研究动态
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DNA-6-甲基鸟嘌呤甲基转移酶基因的甲基化状态与表达之间存在直接的相关性。

Direct correlation between methylation status and expression of the human O-6-methylguanine DNA methyltransferase gene.

发表日期:1991 Aug
作者: R O Pieper, J F Costello, R A Kroes, B W Futscher, U Marathi, L C Erickson
来源: Cancer Communications

摘要:

为了评估DNA胞嘧啶甲基化在O-6-甲基鸟嘌呤DNA甲基转移酶(MGMT)基因表达中的作用,我们研究了基因编码区和周围选择性CpG双核苷酸中的甲基化状态,并将其与13个人类细胞系中MGMT mRNA的稳态表达相关联。此外,长期暴露于5-氮杂胞苷的肿瘤细胞用于评估基因甲基化变化对MGMT表达的影响。这些研究结果表明,多个MGMT基因区域的甲基化程度与基因表达呈正相关而非负相关,并且5-氮杂胞苷诱导的MGMT基因去甲基化与MGMT稳态mRNA表达的明显降低相关,而非诱导。这些结果表明了MGMT基因与甲基化相关的独特、可改变的调节机制。
To assess the role of DNA cytosine methylation in the expression of the O-6-methylguanine DNA methyltransferase (MGMT) gene, the methylation status of selected CpG-containing dinucleotides in and surrounding the coding regions of the gene were examined and correlated with steady state expression of MGMT mRNA in 13 human cell lines. Additionally, tumor cells which exhibited very high levels of MGMT expression were chronically exposed to 5-azacytidine to assess the effects of changes in gene methylation on MGMT expression. Results of these studies demonstrate that the degree of methylation of multiple MGMT gene regions correlates with gene expression, but in a direct rather than an inverse fashion, and that 5-azacytidine-induced demethylation of the MGMT gene correlates with a significant reduction, rather than induction, of MGMT steady-state mRNA expression. These results suggest a unique, potentially alterable methylation-related regulatory mechanism for the MGMT gene.