A Wnt-fall for Gene Regulation: Repression

A major endpoint of the canonical Wnt signaling pathway is a change in the transcription of target genes. The transcription factors lymphoid enhancer factor (LEF) and T cell factor (TCF) serve as the main gatekeepers of these changes by selecting genes to be targeted by the transcriptional coregulator beta-catenin and by defining how target gene expression will be altered. Most research has focused on LEF/TCF:beta-catenin-mediated activation of transcription, but there have been some reports that suggest that this complex also directly represses transcription. A recent study uncovered a new mode of repression of Wnt target genes in which recognition of a novel DNA element by TCF specifies that beta-catenin acts as a transcriptional repressor.