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

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

NATURVETENSKAP Biologi Genetik hsv//swe
NATURAL SCIENCES Biological Sciences Genetics hsv//eng
signalling pathways; TCF/LEF; transcription factors; Wnt signalling; beta-catenin

Lampart, FranziskaUniv Zurich, Switzerland (författare)
Robinson, Mark D.Univ Zurich, Switzerland (författare)
Lentini, AntonioUniv Zurich, Switzerland (författare)
Nestor, ColmLinköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten(Swepub:liu)colne37 (författare)
Cantù, ClaudioLinköpings universitet,Avdelningen för mikrobiologi, infektion och inflammation,Medicinska fakulteten,Univ Zurich, Switzerland(Swepub:liu)claca29 (författare)
Basler, KonradUniv Zurich, Switzerland (författare)
Univ Zurich, SwitzerlandAvdelningen för barns och kvinnors hälsa (creator_code:org_t)

Av författaren/redakt...: Doumpas, Nikolao ...; Lampart, Franzis ...; Robinson, Mark D ...; Lentini, Antonio; Nestor, Colm; Cantù, Claudio; visa fler...; Basler, Konrad; visa färre...

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