biostudies-literatureBlauwkamp TANCI NIH HHS1436-46https://www.ebi.ac.uk/biostudies/studies/S-EPMC2396397biostudies-literatureUnknown27(10)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 defThe EMBO journalNovel TCF-binding sites specify transcriptional repression by Wnt signalling.PMC2396397R01 CA095869R01 CA95869Cadigan KMBlauwkamp TAChang MVfalseNovel 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 def2008-01-01T00:00:00Z2008 May2025-04-04T21:06:18.42Z2019-03-27T00:15:15ZS-EPMC23963971841838310.1038/emboj.2008.80