DNA methylation at CpG island shore and RXR alpha regulate NR2F2 in heart tissues of tetralogy of Fallot patients
DNA methylation at CpG island shore and RXR alpha regulate NR2F2 in heart tissues of tetralogy of Fallot patients
复制标题
CpG岛岸DNA甲基化和RXRα调节法洛四联症患者心脏组织中的NR2F2
DOI：
10.1016/j.bbrc.2020.06.110
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发表时间：
2020
影响因子：
3.1
通讯作者：
Huang Guoying
中科院分区：
文献类型：
--
作者：
Li Xiaodi;Ye Ming;Xu Hongfei;Zhu Yanjie;Gu Ruoyi;Xiaojing Ma;Sheng Wei;Huang Guoying
The nuclear receptor subfamily 2 group F member 2 (NR2F2) gene encodes a ligand-inducible transcription factor involved in angiogenesis and heart development. This study aimed to elucidate the molecular mechanism of epigenetic regulation of NR2F2 in tetralogy of Fallot (TOF) development. In the present study, immunohistochemical staining showed that NR2F2 protein expression was significantly higher in the right ventricular outflow tract (RVOT) tissues of TOF cases compared with controls. The methylation status of the CpG island shore (CGIS) of the NR2F2 gene was decreased in TOF cases, and the CpG site 3 in the CGIS region of NR2F2 promoter was a differential methylation site. Furthermore, the methylation level of the CpG site 3 and the NR2F2 protein expression were significantly negatively correlated in TOF patients. In vitro functional analysis revealed that RXR alpha could upregulate the NR2F2 gene by directly binding to the CGIS in the NR2F2 promoter, while hypomethylation of the NR2F2 promoter via treatment with 5-azacytidine influenced the affinity of RXRa to its binding sites, as shown by ChIP-qPCR. These findings suggest that promoter hypomethylation activates NR2F2 by enhancing RXR alpha binding to NR2F2 CGIS in the development of TOF. (C) 2020 Published by Elsevier Inc.
