Sox17 and β-catenin cooperate to regulate the transcription of endodermal genes

Recent studies have led to a model of the molecular pathway that specifies the endoderm during vertebrate gastrulation. The HMG box transcription factor Sox17 is a key component of this pathway and is essential for endoderm formation; however, the molecular events controlled by Sox17 are largely unknown. We have identified several direct transcriptional targets of Sox17, including Foxa1 and Foxa2. We show that beta-catenin, a component of Wnt signaling pathway, physically interacts with Sox17 and potentiates its transcriptional activation of target genes. We identify a motif in the C terminus of Sox17, which is conserved in all the SoxF subfamily of Sox proteins, and this motif is required for the ability of Sox17 to both transactivate target genes and bind beta-catenin. Nuclear beta-catenin is present in endoderm cells of the gastrula, and depletion of beta-catenin from embryos results in a repression of Sox17 target genes. These data suggest that in a mechanism analogous to Tcf/Lef interacting with beta-catenin, Sox17 and beta-catenin interact to transcribe endodermal target genes.