PMID:9669521

Citation	Johnson, LR, Lamb, KA, Gao, Q, Nowling, TK and Rizzino, A (1998) Role of the transcription factor Sox-2 in the expression of the FGF-4 gene in embryonal carcinoma cells. Mol. Reprod. Dev. 50:377-86
Abstract	It has been shown previously that the FGF-4 gene is regulated by a powerful downstream enhancer in embryonal carcinoma (EC) cells. This enhancer contains an essential HMG motif; however, the transcription factor that binds to the HMG motif in EC cells has not been determined definitively. In earlier studies, this HMG motif was shown to bind a heat-stable, redox-insensitive factor expressed by F9 EC cells. Others have proposed that the transcription factor Sox-2 binds to the FGF-4 enhancer HMG motif. In this study, we demonstrate that the N-terminal half of Sox-2, which contains the DNA binding domain, binds to the FGF-4 enhancer HMG motif and we show that this binding is unaffected by heat and oxidation. In addition, we employed two experimental approaches to demonstrate that Sox-2 regulates the transcription of the FGF-4 gene in EC cells. As part of these studies, an expression plasmid that codes for a dominant-negative form of Sox-2 was used in transient expression assays. In other experiments, a Sox-2 antisense expression plasmid was used. When co-transfected into F9 EC cells along with an FGF-4 promoter/reporter gene construct, each expression plasmid caused a significant reduction in reporter activity. Our studies also demonstrate that Sox-2 affects the expression of the FGF-4 gene in the multipotent EC cell line, P19. Taken together, these studies argue strongly that Sox-2 plays an important role in the expression of the FGF-4 gene in vivo.
Links	PubMed Online version:<377::AID-MRD1>3.0.CO;2-F 10.1002/(SICI)1098-2795(199808)50:4<377::AID-MRD1>3.0.CO;2-F
Keywords	Animals; Carcinoma, Embryonal; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Fibroblast Growth Factor 4; Fibroblast Growth Factors/genetics; Gene Expression Regulation; HMGB Proteins; Mice; Nuclear Proteins/genetics; Nuclear Proteins/physiology; Proto-Oncogene Proteins/genetics; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/physiology; SOXB1 Transcription Factors; Transcription Factors/genetics; Transcription Factors/physiology; Tumor Cells, Cultured
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