title: Krüppel-like factor KLF8 plays a critical role in adipocyte differentiation.
abstract: KLF8 (Krüppel-like factor 8) is a zinc-finger transcription factor known to play an essential role in the regulation of the cell cycle, apoptosis, and differentiation. However, its physiological roles and functions in adipogenesis remain unclear. In the present study, we show that KLF8 acts as a key regulator controlling adipocyte differentiation. In 3T3-L1 preadipocytes, we found that KLF8 expression was induced during differentiation, which was followed by expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Adipocyte differentiation was significantly attenuated by the addition of siRNA against KLF8, whereas overexpression of KLF8 resulted in enhanced differentiation. Furthermore, luciferase reporter assays demonstrated that overexpression of KLF8 induced PPARγ2 and C/EBPα promoter activity, suggesting that KLF8 is an upstream regulator of PPARγ and C/EBPα. The KLF8 binding sites were localized by site mutation analysis to -191 region in C/EBPα promoter and -303 region in PPARγ promoter, respectively. Taken together, these data reveal that KLF8 is a key component of the transcription factor network that controls terminal differentiation during adipogenesis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Haemi
authors.initials: H
authors.lastname: Lee
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yoo Jeong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Hyeonjin
authors.initials: H
authors.lastname: Choi
authors.forename: Hyemin
authors.initials: H
authors.lastname: Lee
authors.forename: Jae-woo
authors.initials: JW
authors.lastname: Kim
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001483:Base Sequence; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002999:Clone Cells; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008938:Mitosis; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; C475812:Klf8 protein, mouse; D051741:Kruppel-Like Transcription Factors; D047495:PPAR gamma; D014157:Transcription Factors