Evolutionary Diversification of Vertebrate TCF/LEF Structure, Function, and Regulation

As a general rule, most genome duplications tend to be lost, and indeed, the complete complement of Wnt signaling components in vertebrates is not four times larger than in invertebrates. The most notable exception, and the most relevant to this chapter, is the TCF/LEF family of DNA-binding factors. Vertebrate and invertebrate TCF/LEF genes share inherited or2uctures and functions. DNA-associated TCF/LEF proteins mediate transcriptional activation when they are bound by nuclear β-catenin, which links to transcriptional coactivators, or they mediate transcriptional repression when bound by transcriptional corepressors. Differential expression of the four vertebrate TCF/LEF genes allows them to be associated with the development of specific tissues, organs, and also diseases; and it provides additional mechanisms for regulating context-specific responses to Wnt signaling. It is interesting to note that the extent of alternative splicing and the degree of similarity to invertebrate orthologs differs among the members of the vertebrate TCF/LEF gene family.