Sequence-Specific Methylation Inhibits the Activity of the Epstein-Barr Virus LMP 1 and BCR2 Enhancer-Promoter Regions

J. Mináróvits, Li Fu Hu, Susanna Minarovits Kormuta, George Klein, Ingemar Ernberg

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Abstract

We reported earlier that variable expression of the Epstein-Barr virus (EBV) encoded membrane protein LMP 1 in nasopharyngeal carcinoma and the host-cell-phenotype-dependent activity of the BCR2 promoter (one of the possible initiator sites for transcripts of Epstein-Barr nuclear antigens) in Burkitt's lymphoma (BL) lines can be related to the methylation status of the 5′-flanking regulatory regions of the BNLF 1 and BCR2 promoter, respectively. Here we report that clones of the BL line Mutu that differ in expression of LMP 1 also show a differential methylation pattern of the LMP 1 regulatory sequences: this region is hypomethylated in an LMP 1 expressing (group III) clone but methylated in a group I clone that does not express LMP 1. We introduced in vitro methylated reporter plasmids carrying BNLF 1 and BCR2 enhancer-promoter sequences into the BL line Raji and found that overall methylation of 5′-CG-3′ sequences by the Spiroplasma methylase SssI significantly reduced their activity compared to unmethylated or mock-methylated controls. Methylation of 5′-CCGG-3′ sequences by Hp all methyltransferase gave similar results. On the contrary, methylation of 5′-GCGC-3′ sequences by Hhal methyltransferase resulted only in a moderate reduction of BNLF 1 enhancer-promoter activity. These data support the notion that methylation at discrete sites within control regions of latent, growth-transformation associated EBV genes may contribute to silencing their expression.

Original languageEnglish
Pages (from-to)661-667
Number of pages7
JournalVirology
Volume200
Issue number2
DOIs
Publication statusPublished - May 1 1994

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Human Herpesvirus 4
Genetic Promoter Regions
Methylation
Burkitt Lymphoma
Clone Cells
Nucleic Acid Regulatory Sequences
Methyltransferases
Spiroplasma
Satellite Viruses
Nuclear Antigens
5' Flanking Region
Membrane Proteins
Plasmids
Phenotype
Growth
Genes

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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Sequence-Specific Methylation Inhibits the Activity of the Epstein-Barr Virus LMP 1 and BCR2 Enhancer-Promoter Regions. / Mináróvits, J.; Hu, Li Fu; Kormuta, Susanna Minarovits; Klein, George; Ernberg, Ingemar.

In: Virology, Vol. 200, No. 2, 01.05.1994, p. 661-667.

Research output: Contribution to journalArticle

Mináróvits, J. ; Hu, Li Fu ; Kormuta, Susanna Minarovits ; Klein, George ; Ernberg, Ingemar. / Sequence-Specific Methylation Inhibits the Activity of the Epstein-Barr Virus LMP 1 and BCR2 Enhancer-Promoter Regions. In: Virology. 1994 ; Vol. 200, No. 2. pp. 661-667.
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