Health Management Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei, Taiwan.
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Biochem Biophys Res Commun. 2020 Dec 17;533(4):1477-1483. doi: 10.1016/j.bbrc.2020.10.047. Epub 2020 Oct 24.
Development of the mammalian central nervous system is an important process, which is accomplished through precise regulations of many different genes. Zinc finger protein 179 (Znf179) is one of the essential genes that plays a critical role in neuronal differentiation. In our previous study, Znf179 knockout mice displayed brain malformation and impaired brain functions. We have also previously shown that Znf179 involves in cell cycle regulation, but the regulatory mechanism of Znf179 expression is not yet fully characterized. Herein, we identified that Purα is an essential factor for the promotor activity of Znf179. We also showed concurrent expression of Znf179 and Purα during neuronal differentiation. We also found that overexpression of Purα increased Znf179 expression in neuronal differentiated P19 cells. Through its direct binding to Znf179, as shown using DAPA, Purα upregulates Znf179 expression, suggesting that Purα is important for the regulation of Znf179 expression during neuronal differentiation. Our data indicated that Purα is involved in the transcriptional regulation of Znf179 gene during neuronal differentiation, and is indispensable during the brain development.
哺乳动物中枢神经系统的发育是一个重要的过程,它是通过许多不同基因的精确调控来完成的。锌指蛋白 179(Znf179)是在神经元分化中起关键作用的必需基因之一。在我们之前的研究中,Znf179 敲除小鼠表现出脑畸形和脑功能障碍。我们之前还表明,Znf179 参与细胞周期调控,但 Znf179 表达的调控机制尚未完全阐明。在此,我们确定 Purα 是 Znf179 启动子活性的必需因素。我们还显示了 Znf179 和 Purα 在神经元分化过程中的同时表达。我们还发现,Purα 的过表达增加了神经元分化的 P19 细胞中 Znf179 的表达。通过 DAPA 显示,Purα 通过直接与 Znf179 结合而上调 Znf179 的表达,表明 Purα 对神经元分化过程中 Znf179 表达的调节很重要。我们的数据表明,Purα 参与了神经元分化过程中 Znf179 基因的转录调控,并且在大脑发育过程中是不可或缺的。