Publications

Abstract

Kruppel-like Factors (Klfs) recognize CACCC and GC-rich sequences in gene regulatory elements. Here we describe the disruption of the murine Basic Kruppel-like Factor (Bklf) or Klf3 gene. Klf3 knockout mice have less white adipose tissue, 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 over-expression of Klf3 blocks 3T3-L1 differentiation. Klf3 represses transcription by recruiting C-terminal Binding Protein (CtBP) co-repressors. 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 de-repressed 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.