Pcgf1 Regulates Early Neural Tube Development Through Histone Methylation in Zebrafish.
Pcgf1 Regulates Early Neural Tube Development Through Histone Methylation in Zebrafish.
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Pcgf1 通过组蛋白甲基化调节斑马鱼的早期神经管发育
DOI：
10.3389/fcell.2020.581636
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发表时间：
2020
影响因子：
5.5
通讯作者：
Hao A
中科院分区：
文献类型：
--
作者：
Li X;Ji G;Zhou J;Du J;Li X;Shi W;Hu Y;Zhou W;Hao A
神经诱导构成神经管生成的初始步骤。 Pcgf1作为6个Pcgf旁系同源基因之一，是一种母系表达基因，但其在神经管发育过程中早期神经诱导中的作用和机制尚未被探索。在本研究中，我们发现抑制Pcgf1的表达后，斑马鱼胚胎表现出头部变小、端脑减少甚至缺失。此外，注射Pcgf1 MO后，斑马鱼胚胎的神经诱导过程异常激活，随后的NSC自我更新受到抑制。体外结果还显示，敲低Pcgf1增加了神经标志物Pax6、Pou3f1和Zfp521的表达水平，但降低了多能标志物Oct4、Hes1和Nanog的表达水平，这进一步证实Pcgf1对于维持P19细胞的多能性是不可或缺的。为了更好地了解 Pcgf1 在早期发育中的作用，我们使用 RNA-seq 分析了 Pcgf1 缺陷的 P19 细胞的 mRNA 图谱。我们发现差异表达基因在许多功能类别中富集，这与发育表型相关，并且Pcgf1的敲低增加了组蛋白去甲基酶的表达。最后，我们的结果表明，Pcgf1 功能丧失降低了 Ngn1 和 Otx2 启动子处的转录抑制标记 H3K27me3 的水平，以及 Pou5f3 和 Nanog 启动子处的转录激活标记 H3K4me3 的水平。总之，我们的研究结果表明，Pcgf1 可能既充当多能维持的促进子，又充当神经诱导的阻遏子。
The neural induction constitutes the initial step in the generation of the neural tube. Pcgf1, as one of six Pcgf paralogs, is a maternally expressed gene, but its role and mechanism in early neural induction during neural tube development have not yet been explored. In this study, we found that zebrafish embryos exhibited a small head and reduced or even absence of telencephalon after inhibiting the expression of Pcgf1. Moreover, the neural induction process of zebrafish embryos was abnormally activated, and the subsequent NSC self-renewal was inhibited after injecting the Pcgf1 MO. The results of in vitro also showed that knockdown of Pcgf1 increased the expression levels of the neural markers Pax6, Pou3f1, and Zfp521, but decreased the expression levels of the pluripotent markers Oct4, Hes1, and Nanog, which further confirmed that Pcgf1 was indispensable for maintaining the pluripotency of P19 cells. To gain a better understanding of the role of Pcgf1 in early development, we analyzed mRNA profiles from Pcgf1-deficient P19 cells using RNA-seq. We found that the differentially expressed genes were enriched in many functional categories, which related to the development phenotype, and knockdown of Pcgf1 increased the expression of histone demethylases. Finally, our results showed that Pcgf1 loss-of-function decreased the levels of transcriptional repression mark H3K27me3 at the promoters of Ngn1 and Otx2, and the levels of transcriptional activation mark H3K4me3 at the promoters of Pou5f3 and Nanog. Together, our findings reveal that Pcgf1 might function as both a facilitator for pluripotent maintenance and a repressor for neural induction.
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