期刊
CELL RESEARCH
卷 20, 期 2, 页码 154-165出版社
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2010.5
关键词
histone demethylase; KIAA1718; KDM7A; neural differentiation; FGF4
类别
资金
- National Basic Research Program of China [2007CB957900, 2006CB943902, 2007CB947101, 2008KR0695, 2009CB941100, 2005CB522704]
- Chinese Academy of Sciences [KSCX2-YW-R-04]
- National Natural Science Foundation of China [90919026, 30870538, 30623003, 30721065, 30830034, 90919046]
- Shanghai Pujiang Program [0757S11361]
- Shanghai Key Project of Basic Science Research [06DJ14001, 06DZ22032, 08DJ1400501]
- Council of Shanghai Municipal Government for Science and Technology [088014199]
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.
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