Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Differentiation / drug effects
-
Cell Differentiation / genetics*
-
Cells, Cultured
-
Embryonic Stem Cells / drug effects
-
Embryonic Stem Cells / metabolism
-
Embryonic Stem Cells / physiology
-
Fibroblast Growth Factor 4 / genetics*
-
Fibroblast Growth Factor 4 / pharmacology
-
Fibroblast Growth Factor 4 / physiology
-
Gene Expression Profiling
-
Gene Expression Regulation, Developmental / drug effects
-
Histone Demethylases / genetics
-
Histone Demethylases / metabolism
-
Histone Demethylases / physiology*
-
Humans
-
Jumonji Domain-Containing Histone Demethylases / genetics
-
Jumonji Domain-Containing Histone Demethylases / metabolism
-
Jumonji Domain-Containing Histone Demethylases / physiology*
-
Mice
-
Models, Biological
-
Neurogenesis / genetics
-
Neurons / metabolism
-
Neurons / physiology*
-
Oligonucleotide Array Sequence Analysis
-
Substrate Specificity
Substances
-
Fgf4 protein, mouse
-
Fibroblast Growth Factor 4
-
Histone Demethylases
-
Jumonji Domain-Containing Histone Demethylases
-
KDM7A protein, human