Novel Epigenetic Controlling of Hypoxia Pathway Related to Overexpression and Promoter Hypomethylation of TET1 and TET2 in RPE Cells
Novel Epigenetic Controlling of Hypoxia Pathway Related to Overexpression and Promoter Hypomethylation of TET1 and TET2 in RPE Cells
复制标题
视网膜色素上皮（RPE）细胞中与TET1和TET2过表达及启动子低甲基化相关的缺氧通路的新型表观遗传调控
DOI：
10.1002/jcb.25965
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发表时间：
2017-10-01
影响因子：
4
通讯作者：
Sabouni, Farzaneh
中科院分区：
文献类型：
--
作者：
Alivand, Mohammad Reza;Soheili, Zahra-Soheila;Sabouni, Farzaneh
DNA的CpG甲基化参与了一种特定的表观遗传记忆，在细胞的分化和异常中起着至关重要的作用。影响基因组甲基化模式畸变的途径有三种，即DNA甲基转移酶（DNMT）、10 - 11易位（泰特）和甲基结合结构域（MBD）蛋白。其中，泰特酶最近被证明是DNA甲基化过程中的主修饰酶。此外，最近的研究强调，不仅表观遗传现象在控制缺氧通路中发挥作用，而且缺氧条件还触发基因组的低甲基化，这可能有助于缺氧通路基因的表达。在这项研究中，我们认为TET 1和TET 2可以在化学缺氧条件下基因组的去甲基化中发挥作用。在此，分别通过实时PCR和甲基化特异性PCR（MSP）来评估上述基因的甲基化状态和mRNA表达。结果表明，化学缺氧条件下，TET 1和TET 2基因在视网膜色素上皮细胞中过表达（P < 0.05），而在化学缺氧条件下，TET 1和TET 2基因启动子区甲基化状态均为低甲基化。因此，化学缺氧不仅导致TET 1和TET 2的过度表达，而且还可以逐渐使相同基因的启动子去甲基化。这是第一项研究表明表观遗传学与上述缺氧途径相关基因表达之间的关系。此外，RPE细胞中的这些关联似乎受到化学缺氧的影响，作为一种机制，可能在缺氧相关疾病（如癌症和缺血）的甲基化模式变化中发挥关键作用。(C)2017 Wiley Periodicals，Inc.
CpG methylation of DNA takes part in a specific epigenetic memory that plays crucial roles in the differentiation and abnormality of the cells. The methylation pattern aberration of genomes is affected in three ways, namely DNA methyltransferase (DNMT), ten-eleven translocation (TET), and methyl-binding domain (MBD) proteins. Of these, TET enzymes have recently been demonstrated to be master modifier enzymes in the DNA methylation process. Additionally, recent studies emphasize that not only epigenetic phenomena play a role in controlling hypoxia pathway, but the hypoxia condition also triggers hypomethylation of genomes that may help with the expression of hypoxia pathway genes. In this study, we suggested that TET1 and TET2 could play a role in the demethylation of genomes under chemical hypoxia conditions. Herein, the evaluating methylation status and mRNA expression of mentioned genes were utilized through real-time PCR and methylation-specific PCR (MSP), respectively. Our results showed that TET1 and TET2 genes were overexpressed (P < 0.05) under chemical hypoxia conditions in Retinal Pigment Epithelial (RPE) cells, whereas the promoter methylation status of them were hypomethylated in the same condition. Therefore, chemical hypoxia not only causes overexpression of TET1 and TET2 but also could gradually do promoter demethylation of same genes. This is the first study to show the relationship between epigenetics and the expression of mentioned genes related to hypoxia pathways. Furthermore, it seems that these associations in RPE cells are subjected to chemical hypoxia as a mechanism that could play a crucial role in methylation pattern changes of hypoxia-related diseases such as cancer and ischemia. (C) 2017 Wiley Periodicals, Inc.