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Ligand-dependent corepressor (LCoR) represses the transcription factor C/EBP during early adipocyte differentiation

文献类型：期刊论文

作者Cao, Hongchao1; Zhang, Shengjie1; Sun, Chao1; Li, Yan1; Wang, Hui1,1; Yu, Shuxian1; Liu, Wei1; Ying, Hao1,3,5; Shan, Shifang2; Liu, Yi2
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
出版日期2017
卷号292期号:46页码:18973-18987
ISSN号0021-9258
关键词adipogenesis CCAAT-enhancer-binding protein (C EBP) nuclear receptor peroxisome proliferator-activated receptor (PPAR) transcription corepressor
DOI10.1074/jbc.M117.793984
文献子类Article
英文摘要Nuclear receptors (NRs) regulate gene transcription by recruiting coregulators, involved in chromatin remodeling and assembly of the basal transcription machinery. The NR-associated protein ligand-dependent corepressor (LCoR) has previously been shown to suppress hepatic lipogenesis by decreasing the binding of steroid receptor coactivators to thyroid hormone receptor. However, the role of LCoR in adipogenesis has not been established. Here, we show that LCoR expression is reduced in the early stage of adipogenesis in vitro. LCoR overexpression inhibited 3T3-L1 adipocyte differentiation, whereas LCoR knockdown promoted it. Using an unbiased affinity purification approach, we identified CCAAT/enhancer-binding protein (C/EBP), a key transcriptional regulator in early adipogenesis, and corepressor C-terminal binding proteins as potential components of an LCoR-containing complex in 3T3-L1 adipocytes. We found that LCoR directly interacts with C/EBP through its C-terminal helix-turn-helix domain, required for LCoR's inhibitory effects on adipogenesis. LCoR overexpression also inhibited C/EBP transcriptional activity, leading to inhibition of mitotic clonal expansion and transcriptional repression of C/EBP and peroxisome proliferator-activated receptor 2 (PPAR2). However, LCoR overexpression did not affect the recruitment of C/EBP to the promoters of C/EBP and PPAR2 in 3T3-L1 adipocytes. Of note, restoration of PPAR2 or C/EBP expression attenuated the inhibitory effect of LCoR on adipogenesis. Mechanistically, LCoR suppressed C/EBP-mediated transcription by recruiting C-terminal binding proteins to the C/EBP and PPAR2 promoters and by modulating histone modifications. Taken together, our results indicate that LCoR negatively regulates early adipogenesis by repressing C/EBP transcriptional activity and add LCoR to the growing list of transcriptional corepressors of adipogenesis.
学科主题Biochemistry & Molecular Biology
WOS关键词MITOTIC CLONAL EXPANSION ; RECEPTOR COREPRESSOR ; 3T3-L1 PREADIPOCYTES ; BINDING-PROTEINS ; ADIPOGENESIS ; COREGULATORS ; BETA ; HOMEOSTASIS ; KINASE ; GENE
语种英语
出版者AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号WOS:000415848000021
版本出版稿
源URL[http://202.127.25.144/handle/331004/1172]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Labs food safety Res, Shanghai 200031, Peoples R China;
2.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Labs Nutr & Metab, Shanghai 200031, Peoples R China;
3.Chinese Acad Sci, Shanghai Xuhui Cent Hosp, Shanghai Clin Ctr, Shanghai 200031, Peoples R China;
4.Fudan Univ, Zhongshan Hosp, Dept Endocrinol & Metab, Shanghai 200031, Peoples R China;
5.Minist Hlth, Key Lab food safety risk Assessment, Beijing 100021, Peoples R China;
6.Nanjing Univ, Model Anim Res Ctr, Nanjing 210061, Jiangsu, Peoples R China;
7.Nanjing Univ, Minist Educt, Key Lab Model Anim Dis Study, Nanjing 210061, Jiangsu, Peoples R China,
推荐引用方式
GB/T 7714		 Cao, Hongchao,Zhang, Shengjie,Sun, Chao,et al. Ligand-dependent corepressor (LCoR) represses the transcription factor C/EBP during early adipocyte differentiation[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2017,292(46):18973-18987.
APA Cao, Hongchao.,Zhang, Shengjie.,Sun, Chao.,Li, Yan.,Wang, Hui.,...&,.(2017).Ligand-dependent corepressor (LCoR) represses the transcription factor C/EBP during early adipocyte differentiation.JOURNAL OF BIOLOGICAL CHEMISTRY,292(46),18973-18987.
MLA Cao, Hongchao,et al."Ligand-dependent corepressor (LCoR) represses the transcription factor C/EBP during early adipocyte differentiation".JOURNAL OF BIOLOGICAL CHEMISTRY 292.46(2017):18973-18987.

入库方式： OAI收割

来源：上海营养与健康研究所

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