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PMID: 18391014 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Targeted disruption of the basic Krüppel-like factor gene (Klf3) reveals a role in adipogenesis.

Molecular and cellular biology ·Vol. 28 ·No. 12 ·2008-06-00 ·Pages 3967-78

Sue N, Jack BH, Eaton SA, Pearson RC, Funnell AP, Turner J, Czolij R, Denyer G, Bao S, Molero-Navajas JC, Perkins A, Fujiwara Y, Orkin SH, Bell-Anderson K, Crossley M

Abstract

Krüppel-like factors (KLFs) recognize CACCC and GC-rich sequences in gene regulatory elements. Here, we describe the disruption of the murine basic Krüppel-like factor gene (Bklf or Klf3). Klf3 knockout mice have less white adipose tissue, and their fat pads contain smaller and fewer cells. Adipocyte differentiation is altered in murine embryonic fibroblasts from Klf3 knockouts. Klf3 expression was studied in the 3T3-L1 cellular system. Adipocyte differentiation is accompanied by a decline in Klf3 expression, and forced overexpression of Klf3 blocks 3T3-L1 differentiation. Klf3 represses transcription by recruiting C-terminal binding protein (CtBP) corepressors. CtBPs bind NADH and may function as metabolic sensors. A Klf3 mutant that does not bind CtBP cannot block adipogenesis. Other KLFs, Klf2, Klf5, and Klf15, also regulate adipogenesis, and functional CACCC elements occur in key adipogenic genes, including in the C/ebpalpha promoter. We find that C/ebpalpha is derepressed in Klf3 and Ctbp knockout fibroblasts and adipocytes from Klf3 knockout mice. Chromatin immunoprecipitations confirm that Klf3 binds the C/ebpalpha promoter in vivo. These results implicate Klf3 and CtBP in controlling adipogenesis.

MeSH Terms
3T3-L1 Cells Adipocytes/cytology,metabolism Adipose Tissue/embryology,metabolism Alcohol Oxidoreductases/metabolism Animals Cell Differentiation DNA-Binding Proteins/metabolism Fibroblasts/metabolism Gene Expression Regulation, Developmental Genotype Kruppel-Like Transcription Factors/genetics,physiology Mice Mice, Knockout Models, Biological Models, Genetic Transcription Factors/genetics,physiology
Chemicals
DNA-Binding Proteins Klf3 protein, mouse Kruppel-Like Transcription Factors Transcription Factors Alcohol Oxidoreductases C-terminal binding protein
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Sue Nancy
School of Molecular and Microbial Biosciences, G08, University of Sydney, Sydney, NSW 2006, Australia.
Jack Briony H A
Eaton Sally A
Pearson Richard C M
Funnell Alister P W
Turner Jeremy
Czolij Robert
Denyer Gareth
Bao Shisan
Molero-Navajas Juan Carlos
Perkins Andrew
Fujiwara Yuko
Orkin Stuart H
Bell-Anderson Kim
Crossley Merlin
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.01942-07
Published
2008-06-00
Epub
2008-00-07
Pages
3967-78
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2423134
Subset
IM
Grants
NHLBI NIH HHS · R01 HL073443 · United States
NHLBI NIH HHS · HL073443 · United States
External Links
PubMed source DOI: 10.1128/MCB.01942-07 PMC Full Text View journal details
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