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All Tcf HMG box transcription factors interact with Groucho-related co-repressors.

Tcf/Lef family transcription factors are the downstream effectors of the Wingless/Wnt signal transduction pathway. Upon Wingless/Wnt signalling, beta-catenin translocates to the nucleus, interacts with Tcf (1-3) and thus activates transcription of target genes (4,5). Tcf factors also interact with members of the Groucho (Grg/TLE) family of transcriptional co-repressors (6). We have now tested all known mammalian Groucho family members for their ability to interact specifically with individual Tcf/Lef family members. Transcriptional activation by any Tcf could be repressed by Grg-1, Grg-2/TLE-2, Grg-3 and Grg-4 in a reporter assay. Specific interactions between Tcf and Grg proteins may be achieved in vivo by tissue- or cell type-limited expression. To address this, we determined the expression of all Tcf and Grg/TLE family members in a panel of cell lines. Within any cell line, several Tcfs and TLEs are co-expressed. Thus, redundancy in Tcf/Grg interactions appears to be the rule. The 'long' Groucho family members containing five domains are repressors of Tcf-mediated transactivation, whereas Grg-5, which only contains the first two domains, acts as a de-repressor. As previously shown for Drosophila Groucho, we show that long Grg proteins interact with histone deacetylase-1. Although Grg-5 contains the GP homology domain that mediates HDAC binding in long Grg proteins, Grg-5 fails to bind this co-repressor, explaining how it can de-repress transcription.

Pubmed ID: 11266540

Authors

  • Brantjes H
  • Roose J
  • van De Wetering M
  • Clevers H

Journal

Nucleic acids research

Publication Data

April 1, 2001

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Binding Sites
  • Binding, Competitive
  • Cell Line
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Humans
  • Jurkat Cells
  • Luciferases
  • Models, Biological
  • Molecular Sequence Data
  • Nuclear Proteins
  • Protein Binding
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae
  • Sequence Homology, Amino Acid
  • Transcription Factors
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Two-Hybrid System Techniques