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

ABSTRACT: During canonical Wnt signalling, the activity of nuclear ?-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 ?-catenin transcriptional targets did not require TCF/LEF factors for their regulation. Consistent with this finding, we observed in a genome-wide analysis that ?-catenin occupied specific genomic regions in the absence of TCF/LEF Finally, we revealed the existence of a transcriptional activity of ?-catenin that specifically appears when TCF/LEF factors are absent, and refer to this as ?-catenin-GHOST response. Collectively, this study uncovers a previously neglected modus operandi of ?-catenin that bypasses the TCF/LEF transcription factors.

SUBMITTER: Doumpas N 

PROVIDER: S-EPMC6331726 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature