Division of Biology 139-74, California Institute of Technology, Pasadena, CA 91125, USA.
Dev Cell. 2010 Sep 14;19(3):460-8. doi: 10.1016/j.devcel.2010.08.009.
The neural crest is a multipotent stem cell-like population that is induced during gastrulation, but only acquires its characteristic morphology, migratory ability, and gene expression profile after neurulation. This raises the intriguing possibility that precursors are actively maintained by epigenetic influences in a stem cell-like state. Accordingly, we report that dynamic histone modifications are critical for proper temporal control of neural crest gene expression in vivo. The histone demethylase, JumonjiD2A (JmjD2A/KDM4A), is expressed in the forming neural folds. Loss of JmjD2A function causes dramatic downregulation of neural crest specifier genes analyzed by multiplex NanoString and in situ hybridization. Importantly, in vivo chromatin immunoprecipitation reveals direct stage-specific interactions of JmjD2A with regulatory regions of neural crest genes, and associated temporal modifications in methylation states of lysine residues directly affected by JmjD2A activity. Our findings show that chromatin modifications directly control neural crest genes in vertebrate embryos via modulating histone methylation.
神经嵴是一种多能干细胞样群体，在原肠胚形成过程中被诱导产生，但只有在神经管形成后才获得其特有的形态、迁移能力和基因表达谱。这提出了一个有趣的可能性，即前体细胞通过表观遗传影响以类似于干细胞的状态被主动维持。因此，我们报告说，动态组蛋白修饰对于体内神经嵴基因表达的适当时间控制至关重要。组蛋白去甲基酶 JumonjiD2A (JmjD2A/KDM4A) 在形成的神经褶中表达。JmjD2A 功能丧失导致多重 NanoString 和原位杂交分析的神经嵴特征基因的显著下调。重要的是，体内染色质免疫沉淀显示 JmjD2A 与神经嵴基因的调控区域之间存在直接的、特定阶段的相互作用，以及与 JmjD2A 活性直接相关的赖氨酸残基的甲基化状态的相关时间修饰。我们的发现表明，染色质修饰通过调节组蛋白甲基化直接控制脊椎动物胚胎中的神经嵴基因。
