Dual-specificity histone demethylase KIAA1718 (KDM7A) regulates neural differentiation through FGF4.
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.
Huang
Chengyang
C
Laboratory of Molecular Cell Biology, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Xiang
Yang
Y
Wang
Yanru
Y
Li
Xia
X
Xu
Longyong
L
Zhu
Ziqi
Z
Zhang
Ting
T
Zhu
Qingqing
Q
Zhang
Kejing
K
Jing
Naihe
N
Chen
Charlie Degui
CD
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051519:Fibroblast Growth Factor 4 / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D013379:Substrate Specificity
C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C548973:KDM7A protein, human