Gu Xi, Wang Xuemin, Su Dazhuang, Su Xiaohong, Lin Lifang, Li Shuji, Wu Qiaoqi, Liu Shuhu, Zhang Peidong, Zhu Xinhong, Jiang Xiaodan
Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Guangzhou, China.
Department of Neurobiology, Southern Medical University, Guangzhou, China.
Front Mol Neurosci. 2018 Feb 28;11:46. doi: 10.3389/fnmol.2018.00046. eCollection 2018.
Polycomb group (PcG) proteins regulate the epigenetic status of transcription regulatory states during development. Progression from pluripotency to differentiation requires the sequential activation and repression of different PcG target genes, however, the relationship between early patterning signals, PcG expression, and the development of the central nervous system is still unclear. Using various models of neuronal differentiation, we provide evidence that CBX2 is a negative regulator of neuronal differentiation. Knock-down of CBX2 expression promotes neurite development, while overexpression of CBX2 inhibits neurite development. Further, we found that CBX2 is a direct target gene of miR-124. During neuronal differentiation, CBX2 was decreased while miR-124 was increased. Mechanistically, CBX2 directly interacts with the promoter region of several neuro-associated genes and regulates their expression. We found that the neuron-specific GAP-43 gene could contribute to the stimulating effect on neurite development associated with inhibition of CBX2.
多梳蛋白家族（PcG）蛋白在发育过程中调节转录调控状态的表观遗传状态。从多能性向分化的转变需要不同的PcG靶基因依次激活和抑制，然而，早期模式信号、PcG表达与中枢神经系统发育之间的关系仍不清楚。利用各种神经元分化模型，我们提供证据表明CBX2是神经元分化的负调节因子。敲低CBX2表达促进神经突发育，而CBX2过表达抑制神经突发育。此外，我们发现CBX2是miR-124的直接靶基因。在神经元分化过程中，CBX2减少而miR-124增加。机制上，CBX2直接与几个神经相关基因的启动子区域相互作用并调节它们的表达。我们发现神经元特异性GAP-43基因可能有助于对与抑制CBX2相关的神经突发育的刺激作用。
