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The EMBO Journal
Article . 2008 . Peer-reviewed
License: Wiley TDM
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The EMBO Journal
Article
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The EMBO Journal
Article . 2008
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Novel TCF-binding sites specify transcriptional repression by Wnt signalling

Authors: Blauwkamp, Timothy A; Chang, Mikyung V; Cadigan, Ken M;

Novel TCF-binding sites specify transcriptional repression by Wnt signalling

Abstract

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.

Keywords

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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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    96
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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
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    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
96
Top 10%
Top 10%
Top 10%
gold