Epigenetics of Latent Epstein-Barr Virus Genomes: High Resolution Methylation Analysis of the Bidirectional Promoter Region of Latent Membrane Protein 1 and 2B Genes
| Autor: | Joerg Uhlig, Dorina Ujvari, Daniel Salamon, Hans Helmut Niller, Hans Wolf, Hui Li, George Berencsi, Mária Takács, Janos Minarovits, Judit Segesdi, Sanna Myöhänen |
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| Rok vydání: | 2001 |
| Předmět: |
Herpesvirus 4
Human Clinical Biochemistry Promoter Genome Viral Methylation DNA Methylation Biology Biochemistry DNA-binding protein Molecular biology Virus Latency Viral Matrix Proteins stomatognathic diseases Epigenetics of physical exercise CpG site Regulatory sequence hemic and lymphatic diseases DNA Viral DNA methylation Humans CpG Islands Epigenetics Promoter Regions Genetic Sequence Analysis Molecular Biology |
| Zdroj: | Biological Chemistry. 382 |
| ISSN: | 1431-6730 |
| Popis: | We analysed the methylation patterns of CpG dinucleotides in a bidirectional promoter region (LRS, LMP 1 regulatory sequences) of latent Epstein-Barr virus (EBV) genomes using automated fluorescent genomic sequencing after bisulfite-induced modification of DNA. Transcripts for two latent membrane proteins, LMP 1 (a transforming protein) and LMP 2B, are initiated in this region in opposite directions. We found that B cell lines and a clone expressing LMP 1 carried EBV genomes with unmethylated or hypomethylated LRS, while highly methylated CpG dinucleotides were present at each position or at discrete sites and within hypermethylated regions in LMP 1 negative cells. Comparison of high resolution methylation maps suggests that CpG methylation-mediated direct interference with binding of nuclear factors LBF 2, 3, 7, AML1/LBF1, LBF5 and LBF6 or methylation of CpGs within an E-box sequence (where activators as well as repressors can bind) is not the major mechanism in silencing of the LMP 1 promoter. Although a role for CpG methylation within binding sites of Sp1 and 3, ATF/CRE and a sis-inducible factor (SIF) cannot be excluded, hypermethylation of LRS or regions within LRS in LMP 1 negative cells suggests a role for an indirect mechanism, via methylcytosine binding proteins, in silencing of the LMP 1 promoter. |
| Databáze: | OpenAIRE |
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