title: MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells.
abstract: Chromatin remodeling is important for cell differentiation. Histone methyltransferase EZH2 and histone demethylase JMJD3 (KDM6B) modulate levels of histone H3 lysine 27 trimethylation (H3K27me3). Interplay between the two modulators influence lineage specification in stem cells. Here, we identified microRNA MIR146A to be a negative regulator of JMJD3. In the osteogenic differentiation of human mesenchymal stem cells (hMSCs), we observed an upregulation of JMJD3 and a downregulation of MIR146A. Blocking JMJD3 activity in differentiating hMSCs reduced transcript levels of osteogenic gene RUNX2. H3K27me3 levels decreased at the RUNX2 promoter during cell differentiation. Modulation of MIR146A levels in hMSCs altered JMJD3 and RUNX2 expression and affected osteogenic differentiation. We conclude that JMJD3 promotes osteogenesis in differentiating hMSCs, with MIR146A regulating JMJD3.
authors.affiliation: Driskill Graduate Program, Departments of Pediatrics and Obstetrics & Gynecology, Northwestern University Feinberg School of Medicine, and Human Molecular Genetics Program, Ann & Robert H. Lurie Children's Hospital of Chicago Research Center, Chicago, IL 60611, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Huszar
authors.affiliation: Driskill Graduate Program, Departments of Pediatrics and Obstetrics & Gynecology, Northwestern University Feinberg School of Medicine, and Human Molecular Genetics Program, Ann & Robert H. Lurie Children's Hospital of Chicago Research Center, Chicago, IL 60611, USA. Electronic address: c-payne@northwestern.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Payne
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D015536:Down-Regulation; D004794:Enzyme Repression; D006657:Histones / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics*; D010012:Osteogenesis; D011485:Protein Binding; D034622:RNA Interference
chemical_list: D020413:3' Untranslated Regions; D006657:Histones; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human
keywords: Cell differentiation; Jumonji domain containing 3; MIR146A; MicroRNA; Osteogenesis; Stem cells
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