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MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells
Author(s) -
Huszar Jessica M.,
Payne Christopher J.
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.03.057
Subject(s) - mesenchymal stem cell , demethylase , runx2 , downregulation and upregulation , microbiology and biotechnology , histone h3 , cellular differentiation , biology , prc2 , histone , ezh2 , histone methyltransferase , stem cell , cancer research , chemistry , gene expression , genetics , gene
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 .