How do they do Wnt they do: regulation of transcription by the Wnt/ß-catenin pathway

Wnt/beta-catenin signalling is known to play many roles in metazoan development and tissue homeostasis. Misregulation of the pathway has also been linked to many human diseases. In this review, specific aspects of the pathways involvement in these processes are discussed, with an emphasis on how Wnt/beta-catenin signalling regulates gene expression in a cell and temporally specific manner. The T-cell factor (TCF) family of transcription factors, which mediate a large portion of Wnt/beta-catenin signalling, will be discussed in detail. Invertebrates contain a single TCF gene that contains two DNA-binding domains, the high mobility group (HMG) domain and the C-clamp, which increases the specificity of DNA binding. In vertebrates, the situation is more complex, with four TCF genes producing many isoforms that contain the HMG domain, but only some of which possess a C-clamp. Vertebrate TCFs have been reported to act in concert with many other transcription factors, which may explain how they obtain sufficient specificity for specific DNA sequences, as well as how they achieve a wide diversity of transcriptional outputs in different cells.