Volume 24, No 10, Oct 2014
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 24 Issue 10, October 2014: 1231-1249
ORIGINAL ARTICLES
Plant homeodomain finger protein 2 promotes bone formation by demethylating and activating Runx2 for osteoblast differentiation
Hye-Jin Kim1, Jong-Wan Park1,2,3, Kyoung-Hwa Lee1,2, Haejin Yoon1, Dong Hoon Shin1,2, Uk-Il Ju1, Seung Hyeok Seok4, Seung Hyeon Lim5, Zang Hee Lee6, Hong-Hee Kim6 and Yang-Sook Chun1,2
1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea
2Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea
3Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea
4Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea
5Institute for Experimental Animals, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea
6Department of Cell and Developmental Biology, Seoul National University School of Dentistry, Seoul 110-749, Republic of Korea
Correspondence: Jong-Wan Park, E-mail: parkjw@snu.ac.kr; Yang-Sook Chun,(chunys@snu.ac.kr)
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.
10.1038/cr.2014.127
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