Host cell-dependent expression of latent Epstein-Barr virus genomes: Regulation by DNA methylation

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Abstract

Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus associated with a wide spectrum of malignant neoplasms. Expression of latent (growth transformation-associated) EBV genes is host cell specific. Transcripts for EBV-encoded nuclear antigens (EBNAs) are initiated at one of the alternative promoters: Wp, Cp (for EBNA1-6), or Qp (for EBNA1 only). Wp is active shortly after EBV infection of human B cells in vitro but is progressively methylated and silenced in established lymphoblastoid cell lines (LCLs). In parallel Cp, an unmethylated, lymphoid-specific promoter is switched on. In contrast, Cp is methylated and silent in Burkitt's lymphoma (BL) cell lines, which keep the phenotype of BL biopsy cells (group I BL lines). These cells use Qp for the initiation of EBNA1 messages. Qp is unmethylated both in group I BLs (Qp on) and in LCLs (Qp off). Thus, DNA methylation does not play a role in silencing Qp. In LCLs and nasopharyngeal carcinoma (NPC) cells, transcripts for latent membrane protein 1 (LMP1) are initiated from LMP1p, a promoter regulated by CpG methylation. LMP1p is silent in group I BL lines but can be activated by demethylating agents. Promoter silencing by CpG methylation involves both direct interference with transcription factor binding (Wp, Cp) and indirect mechanisms involving the recruitment of histone deacetylases (LMP1p). A dyad symmetry sequence (DS) within oriP (the latent origin of EBV replication) and intragenic RNA polymerase III control regions of EBER 1 and 2 transcription units are invariably unmethylated in EBV-carrying cells.

Original languageEnglish
Pages (from-to)133-156
Number of pages24
JournalAdvances in Cancer Research
Volume89
DOIs
Publication statusPublished - 2003

Fingerprint

DNA Methylation
Human Herpesvirus 4
Burkitt Lymphoma
Genome
Cell Line
Methylation
Epstein-Barr Virus Nuclear Antigens
RNA Polymerase III
Epstein-Barr Virus Infections
Histone Deacetylases
Virus Replication
Membrane Proteins
B-Lymphocytes
Transcription Factors
Phenotype
Biopsy
Growth
Genes
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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title = "Host cell-dependent expression of latent Epstein-Barr virus genomes: Regulation by DNA methylation",
abstract = "Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus associated with a wide spectrum of malignant neoplasms. Expression of latent (growth transformation-associated) EBV genes is host cell specific. Transcripts for EBV-encoded nuclear antigens (EBNAs) are initiated at one of the alternative promoters: Wp, Cp (for EBNA1-6), or Qp (for EBNA1 only). Wp is active shortly after EBV infection of human B cells in vitro but is progressively methylated and silenced in established lymphoblastoid cell lines (LCLs). In parallel Cp, an unmethylated, lymphoid-specific promoter is switched on. In contrast, Cp is methylated and silent in Burkitt's lymphoma (BL) cell lines, which keep the phenotype of BL biopsy cells (group I BL lines). These cells use Qp for the initiation of EBNA1 messages. Qp is unmethylated both in group I BLs (Qp on) and in LCLs (Qp off). Thus, DNA methylation does not play a role in silencing Qp. In LCLs and nasopharyngeal carcinoma (NPC) cells, transcripts for latent membrane protein 1 (LMP1) are initiated from LMP1p, a promoter regulated by CpG methylation. LMP1p is silent in group I BL lines but can be activated by demethylating agents. Promoter silencing by CpG methylation involves both direct interference with transcription factor binding (Wp, Cp) and indirect mechanisms involving the recruitment of histone deacetylases (LMP1p). A dyad symmetry sequence (DS) within oriP (the latent origin of EBV replication) and intragenic RNA polymerase III control regions of EBER 1 and 2 transcription units are invariably unmethylated in EBV-carrying cells.",
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AU - Li, Hui

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N2 - Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus associated with a wide spectrum of malignant neoplasms. Expression of latent (growth transformation-associated) EBV genes is host cell specific. Transcripts for EBV-encoded nuclear antigens (EBNAs) are initiated at one of the alternative promoters: Wp, Cp (for EBNA1-6), or Qp (for EBNA1 only). Wp is active shortly after EBV infection of human B cells in vitro but is progressively methylated and silenced in established lymphoblastoid cell lines (LCLs). In parallel Cp, an unmethylated, lymphoid-specific promoter is switched on. In contrast, Cp is methylated and silent in Burkitt's lymphoma (BL) cell lines, which keep the phenotype of BL biopsy cells (group I BL lines). These cells use Qp for the initiation of EBNA1 messages. Qp is unmethylated both in group I BLs (Qp on) and in LCLs (Qp off). Thus, DNA methylation does not play a role in silencing Qp. In LCLs and nasopharyngeal carcinoma (NPC) cells, transcripts for latent membrane protein 1 (LMP1) are initiated from LMP1p, a promoter regulated by CpG methylation. LMP1p is silent in group I BL lines but can be activated by demethylating agents. Promoter silencing by CpG methylation involves both direct interference with transcription factor binding (Wp, Cp) and indirect mechanisms involving the recruitment of histone deacetylases (LMP1p). A dyad symmetry sequence (DS) within oriP (the latent origin of EBV replication) and intragenic RNA polymerase III control regions of EBER 1 and 2 transcription units are invariably unmethylated in EBV-carrying cells.

AB - Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus associated with a wide spectrum of malignant neoplasms. Expression of latent (growth transformation-associated) EBV genes is host cell specific. Transcripts for EBV-encoded nuclear antigens (EBNAs) are initiated at one of the alternative promoters: Wp, Cp (for EBNA1-6), or Qp (for EBNA1 only). Wp is active shortly after EBV infection of human B cells in vitro but is progressively methylated and silenced in established lymphoblastoid cell lines (LCLs). In parallel Cp, an unmethylated, lymphoid-specific promoter is switched on. In contrast, Cp is methylated and silent in Burkitt's lymphoma (BL) cell lines, which keep the phenotype of BL biopsy cells (group I BL lines). These cells use Qp for the initiation of EBNA1 messages. Qp is unmethylated both in group I BLs (Qp on) and in LCLs (Qp off). Thus, DNA methylation does not play a role in silencing Qp. In LCLs and nasopharyngeal carcinoma (NPC) cells, transcripts for latent membrane protein 1 (LMP1) are initiated from LMP1p, a promoter regulated by CpG methylation. LMP1p is silent in group I BL lines but can be activated by demethylating agents. Promoter silencing by CpG methylation involves both direct interference with transcription factor binding (Wp, Cp) and indirect mechanisms involving the recruitment of histone deacetylases (LMP1p). A dyad symmetry sequence (DS) within oriP (the latent origin of EBV replication) and intragenic RNA polymerase III control regions of EBER 1 and 2 transcription units are invariably unmethylated in EBV-carrying cells.

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