Exp Mol Med.  2011 Jul;43(7):401-410. 10.3858/emm.2011.43.7.044.

The role of promoter methylation in Epstein-Barr virus (EBV) microRNA expression in EBV-infected B cell lines

• Kim DN
• Song YJ
• Lee SK

• KMID: 1015459
• DOI: http://doi.org/10.3858/emm.2011.43.7.044

Abstract

Epstein-Barr virus (EBV) microRNAs (miRNAs) are expressed in EBV-associated tumors and cell lines, but the regulation mechanism of their expression is unclear yet. We investigated whether the expression of EBV miRNAs is epigenetically regulated in EBV-infected B cell lines. The expression of BART miRNAs was inversely related with the methylation level of the BART promoter at both steady-state and following 5-aza-2'-deoxycytidine treatment of the cells. The expression of BHRF1 miRNAs also became detectable with the demethylation of Cp/Wp in latency I EBV-infected cell lines. Furthermore, in vitro methylation of the BART and Cp promoters reduced the promoter-driven transactivation. In contrast, tricostatin A had little effect on the expression of EBV miRNA expression as well as on the BART and Cp/Wp promoters. Our results suggest that promoter methylation, but not histone acetylation, plays a role in regulation of the EBV miRNA expression in EBV-infected B cell lines.

Keyword

decitabine; DNA methylation; Herpesvirus 4, human; microRNAs; promoter regions, genetic

MeSH Terms

Azacitidine/analogs & derivatives/pharmacology
B-Lymphocytes/metabolism/virology
Cell Line
*DNA Methylation
DNA Modification Methylases/antagonists & inhibitors
Gene Expression Regulation, Viral
Gene Silencing
Herpesvirus 4, Human/*genetics/physiology
Humans
MicroRNAs/genetics/*metabolism
*Promoter Regions, Genetic
RNA, Viral/genetics/*metabolism
Viral Proteins/genetics