Hashimoto Yusuke, Myojin Reiko, Katoh Naohiro, Ohtsu Masaya, Tashiro Fumio, Onoda Fumitoshi, Murakami Yasufumi
Laboratory of Genome Biology, Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
Biochem Biophys Res Commun. 2009 Dec 11;390(2):223-9. doi: 10.1016/j.bbrc.2009.09.090. Epub 2009 Sep 26.
The basic helix-loop-helix transcription factor Hand2 is induced by bone morphogenetic proteins (BMPs) in neural crest-derived precursor cells during the early stage of development of the autonomic nervous system (ANS). Previous studies showed that Hand2 was essential for the ANS differentiation. However, regulatory mechanism of pluripotent genes has not been elucidated in ANS differentiation. Here, we show that Hand2 regulated nanog expression in ANS differentiation. Our studies demonstrated that the forced expression of Hand2 promoted the ANS differentiation program in P19 embryonal carcinoma (EC) cells without aggregation. Furthermore, our results suggested that Hand2 bound to the promoter of nanog, a gene required for embryonic stem cells self-renewal, and suppressed nanog expression after Hand2 induction. The rapid downregulation of nanog mRNA during ANS differentiation correlated with the Hand2 transcriptional activity and nanog promoter methylation. These findings are evidence for a presence of the novel regulatory mechanism of nanog in ANS differentiation.
在自主神经系统（ANS）发育早期，神经嵴衍生的前体细胞中的骨形态发生蛋白（BMPs）可诱导基本螺旋-环-螺旋转录因子Hand2表达。先前的研究表明，Hand2对ANS分化至关重要。然而，多能基因在ANS分化中的调控机制尚未阐明。在此，我们发现Hand2在ANS分化过程中调控Nanog表达。我们的研究表明，Hand2的强制表达可促进P19胚胎癌细胞在无聚集情况下的ANS分化程序。此外，我们的结果提示，Hand2与胚胎干细胞自我更新所需的Nanog基因启动子结合，并在Hand2诱导后抑制Nanog表达。ANS分化过程中Nanog mRNA的快速下调与Hand2转录活性及Nanog启动子甲基化相关。这些发现证明了Nanog在ANS分化中存在新的调控机制。
