Krüppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesis.
Krüppel-like factors (KLFs) as a family of zinc-finger transcription factors involve in the regulation of many physiological processes. In these studies, KLF9 was characterized for its role in adipogenesis. The expression of KLF9 was markedly upregulated during the middle stage of 3T3-L1 adipocyte differentiation, and inhibition of KLF9 by RNAi impaired adipogenesis. Using promoter deletion and mutation analysis, we identified two KLF9-binding sites within the 0.6-kb region of the PPARγ2 proximal promoter, indicating that KLF9 interacts with the PPARγ2 promoter. Furthermore, we found that KLF9 could synergistically activate PPARγ2 promoter by directly interacting with C/EBPα. In addition, overexpression of PPARγ2 rescued the impairment of adipocyte differentiation induced by KLF9 knockdown, which supports that PPARγ2 is a downstream target of KLF9. Collectively, our results indicate KLF9 as a key pro-adipogenic transcription factor through regulation of PPARγ2 expression with C/EBPα at the middle stage of adipogenesis.
Pei
H
H
Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai, China.
Yao
Y
Y
Yang
Y
Y
Liao
K
K
Wu
J-R
JR
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002454:Cell Differentiation; D004252:DNA Mutational Analysis; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D015533:Transcriptional Activation
D022763:CCAAT-Enhancer-Binding Protein-alpha; C489675:Klf9 protein, mouse; D051741:Kruppel-Like Transcription Factors; D047495:PPAR gamma; D034741:RNA, Small Interfering