Wnt-induced transcriptional activation is exclusively mediated by TCF/LEF.

ABSTRACT: Active canonical Wnt signaling results in recruitment of ?-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 ?-catenin and tether it to DNA. Here, we describe the genome-wide pattern of ?-catenin DNA binding in murine intestinal epithelium, Wnt-responsive colorectal cancer (CRC) cells and HEK293 embryonic kidney cells. We identify two classes of ?-catenin binding sites. The first class represents the majority of the DNA-bound ?-catenin and co-localizes with TCF4, the prominent TCF/LEF family member in these cells. The second class consists of ?-catenin binding sites that co-localize with a minimal amount of TCF4. The latter consists of lower affinity ?-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 ?-catenin/DNA interaction of both classes of binding sites, implying that the second class comprises low affinity TCF-DNA complexes. Our results indicate that ?-catenin is tethered to chromatin overwhelmingly through the TCF/LEF transcription factors in these three systems.

SUBMITTER: Schuijers J 

PROVIDER: S-EPMC3989608 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature