title: Epigenetic regulation of miR-302 by JMJD1C inhibits neural differentiation of human embryonic stem cells.
abstract: It has been recently reported that the regulatory circuitry formed by OCT4, miR-302, and NR2F2 controls both pluripotency and neural differentiation of human embryonic stem cells (hESCs). We show here that JMJD1C, a histone 3 lysine 9 (H3K9) demethylase expressed in hESCs, directly interacts with this circuitry. hESCs with stable knockdown of JMJD1C remain pluripotent while having reduced miR-302 expression, decreased BMP signaling, and enhanced TGFβ signaling. JMJD1C binds to the miR-302 promoter and reduces H3K9 methylation. Withdrawal of basic fibroblast growth factor (bFGF) from the culture induces neural differentiation of the knockdown, but not the control, cells within 3 days, accompanied by elevated NR2F2 expression. This can be attenuated with miR-302 mimics or an H3K9 methytransferase inhibitor. Together, our findings suggest that JMJD1C represses neural differentiation of hESCs at least partially by epigenetically sustaining miR-302 expression and that JMJD1C knockdown is sufficient to trigger neural differentiation upon withdrawal of exogenous bFGF.
authors: From the Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030 and.
authors: Jianle
authors: J
authors: Wang
authors: Jung W
authors: JW
authors: Park
authors: Hicham
authors: H
authors: Drissi
authors: Xiaofang
authors: X
authors: Wang
authors: Ren-He
authors: RH
authors: Xu
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D051838:COUP Transcription Factor I / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D051838:COUP Transcription Factor I; C532169:MIRN302A microRNA, human; D035683:MicroRNAs; C497589:NR2F1 protein, human; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; C520448:JMJD1C protein, human; D056484:Jumonji Domain-Containing Histone Demethylases; D010089:Oxidoreductases, N-Demethylating
keywords: Embryonic Stem Cell; Epigenetics; Histone Methylation; MicroRNA; Neurodifferentiation