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为了研究LRP15基因启动子区的甲基化状况及其与基因表达的关系,探讨LRP15基因的甲基化调控机 制,采用甲基化特异性聚合酶链反应(MS-PCR)检测LRP15基因启动子区的甲基化状况,应用甲基化抑制剂5-杂 氮-2’-脱氧胞嘧啶(CdR)及去乙酰化酶抑制刑曲古抑菌素(TSA)诱导CpG岛去甲基化及组蛋白乙酰化,观察启动 子区CpG岛甲基化与基因表达的关系。结果显示:白血病细胞系K562中LRP15基因启动子区呈高甲基化状态, 并抑制了该基因的表达。单独应用或联合TSA应用CdR均可去除该基因启动子区的高甲基化状态.并诱导该基 因的表达。这表明LRP15基因的表达受到启动子区甲基化的调控;该基因在K562细胞系中不表达与其启动子区 高甲基化及组蛋白去乙酰化密切相关。结论:甲基转移酶抑制剂与去乙酰化酶抑制剂在白血病治疗中可能具有一 定的价值。
In order to study the methylation status of LRP15 gene promoter region and its relationship with gene expression, investigate the mechanism of methylation of LRP15 gene, detect the promoter of LRP15 gene by methylation specific polymerase chain reaction (MS-PCR) Methylation inhibitor 5-aza-2’-deoxycytidine (CdR) and deacetylase inhibit quinquristotoxin (TSA) -induced CpG island demethylation and Histone acetylation, CpG island methylation observed gene promoter and its relationship with the gene expression. The results showed that the promoter region of LRP15 gene in leukemia cell line K562 was hypermethylated and inhibited the expression of LRP15 gene. CdR alone or in combination with TSA could remove the hypermethylation status of the promoter and induce the gene expression. This indicates that the expression of LRP15 gene is regulated by promoter methylation. The lack of expression of this gene in K562 cell line is closely related to hypermethylation of promoter region and histone deacetylation. Conclusions: Methyltransferase inhibitors and sirtuin inhibitors may have some value in the treatment of leukemia.