title: Wnt-induced transcriptional activation is exclusively mediated by TCF/LEF.
abstract: Active canonical Wnt signaling results in recruitment of β-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 β-catenin and tether it to DNA. Here, we describe the genome-wide pattern of β-catenin DNA binding in murine intestinal epithelium, Wnt-responsive colorectal cancer (CRC) cells and HEK293 embryonic kidney cells. We identify two classes of β-catenin binding sites. The first class represents the majority of the DNA-bound β-catenin and co-localizes with TCF4, the prominent TCF/LEF family member in these cells. The second class consists of β-catenin binding sites that co-localize with a minimal amount of TCF4. The latter consists of lower affinity β-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 β-catenin/DNA interaction of both classes of binding sites, implying that the second class comprises low affinity TCF-DNA complexes. Our results indicate that β-catenin is tethered to chromatin overwhelmingly through the TCF/LEF transcription factors in these three systems.
authors.affiliation: Hubrecht Institute-KNAW, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Jurian
authors.initials: J
authors.lastname: Schuijers
authors.forename: Michal
authors.initials: M
authors.lastname: Mokry
authors.forename: Pantelis
authors.initials: P
authors.lastname: Hatzis
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
mesh_terms: D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D046228:Microarray Analysis; D051820:TCF Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics*; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D002843:Chromatin; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin