| First Author | Zhao QH | Year | 2013 |
| Journal | FEBS J | Volume | 280 |
| Issue | 22 | Pages | 5801-14 |
| PubMed ID | 23981481 | Mgi Jnum | J:216715 |
| Mgi Id | MGI:5609245 | Doi | 10.1111/febs.12500 |
| Citation | Zhao QH, et al. (2013) PPARgamma forms a bridge between DNA methylation and histone acetylation at the C/EBPalpha gene promoter to regulate the balance between osteogenesis and adipogenesis of bone marrow stromal cells. FEBS J 280(22):5801-14 |
| abstractText | The balance between osteogenesis and adipogenesis of bone marrow stromal cells is impaired in many human diseases. Knowledge of how to fine-tune this balance is of medical importance. CCAAT/enhancer binding protein alpha (C/EBPalpha) has been shown to regulate the balance between osteogenesis and adipogenesis of C3H10T1/2 cells, with epigenetic modifications of the C/EBPalpha promoter playing an important role. The present study aimed to elucidate the underlying molecular mechanisms. The results showed that peroxisome proliferator-activated receptor gamma (PPARgamma) binds the -1286 bp/-1065 bp region of the C/EBPalpha promoter to activate C/EBPalpha expression during osteogenesis and adipogenesis of C3H10T1/2 cells. DNA hypermethylation in the -1286 bp/-1065 bp region, observed at the terminal stage of osteogenesis, prevented PPARgamma binding, and then histone deacetylase 1 (HDAC1) occupied this region to reduce the level of histone acetylation. We regulated the balance between osteogenesis and adipogenesis of mouse bone marrow stromal cells through modulation of DNA methylation and histone acetylation status. In addition, in bone marrow stromal cells from the glucocorticoid-induced osteoporosis (GIO) mouse, hypomethylation of CpG sites, higher binding of PPARgamma, acetylated histones 3 and 4, and reduced binding of HDAC1 in the -1286 bp/-1065 bp region of C/EBPalpha promoter were observed, compared with normal mice. This study provides a deeper insight into the molecular mechanisms underlying the balance between osteogenesis and adipogenesis regulated by C/EBPalpha in synergy with PPARgamma, and suggests a molecular model for how DNA methylation and histone acetylation are linked by PPARgamma to regulate differentiation of bone marrow stromal cells. |
