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Doumpas N, Lampart F, Robinson MD, Lentini A, Nestor CE, Cantù C, Basler K
EMBO J. 38 (2) - [2019-01-15; online 2018-11-13]
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.
PubMed 30425074
DOI 10.15252/embj.201798873
Crossref 10.15252/embj.201798873
pmc: PMC6331726
pii: embj.201798873