KIAA1718 is a dual specific histone demethylase involved in early neural development

Histone methylation is a complex posttranslational modification regulating transcription and chromatin dynamics, and plays important roles in development and disease processes. Recent studies indicate that histone lysine methylation is a reversible modification and several JmjC-domain-containing proteins have been identified as histone lysine demethylases. Here we show that KIAA1718, a JmjC-domain-containing protein, is a histone demethylase. KIAA1718 demethylated dimethylation of H3 lysine 9 and 27 (H3K9me2 and H3K27me2), two important epigenetic marks associated with embryonic development6-10. In mouse embryonic stem cells (ESCs), KIAA1718 expression increased at the early phase of neural differentiation. RNA interference inhibition of KIAA1718 blocked neural differentiation and the effect was rescued by wild-type human gene, but not by a catalytically inactive mutant. In chick embryos, KIAA1718 is exclusively expressed in the epiblast cells of the primitive streak, an organizer contributing to neural induction. Knockdown of KIAA1718 resulted in defects in neural formation, while its overexpression led to neural expansion. The pro-neural effect is mediated through transcriptional activation of FGF4, a growth factor implicated in neural induction. Thus, our study identifies a dual specific histone demethylase as a novel epigenetic factor integrated with growth factor signaling, which has important roles in the early neural development.

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