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  • The EMBO Journal (2006) 25, 2326 - 2337
  • doi:10.1038/sj.emboj.7601147

Published online: 25 May 2006

HIC1 attenuates Wnt signaling by recruitment of TCF-4 and bold beta-catenin to the nuclear bodies

Tomas Valenta, Jan Lukas, Lenka Doubravska, Bohumil Fafilek and Vladimir Korinek

  1. Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Correspondence to:

Vladimir Korinek, Institute of Molecular Genetics AS CR, Videnska 1083, 142 20 Prague 4, Czech Republic. Tel.: +4202 41062471; Fax: 4202 44472282; E-mail: korinek@biomed.cas.cz

Received 25 November 2005; Accepted 25 April 2006

The hypermethylated in cancer 1 (HIC1) gene is epigenetically inactivated in cancer, and in addition, the haploinsufficiency of HIC1 is linked to the development of human Miller–Dieker syndrome. HIC1 encodes a zinc-finger transcription factor that acts as a transcriptional repressor. Additionally, the HIC1 protein oligomerizes via the N-terminal BTB/POZ domain and forms discrete nuclear structures known as HIC1 bodies. Here, we provide evidence that HIC1 antagonizes the TCF/beta-catenin-mediated transcription in Wnt-stimulated cells. This appears to be due to the ability of HIC1 to associate with TCF-4 and to recruit TCF-4 and beta-catenin to the HIC1 bodies. As a result of the recruitment, both proteins are prevented from association with the TCF-binding elements of the Wnt-responsive genes. These data indicate that the intracellular amounts of HIC1 protein can modulate the level of the transcriptional stimulation of the genes regulated by canonical Wnt/beta-catenin signaling.

  • Keywords:

    • beta-catenin,
    • nuclear HIC1 bodies,
    • TCF-4,
    • Wnt signaling