The NuRD chromatin remodelling complex regulates brain cortical development

Dynamic changes of histone epigenetic modifications and chromatin structure represent an universal mechanism by which cells adapt their transcriptional response to rapidly changing environmental conditions. During neuronal development, extensive chromatin remodeling takes place allowing the transition of pluripotent cells into differentiated neurons. Here we report that the ATP-dependent chromatin remodeling complex NuRD, which couples ATP-dependent nucleosome sliding with histone deacetylase activity, is a major remodeling complex in embryonic brain and plays an instructive role during mouse neuronal development. Importantly, the ATPase subunits of NuRD complex CHD3, CHD4 and CHD5 undergo a functional switch, thereby regulating distinct aspects of neuronal differentiation and migration in a sequential and mostly non-overlapping manner. We conclude that the recruitment of NuRD complexes containing specific CHDs to gene promoters and enhancers plays an instructive role in brain development. Gene expression analysis was performed in the mouse embryonic cortex at three developmental stages: E12.5, E15.5 and E18.5 using total RNA obtained from four embryos for each time point.组蛋白表观遗传修饰与染色质结构的动态变化，是细胞适配快速变化的环境条件、调控转录应答的普遍机制。在神经元发育过程中，广泛的染色质重塑事件会发生，使得多能细胞向终末分化神经元转化。本研究报道，同时耦联ATP依赖型核小体滑动与组蛋白去乙酰化酶活性的ATP依赖型染色质重塑复合物NuRD，是胚胎脑中的主要重塑复合物，并在小鼠神经元发育过程中发挥指导性作用。尤为关键的是，NuRD复合物的ATP酶亚基CHD3、CHD4与CHD5会发生功能转换，进而以时序性且基本无重叠的方式，调控神经元分化与迁移的不同方面。本研究结论认为，将携带特定CHD亚型的NuRD复合物招募至基因启动子与增强子区域，这一过程在脑发育中发挥指导性作用。本研究在小鼠胚胎皮层的三个发育阶段（E12.5、E15.5与E18.5）开展基因表达分析，每个时间点均使用来自4个胚胎的总RNA进行实验。