MUC1 expression is regulated by DNA methylation and histone H3 lysine 9 modification in cancer cells
MUC1 expression is regulated by DNA methylation and histone H3 lysine 9 modification in cancer cells
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DOI：
10.1158/0008-5472.can-07-6844
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发表时间：
2008-04-15
期刊：
影响因子：
11.2
通讯作者：
Yonezawa, Suguru
中科院分区：
文献类型：
--
作者：
Yamada, Norishige;Nishida, Yukari;Yonezawa, Suguru
MUC1是一种跨膜粘蛋白，在多种癌症中高度表达，并与恶性潜能相关。重要的癌症相关基因如p16和E-cadherin受表观遗传控制；然而，MUC1在表观遗传学中一直被忽视。本文首次报道了MUC1基因表达受DNA甲基化和MUC1启动子H3- k9修饰的调控。最近开发的MassARRAY检测方法用于研究- 2753至+263的184个CpG位点的DNA甲基化状态。在转录起始位点附近，muc1阴性癌细胞系（如MDA-MB-453）的DNA甲基化水平较高，而muc1阳性细胞系（如MCF-7）的DNA甲基化水平较低。组蛋白H3-K9修饰状态也与MUC1基因表达密切相关。此外，用DNA甲基化抑制剂5-aza-2'-脱氧胞苷处理MUC1阴性细胞后，MUC1 mRNA的表达恢复。我们的研究结果表明，DNA甲基化和5'侧区组蛋白H3-K9修饰在MUC1基因表达中起着关键作用，本研究将MUC1定义为表观遗传控制基因类的新成员。了解MUC1的表观遗传变化可能对癌症患者具有重要意义。
MUC1 is a transmembrane mucin that is highly expressed in various cancers and correlates with malignant potential. Important cancer-related genes such as p16 and E-cadherin are controlled epigenetically; however, MUC1 has been overlooked in epigenetics. Herein, we provide the first report that MUC1 gene expression is regulated by DNA methylation and histone H3 lysine 9 (H3-K9) modification of the MUC1 promoter. The recently developed MassARRAY assay was performed to investigate the DNA methylation status of 184 CpG sites from -2,753 to +263. Near the transcriptional start site, the DNA methylation level of MUC1-negative cancer cell lines (e.g., MDA-MB-453) was high, whereas that of MUC1-positive cell lines (e.g., MCF-7) was low. Histone H3-K9 modification status was also closely related to MUC1 gene expression. Furthermore, MUC1 mRNA expression in MUC1-negative cells was restored by treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine. Our results indicate that DNA methylation and histone H3-K9 modification in the 5' flanking region play a critical role in MUC1 gene expression, and this study defines MUC1 as a new member of the class of epigenetically controlled genes. An understanding of the epigenetic changes of MUC1 may be of importance for cancer patients.