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元祖细胞（NPCs）细胞周期动力学的一种假定机制。在体内研究了组蛋白脱乙酰酶在形成大脑新皮层的NPCs细胞周期调控中的作用。在NPCs中以时间依赖的方式产生了能过表达组蛋白去乙酰化酶Sir2蛋白的双转基因小鼠。我们检测到胚胎日(E) 16的细胞周期长度短暂缩短，因为从E14到E16开始给药多西环素，NPCs中Sir2过表达。这一结果表明，组蛋白的去乙酰化可能在新皮层投射神经元的产生和大脑皮层异常的发病机制中起关键作用。

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.