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

  • Doumpas N Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
  • Lampart F Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
  • Robinson MD Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
  • Lentini A SIB Swiss Institute of Bioinformatics, University of Zurich, Zurich, Switzerland.
  • Nestor CE Department of Clinical and Experimental Medicine (IKE), Faculty of Health Sciences, Linköping University, Linköping, Sweden.
  • Cantù C Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland claudio.cantu@liu.se kb@imls.uzh.ch.
  • Basler K Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland claudio.cantu@liu.se kb@imls.uzh.ch.
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  • 2018-11-15
Published in:
  • The EMBO journal. - 2019
TCF/LEF
Wnt signalling
signalling pathways
transcription factors
β‐catenin
CRISPR-Cas Systems
Gene Editing
Gene Expression Profiling
Gene Expression Regulation
HEK293 Cells
Humans
TCF Transcription Factors
Transcription, Genetic
Whole Exome Sequencing
Wnt Signaling Pathway
beta Catenin
English 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.
Language
  • English
Open access status
green
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Persistent URL
https://folia.unifr.ch/global/documents/7071
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