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

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.
Mesh Terms:
Animals, Axin Protein, Cell Nucleus, Culture Media, Conditioned, Cytoskeletal Proteins, DNA-Binding Proteins, Gene Expression Regulation, Humans, Kruppel-Like Transcription Factors, Mice, Promoter Regions, Genetic, Protein Binding, RNA Interference, Signal Transduction, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein, Transcription Factors, Transcription, Genetic, Wnt Proteins, beta Catenin
EMBO J.
Date: Jun. 07, 2006
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