ArticlePLoS pathogens2012
BZLF1 governs CpG-methylated chromatin of Epstein-Barr Virus reversing epigenetic repression.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
72 citing papers in PubMed, 94 citations in OpenAlex.
- Proteomic screening identifies HNRNPA2B1 as an epigenetic repressor of Epstein-Barr virus reactivation.Journal of virology · 2026Article
- Reconstructing EBV reactivation and DNA damage response kinetics in morphologic pseudotime.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Neuroinflammation as a result of non-neurotropic herpesvirus infection.Immunology and cell biology · 2026Review
- Locus-specific proteomics identifies novel regulators of Epstein-Barr virus lytic reactivation.Journal of virology · 2026Article
- 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
- Proteomic Screening Identifies HNRNPA2B1 as an Epigenetic Repressor of Epstein-Barr Virus Reactivation.bioRxiv : the preprint server for biology · 2026Article
- Reconstructing EBV reactivation and DNA damage response kinetics in morphologic pseudotime.bioRxiv : the preprint server for biology · 2025Article
- Epstein-Barr virus pathogenesis and emerging control strategies.Nature reviews. Microbiology · 2025Review
- Assessing the fitness of Epstein-Barr virus following its reactivation.Journal of virology · 2025Article
- Chromatin Control of EBV Infection and Latency.Current topics in microbiology and immunology · 2025Article
- Article
- Research landmarks on the 60th anniversary of Epstein-Barr virus.Science China. Life sciences · 2025Review
- Epstein-Barr virus induces host shutoff extensively via BGLF5-independent mechanisms.Cell reports · 2024Article
- Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.PLoS pathogens · 2024Article
- Epstein-Barr Viruses: Their Immune Evasion Strategies and Implications for Autoimmune Diseases.International journal of molecular sciences · 2024Review
- Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.bioRxiv : the preprint server for biology · 2024Article
- Article
- Epigenetic and epitranscriptomic regulation during oncogenicFrontiers in microbiology · 2024Review
- Targeting latent viral infection in EBV-associated lymphomas.Frontiers in immunology · 2024Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Epigenetic mechanisms are essential for the regulation of all genes in mammalian cells but transcriptional repression including DNA methylation are also major epigenetic mechanisms of defense inactivating potentially harmful pathogens. Epstein-Barr Virus (EBV), however, has evolved to take advantage of CpG methylated DNA to regulate its own biphasic life cycle. We show here that latent EBV DNA has an extreme composition of methylated CpG dinucleotides with a bimodal distribution of unmethylated or fully methylated DNA at active latent genes or completely repressed lytic promoters, respectively. We find this scenario confirmed in primary EBV-infected memory B cells in vivo. Extensive CpG methylation of EBV's DNA argues for a very restricted gene expression during latency. Above-average nucleosomal occupancy, repressive histone marks, and Polycomb-mediated epigenetic silencing further shield early lytic promoters from activation during latency. The very tight repression of viral lytic genes must be overcome when latent EBV enters its lytic phase and supports de novo virus synthesis in infected cells. The EBV-encoded and AP-1 related transcription factor BZLF1 overturns latency and initiates virus synthesis in latently infected cells. Paradoxically, BZLF1 preferentially binds to CpG-methylated motifs in key viral promoters for their activation. Upon BZLF1 binding, we find nucleosomes removed, Polycomb repression lost, and RNA polymerase II recruited to the activated early promoters promoting efficient lytic viral gene expression. Surprisingly, DNA methylation is maintained throughout this phase of viral reactivation and is no hindrance to active transcription of extensively CpG methylated viral genes as thought previously. Thus, we identify BZLF1 as a pioneer factor that reverses epigenetic silencing of viral DNA to allow escape from latency and report on a new paradigm of gene regulation.
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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.