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启动子CpGs位点甲基化所致BRCA1基因转录抑制作用的位点特异性 被引量:4

The specific methylated site within CpG island of BRCA1 gene for transcriptional repression
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摘要 目的 研究 BRCA1基因 Cp G岛内各个 Cp Gs位点甲基化与转录水平的关系 ,探讨甲基化所致转录抑制作用的特异性 Cp G位点 ,以阐明 DNA甲基化的作用方式。方法 以 Rice等研究数据为材料 ,用方差分析和多因素线性回归模型等方法进行统计再分析。结果  BRCA1基因 Cp G岛 +8~ +44、- 189~ - 19、- 379~ - 2 5 8、- 37~ - 19和 - 80~ - 19区段内 Cp Gs的甲基化与基因转录抑制有关 ,这些区段内 Cp Gs位点的甲基化数目越多 ,基因转录水平越低。多因素线性回归模型分析表明 ,- 80~ - 19区段的甲基化与转录抑制关系密切。并以 - 2 9Cp G位点甲基化引起的转录抑制作用最强。结论  Cp G岛甲基化引起的转录抑制与 Cp Gs位点有关 ,具有位点的特异性。 Objective To identify the specific CpG region or site(s) wich are involved in the expression repression and gene silencing. Methods Rice'data (Carcinogenensis 2000,21(9):1761-1765) were reanalyzed, in which Rice JC et al. concluded that the aberrant cytosine methylation of BRCA1 promoter is directly correlated with decreased levels of BRCA1 expression in human breast cancer. The levels of transcription of BRCA1 gene in different patterns of methylation at different CpG region(s) or site(s) in CpG island were compared with one-way ANOVA and the specific regions or sites were studied with multiple linea regression model. Results The results indicated the methylation of -80^-19 fragment was an important region for transcriptional repression compared with other four fragments (+8^+44,-189^-127,-379^-258,-567^-440) in CpG island. The methylated cytosine at -29 CpG site in 80^-19 region was critical for expression repression of BRCA1 gene. Conclusion There are specific methylated region (site) in CpG island for transcriptional repression of BRCA1 gene.
出处 《实用肿瘤杂志》 CAS 北大核心 2003年第6期444-447,共4页 Journal of Practical Oncology
基金 国家自然科学基金资助 (基金编号30 0 70 343)
关键词 启动子 CpGs位点 甲基化 BRCA1基因转录 抑制作用 位点特异性 CpG islands genes genes,BRCA1 transcription,genetic methylation
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