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Kennell, JA, O'Leary, EE, Gummow, BM, Hammer, GD and MacDougald, OA (2003) T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors. Mol. Cell. Biol. 23:5366-75
We have cloned T-cell factor 4N (TCF-4N), an alternative isoform of TCF-4, from developing pituitary and 3T3-L1 preadipocytes. This protein contains the N-terminal interaction domain for beta-catenin but lacks the DNA binding domain. While TCF-4N inhibited coactivation by beta-catenin of a TCF/lymphoid-enhancing factor (LEF)-dependent promoter, TCF-4N potentiated coactivation by beta-catenin of several non-TCF/LEF-dependent promoters. For example, TCF-4N synergized with beta-catenin to activate the alpha-inhibin promoter through functional and physical interactions with the orphan nuclear receptor steroidogenic factor 1 (SF-1). In addition, TCF-4N and beta-catenin synergized with the adipogenic transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) to induce leptin promoter activity. The mechanism by which beta-catenin and TCF-4N coactivated C/EBPalpha appeared to involve p300, based upon synergy between these important transcriptional regulators. Consistent with TCF-4N's redirecting the actions of beta-catenin in cells, ectopic expression of TCF-4N in 3T3-L1 preadipocytes partially relieved the block of adipogenesis caused by beta-catenin. Thus, we propose that TCF-4N inhibits coactivation by beta-catenin of TCF/LEF transcription factors and potentiates the coactivation by beta-catenin of other transcription factors, such as SF-1 and C/EBPalpha.
3T3 Cells; Adipocytes/metabolism; Animals; CCAAT-Enhancer-Binding Protein-alpha/metabolism; Cell Differentiation; Cell Line; Cloning, Molecular; Cytoskeletal Proteins/metabolism; DNA/metabolism; DNA-Binding Proteins/metabolism; Fushi Tarazu Transcription Factors; Genes, Reporter; Homeodomain Proteins; Humans; Immunoblotting; Leptin/metabolism; Luciferases/metabolism; Lymphoid Enhancer-Binding Factor 1; Mice; Models, Biological; Models, Genetic; Pituitary Gland/cytology; Plasmids/metabolism; Precipitin Tests; Promoter Regions, Genetic; Protein Binding; Protein Isoforms; Protein Structure, Tertiary; Receptors, Cytoplasmic and Nuclear; Retroviridae/genetics; Steroidogenic Factor 1; TCF Transcription Factors; Trans-Activators/metabolism; Transcription Factor 7-Like 2 Protein; Transcription Factors/chemistry; Transcription Factors/metabolism; Transcription Factors/physiology; Transcription, Genetic; Transfection; beta Catenin
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