Epigenetics of latent Epstein-Barr virus genomes: High resolution methylation analysis of the bidirectional promoter region of latent membrane protein 1 and 2B genes

Takacs, Maria and Salamon, Daniel and Myoehaenen, Sanna and Li, Hui and Segesdi, Judit and Ujvari, Dorina and Uhlig, Joerg and Niller, Hans-Helmut and Wolf, Hans and Berencsi, George and Minarovits, Janos (2001) Epigenetics of latent Epstein-Barr virus genomes: High resolution methylation analysis of the bidirectional promoter region of latent membrane protein 1 and 2B genes. BIOLOGICAL CHEMISTRY, 382 (4). pp. 699-705. ISSN 1431-6730

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Abstract

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, L8F5 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.

Item Type: Article
Uncontrolled Keywords: PHENOTYPE-DEPENDENT CONTROL; NUCLEAR ANTIGEN-2; HISTONE DEACETYLASE; BINDING-PROTEIN; TRANSCRIPTION FACTORS; REGULATORY REGION; DNA METHYLATION; CIS-ELEMENT; J-KAPPA; EXPRESSION; bisulfite modification; Burkitt's lymphoma; lymphoblastoid cell line; promoter methylation; viral latency
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Depositing User: Dr. Gernot Deinzer
Date Deposited: 07 Feb 2022 07:02
Last Modified: 07 Feb 2022 07:02
URI: https://pred.uni-regensburg.de/id/eprint/41521

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