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

Nature volume 395, pages 608–612 (1998)Cite this article

Abstract

Tcf/Lef transcription factors mediate signalling from Wingless/Wnt proteins by recruiting Armadillo/β-catenin as a transcriptional co-activator1,2,3,4,5,6,7. However, studies of Drosophila, Xenopus and Caenorhabditis elegans have indicated that Tcf factors may also be transcriptional repressors6,8,9,10,11,12,13. 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 β-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.

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Figure 1: Physical interaction between Groucho (Gro)-related proteins and Tcf.
Figure 2: Gro represses Arm–Tcf-driven transactivation of a Tcf reporter.
Figure 3: XGrg-4 represses Siamois promoter activity in vivo.
Figure 4: Dorsal injection of XGrg-4 suppresses endogenous axis formation.

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Acknowledgements

We thank M. Peifer and A. Bejsovec for sharing unpublished information; C. Lobe and K. Koop for Grg cDNAs; S. Stifani for TLE cDNAs and helpful comments; W. C. Smith for Xnr3 and Xnoggin cDNA; D. Kimelman for siamois reporter constructs; and R. Medema for biochemical advice.

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  1. Olivier Destrée and Hans Clevers: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Immunology, University Hospital, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

    Jeroen Roose, Jolanda Hurenkamp, Helen Brantjes, Petra Moerer, Marc van de Wetering & Hans Clevers

  2. Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands

    Miranda Molenaar, Josi Peterson & Olivier Destrée

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  1. Jeroen Roose
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Correspondence to Hans Clevers.

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Roose, J., Molenaar, M., Peterson, J. et al. The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature 395, 608–612 (1998). https://doi.org/10.1038/26989

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