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Wnt‐induced transcriptional activation is exclusively mediated by TCF / LEF
Author(s) -
Schuijers Jurian,
Mokry Michal,
Hatzis Pantelis,
Cuppen Edwin,
Clevers Hans
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/embj.201385358
Subject(s) - biology , wnt signaling pathway , microbiology and biotechnology , genetics , signal transduction
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 HEK 293 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 TCF 4, 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 TCF 4. 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 TCF 4 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.