TCF/LEF dependent and independent transcriptional regulation of Wnt/β-catenin target genes

EMBO J. 2019 Jan 15;38(2):e98873. doi: 10.15252/embj.201798873. Epub 2018 Nov 13.


During canonical Wnt signalling, the activity of nuclear β-catenin is largely mediated by the TCF/LEF family of transcription factors. To challenge this view, we used the CRISPR/Cas9 genome editing approach to generate HEK 293T cell clones lacking all four TCF/LEF genes. By performing unbiased whole transcriptome sequencing analysis, we found that a subset of β-catenin transcriptional targets did not require TCF/LEF factors for their regulation. Consistent with this finding, we observed in a genome-wide analysis that β-catenin occupied specific genomic regions in the absence of TCF/LEF Finally, we revealed the existence of a transcriptional activity of β-catenin that specifically appears when TCF/LEF factors are absent, and refer to this as β-catenin-GHOST response. Collectively, this study uncovers a previously neglected modus operandi of β-catenin that bypasses the TCF/LEF transcription factors.

Keywords: TCF/LEF; Wnt signalling; signalling pathways; transcription factors; β‐catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CRISPR-Cas Systems
  • Exome Sequencing / methods
  • Gene Editing
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • TCF Transcription Factors / genetics*
  • TCF Transcription Factors / metabolism
  • Transcription, Genetic*
  • Wnt Signaling Pathway
  • beta Catenin / metabolism*


  • CTNNB1 protein, human
  • TCF Transcription Factors
  • beta Catenin