摘要
histone H3 离氨酸的 Dimethylations 9 和离氨酸 27 是与抄写压抑联系的重要 epigenetic 标记。这里，我们作为为这二个镇压标记特定的新奇 histone demethylase 识别了 KIAA1718 (KDM7A ) 。用老鼠胚胎的干细胞，我们证明那 KIAA1718 表情在神经区别的早阶段增加了。基因击倒堵住的神经区别和效果被野类型的人的基因，并且不由催化地不活跃的异种救。另外， KIAA1718 的 overexpression 加速了神经区别。我们提供 KDM7A 的支持 neural 区别效果通过 FGF4 的直接 transcriptional 激活被调停的证据，一个信号分子在神经区别含有。因此，我们的学习识别了通过 FGF4 调整神经区别的双特性的 histone demethylase。
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.
基金
Supplementary information is linked to the online version of the paper on the Cell Research website.Acknowledgments We thank Anning Lin （The University of Chicago） for the critical reading of the paper, members in the Chen lab for technical help, the cell biology and molecular biology core facilities for confocal study and Q-PCR, and Shanghai Biochip Co Ltd. for microarray analysis. The H3K27me2 antibody was kindly provided by Li Tang （Fudan University） and Thomas Jenuwein （Research Institute of Molecular Pathology, The Vienna Biocenter）. This work was supported by the National Basic Research Program of China （2007CB957900, 2006CB943902, 2007CB947101, 2008KR0695, 2009CB941100, 2005CB522704）, the Chinese Academy of Sciences （KSCX2-YW-R-04）, the National Natural Science Foundation of China （90919026, 30870538,30623003, 30721065, 30830034, 90919046）, the Shanghai Pujiang Program （0757S11361）, the Shanghai Key Project of Basic Science Research （06DJ14001, 06DZ22032, 08DJ1400501）, and the Council of Shanghai Municipal Government for Science and Technology （088014199）.
