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.
| Original language | English |
|---|---|
| Pages (from-to) | 146-56 |
| Number of pages | 11 |
| Journal | EMBO Journal |
| Volume | 33 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 13 Jan 2014 |
Keywords
- Animals
- Binding Sites
- Cells, Cultured
- Chromatin
- Gene Expression Profiling
- HEK293 Cells
- Humans
- Mice
- Microarray Analysis
- TCF Transcription Factors
- Transcriptional Activation
- Wnt Proteins
- beta Catenin