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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1850-1856 |
| Number of pages | 7 |
| Journal | FEBS Letters |
| Volume | 588 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 2 2014 |
Funding
The authors thank Kristin Kalita for her contribution towards identifying MIR146A as a target of JMJD3 in preliminary experiments, and Dr. Jenny Kerschner for her careful review of the manuscript. We gratefully acknowledge the Children’s Research Fund of the Ann & Robert H. Lurie Children’s Hospital of Chicago Research Center for its generous financial support. C.J.P. is the recipient of an NIH Pathway-to-Independence Award from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R00 HD055330).
Keywords
- Cell differentiation
- Jumonji domain containing 3
- MIR146A
- MicroRNA
- Osteogenesis
- Stem cells
ASJC Scopus subject areas
- Genetics
- Molecular Biology
- Biophysics
- Structural Biology
- Biochemistry
- Cell Biology