| First Author | Schuijers J | Year | 2014 |
| Journal | EMBO J | Volume | 33 |
| Issue | 2 | Pages | 146-56 |
| PubMed ID | 24413017 | Mgi Jnum | J:206459 |
| Mgi Id | MGI:5550311 | Doi | 10.1002/embj.201385358 |
| Citation | Schuijers J, et al. (2014) Wnt-induced transcriptional activation is exclusively mediated by TCF/LEF. EMBO J 33(2):146-56 |
| abstractText | Active canonical Wnt signaling results in recruitment of beta-catenin to DNA by TCF/LEF family members, leading to transcriptional activation of TCF target genes. However, additional transcription factors have been suggested to recruit beta-catenin and tether it to DNA. Here, we describe the genome-wide pattern of beta-catenin DNA binding in murine intestinal epithelium, Wnt-responsive colorectal cancer (CRC) cells and HEK293 embryonic kidney cells. We identify two classes of beta-catenin binding sites. The first class represents the majority of the DNA-bound beta-catenin and co-localizes with TCF4, the prominent TCF/LEF family member in these cells. The second class consists of beta-catenin binding sites that co-localize with a minimal amount of TCF4. The latter consists of lower affinity beta-catenin binding events, does not drive transcription and often does not contain a consensus TCF binding motif. Surprisingly, a dominant-negative form of TCF4 abrogates the beta-catenin/DNA interaction of both classes of binding sites, implying that the second class comprises low affinity TCF-DNA complexes. Our results indicate that beta-catenin is tethered to chromatin overwhelmingly through the TCF/LEF transcription factors in these three systems. |
