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- Doumpas, Nikolaos, et al.
(författare)
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TCF/LEF dependent and independent transcriptional regulation of Wnt/beta-catenin target genes
- 2019
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Ingår i: EMBO Journal. - : WILEY. - 0261-4189 .- 1460-2075. ; 38:2
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Tidskriftsartikel (refereegranskat)abstract
- During canonical Wnt signalling, the activity of nuclear beta-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 beta-catenin transcriptional targets did not require TCF/LEF factors for their regulation. Consistent with this finding, we observed in a genome-wide analysis that beta-catenin occupied specific genomic regions in the absence of TCF/LEF. Finally, we revealed the existence of a transcriptional activity of beta-catenin that specifically appears when TCF/LEF factors are absent, and refer to this as beta-catenin-GHOST response. Collectively, this study uncovers a previously neglected modus operandi of beta-catenin that bypasses the TCF/LEF transcription factors.
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