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Article

  • The EMBO Journal (2006) 25, 2735 - 2745
  • doi:10.1038/sj.emboj.7601153

Published online: 18 May 2006

C-terminal-binding protein directly activates and represses Wnt transcriptional targets in Drosophila

Ming Fang, Jiong Li, Timothy Blauwkamp, Chandan Bhambhani, Nathan Campbella and Ken M Cadigan

  1. Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA

Correspondence to:

Ken M Cadigan, Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 North University Avenue, Ann Arbor, MI 48109-1048, USA. Tel.: +1 734 936 3246; Fax: +1 734 647 0884; E-mail: cadigan@umich.edu

aPresent address: Department of Biochemistry and Molecular Biology, University of Texas-Medical School, 6431 Fannin, Houston, TX 77030, USA

Received 16 December 2005; Accepted 27 April 2006

Regulation of Wnt transcriptional targets is thought to occur by a transcriptional switch. In the absence of Wnt signaling, sequence-specific DNA-binding proteins of the TCF family repress Wnt target genes. Upon Wnt stimulation, stabilized beta-catenin binds to TCFs, converting them into transcriptional activators. C-terminal-binding protein (CtBP) is a transcriptional corepressor that has been reported to inhibit Wnt signaling by binding to TCFs or by preventing beta-catenin from binding to TCF. Here, we show that CtBP is also required for the activation of some Wnt targets in Drosophila. CtBP is recruited to Wnt-regulated enhancers in a Wnt-dependent manner, where it augments Armadillo (the fly beta-catenin) transcriptional activation. We also found that CtBP is required for repression of a subset of Wnt targets in the absence of Wnt stimulation, but in a manner distinct from previously reported mechanisms. CtBP binds to Wnt-regulated enhancers in a TCF-independent manner and represses target genes in parallel with TCF. Our data indicate dual roles for CtBP as a gene-specific activator and repressor of Wnt target gene transcription.

  • Keywords:

    • Armadillo,
    • CtBP,
    • TCF,
    • Wingless,
    • Wnt