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TCF/LEF dependent and independent transcriptional regulation of Wnt/beta-catenin target genes
Univ Zurich, Switzerland.
Univ Zurich, Switzerland.
Univ Zurich, Switzerland.
Univ Zurich, Switzerland.
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2019 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 38, no 2, article id e98873Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
WILEY , 2019. Vol. 38, no 2, article id e98873
Keywords [en]
signalling pathways; TCF/LEF; transcription factors; Wnt signalling; beta-catenin
National Category
Genetics
Identifiers
URN: urn:nbn:se:liu:diva-154326DOI: 10.15252/embj.201798873ISI: 000455915300014PubMedID: 30425074OAI: oai:DiVA.org:liu-154326DiVA, id: diva2:1285531
Note

Funding Agencies|EMBO long-term fellowship; University of Zurich; Knut and Alice Wallenberg Foundation

Available from: 2019-02-04 Created: 2019-02-04 Last updated: 2019-02-04

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CiteExportLink to record
Permanent link

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Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf