It remains unknown whether H3K4 methylation, an epigenetic modification associated with gene activation, regulates fate determination of the postnatal neural stem and progenitor cells (NSPCs). By inactivating the Dpy30 subunit of the major H3K4 methyltransferase complexes in specific regions of mouse brain, we demonstrate a crucial role of efficient H3K4 methylation in maintaining both the self-renewal and differentiation capacity of postnatal NSPCs. Dpy30 deficiency disrupts development of hippocampus and especially the dentate gyrus and subventricular zone, the major regions for postnatal NSC activities. Dpy30 is indispensable for sustaining the self-renewal and proliferation of NSPCs in a cell-intrinsic manner and also enables the differentiation of mouse and human neural progenitor cells to neuronal and glial lineages. Dpy30 directly regulates H3K4 methylation and the induction of several genes critical in neurogenesis. These findings link a prominent epigenetic mechanism of gene expression to the fundamental properties of NSPCs and may have implications in neurodevelopmental disorders.

中文翻译：

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染色质调节剂维持自我更新，并能使产后神经干细胞和祖细胞分化。

H3K4甲基化（一种与基因激活相关的表观遗传修饰）是否会调节出生后神经干细胞和祖细胞（NSPC）的命运，仍然未知。通过灭活小鼠脑中特定区域的主要H3K4甲基转移酶复合物的Dpy30亚基，我们证明了有效的H3K4甲基化在维持产后NSPC的自我更新和分化能力中的关键作用。Dpy30缺乏症会破坏海马的发育，尤其是齿状回和脑室下区，这是产后NSC活动的主要区域。Dpy30对于以细胞内在的方式维持NSPC的自我更新和增殖是必不可少的，并且还能够使小鼠和人类神经祖细胞分化为神经元和神经胶质谱系。Dpy30直接调节H3K4甲基化和几种对神经发生至关重要的基因的诱导。这些发现将基因表达的突出表观遗传机制与NSPC的基本特性联系起来，并且可能与神经发育障碍有关。