Novel TCF-binding sites specify transcriptional repression by Wnt signalling
Novel TCF-binding sites specify transcriptional repression by Wnt signalling
Both transcriptional activation and repression have essential functions in maintaining proper spatial and temporal control of gene expression. Although Wnt signalling is often associated with gene activation, we have identified several directly repressed targets of Wnt signalling in Drosophila. Here, we explore how individual Wnt target genes are specified for signal-induced activation or repression. Similar to activation, repression required binding of Armadillo (Arm) to the N terminus of TCF. However, TCF/Arm mediated repression by binding to DNA motifs that are markedly different from typical TCF-binding sites. Conversion of the novel motifs to standard TCF-binding sites reversed the mode of regulation, resulting in Wnt-mediated activation instead of repression. A mutant form of Arm defective in activation was still functional for repression, indicating that distinct domains of the protein are required for each activity. This study suggests that the sequence of TCF-binding sites allosterically regulates the TCF/Arm complex to effect either transcriptional activation or repression.
- University of Michigan–Flint United States
- University of Michigan United States
- University of Michigan–Ann Arbor United States
- UNIVERSITY OF MICHIGAN AT ANN ARBOR
Transcriptional Activation, Embryo, Nonmammalian, Hemocytes, Transcription, Genetic, Armadillo, Down-Regulation, Axin Protein, Health Sciences, Animals, Drosophila Proteins, Cellular and Developmental Biology, Allosteric, Adaptor Proteins, Signal Transducing, Armadillo Domain Proteins, Binding Sites, β‐Catenin, Base Sequence, Molecular, Glycosyltransferases, TCF, DNA, Repressor Proteins, Drosophila melanogaster, Gene Expression Regulation, Wingless, RNA Interference, Signal Transduction, Transcription Factors
Transcriptional Activation, Embryo, Nonmammalian, Hemocytes, Transcription, Genetic, Armadillo, Down-Regulation, Axin Protein, Health Sciences, Animals, Drosophila Proteins, Cellular and Developmental Biology, Allosteric, Adaptor Proteins, Signal Transducing, Armadillo Domain Proteins, Binding Sites, β‐Catenin, Base Sequence, Molecular, Glycosyltransferases, TCF, DNA, Repressor Proteins, Drosophila melanogaster, Gene Expression Regulation, Wingless, RNA Interference, Signal Transduction, Transcription Factors
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