Graduate School of Pharmacy, Ritsumeikan University, Kusatsu, Shiga, 525-8577, Japan.
Graduate School of Pharmacy, Ritsumeikan University, Kusatsu, Shiga, 525-8577, Japan; Department of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, 525-8577, Japan.
Biochem Biophys Res Commun. 2022 Nov 12;629:78-85. doi: 10.1016/j.bbrc.2022.08.068. Epub 2022 Sep 1.
Histone acetylation and deacetylation are associated with diverse biological phenomena via gene transcription, and histone deacetylases (HDACs) regulate protein deacetylation. HDAC8 is associated with childhood neurological disorders that develop in the uterus and may contribute to neurodevelopment. In our previous studies, we found that HDAC8 regulates neuronal differentiation in P19 pluripotent embryonic carcinoma cells (P19EC cells) by regulating embryoid body (EB) formation. However, the mechanism through which HDAC8 is involved in EB formation and neuronal differentiation remains unclear. Here, we show that HDAC8 regulates EB formation and neuronal differentiation by regulating the canonical Hedgehog (Hh) signaling pathway in P19EC cells. We found that HDAC8 is possibly involved in regulating the expression of the Smoothened receptor (Smo), an important receptor in canonical Hh signaling, and treatment with a Smo agonist restored EB formation ability, which was reduced in HDAC8 knockout P19EC cells. Our results demonstrate that HDAC8 functions in EB formation, which is involved in the Hh signaling pathway that is important for embryonic development.
组蛋白乙酰化和去乙酰化通过基因转录与多种生物学现象相关，组蛋白去乙酰化酶 (HDACs) 调节蛋白质去乙酰化。HDAC8 与在子宫中发育的儿童神经发育障碍有关，可能有助于神经发育。在我们之前的研究中，我们发现 HDAC8 通过调节类胚体 (EB) 的形成来调节 P19 多能胚胎癌细胞 (P19EC 细胞) 中的神经元分化。然而，HDAC8 参与 EB 形成和神经元分化的机制尚不清楚。在这里，我们表明 HDAC8 通过调节 P19EC 细胞中的经典 Hedgehog (Hh) 信号通路来调节 EB 的形成和神经元分化。我们发现 HDAC8 可能参与调节 Smoothened 受体 (Smo) 的表达，Smo 是经典 Hh 信号的重要受体，Smo 激动剂的治疗恢复了在 HDAC8 敲除 P19EC 细胞中降低的 EB 形成能力。我们的结果表明，HDAC8 在 EB 形成中发挥作用，这与胚胎发育中重要的 Hh 信号通路有关。
