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

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

We analyzed 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.

Original languageEnglish
Pages (from-to)699-705
Number of pages7
JournalBiological Chemistry
Volume382
Issue number4
DOIs
Publication statusPublished - Apr 1 2001

Keywords

  • Bisulfite modication
  • Burkitt's lymphoma
  • Lymphoblastoid cell line
  • Promoter methylation
  • Viral latency

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

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