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.
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.
Mesh Terms:
3T3 Cells, Adipocytes, Animals, CCAAT-Enhancer-Binding Protein-alpha, Cell Differentiation, Cell Line, Cloning, Molecular, Cytoskeletal Proteins, DNA, DNA-Binding Proteins, Fushi Tarazu Transcription Factors, Genes, Reporter, Homeodomain Proteins, Humans, Immunoblotting, Leptin, Luciferases, Lymphoid Enhancer-Binding Factor 1, Mice, Models, Biological, Models, Genetic, Pituitary Gland, Plasmids, Precipitin Tests, Promoter Regions, Genetic, Protein Binding, Protein Isoforms, Protein Structure, Tertiary, Receptors, Cytoplasmic and Nuclear, Retroviridae, Steroidogenic Factor 1, TCF Transcription Factors, Trans-Activators, Transcription Factors, Transcription, Genetic, Transfection, beta Catenin
3T3 Cells, Adipocytes, Animals, CCAAT-Enhancer-Binding Protein-alpha, Cell Differentiation, Cell Line, Cloning, Molecular, Cytoskeletal Proteins, DNA, DNA-Binding Proteins, Fushi Tarazu Transcription Factors, Genes, Reporter, Homeodomain Proteins, Humans, Immunoblotting, Leptin, Luciferases, Lymphoid Enhancer-Binding Factor 1, Mice, Models, Biological, Models, Genetic, Pituitary Gland, Plasmids, Precipitin Tests, Promoter Regions, Genetic, Protein Binding, Protein Isoforms, Protein Structure, Tertiary, Receptors, Cytoplasmic and Nuclear, Retroviridae, Steroidogenic Factor 1, TCF Transcription Factors, Trans-Activators, Transcription Factors, Transcription, Genetic, Transfection, beta Catenin
Mol. Cell. Biol.
Date: Aug. 01, 2003
PubMed ID: 12861022
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