Epigenetics of Latent Epstein-Barr Virus Genomes: High Resolution Methylation Analysis of the Bidirectional Promoter Region of Latent Membrane Protein 1 and 2B Genes
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Maria Takacs
Abstract
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.
Copyright © 2001 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Vaccine Development: from Empirical Medicine to Molecularly Designed Therapy
- Dendritic Cells for Specific Cancer Immunotherapy
- Intracellular Bacteria as Targets and Carriers for Vaccination
- Bacteria-Mediated Transfer of Eukaryotic Expression Plasmids into Mammalian Host Cells
- Revealing the Potential of DNA-Based Vaccination: Lessons Learned from the Hepatitis B Virus Surface Antigen
- Progress toward a Malaria Vaccine: Efficient Induction of Protective Anti-Malaria Immunity
- Peptide Vaccines and Peptide Libraries
- Defined Synthetic Vaccines
- Antimicrobial Peptides: Properties and Applicability
- G-Quadruplex DNA Structures Variations on a Theme
- The Role of Heat Shock Proteins and Their Receptors in the Activation of the Immune System
- Transcriptional Repression Mediated by the KRAB Domain of the Human C2H2 Zinc Finger Protein Kox1/ZNF10 Does Not Require Histone Deacetylation
- Structure and Evolution of 4-Coumarate:Coenzyme A Ligase (4CL) Gene Families
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- The Cytosine N4-Methyltransferase M.PvuII Also Modifies Adenine Residues
- Expression of the Human Menkes ATPase in Xenopus laevis Oocytes
