Research Institute of Immunobiology Department of Medical Lifescience College of Medicine The Catholic University of Korea Seoul.
Exp Mol Med. 2011 Jul 30;43(7):401-10. doi: 10.3858/emm.2011.43.7.044.
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.
EBV 微 RNA(miRNA)在 EBV 相关肿瘤和细胞系中表达,但它们的表达调控机制尚不清楚。我们研究了 EBV 感染的 B 细胞系中 EBV miRNA 的表达是否受到表观遗传调控。BART miRNA 的表达与 BART 启动子的甲基化水平呈负相关,无论是在细胞的稳定状态下还是在 5-氮杂-2'-脱氧胞苷处理后。潜伏 I 型 EBV 感染细胞系中 Cp/Wp 的去甲基化也使 BHRF1 miRNA 的表达变得可检测。此外,BART 和 Cp 启动子的体外甲基化降低了启动子驱动的转录激活。相比之下,曲古抑菌素 A 对 EBV miRNA 表达以及 BART 和 Cp/Wp 启动子的表达几乎没有影响。我们的结果表明,启动子甲基化而非组蛋白乙酰化在 EBV 感染的 B 细胞系中 EBV miRNA 表达的调控中起作用。