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CpG-Methylation Regulates a Class of Epstein-Barr Virus Promoters
| Content Provider | CiteSeerX |
|---|---|
| Author | Bergbauer, Martin Kalla, Markus Schmeinck, Anne Rothbauer, Ulrich Strom, Tim M. Hammerschmidt, Wolfgang |
| 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 |
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| Access Restriction | Open |
| Subject Keyword | Epstein-barr Virus Promoter Viral Dna Viral Gene Zta-induced Expression Epigenetic Silencing Epstein-barr Virus Virus Synthesis Master Gene Nuclear Protein Sequence-dependent Manner Viral Gene Repression Lytic Phase Essential Role Gene Expression Methyl-zta-responsive Element Transcription Factor Cpg-methylated Dna Cpg-methylated Promoter Novel Dna Recognition Motif Genome-wide Screen Herpes Virus Latency Human Cell Binding Characteristic Cpg-free Zres Bipartite Dna Recognition Element Superior Dna Binding Silent Promoter Ap-1 Family Dna Methylation Major Modification Mammalian Gene Regulation Eukaryotic Genome |
| Content Type | Text |
