Department of Pediatrics, Affiliated Hospital of Nantong University, 20 Xi Si Road, Nantong, 226001, Jiangsu Province, China.
Department of Pediatrics, Yin Shan Lake Hospital of Wuzhong District, Suzhou, 215100, Jiangsu Province, China.
J Mol Histol. 2018 Apr;49(2):147-155. doi: 10.1007/s10735-018-9754-7. Epub 2018 Jan 12.
The EphA5 receptor is well established as an axon guidance molecule during neural system development and plays an important role in dendritic spine formation and synaptogenesis. Our previous study has showed that EphA5 is decreased in the developing brain of congenital hypothyroidism (CH) and the EphA5 promoter methylation modification participates in its decrease. c-Fos, a well-kown transcription factor, has been considered in association with brain development. Bioinformatics analysis showed that the EphA5 promoter region contained five putative c-fos binding sites. The chromatin immunoprecipitation (ChIP) assays were used to assess the direct binding of c-fos to the EphA5 promoter. Furthermore, dual-luciferase assays showed that these three c-fos protein binding sites were positive regulatory elements for EphA5 expression in PC12 cells. Moreover, We verified c-fos positively regulation for EphA5 expression in CH model. Q-PCR and Western blot showed that c-fos overexpression could upregulate EphA5 expression in hippocampal neurons of rats with CH. Our results suggest that c-fos positively regulates EphA5 expression in CH rat model.
EphA5 受体是神经系统发育过程中的一种轴突导向分子，在树突棘形成和突触发生中发挥重要作用。我们之前的研究表明，EphA5 在先天性甲状腺功能减退症 (CH) 发育中的大脑中减少，并且 EphA5 启动子甲基化修饰参与了其减少。c-Fos，一种众所周知的转录因子，被认为与大脑发育有关。生物信息学分析表明，EphA5 启动子区域包含五个推定的 c-fos 结合位点。染色质免疫沉淀 (ChIP) 分析用于评估 c-fos 与 EphA5 启动子的直接结合。此外，双荧光素酶报告基因检测表明，这三个 c-fos 蛋白结合位点是 PC12 细胞中 EphA5 表达的正调控元件。此外，我们验证了 c-fos 在 CH 模型中对 EphA5 表达的正向调节。qPCR 和 Western blot 显示，c-fos 过表达可上调 CH 大鼠海马神经元中 EphA5 的表达。我们的结果表明，c-fos 正向调节 CH 大鼠模型中 EphA5 的表达。
