The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors

Tcf/Lef transcription factors mediate signalling from Wingless/ Wnt proteins by recruiting Armadillo/beta-catenin as a transcriptional co-activator(1-7). However, studies of Drosophila, Xenopus and Caenorhabditis elegans have indicated that Tcf factors may also be transcriptional repressors(6,8-13). Here we show that Tcf factors physically interact with members of the Groucho family of transcriptional repressors. In transient transfection assays, the Xenopus Groucho homologue XGrg-4 inhibited activation of transcription of synthetic Tcf reporter genes. In contrast, the naturally truncated Groucho-family member XGrg-5 enhanced transcriptional activation. Injection of XGrg-4 into Xenopus embryos repressed transcription of Siamois and Xnr-3, endogenous targets of beta-catenin-Tcf. Dorsal injection of XGrg-4 had a ventralizing effect on Xenopus embryos. Secondary-axis formation induced by a dominant-positive Armadillo-Tcf fusion protein was inhibited by XGrg-4 and enhanced by XGrg-5, These data indicate that expression of Tcf target genes is regulated by a balance between Armadillo and Groucho.