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TCF/LEF dependent and independent regulation of Wnt/beta-catenin transcription

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 simultaneously carrying loss-of-function alleles of all four TCF/LEF genes. Exploiting unbiased whole transcriptome sequencing studies, 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.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Homo sapiens

SUBMITTER: Mark Robinson

PROVIDER: E-MTAB-7028 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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ChIP-seq experiment of mouse embryonic stem cells (mESCs), assessing beta-catenin DNA binding in wild type mESCs and TCF/LEF quadruple knock-out mESCs.

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2022-04-15 | PXD026263 | Pride

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