title: Atypical Transcriptional Activation by TCF via a Zic Transcription Factor in C. elegans Neuronal Precursors.
abstract: Transcription factors of the TCF family are key mediators of the Wnt/β-catenin pathway. TCF usually activates transcription on cis-regulatory elements containing TCF binding sites when the pathway is active and represses transcription when the pathway is inactive. However, some direct targets display an opposite regulation (activated by TCF in the absence of Wnt), but the mechanism behind this atypical regulation remains poorly characterized. Here, we use the cis-regulatory region of an opposite target gene, ttx-3, to dissect the mechanism of this atypical regulation. Using a combination of genetic, molecular, and biochemical experiments, we establish that, in the absence of Wnt pathway activation, TCF activates ttx-3 expression via a Zic binding site by forming a complex with a Zic transcription factor. This mechanism is later reinforced by specific bHLH factors. This study reveals an atypical mode of action for TCF that may apply to other binary decisions mediated by Wnt signaling.
authors.affiliation: Aix-Marseille Université, CNRS, Institut de Biologie du Développement de Marseille, 13288 Marseille Cedex 9, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Murgan
authors.affiliation: Aix-Marseille Université, CNRS, Institut de Biologie du Développement de Marseille, 13288 Marseille Cedex 9, France.
authors.forename: Willi
authors.initials: W
authors.lastname: Kari
authors.affiliation: Aix-Marseille Université, CNRS, Institut de Biologie du Développement de Marseille, 13288 Marseille Cedex 9, France.
authors.forename: Ute
authors.initials: U
authors.lastname: Rothbächer
authors.affiliation: Aix-Marseille Université, CNRS, Institut de Biologie du Développement de Marseille, 13288 Marseille Cedex 9, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Iché-Torres
authors.affiliation: Aix-Marseille Université, CNRS, Institut de Biologie du Développement de Marseille, 13288 Marseille Cedex 9, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Mélénec
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: or38@columbia.edu.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hobert
authors.affiliation: Aix-Marseille Université, CNRS, Institut de Biologie du Développement de Marseille, 13288 Marseille Cedex 9, France; Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: vincent.bertrand@univ-amu.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Bertrand
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008959:Models, Neurological; D058953:Neural Stem Cells / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D060449:Wnt Signaling Pathway
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D009479:Neuropeptides; D051820:TCF Transcription Factors; D014157:Transcription Factors; C106515:HLH-3 protein, C elegans; C465015:REF-2 protein, C elegans; C502083:Sys-1 protein, C elegans; C108368:TTX-3 protein, C elegans; C096787:pop-1 protein, C elegans