TY - JOUR
T1 - Targeted disruption of the basic Krüppel-like factor gene (Klf3) reveals a role in adipogenesis
AU - Sue, Nancy
AU - Jack, Briony H.A.
AU - Eaton, Sally A.
AU - Pearson, Richard C.M.
AU - Funnell, Alister P.W.
AU - Turner, Jeremy
AU - Czolij, Robert
AU - Denyer, Gareth
AU - Bao, Shisan
AU - Molero-Navajas, Juan Carlos
AU - Perkins, Andrew
AU - Fujiwara, Yuko
AU - Orkin, Stuart H.
AU - Bell-Anderson, Kim
AU - Crossley, Merlin
PY - 2008/6
Y1 - 2008/6
N2 - 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/ebpα promoter. We find that C/ebpα is derepressed in Klf3 and Ctbp knockout fibroblasts and adipocytes from Klf3 knockout mice. Chromatin immunoprecipitations confirm that Klf3 binds the C/ebpα promoter in vivo. These results implicate Klf3 and CtBP in controlling adipogenesis.
AB - 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/ebpα promoter. We find that C/ebpα is derepressed in Klf3 and Ctbp knockout fibroblasts and adipocytes from Klf3 knockout mice. Chromatin immunoprecipitations confirm that Klf3 binds the C/ebpα promoter in vivo. These results implicate Klf3 and CtBP in controlling adipogenesis.
UR - http://www.scopus.com/inward/record.url?scp=44949253118&partnerID=8YFLogxK
U2 - 10.1128/MCB.01942-07
DO - 10.1128/MCB.01942-07
M3 - Article
C2 - 18391014
AN - SCOPUS:44949253118
SN - 0270-7306
VL - 28
SP - 3967
EP - 3978
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 12
ER -