Plant homeodomain finger protein 2 promotes bone formation by demethylating and activating Runx2 for osteoblast differentiation  

作　　者：Hye-Jin Kim Jong-Wan Park Kyotmg-Hwa Lee Haejin Yoon Dong Hoon Shin Uk-Il Ju Seung Hyeok Seok Seung Hyeon Lim Zang Hee Lee Hong-Hee Kim Yang-Sook Chun 

机构地区：[1]Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea [2]Ischemic/ Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea [3]Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea [4]Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea [5]Institute for Experimental Animals, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea [6]Department of Cell and Developmental Biology, Seoul National University School of Dentistry, Seoul 110-749, Republic of Korea

出　　处：《Cell Research》2014年第10期1231-1249,共19页细胞研究（英文版）

摘　　要：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 tran-scription 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 differ- entiating 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 osteohlasts 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.

关 键 词：PHF2 SUV39H1 RUNX2 lysine methylation osteoblast differentiation 

分 类 号：Q513.1[生物学—生物化学] TB39[一般工业技术—材料科学与工程]