Laboratory of Molecular Cell Biology, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Cell Res. 2010 Feb;20(2):154-65. doi: 10.1038/cr.2010.5. Epub 2010 Jan 19.
Dimethylations of histone H3 lysine 9 and lysine 27 are important epigenetic marks associated with transcription repression. Here, we identified KIAA1718 (KDM7A) as a novel histone demethylase specific for these two repressing marks. Using mouse embryonic stem cells, we demonstrated that KIAA1718 expression increased at the early phase of neural differentiation. Knockdown of the gene blocked neural differentiation and the effect was rescued by the wild-type human gene, and not by a catalytically inactive mutant. In addition, overexpression of KIAA1718 accelerated neural differentiation. We provide the evidence that the pro-neural differentiation effect of KDM7A is mediated through direct transcriptional activation of FGF4, a signal molecule implicated in neural differentiation. Thus, our study identified a dual-specificity histone demethylase that regulates neural differentiation through FGF4.
组蛋白 H3 赖氨酸 9 和赖氨酸 27 的二甲基化是与转录抑制相关的重要表观遗传标记。在这里，我们鉴定出 KIAA1718（KDM7A）是一种特异性针对这两种抑制标记的新型组蛋白去甲基化酶。利用小鼠胚胎干细胞，我们证明了 KIAA1718 的表达在神经分化的早期阶段增加。该基因的敲低阻断了神经分化，而野生型人基因可以挽救该作用，而催化活性缺失突变体则不能。此外，KIAA1718 的过表达加速了神经分化。我们提供的证据表明，KDM7A 的促神经分化作用是通过直接转录激活 FGF4 介导的，FGF4 是一种与神经分化相关的信号分子。因此，我们的研究鉴定出一种双特异性组蛋白去甲基化酶，它通过 FGF4 调节神经分化。
