TCF/LEF dependent and independent transcriptional regulation of Wnt/{beta}-catenin target genes

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.

Source: EMBO Journal - January 15, 2019 Category: Molecular Biology Authors: Doumpas, N., Lampart, F., Robinson, M. D., Lentini, A., Nestor, C. E., Cantu, C., Basler, K. Tags: Signal Transduction, Transcription Articles Source Type: research