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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Epigenetics of Latent Epstein-Barr Virus Genomes: High Resolution Methylation Analysis of the Bidirectional Promoter Region of Latent Membrane Protein 1 and 2B Genes

Maria Takacs / Daniel Salamon / Sanna Myöhänen / Hui Li / Judit Segesdi / Dorina Ujvari / Joerg Uhlig / Hans-Helmut Niller / Hans Wolf / George Berencsi / Janos Minarovits
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/BC.2001.083


We analysed the methylation patterns of CpG dinucleotides in a bidirectional promoter region (LRS, LMP 1 regulatory sequences) of latent EpsteinBarr virus (EBV) genomes using automated fluorescent genomic sequencing after bisulfiteinduced 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 methylationmediated direct interference with binding of nuclear factors LBF 2, 3, 7, AML1/LBF1, LBF5 and LBF6 or methylation of CpGs within an Ebox 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 sisinducible 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.

Published Online: 2005-06-01

Published in Print: 2001-04-27

Citation Information: Biological Chemistry. Volume 382, Issue 4, Pages 699–705, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2001.083, June 2005

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