Krüppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation.
Krüppel-like factor 5 (KLF5) is a zinc-finger transcription factor known to play a pivotal role in the pathogenesis of cardiovascular disease. Here, we show that neonatal heterozygous KLF5 knockout mice exhibit a marked deficiency in white adipose tissue development, suggesting that KLF5 is also required for adipogenesis. In 3T3-L1 preadipocytes, KLF5 expression was induced at an early stage of differentiation, and this was followed by expression of PPARgamma2. Constitutive overexpression of dominant-negative KLF5 inhibited adipocyte differentiation, whereas overexpression of wild-type KLF5 induced differentiation even without hormonal stimulation. Moreover, embryonic fibroblasts obtained from KLF5+/- mice showed much attenuated adipocyte differentiation, confirming the key role played by KLF5 in adipocyte differentiation. KLF5 expression is induced by C/EBPbeta and delta. KLF5, in turn, acts in concert with C/EBPbeta/delta to activate the PPARgamma2 promoter. This study establishes KLF5 as a key component of the transcription factor network controlling adipocyte differentiation.
Oishi
Yumiko
Y
Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
Manabe
Ichiro
I
Tobe
Kazuyuki
K
Tsushima
Kensuke
K
Shindo
Takayuki
T
Fujiu
Katsuhito
K
Nishimura
Go
G
Maemura
Koji
K
Yamauchi
Toshimasa
T
Kubota
Naoto
N
Suzuki
Ryo
R
Kitamura
Toshio
T
Akira
Shizuo
S
Kadowaki
Takashi
T
Nagai
Ryozo
R
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D006367:HeLa Cells; D006579:Heterozygote; D006801:Humans; D047468:Immunoprecipitation; D051741:Kruppel-Like Transcription Factors; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D009154:Mutation; D041681:NIH 3T3 Cells; D047495:PPAR gamma / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; C497253:Cebpd protein, mouse; D002843:Chromatin; C118391:Klf5 protein, mouse; D051741:Kruppel-Like Transcription Factors; D047495:PPAR gamma; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta; D008156:Luciferases