Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling.

Abstract

T-cell factor (TCF), a high-mobility-group domain protein, is the transcription factor activated by Wnt/Wingless signalling. When signalling occurs, TCF binds to its coactivator, beta-catenin/Armadillo, and stimulates the transcription of the target genes of Wnt/Wingless by binding to TCF-responsive enhancers. Inappropriate activation of TCF in the colon epithelium and other cells leads to cancer. It is therefore desirable for unstimulated cells to have a negative control mechanism to keep TCF inactive. Here we report that Drosophila CREB-binding protein (dCBP) binds to dTCF. dCBP mutants show mild Wingless overactivation phenotypes in various tissues. Consistent with this, dCBP loss-of-function suppresses the effects of armadillo mutation. Moreover, our data show that dCBP acetylates a conserved lysine in the Armadillo-binding domain of dTCF, and that this acetylation lowers the affinity of Armadillo binding to dTCF. Although CBP is a coactivator of other transcription factors, our data show that CBP represses TCF.