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Cited by 186

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Targeted Disruption of the Basic Krüppel-Like Factor Gene (Klf3) Reveals a Role in Adipogenesis

Open access
Sue, Nancy, 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·2008·Molecular and Cellular Biology

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.

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Metadata

Authors
Sue, N., Jack, B. H. A., Eaton, S. A., Pearson, R. C. M., Funnell, A. P. W., Turner, J., Czolij, R., Denyer, G., Bao, S., Molero-Navajas, J. C., Perkins, A., Fujiwara, Y., Orkin, S. H., Bell-Anderson, K., & Crossley, M.
Venue
Molecular and Cellular Biology
Published
2008-06-01
Volume
28
Issue
12
Pages
3967-3978
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2110269473
Cited by
186
References
3
FWCI
4.34
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Targeted Disruption of the Basic Krüppel-Like Factor Gene (Klf3) Reveals a Role in Adipogenesis. https://app.cochat.ai/papers/10.1128/mcb.01942-07
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Sue, N., Jack, B. H. A., Eaton, S. A., Pearson, R. C. M., Funnell, A. P. W., Turner, J., Czolij, R., Denyer, G., Bao, S., Molero-Navajas, J. C., Perkins, A., Fujiwara, Y., Orkin, S. H., Bell-Anderson, K., & Crossley, M. (2008). Targeted Disruption of the Basic Krüppel-Like Factor Gene (Klf3) Reveals a Role in Adipogenesis. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.01942-07

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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