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Stem Cell Technology: Epigenetics, Genomics, Proteomics and Metabonomics
Version of Record online: 19 DEC 2012
Copyright © 2012 AlphaMed Press
Volume 31, Issue 1, pages 126–136, January 2013
How to Cite
Du, J., Ma, Y., Ma, P., Wang, S. and Fan, Z. (2013), Demethylation of Epiregulin Gene by Histone Demethylase FBXL11 and BCL6 Corepressor Inhibits Osteo/dentinogenic Differentiation. STEM CELLS, 31: 126–136. doi: 10.1002/stem.1255
Author contributions: J.D.: data analysis and interpretation, financial support, and manuscript writing, Y.M. and P.M.: collection and/or assembly of data; S.W.: conception and design, financial support, and manuscript writing; Z.F.: conception and design, data analysis and interpretation, financial support, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS October 16, 2012.
- Issue online: 19 DEC 2012
- Version of Record online: 19 DEC 2012
- Accepted manuscript online: 16 OCT 2012 01:31PM EST
- Manuscript Accepted: 14 SEP 2012
- National Natural Science Foundation of China. Grant Numbers: 81070798, 81170931
- National Basic Research Program of China. Grant Number: 2010CB944801
- Funding Project to Science Facility in Institutions of Higher Learning Under the jurisdiction of Beijing Municipality. Grant Number: PXM2011_014226_07_000066
- Beijing Funding Project for “Tens-Hundreds-Thousands” Outstanding Health Staff
- Beijing Science and Technology Funding Project for Outstanding Returned Overseas Chinese Scholars
- Scientific Research foundation for the Returned Overseas Chinese Scholars, State Education Ministry. Grant Numbers: 2012-940, 2011-1568
- Histone demethylase;
- Mesenchymal stem cells
Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but the molecular mechanism underlying directed differentiation remains unclear; this has restricted potential MSC applications. Histone methylation, controlled by histone methyltransferases and demethylases, may play a key role in MSC differentiation. Here, we investigated FBXL11, a histone demethylase, lysine (K)-specific demethylase 2A, which is evolutionarily conserved, ubiquitously expressed, and a member of the JmjC-domain-containing histone demethylase family. We tested whether FBXL11 could inhibit the osteo/dentinogenic differentiation potential in MSC cells with gain- and loss-of-function assays. We found that FBXL11 regulated osteo/dentinogenic differentiation in MSC cells. Furthermore, we found that the gene encoding the epidermal growth factor, Epiregulin (EREG), was a downstream target of FBXL11, and that EREG mediated FBXL11 regulation of MSC differentiation. Moreover, we found that the FBXL11 histone demethylase function was activated by associating with BCL6 corepressor, and this complex could repress EREG transcription by increasing histone K4/36 methylation in the EREG promoter. In conclusion, our results elucidated a new function for FBXL11 and EREG, explored the molecular mechanism underlying directed differentiation in MSC cells, and identified potential target genes for improving tissue regeneration techniques. STEM Cells2013;31:126–136