College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
College of Pharmacy, Seoul National University, Seoul151-742, Republic of Korea.
ACS Chem Neurosci. 2021 Feb 3;12(3):441-446. doi: 10.1021/acschemneuro.0c00613. Epub 2021 Jan 22.
Members of the lysine-specific histone demethylase 5 (KDM5/JARID1) family are known to play important roles in stem cell fate determination. Here, using the KDM5 inhibitor C70 (KDM5-C70), we demonstrated that the histone demethylase activity of the KDM5 enzyme is essential for the repression of astrocytic differentiation of neural stem cells (NSCs). KDM5-C70 treatment activated the ( gene by increasing the trimethylation of histone H3 lysine 4 in the promoter regions and subsequently induced astrocytogenesis in NSCs. In addition, treatment of NSCs with KDM5-C70 activated Janus kinase-signal transducer and activator of transcription (JAK-STAT3) signaling and increased the mRNA expression of (). Our data provide evidence that KDM5 is a promising target for NSC fate modulation and suggest that epigenetic regulation is important for NSC fate determination.
赖氨酸特异性组蛋白去甲基酶 5（KDM5/JARID1）家族的成员被认为在干细胞命运决定中发挥重要作用。在这里，我们使用 KDM5 抑制剂 C70（KDM5-C70），证明了 KDM5 酶的组蛋白去甲基酶活性对于抑制神经干细胞（NSC）向星形胶质细胞分化是必不可少的。KDM5-C70 处理通过增加启动子区域组蛋白 H3 赖氨酸 4 的三甲基化来激活 （基因，随后诱导 NSCs 发生星形胶质细胞生成。此外，用 KDM5-C70 处理 NSCs 激活了 Janus 激酶信号转导和转录激活因子（JAK-STAT3）信号，并增加了 （）的 mRNA 表达。我们的数据提供了证据表明 KDM5 是 NSC 命运调节的有前途的靶标，并表明表观遗传调控对于 NSC 命运决定很重要。
