title: Tudor-SN, a novel coactivator of peroxisome proliferator-activated receptor γ protein, is essential for adipogenesis.
abstract: Adipogenesis, in which mesenchymal precursor cells differentiate into mature adipocytes, is a well orchestrated process. In the present study we identified Tudor-SN as a novel co-activator of the transcription factor peroxisome proliferator-activated receptor γ (PPARγ). We provide the first evidence that Tudor-SN and PPARγ exist in the same complex. Both are up-regulated by the early factor C/EBPβ during adipogenesis and significantly influence the regulation of PPARγ target genes in both 3T3-L1 pre-adipocyte and mouse embryonic fibroblasts (MEF) upon exposure to a mixture of hormonal mixture. Moreover, aP2-PPARγ response element (PPRE) interacts with both PPARγ and Tudor-SN, and the gene transcriptional activation of PPRE-luc is enhanced by ectopic expression of Tudor-SN. Deletion of Tudor-SN protein (MEF-KO) affects but does not completely abolish the association of PPARγ and aP2-PPRE. Loss-of-function studies further verified that Tudor-SN is required for adipogenesis, as deletion of Tudor-SN (MEF-KO) impairs dexamethasone, 3-isobutyl-1-methylxanthine, and insulin (DMI)-induced adipocyte differentiation and the expression of PPARγ target genes, such as aP2 and adipsin. Furthermore, H3 acetylation levels were lower in MEF-KO than MEF-WT. Both HDAC1 and HDAC3 are stably associated with PPARγ in MEF-KO, whereas only a small amount of association was observed in MEF-WT after 5 days of treatment during adipogenesis. PPARγ requires various co-activators or co-repressors, which may dynamically associate with and regulate the higher order chromatin remodeling of the promoter region of PPARγ-bound target genes; Tudor-SN is likely one of these co-activators.
authors: From the Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences.
authors: Zhongchao
authors: Z
authors: Duan
authors: Xiujuan
authors: X
authors: Zhao
authors: Xiao
authors: X
authors: Fu
authors: Chao
authors: C
authors: Su
authors: Lingbiao
authors: L
authors: Xin
authors: Juha
authors: J
authors: Saarikettu
authors: Xi
authors: X
authors: Yang
authors: Zhi
authors: Z
authors: Yao
authors: Olli
authors: O
authors: Silvennoinen
authors: Minxin
authors: M
authors: Wei
authors: Jie
authors: J
authors: Yang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002478:Cells, Cultured; D004720:Endonucleases; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D009687:Nuclear Proteins; D047495:PPAR gamma; D004720:Endonucleases; C490640:Snd1 protein, mouse
keywords: Adipogenesis; C/EBP Transcription Factor; C/EBPβ; HDAC; Histone Deacetylase; Histone Modification; PPARγ; Peroxisome Proliferator-activated Receptor (PPAR); Tudor-SN