| First Author | Chodaparambil JV | Year | 2014 |
| Journal | EMBO J | Volume | 33 |
| Issue | 7 | Pages | 719-31 |
| PubMed ID | 24596249 | Mgi Jnum | J:208139 |
| Mgi Id | MGI:5561161 | Doi | 10.1002/embj.201387188 |
| Citation | Chodaparambil JV, et al. (2014) Molecular functions of the TLE tetramerization domain in Wnt target gene repression. EMBO J 33(7):719-31 |
| abstractText | Wnt signaling activates target genes by promoting association of the co-activator beta-catenin with TCF/LEF transcription factors. In the absence of beta-catenin, target genes are silenced by TCF-mediated recruitment of TLE/Groucho proteins, but the molecular basis for TLE/TCF-dependent repression is unclear. We describe the unusual three-dimensional structure of the N-terminal Q domain of TLE1 that mediates tetramerization and binds to TCFs. We find that differences in repression potential of TCF/LEFs correlates with their affinities for TLE-Q, rather than direct competition between beta-catenin and TLE for TCFs as part of an activation-repression switch. Structure-based mutation of the TLE tetramer interface shows that dimers cannot mediate repression, even though they bind to TCFs with the same affinity as tetramers. Furthermore, the TLE Q tetramer, not the dimer, binds to chromatin, specifically to K20 methylated histone H4 tails, suggesting that the TCF/TLE tetramer complex promotes structural transitions of chromatin to mediate repression. |
