Sinclair A J, Palmero I, Holder A, Peters G, Farrell P J
Ludwig Institute for Cancer Research, St. Mary's Hospital Medical School, London, United Kingdom.
J Virol. 1995 Feb;69(2):1292-5. doi: 10.1128/JVI.69.2.1292-1295.1995.
The cyclin D2 gene is not expressed in resting primary B lymphocytes or in group I Burkitt's lymphoma (BL) cell lines that retain the characteristics of authentic BL cells. Expression of cyclin D2 is induced in primary B lymphocytes following infection with Epstein-Barr virus (EBV) or transfection of the EBV genes EBNA-LP and EBNA-2. However, attempts to induce cyclin D2 expression in BL cell lines by the enforced expression of EBV genes were unsuccessful. Since the demethylation agent 5-azacytidine has been shown to modulate viral gene expression in BL cells, we explored the possibility that methylation plays a significant role in the control of cyclin D2 expression. We show that 5-azacytidine treatment of the Mutu CI 179 BL cell line led to expression of cyclin D2 RNA and that expression correlated with differences in the methylation status of a CCGG restriction enzyme site near the transcription initiation region of the cyclin D2 gene. Thus, methylation appears to play a direct role in the regulation of the cyclin D2 locus in BL.
细胞周期蛋白D2基因在静息的原代B淋巴细胞或保留真性伯基特淋巴瘤（BL）细胞特征的I组BL细胞系中不表达。在用爱泼斯坦-巴尔病毒（EBV）感染或转染EBV基因EBNA-LP和EBNA-2后，原代B淋巴细胞中会诱导细胞周期蛋白D2的表达。然而，通过强制表达EBV基因来诱导BL细胞系中细胞周期蛋白D2表达的尝试未成功。由于已证明去甲基化剂5-氮杂胞苷可调节BL细胞中的病毒基因表达，我们探讨了甲基化在细胞周期蛋白D2表达调控中起重要作用的可能性。我们发现，用5-氮杂胞苷处理Mutu CI 179 BL细胞系可导致细胞周期蛋白D2 RNA的表达，且该表达与细胞周期蛋白D2基因转录起始区域附近CCGG限制性酶切位点甲基化状态的差异相关。因此，甲基化似乎在BL中细胞周期蛋白D2基因座的调控中起直接作用。
