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 β-catenin but lacks the DNA binding domain. While TCF-4N inhibited coactivation by β-catenin of a TCF/lymphoid-enhancing factor (LEF)-dependent promoter, TCF-4N potentiated coactivation by β-catenin of several non-TCF/LEF-dependent promoters. For example, TCF-4N synergized with β-catenin to activate the α-inhibin promoter through functional and physical interactions with the orphan nuclear receptor steroidogenic factor 1 (SF-1). In addition, TCF-4N and β-catenin synergized with the adipogenic transcription factor CCAAT/enhancer binding protein α (C/EBPα) to induce leptin promoter activity. The mechanism by which β-catenin and TCF-4N coactivated C/EBPα appeared to involve p300, based upon synergy between these important transcriptional regulators. Consistent with TCF-4N′ s redirecting the actions of β-catenin in cells, ectopic expression of TCF-4N in 3T3-L1 preadipocytes partially relieved the block of adipogenesis caused by β-catenin. Thus, we propose that TCF-4N inhibits coactivation by β-catenin of TCF/LEF transcription factors and potentiates the coactivation by β-catenin of other transcription factors, such as SF-1 and C/EBPα.