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


Doumpas, Nikolaos; Lampart, Franziska; Robinson, Mark D; Lentini, Antonio; Nestor, Colm E; Cantù, Claudio; Basler, Konrad (2019). TCF/LEF dependent and independent transcriptional regulation of Wnt/β-catenin target genes. EMBO Journal Online, 38(2):e98873.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Life Sciences > General Neuroscience
Life Sciences > Molecular Biology
Life Sciences > General Biochemistry, Genetics and Molecular Biology
Life Sciences > General Immunology and Microbiology
Language:English
Date:15 January 2019
Deposited On:13 Mar 2019 14:21
Last Modified:01 Aug 2020 16:16
Publisher:Nature Publishing Group
ISSN:0261-4189
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.15252/embj.201798873
PubMed ID:30425074

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