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TCF/LEF dependent and independent transcriptional regulation of Wnt/beta-catenin target genes
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- Doumpas, Nikolaos (author)
- Univ Zurich, Switzerland
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- Lampart, Franziska (author)
- Univ Zurich, Switzerland
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- Robinson, Mark D. (author)
- Univ Zurich, Switzerland
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- (creator_code:org_t)
- 2018-11-13
- 2019
- English.
- In: EMBO Journal. - : WILEY. - 0261-4189 .- 1460-2075. ; 38:2
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
Keyword
- signalling pathways; TCF/LEF; transcription factors; Wnt signalling; beta-catenin
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Basler, Konrad
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- NATURAL SCIENCES
- NATURAL SCIENCES
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- EMBO Journal
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- Linköping University
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