State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Sino-Danish College at University of Chinese Academy of Sciences, Beijing 100049, China.
Cell Rep. 2018 Feb 27;22(9):2279-2293. doi: 10.1016/j.celrep.2018.02.019.
The precise function and role of nucleosome assembly protein 1-like 1 (Nap1l1) in brain development are unclear. Here, we find that Nap1l1 knockdown decreases neural progenitor cell (NPC) proliferation and induces premature neuronal differentiation during cortical development. A similar deficiency in embryonic neurogenesis was observed in Nap1l1 knockout (KO) mice, which were generated using the CRISPR-Cas9 system. RNA sequencing (RNA-seq) analysis indicates that Ras-associated domain family member 10 (RassF10) may be the downstream target of Nap1l1. Furthermore, we found that Nap1l1 regulates RassF10 expression by promoting SETD1A-mediated H3K4 trimethylation at the RassF10 promoter. Nap1l1 KO defects may be rescued by RassF10 overexpression, suggesting that Nap1l1 controls NPC differentiation through RassF10. Our findings reveal an essential role for the Nap1l1 histone chaperone in cortical neurogenesis during early embryonic brain development.
核小体组装蛋白 1 样蛋白 1（Nap1l1）在大脑发育中的精确功能和作用尚不清楚。在这里，我们发现 Nap1l1 敲低会减少皮质发育过程中的神经祖细胞（NPC）增殖并诱导过早的神经元分化。使用 CRISPR-Cas9 系统生成的 Nap1l1 敲除（KO）小鼠中也观察到胚胎神经发生的类似缺陷。RNA 测序（RNA-seq）分析表明，Ras 相关结构域家族成员 10（RassF10）可能是 Nap1l1 的下游靶标。此外，我们发现 Nap1l1 通过促进 SETD1A 介导的 RassF10 启动子处的 H3K4 三甲基化来调节 RassF10 表达。RassF10 的过表达可以挽救 Nap1l1 KO 的缺陷，表明 Nap1l1 通过 RassF10 控制 NPC 分化。我们的研究结果揭示了 Nap1l1 组蛋白伴侣在早期胚胎大脑发育过程中的皮质神经发生中的重要作用。
