Dual-specificity histone demethylase KIAA1718 （KDM7A） regulates neural differentiation through FGF4  

作　　者：Chengyang Huang Yang Xiang Yanru Wang Xia Li Longyong Xu Ziqi Zhu Ting Zhang Qingqing Zhu Kejing Zhang Naihe Jing Charlie Degui Chen 

机构地区：[1]Laboratory of Molecular Cell Biology [2]State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China

出　　处：《Cell Research》2010年第2期154-165,共12页细胞研究（英文版）

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）.

摘　　要：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.

关 键 词：histone demethylase KIAA1718 KDM7A neural differentiation FGF4 

分 类 号：Q42[生物学—神经生物学] S511[生物学—生理学]