T-Cell Factor 4N (TCF-4N), a Novel Isoform of Mouse TCF-4, Synergizes with β-Catenin To Coactivate C/EBPα and Steroidogenic Factor 1 Transcription Factors
Copyright policy )T-Cell Factor 4N (TCF-4N), a Novel Isoform of Mouse TCF-4, Synergizes with β-Catenin To Coactivate C/EBPα 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.
- University of Michigan–Ann Arbor United States
- University of Michigan–Flint United States
Homeodomain Proteins, Leptin, Lymphoid Enhancer-Binding Factor 1, Immunoblotting, Fushi Tarazu Transcription Factors, Cell Differentiation, 3T3 Cells, DNA, Models, Biological, Cell Line, DNA-Binding Proteins, Cytoskeletal Proteins, Mice, Genes, Reporter, Adipocytes, CCAAT-Enhancer-Binding Protein-alpha, Animals, Humans, Cloning, Molecular, Luciferases
Homeodomain Proteins, Leptin, Lymphoid Enhancer-Binding Factor 1, Immunoblotting, Fushi Tarazu Transcription Factors, Cell Differentiation, 3T3 Cells, DNA, Models, Biological, Cell Line, DNA-Binding Proteins, Cytoskeletal Proteins, Mice, Genes, Reporter, Adipocytes, CCAAT-Enhancer-Binding Protein-alpha, Animals, Humans, Cloning, Molecular, Luciferases
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