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. However, studies of Drosophila, Xenopus and Caenorhabditis elegans have indicated that Tcf factors may also be transcriptional repressors. 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.
Department of Immunology, University Hospital, Utrecht, The Netherlands.
J
J
Roose
M
M
Molenaar
J
J
Peterson
J
J
Hurenkamp
H
H
Brantjes
P
P
Moerer
M
M
van de Wetering
O
O
Destrée
H
H
Clevers
D000818:Animals; D051186:Armadillo Domain Proteins; D051792:Basic Helix-Loop-Helix Proteins; D019556:COS Cells; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins; D024002:HMGB Proteins; D019476:Insect Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058127:Transcription Factor 3; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins
D051186:Armadillo Domain Proteins; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D024002:HMGB Proteins; D019476:Insect Proteins; D011506:Proteins; D012097:Repressor Proteins; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058127:Transcription Factor 3; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D029867:Xenopus Proteins; C544917:Tcf3 protein, Xenopus; C115161:aes protein, Xenopus; C091023:gro protein, Drosophila