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PMID: 18396140 Published · ppublish English Journal Article

Transcriptional regulation of adipogenesis by KLF4.

Cell metabolism ·Vol. 7 ·No. 4 ·2008-04-00 ·Pages 339-47

Birsoy K, Chen Z, Friedman J

Abstract

While adipogenesis is known to be controlled by a complex network of transcription factors, less is known about the transcriptional cascade that initiates this process. We report here the characterization of Krüppel-like factor 4 (KLF4) as an essential early regulator of adipogenesis. Klf4 is expressed in 3T3-L1 cells within 30 min after exposure to a standard adipogenic cocktail of insulin, glucocorticoids, and IBMX. Knockdown of KLF4 inhibits adipogenesis and downregulates C/EBPbeta levels. KLF4 binds directly to the C/EBPbeta (Cebpb) promoter as shown by chromatin immunoprecipitation and gel shift assays and, together with Krox20, cooperatively transactivates a C/EBPbeta reporter. C/EBPbeta knockdown increases levels of KLF4 and Krox20, suggesting that C/EBPbeta normally suppresses Krox20 and KLF4 expression via a tightly controlled negative feedback loop. KLF4 is specifically induced in response to cAMP, which by itself can partially activate adipogenesis. These data suggest that KLF4 functions as an immediate early regulator of adipogenesis to induce C/EBPbeta.

MeSH Terms
1-Methyl-3-isobutylxanthine/pharmacology 3T3-L1 Cells Adipogenesis/genetics Animals CCAAT-Enhancer-Binding Protein-beta/genetics,metabolism Cell Differentiation Dexamethasone Early Growth Response Protein 2/metabolism Feedback, Physiological Gene Expression Regulation, Developmental Insulin Kruppel-Like Factor 4 Kruppel-Like Transcription Factors/deficiency,genetics,metabolism Mice Protein Binding Transcription, Genetic/genetics Transcriptional Activation/genetics
Chemicals
CCAAT-Enhancer-Binding Protein-beta Early Growth Response Protein 2 Insulin Klf4 protein, mouse Kruppel-Like Factor 4 Kruppel-Like Transcription Factors Dexamethasone 1-Methyl-3-isobutylxanthine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Birsoy Kivanç
Laboratory of Molecular Genetics, Rockefeller University, New York, NY 10021, USA.
Chen Zhu
Friedman Jeffrey
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Article Info
Journal
Cell metabolism
Abbr.
Cell Metab
ISSN
1550-4131
DOI
10.1016/j.cmet.2008.02.001
Published
2008-04-00
Pages
339-47
Language
English
Region
United States
NLM ID
101233170
PMCID
PMC2430156
Subset
IM
Grants
NIDDK NIH HHS · R01 DK041096 · United States
NIDDK NIH HHS · R01 DK041096-18 · United States
External Links
PubMed source DOI: 10.1016/j.cmet.2008.02.001 PMC Full Text View journal details
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