title: G9a is transactivated by C/EBPβ to facilitate mitotic clonal expansion during 3T3-L1 preadipocyte differentiation.
abstract: In 3T3-L1 preadipocyte differentiation, the CCAAT/enhancer-binding protein-β (C/EBPβ) is an important early transcription factor that activates cell cycle genes during mitotic clonal expansion (MCE), sequentially activating peroxisome proliferator-activated receptor-γ (PPARγ) and C/EBPα during terminal differentiation. Although C/EBPβ acquires its DNA binding activity via dual phosphorylation at about 12-16 h postinduction, the expression of PPARγ and C/EBPα is not induced until 36-72 h. The delayed expression of PPARγ and C/EBPα ensures the progression of MCE, but the mechanism responsible for the delay remains elusive. We provide evidence that G9a, a major euchromatic methyltransferase, is transactivated by C/EBPβ and represses PPARγ and C/EBPα through H3K9 dimethylation of their promoters during MCE. Inhibitor- or siRNA-mediated G9a downregulation modestly enhances PPARγ and C/EBPα expression and adipogenesis in 3T3-L1 preadipocytes. Conversely, forced expression of G9a impairs the accumulation of triglycerides. Thus, this study elucidates an epigenetic mechanism for the delayed expression of PPARγ and C/EBPα.
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Qian
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: You-You
authors.initials: YY
authors.lastname: Zhang
authors.forename: Zhi-Chun
authors.initials: ZC
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Shou
authors.forename: Qi-Qun
authors.initials: QQ
authors.lastname: Tang
authors.forename: Xi
authors.initials: X
authors.lastname: Li
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D000818:Animals; D001391:Azo Compounds; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis* / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D004396:Coloring Agents; D003640:Dealkylation; D011495:Histone-Lysine N-Methyltransferase / Q000096:biosynthesis* / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D047495:PPAR gamma / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators; D015533:Transcriptional Activation / Q000235:genetics / Q000502:physiology
chemical_list: D001391:Azo Compounds; D022782:CCAAT-Enhancer-Binding Protein-beta; D004396:Coloring Agents; D006657:Histones; D047495:PPAR gamma; D034741:RNA, Small Interfering; D015534:Trans-Activators; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase; C011049:oil red O
keywords: C/EBPβ; G9a; mitotic clonal expansion