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

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

Author information

1
Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
2
SIB Swiss Institute of Bioinformatics, University of Zurich, Zurich, Switzerland.
3
Department of Clinical and Experimental Medicine (IKE), Faculty of Health Sciences, Linköping University, Linköping, Sweden.
4
Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland claudio.cantu@liu.se kb@imls.uzh.ch.
5
Wallenberg Centre for Molecular Medicine (WCMM), Linköping University, Linköping, Sweden.

Abstract

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

PMID:
30425074
PMCID:
PMC6331726
[Available on 2020-01-15]
DOI:
10.15252/embj.201798873

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