Promoter demethylation mediates the expression of ZNF645, a novel cancer/testis gene
Promoter demethylation mediates the expression of ZNF645, a novel cancer/testis gene
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DOI：
10.5483/bmbrep.2010.43.6.400
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发表时间：
2010-06-30
期刊：
影响因子：
3.8
通讯作者：
Zhang, Sizhong
中科院分区：
文献类型：
--
作者：
Bai, Gang;Liu, Yunqiang;Zhang, Sizhong
肿瘤/睾丸(CT)抗原表现出高度的组织限制性表达，被认为是癌症疫苗的有前途的靶点。在这里，我们发现了一个新的CT基因ZNF645，它在正常人睾丸和肺癌患者中限制性表达(68.3%)。为了研究ZNF645基因启动子的甲基化状态，我们进行了亚硫酸氢盐基因组测序，发现ZNF645基因启动子上的CpG岛在正常肺组织中高度甲基化，而在正常人类睾丸和肺癌组织中有高度去甲基化。DNA去甲基化试剂5‘-氮-2’-脱氧胞苷对A549和HEK293T细胞的ZNF645也有明显的激活作用。双荧光素酶分析表明，CpG岛区甲基化抑制了ZNF645的启动子活性。因此，我们认为ZNF645是一个CT基因，通过其启动子区域的去甲基化在人睾丸和肺癌中被激活。[BMB报告2010；43(6)：400-406]
Cancer/testis (CT) antigens exhibit highly tissue-restricted expression and are considered promising targets for cancer vaccines. Here we identified a novel CT gene ZNF645 which restrictively expresses in normal human testes and lung cancer patients (68.3%). To investigate the promoter methylation status of ZNF645, we carried out bisulfite genomic sequencing and found that the CpG island in its promoter was heavily methylated in normal lung tissues without the expression of ZNF645, whereas there was high demethylation in normal human testes and lung carcinoma tissues with its expression. Also ZNF645 could be remarkably activated in A549 and HEK293T cells treated by DNA demethylation agent 5'-aza-2'-deoxycytidine. And the dual luciferase assay revealed that the promoter activity of the ZNF645 was inhibited by methylation of the CpG island region. Therefore, we proposed that ZNF645 is a CT gene and activated in human testis and lung cancers by demethylation of its promoter region. [BMB reports 2010; 43(6): 400-406]