title: Suv39h1 mediates AP-2α-dependent inhibition of C/EBPα expression during adipogenesis.
abstract: Previous studies have shown that CCAAT/enhancer-binding protein α (C/EBPα) plays a very important role during adipocyte terminal differentiation and that AP-2α (activator protein 2α) acts as a repressor to delay the expression of C/EBPα. However, the mechanisms by which AP-2α prevents the expression of C/EBPα are not fully understood. Here, we present evidence that Suv39h1, a histone H3 lysine 9 (H3K9)-specific trimethyltransferase, and G9a, a euchromatic methyltransferase, both interact with AP-2α and enhance AP-2α-mediated transcriptional repression of C/EBPα. Interestingly, we discovered that G9a mediates dimethylation of H3K9, thus providing the substrate, which is methylated by Suv39h1, to H3K9me3 on the C/EBPα promoter. The expression level of AP-2α was consistent with enrichment of H3K9me2 and H3K9me3 on the C/EBPα promoter in 3T3-L1 preadipocytes. Knockdown of Suv39h markedly increased C/EBPα expression and promoted adipogenesis. Conversely, ectopic expression of Suv39h1 delayed C/EBPα expression and impaired the accumulation of triglyceride, while simultaneous knockdown of AP-2α or G9a partially rescued this process. These findings indicate that Suv39h1 enhances AP-2α-mediated transcriptional repression of C/EBPα in an epigenetic manner and further inhibits adipocyte differentiation.
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China Institute of Stem Cell and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Zhi-Chun
authors.initials: ZC
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China Institute of Stem Cell and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China Institute of Stem Cell and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China Institute of Stem Cell and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China Institute of Stem Cell and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Qian
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China Institute of Stem Cell and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wen
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China Institute of Stem Cell and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Qi-Qun
authors.initials: QQ
authors.lastname: Tang
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China Institute of Stem Cell and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China lixi@shmu.edu.cn.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D044127:Epigenesis, Genetic; D055785:Gene Knockdown Techniques; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D008780:Methyltransferases / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D047495:PPAR gamma / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D050656:Transcription Factor AP-2 / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D047495:PPAR gamma; D012097:Repressor Proteins; D050656:Transcription Factor AP-2; C498700:Suv39h1 protein, mouse; D008780:Methyltransferases; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase
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