ArticlePLoS pathogens2008
Methylated DNA recognition during the reversal of epigenetic silencing is regulated by cysteine and serine residues in the Epstein-Barr virus lytic switch protein.
Article in PLoS pathogens, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 38 citations in OpenAlex.
- BPabZIP, a new bZIP protein motif that promotes binding near, and displacement of, nucleosomes.bioRxiv : the preprint server for biology · 2026Article
- Methyl-qPCR: a new method to investigate Epstein-Barr virus infection in post-transplant lymphoproliferative diseases.Clinical epigenetics · 2022Article
- Altering the Double-Stranded DNA Specificity of the bZIP Domain of Zta with Site-Directed Mutagenesis at N182.ACS omega · 2022Article
- Epstein-Barr Virus Lytic Replication Induces ACE2 Expression and Enhances SARS-CoV-2 Pseudotyped Virus Entry in Epithelial Cells.Journal of virology · 2021Article
- Replacing C189 in the bZIP domain of Zta with S, T, V, or A changes DNA binding specificity to four types of double-stranded DNA.Biochemical and biophysical research communications · 2018Article
- The Epstein-Barr Virus B-ZIP Protein Zta Recognizes Specific DNA Sequences Containing 5-Methylcytosine and 5-Hydroxymethylcytosine.Biochemistry · 2017Article
- Methyl-dependent and spatial-specific DNA recognition by the orthologous transcription factors human AP-1 and Epstein-Barr virus Zta.Nucleic acids research · 2017Article
- 5-Methylcytosine (5mC) and 5-Hydroxymethylcytosine (5hmC) Enhance the DNA Binding of CREB1 to the C/EBP Half-Site Tetranucleotide GCAA.Biochemistry · 2016Article
- ERK/c-Jun Recruits Tet1 to Induce Zta Expression and Epstein-Barr Virus Reactivation through DNA Demethylation.Scientific reports · 2016Article
- Transcription factors as readers and effectors of DNA methylation.Nature reviews. Genetics · 2016Review
- Repression of CIITA by the Epstein-Barr virus transcription factor Zta is independent of its dimerization and DNA binding.The Journal of general virology · 2016Article
- c-Jun/c-Fos heterodimers regulate cellular genes via a newly identified class of methylated DNA sequence motifs.Nucleic acids research · 2014Article
- Keeping it quiet: chromatin control of gammaherpesvirus latency.Nature reviews. Microbiology · 2013Review
- Article
- Epigenetic regulation of EBV and KSHV latency.Current opinion in virology · 2013Review
- Epstein-Barr virus-induced epigenetic alterations following transient infection.International journal of cancer · 2013Article
- Genome-wide analyses of Zta binding to the Epstein-Barr virus genome reveals interactions in both early and late lytic cycles and an epigenetic switch leading to an altered binding profile.Journal of virology · 2012Article
- BZLF1 governs CpG-methylated chromatin of Epstein-Barr Virus reversing epigenetic repression.PLoS pathogens · 2012Article
- Methylation profiling of Epstein-Barr virus immediate-early gene promoters, BZLF1 and BRLF1 in tumors of epithelial, NK- and B-cell origins.BMC cancer · 2012Article
- Dynamic chromatin environment of key lytic cycle regulatory regions of the Epstein-Barr virus genome.Journal of virology · 2012Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with various malignancies, including Burkitt's lymphoma and nasopharyngeal carcinoma. Like all herpesviruses, the EBV life cycle alternates between latency and lytic replication. During latency, the viral genome is largely silenced by host-driven methylation of CpG motifs and, in the switch to the lytic cycle, this epigenetic silencing is overturned. A key event is the activation of the viral BRLF1 gene by the immediate-early protein Zta. Zta is a bZIP transcription factor that preferentially binds to specific response elements (ZREs) in the BRLF1 promoter (Rp) when these elements are methylated. Zta's ability to trigger lytic cycle activation is severely compromised when a cysteine residue in its bZIP domain is mutated to serine (C189S), but the molecular basis for this effect is unknown. Here we show that the C189S mutant is defective for activating Rp in a Burkitt's lymphoma cell line. The mutant is compromised both in vitro and in vivo for binding two methylated ZREs in Rp (ZRE2 and ZRE3), although the effect is striking only for ZRE3. Molecular modeling of Zta bound to methylated ZRE3, together with biochemical data, indicate that C189 directly contacts one of the two methyl cytosines within a specific CpG motif. The motif's second methyl cytosine (on the complementary DNA strand) is predicted to contact S186, a residue known to regulate methyl-ZRE recognition. Our results suggest that C189 regulates the enhanced interaction of Zta with methylated DNA in overturning the epigenetic control of viral latency. As C189 is conserved in many bZIP proteins, the selectivity of Zta for methylated DNA may be a paradigm for a more general phenomenon.
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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.