ArticlePLoS pathogens2010
CpG-methylation regulates a class of Epstein-Barr virus promoters.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 113 citations in OpenAlex.
- Arginine metabolism supportsmBio · 2026Article
- Epstein-Barr Virus-host epigenetic interplay: mechanisms of regulation and therapeutic potential.Clinical epigenetics · 2026Review
- A System-Level Perspective on Epstein-Barr Virus Persistence: The Partial Lytic Reactivation.International journal of molecular sciences · 2026Review
- Epstein-Barr virus and human MiRNAs crosstalk: orchestrating latency, lytic cycle, and immune system modulation.Folia microbiologica · 2026Review
- Interaction between HIV-1 Tat and EBV Zta favours immune escape of B cells by downregulating HLA-ABC expression.Cellular and molecular life sciences : CMLS · 2026Article
- Arginine Metabolism SupportsbioRxiv : the preprint server for biology · 2025Article
- E2F1 suppresses Epstein-Barr virus lytic reactivation through cellular and viral transcriptional networks.PLoS pathogens · 2025Article
- The GC% landscape of the Nucleocytoviricota.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2024Article
- Epigenetic and epitranscriptomic regulation during oncogenicFrontiers in microbiology · 2024Review
- Identifying the key regulators orchestrating Epstein-Barr virus reactivation.Frontiers in microbiology · 2024Review
- Epstein-Barr virus and host cell 3D genome organization.Journal of medical virology · 2023Review
- Three-Dimensional Chromatin Structure of the EBV Genome: A Crucial Factor in Viral Infection.Viruses · 2023Review
- EBV dUTPase: A Novel Modulator of Inflammation and the Tumor Microenvironment in EBV-Associated Malignancies.Cancers · 2023Review
- Methionine metabolism controls the B cell EBV epigenome and viral latency.Cell metabolism · 2022Article
- Rta is the principal activator of Epstein-Barr virus epithelial lytic transcription.PLoS pathogens · 2022Article
- Epstein-Barr Virus miR-BHRF1-3 Targets the BZLF1 3'UTR and Regulates the Lytic Cycle.Journal of virology · 2022Article
- Epigenetic control of the Epstein-Barr lifecycle.Current opinion in virology · 2022Review
- Structural basis of DNA methylation-dependent site selectivity of the Epstein-Barr virus lytic switch protein ZEBRA/Zta/BZLF1.Nucleic acids research · 2022Article
- Epstein-Barr Virus Lytic Replication Induces ACE2 Expression and Enhances SARS-CoV-2 Pseudotyped Virus Entry in Epithelial Cells.Journal of virology · 2021Article
- Epstein-Barr virus inactivates the transcriptome and disrupts the chromatin architecture of its host cell in the first phase of lytic reactivation.Nucleic acids research · 2021Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian gene regulation. In general, cytosine-phosphatidyl-guanosine (CpG)-methylated promoters are transcriptionally repressed and nuclear proteins such as MECP2, MBD1, MBD2, and MBD4 bind CpG-methylated DNA and contribute to epigenetic silencing. Methylation of viral DNA also regulates gene expression of Epstein-Barr virus (EBV), which is a model of herpes virus latency. In latently infected human B cells, the viral DNA is CpG-methylated, the majority of viral genes is repressed and virus synthesis is therefore abrogated. EBV's BZLF1 encodes a transcription factor of the AP-1 family (Zta) and is the master gene to overcome viral gene repression. In a genome-wide screen, we now identify and characterize those viral genes, which Zta regulates. Among them are genes essential for EBV's lytic phase, which paradoxically depend on strictly CpG-methylated promoters for their Zta-induced expression. We identified novel DNA recognition motifs, termed meZRE (methyl-Zta-responsive element), which Zta selectively binds in order to 'read' DNA in a methylation- and sequence-dependent manner unlike any other known protein. Zta is a homodimer but its binding characteristics to meZREs suggest a sequential, non-palindromic and bipartite DNA recognition element, which confers superior DNA binding compared to CpG-free ZREs. Our findings indicate that Zta has evolved to transactivate cytosine-methylated, hence repressed, silent promoters as a rule to overcome epigenetic silencing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.