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PPAR γ forms a bridge between DNA methylation and histone acetylation at the C / EBP α gene promoter to regulate the balance between osteogenesis and adipogenesis of bone marrow stromal cells
Author(s) -
Zhao Qinghua,
Wang Shouguo,
Liu Shaoxian,
Li Jipeng,
Zhang Yongxing,
Sun Zhongyi,
Fan Qiming,
Tian Jiwei
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12500
Subject(s) - adipogenesis , histone , dna methylation , chemistry , histone deacetylase , epigenetics , hdac1 , microbiology and biotechnology , ccaat enhancer binding proteins , histone h3 , stromal cell , biology , cancer research , gene expression , transcription factor , biochemistry , nuclear protein , dna , adipose tissue , gene
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 α ( C / EBP α) has been shown to regulate the balance between osteogenesis and adipogenesis of C3H10T1/2 cells, with epigenetic modifications of the C / EBP α promoter playing an important role. The present study aimed to elucidate the underlying molecular mechanisms. The results showed that peroxisome proliferator‐activated receptor γ ( PPAR γ) binds the −1286 bp/−1065 bp region of the C/ EBP α promoter to activate C / EBP α 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 PPAR γ binding, and then histone deacetylase 1 ( HDAC 1) 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 PPAR γ, acetylated histones 3 and 4, and reduced binding of HDAC 1 in the −1286 bp/−1065 bp region of C/ EBP α 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/ EBP α in synergy with PPAR γ, and suggests a molecular model for how DNA methylation and histone acetylation are linked by PPAR γ to regulate differentiation of bone marrow stromal cells.