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| Content Provider | PubMed Central |
|---|---|
| Author | Kim, Hye-jin Park, Jong-wan Lee, Kyoung-hwa Yoon, Haejin Shin, Dong Hoon Ju, Uk-il Seok, Seung Hyeok Lim, Seung Hyeon Lee, Zang Hee Kim, Hong-hee Chun, Yang-sook |
| Copyright Year | 2014 |
| Abstract | Plant homeodomain finger protein 2 (PHF2), which contains a plant homeodomain and a Jumonji-C domain, is an epigenetic regulator that demethylates lysine 9 in histone 3 (H3K9me2). On the other hand, runt-related transcription factor 2 (Runx2) plays essential roles in bone development and regeneration. Given previous reports that the PHF2 mutation can cause dwarfism in mice and that PHF2 expression is correlated with that of Runx2 in differentiating thymocytes, we investigated whether PHF2 regulates Runx2-mediated bone formation. Overexpression of PHF2 facilitated bone development in newborn mice, and viral shRNA-mediated knockdown of PHF2 delayed calvarial bone regeneration in adult rats. In primary osteoblasts and C2C12 precursor cells, PHF2 enhances osteoblast differentiation by demethylating Runx2, while suppressor of variegation 3-9 homolog 1 (SUV39H1) inhibits bone formation by methylating it. The PHF2-Runx2 interaction is mediated by the Jumonji-C and Runt domains of the two proteins, respectively. The interaction between Runx2 and osteocalcin promoter is regulated by the methylation status of Runx2, i.e., the interaction is augmented when Runx2 is demethylated. Our results suggest that SUV39H1 and PHF2 reciprocally regulate osteoblast differentiation by modulating Runx2-driven transcription at the post-translational level. This study may provide a theoretical basis for the development of new therapeutic modalities for patients with impaired bone development or delayed fracture healing. |
| Related Links | http://dx.doi.org/10.1038/cr.2014.127 |
| Ending Page | 1249 |
| Page Count | 19 |
| Starting Page | 1231 |
| File Format | |
| ISSN | 17487838 |
| e-ISSN | 17487838 |
| Journal | Cell Research |
| Issue Number | 10 |
| Volume Number | 24 |
| Language | English |
| Publisher | Nature Publishing Group |
| Publisher Date | 2014-10-01 |
| Access Restriction | Open |
| Rights Holder | Nature Publishing Group |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology |
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