Role of the transcription factor Sox-2 in the expression of the FGF-4 gene in embryonal carcinoma cells

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. Mol. Reprod. Dev. 50:377–386, 1998. © 1998 Wiley‐Liss, Inc.

Mechanisms Regulating Stemness and Differentiation in Embryonal Carcinoma Cells

“…Similarly, Nanog controls the expression of Ccnd1 , as seen when Nanog is depleted or overexpressed in P19 cells [125] and by retinoids in NTERA-2 cells, which promotes the ubiquitination and degradation of Cyclin D1 [67]. In addition to these studies and others involving c-Myc [104, 126–130], Oct4 [110, 131–133], and Sox2 [111, 112], further evidence that pluripotency genes must be developmentally regulated in the early embryo came from reports that Nanog [134, 135] and Foxm1 [136] are downregulated in P19 and F9 cells in response to RA treatment. Foxm1, a member of the Forkhead box of transcription factors, is an interesting example as we now know it plays pivotal roles in cell proliferation, differentiation, and self-renewal and acts downstream of canonical Wnt/ β -catenin signaling [137, 138].…”

Splice blocking of zygotic sox31 leads to developmental arrest shortly after Mid‐Blastula Transition and induces apoptosis in zebrafish

“…We found that most of the splicing variants characterised would encode proteins lacking an intact HMG DNA binding domain or functional C terminal region. Such aberrant proteins would act as dominant negative forms, inhibiting the activity of sox31 as well as other SoxB1 genes [16,17]. In support of this idea, the dominant negative effect could be rescued by co-injection of sox31 translation block morpholino (Tb MO) ( Fig.…”

SOX14 is a candidate gene for limb defects associated with BPES and M�bius syndrome

“…As a transcription factor, SOX14 may be involved in the transcriptional regulation of a signalling molecule such as FGF8. SOX2 has been implicated in the regulation of FGFs, as in vitro studies have shown that SOX2 activates FGF4 expression (Johnson et al 1998;Yuan et al 1995). SOX14 has been shown to act as a repressor of transcription (Uchikawa et al 1999).…”