to measure the relative abundance of viral miRNA species that linked to individual viral genome locations in combination with microarray evaluation in a subset of representative lymphoid and epithelial tumor cells undergoing various types of EBV latent infection. The results showed that miR-BHRF1 family and miR-BART family are expressed differentially in a tissue-dependent and latency-dependent manner. In particular, in NPC tissue and the only EBV consistently harboring cell line C666-1 with latency type II, there were highly abundant miR-BART family but not miR-BHRF1 family members that accounted for more than 10% of the whole known human miRNA library, implicating their important roles in maintaining EBV latent infection and driving NPC tumorigenesis. In addition, EBV miRNAome-based clustering analysis could classify three distinct EBV latency types, meanwhile, for the first time, we found and subsequently evaluated a novel secret latent switch in BL cell line Daudi from type I to III, which was unable to be identified by traditional latent biomarkers. Together, our data provided an in-depth and comparative profiling of EBV miRNA transcriptome in correspondence with three EBV latent infections, suggesting that different viral miRNA species were involved in divergent host cell carcinogenesis. Finally, EBV miRNAome, as a cluster of novel latency biomarkers expressed variedly in tumor cells, greatly complements and improves the classical typing criteria in conjunction with other latently expressed marker genes. 2 NPC tissue samples and 2 NPC cell lines and 5 lymphocytic cell lines
2012-07-06 | E-GEOD-33225 | biostudies-arrayexpress
Project description:Comprehensive Profiling of Epstein-Barr Virus-Encoded miRNAome Associated with Specific Latent Type in Tumor Cells Epstein-Barr virus (EBV) is an etiological cause of many human lymphocytic and epithelial malignancies. EBV expressed different genes associated with three latent types. So far as many as 44 EBV-encoded miRNA species have been found but their comprehensive and comparative profiling is not well documented in three latent infection states linked to various tumor cells. In this study, we utilized the polyA-tailed quantitative real time RT-PCR procedure to measure the relative abundance of viral miRNA species that linked to individual viral genome locations in combination with microarray evaluation in a subset of representative lymphoid and epithelial tumor cells undergoing various types of EBV latent infection. The results showed that miR-BHRF1 family and miR-BART family are expressed differentially in a tissue-dependent and latency-dependent manner. In particular, in NPC tissue and the only EBV consistently harboring cell line C666-1 with latency type II, there were highly abundant miR-BART family but not miR-BHRF1 family members that accounted for more than 10% of the whole known human miRNA library, implicating their important roles in maintaining EBV latent infection and driving NPC tumorigenesis. In addition, EBV miRNAome-based clustering analysis could classify three distinct EBV latency types, meanwhile, for the first time, we found and subsequently evaluated a novel secret latent switch in BL cell line Daudi from type I to III, which was unable to be identified by traditional latent biomarkers. Together, our data provided an in-depth and comparative profiling of EBV miRNA transcriptome in correspondence with three EBV latent infections, suggesting that different viral miRNA species were involved in divergent host cell carcinogenesis. Finally, EBV miRNAome, as a cluster of novel latency biomarkers expressed variedly in tumor cells, greatly complements and improves the classical typing criteria in conjunction with other latently expressed marker genes.
2012-07-07 | GSE33225 | GEO
Project description:NKL homeobox genes encode developmental transcription factors regulating basic processes in cell differentiation. According to their physiological expression pattern in early hematopoiesis and B-cell development, particular members of this homeobox gene subclass constitute an NKL-code. These B-cell specific genes generate a regulatory network and their deregulation is implicated in B-cell lymphomagenesis. Epstein-Barr virus (EBV) infects B-cells and influences the activity of signalling pathways including JAK/STAT and several genes encoding developmental regulators. Therefore, EBV-infection impacts the pathogenesis and the outcome of B-cell malignancies including Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL). Here, we isolated EBV-positive and EBV-negative subclones from the DLBCL derived cell line DOHH-2. These subclones served as model to investigate the role of EBV in deregulation of the B-cell specific NKL-code members HHEX, HLX, MSX1 and NKX6-3. We showed that the EBV-encoded factors LMP1 and LMP2A activated the expression of HLX via STAT3. HLX in turn repressed NKX6-3, SPIB and IL4R which normally mediate plasma cell differentiation. In addition, HLX repressed pro-apoptotic factor BCL2L11/BIM supporting cell survival. Thus, EBV aberrantly activated HLX thereby disturbing both B-cell differentiation and apoptosis in DLBCL. The results of our study contribute to better understand the pathogenic role of EBV in B-cell malignancies.
2019-05-06 | GSE125420 | GEO
Project description:Epstein-Barr virus (EBV) infection of primary human B cells drives their indefinite proliferation into lymphoblastoid cell lines (LCLs). B cell immortalization depends on expression of viral latency genes as well as the regulation of host genes. Given the important role of miRNAs in regulating fundamental cellular processes, in this study we assayed changes in host miRNA expression during primary B cell infection by EBV. We observed and validated dynamic changes in several miRNAs from early proliferation through immortalization; oncogenic miRNAs were induced and tumor suppressor miRNAs were largely repressed. However, one miRNA described as a p53-targeted tumor suppressor, miR-34a, was strongly induced by EBV infection and expressed in many EBV and KSHV-infected lymphoma cell lines. The EBV latent membrane protein 1 (LMP1) was sufficient to induce miR-34a requiring downstream NFM-NM-:B activation, but independent of functional p53. Furthermore, over-expression of miR-34a was not toxic in several B lymphoma cell lines and inhibition of miR-34a impaired the growth of EBV transformed cells. This study identifies a pro-growth role for a tumor suppressive miRNA in oncogenic virus-mediated transformation highlighting the importance of studying miRNA function in different cellular contexts. miRNA expression profiling of human B-cells, EBV-infected, proliferating B cells and Monoclonal LCLs from 3 different donors was conducted with the use of up to 2 M-NM-<g total RNA for sample
2012-04-19 | E-GEOD-36926 | biostudies-arrayexpress
Project description:Our appreciation for the extent of Epstein Barr virus (EBV) transcriptome complexity continues to grow through findings of EBV encoded microRNAs, new long non-coding RNAs, and hundreds of new polyadenylated lytic transcripts. Here we report an additional layer to the EBV transcriptome through the identification of a repertoire of latent and lytic viral circRNAs. Utilizing RNase R-sequencing with cell models representing latency types I, II, and III, we identified circRNAs expressed from the latency Cp promoter involving backsplicing from the W1 and W2 exons to the C1 exon, from the EBNA BamHI U exon, and from the latency long-non-coding RPMS1 locus. We also identified circRNAs expressed during reactivation including an exon 8-to-2 backspliced LMP2 transcript and a highly expressed circRNA derived from the BHLF1 gene. Altogether we identified over 30 EBV circRNA candidates and validated and determined the structural features, expression profiles and nuclear-cytoplasmic distributions of several prominent viral circRNAs. Further, we show that two RPMS1 circRNAs are expressed in stomach cancer specimens. This study increases the known EBV latency and lytic transcriptome repertoires to include viral circRNAs and provides an essential foundation for investigations into the functions of this new class of EBV transcripts in EBV biology and disease.
2018-07-12 | GSE116675 | GEO
Project description:Epstein-Barr virus (EBV) infection of primary human B cells drives their indefinite proliferation into lymphoblastoid cell lines (LCLs). B cell immortalization depends on expression of viral latency genes as well as the regulation of host genes. Given the important role of miRNAs in regulating fundamental cellular processes, in this study we assayed changes in host miRNA expression during primary B cell infection by EBV. We observed and validated dynamic changes in several miRNAs from early proliferation through immortalization; oncogenic miRNAs were induced and tumor suppressor miRNAs were largely repressed. However, one miRNA described as a p53-targeted tumor suppressor, miR-34a, was strongly induced by EBV infection and expressed in many EBV and KSHV-infected lymphoma cell lines. The EBV latent membrane protein 1 (LMP1) was sufficient to induce miR-34a requiring downstream NFκB activation, but independent of functional p53. Furthermore, over-expression of miR-34a was not toxic in several B lymphoma cell lines and inhibition of miR-34a impaired the growth of EBV transformed cells. This study identifies a pro-growth role for a tumor suppressive miRNA in oncogenic virus-mediated transformation highlighting the importance of studying miRNA function in different cellular contexts.
2012-04-20 | GSE36926 | GEO
Project description:Epstein-Barr virus (EBV) is an oncogenic human herpesvirus involved in the pathogenesis of Burkitt’s lymphoma (BL) and various other lymphoproliferative disorders. In BL, EBV protein expression is restricted to the EBNA-1, but small non-coding RNAs such as the EBERs and micro (mi)RNAs can also be detected. miRNAs play major roles in crucial processes such as proliferation, differentiation and cell death. It has recently become clear that alteration in the expression profile of miRNAs contribute to the pathogenesis of a number of malignancies. During latent infection, EBV expresses 25 viral pre-miRNAs and modulates the expression of specific cellular miRNAs, such as miR-155 and miR-146, which potentially play a role in oncogenesis. Here, we established the small RNA expression profiles of three BL cell lines. Using large-scale sequencing coupled to northern blot and real-time RT-PCR analysis validation, we demonstrated the differential expression of some cellular and viral miRNAs. High-level expression of the miR-183-96-182 cluster and EBV miR-BART cluster was significantly associated with EBV type I latency. This expression was not affected by viral reactivation since TGF-ß1 stimulation did not significantly change the miRNA profiles. However, the expression of latent membrane protein (LMP)-1 triggered down-regulation of the expression of the miR-183-96-182 cluster. We further show that this effect involves the AKT signaling pathway.
2015-09-25 | GSE65752 | GEO
Project description:Epstein-Barr virus (EBV) Rta is a latent-lytic molecular switch evolutionarily conserved in all gamma-herpesviruses. In previous studies, doxycycline-inducible Rta was shown to potently produce an irreversible G1 arrest followed by cellular senescence in 293 cells. Here, we demonstrate that in this system the inducible Rta not only reactivates resident genome of EBV but also that of Kaposi’s sarcoma-associated herpesvirus (KSHV), to similar efficiency. However, Rta-induced senescence program was terminated by the robust viral lytic cycle replication that eventually caused cell death. Furthermore, prior to the abrupt expression of immediate-early protein (EBV BZLF1 or KSHV RTA), Rta simultaneously down-regulates cell cycle activators (c-Myc, CDK6, CCND2) and up-regulates senescence-related genes (p21, 14-3-3s). Since Rta is a viral immediate-early transcriptional activator, it is envisioned that during the initial stage of viral reactivation, Rta may engage to modulate the host transcriptome, to halt cell cycle progression, and to maintain an ideal environment for manufacturing infectious virions. Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE24585: Expression profiling of host genes modulated by Epstein-Barr virus (EBV) Rta in HEK293 cells GSE24586: Expression profiling of host genes modulated by Epstein-Barr virus Rta in nasopharyngeal carcinoma cells
2011-03-31 | E-GEOD-24587 | biostudies-arrayexpress
Project description:The Epstein Barr virus (EBV) encoded latent membrane protein-1 (LMP1) is a functional homologue of the tumor necrosis factor receptor family and contributes substantially to the oncogenic potential of EBV through activation of Nuclear Factor-kappaB (NF-kappaB). MicroRNAs (miRNAs) are a class of small RNA molecules that are involved in the regulation of cellular processes such as growth, development, and apoptosis, and have recently been linked to cancer phenotypes. Through miRNA microarray analysis, we demonstrate that LMP1 dysregulates the expression of several cellular miRNAs, including the most highly regulated of these, miR-146a. Quantitative RT-PCR analysis confirmed induced expression of miR-146a by LMP1. Analysis of miR-146a expression in EBV latency type III and type I cell lines revealed substantial expression of miR-146a in type III (which express LMP1) but not in type I cell lines. Reporter studies demonstrated that LMP1 induces miR-146a predominantly through two NF-kappaB binding sites in the miR-146a promoter and identified a role for an OCT-1 site in conferring basal and induced expression. Array analysis of cellular mRNAs expressed in Akata cells transduced with an miR-146a expressing retrovirus identified genes that are directly or indirectly regulated by miR-146a, including a group of interferon responsive genes that are inhibited by miR-146a. Since miR-146a is known to be induced by agents that activate the interferon response pathway (including LMP1), these results suggest that miR-146a functions in a negative feedback loop to modulate the intensity and/or duration of the interferon response. Keywords: Analysis of gene expression changes altered by the microRNA, miR-146a EBV positive Burkitt's lymphoma cell line, Akata, was infected with the control retrovirus, pEhyg, or the miR-146a expressing retrovirus, pEhyg-miR-146a. Two infections were carried out for control retrovirus and two infections were carried out with the pEhyg-miR-146a retrovirus. Total RNA was prepared from each of the 4 infections. Control and miR-146a infection set 1 was subjected to dual color array analysis on chip 1. Control and miR-146a infection set 2 was subjected to dual color array analysis on second array of chip 1. Dye swaps of each of these were carried out on two arrays from a second chip (chip 2).
2008-01-03 | E-GEOD-10057 | biostudies-arrayexpress