Tissue-specific derepression of TCF/LEF controls the activity of the Wnt/β-catenin pathway

Fu-I Lu, Yong-Hua Sun, Chang-Yong Wei, Christine Thisse and Bernard Thisse ()
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Fu-I Lu: University of Virginia
Yong-Hua Sun: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université de Strasbourg
Chang-Yong Wei: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences
Christine Thisse: University of Virginia
Bernard Thisse: University of Virginia

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: Abstract Upon stimulation by Wnt ligands, the canonical Wnt/β-catenin signalling pathway results in the stabilization of β-catenin and its translocation into the nucleus to form transcriptionally active complexes with sequence-specific DNA-binding T-cell factor/lymphoid enhancer factor (TCF/LEF) family proteins. In the absence of nuclear β-catenin, TCF proteins act as transcriptional repressors by binding to Groucho/Transducin-Like Enhancer of split (TLE) proteins that function as co-repressors by interacting with histone deacetylases whose activity leads to the generation of transcriptionally silent chromatin. Here we show that the transcription factor Ladybird homeobox 2 (Lbx2) positively controls the Wnt/β-catenin signalling pathway in the posterior lateral and ventral mesoderm of the zebrafish embryo at the gastrula stage, by directly interfering with the binding of Groucho/TLE to TCF, thereby preventing formation of transcription repressor complexes. These findings reveal a novel level of regulation of the canonical Wnt/β-catenin signalling pathway occurring in the nucleus and involving tissue-specific derepression of TCF by Lbx2.

Date: 2014
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DOI: 10.1038/ncomms6368

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