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 RIS Download
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