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

Jurian Schuijers, Michal Mokry, Pantelis Hatzis, Edwin Cuppen, Hans Clevers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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 languageEnglish
Pages (from-to)146-56
Number of pages11
JournalEMBO Journal
Volume33
Issue number2
DOIs
Publication statusPublished - 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

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