EPIGENETIC REGULATION OF CELL CYCLE KINETICS OF MURINE NEURONAL STEM CELLS BY HISTONE DEACETYLASE

表观遗传机制被认为是控制神经前体细胞周期动力学的一种可能机制。我们研究了组蛋白脱乙酰酶功能亢进在体内形成大脑新皮质的鼻咽癌细胞周期调节中的作用。建立了双转基因小鼠，能够以时间依赖的方式在鼻咽癌细胞中过表达组蛋白脱乙酰酶Sir2蛋白。我们检测到胚胎第16天细胞周期长度的一过性缩短，因为从E14到E16开始给多西环素的NPC中Sir2过表达。这一结果提示，组蛋白去乙酰化可能在新皮质投射神经元的产生以及大脑皮层异常的发病机制中起重要作用。

Epigenetic mechanisms is considered to be a putative machinery for controlling cell cycle kinetics of neuronal progenitor cells (NPCs). We investigated effects of overfunction of histone deacetylase in cell cycle regulation in NPCs which forms cerebral neocortex in vivo. Double-transgenic mice were generated that were capable of overexpressing histone deacetylase Sir2 proteins in NPCs in time dependent manner. We detected transient shortening of the length of the cell cycle on embryonic day (E) 16 as Sir2 were overexpressed in NPCs by doxycycline administration starting from E14 to E16. This result indicate that deacetylation of histone may play a critical role in production of projection neurons in neocortex as well as pathogenesis of cerebral cortical abnormality.