title: Cell-context dependent TCF/LEF expression and function: alternative tales of repression, de-repression and activation potentials.
abstract: Wnt signaling controls cell specification and fate during development and adult tissue homeostasis by converging on a small family of DNA binding factors, the T-cell factor/lymphoid enhancer factor (TCF/LEF) family. In response to Wnt signals, TCF/LEF members undergo a transcriptional switch from repression to activation mediated in part by nuclear β-catenin binding and recruitment of co-activator complexes. In mammals, the specificity and fine tuning of this transcriptional switch is also achieved by the cell-context-dependent expression of four members (TCF7, TCF7L1, TCF7L2, and LEF1) and numerous variants, which display differential DNA binding affinity and specificity, repression strength, activation potential, and regulators. TCF7/LEF1 variants are generated by alternative promoters, alternative exon cassettes, and alternative donor/acceptor splicing sites, allowing combinatorial insertion/exclusion of modular functional and regulatory domains. In this review we present mounting evidence for the interdependency of TCF7/LEF1 variant expression and functions with cell lineage and cell state. We also illustrate how the p53 and nuclear receptor family of transcription factors, known to control cell fate and to inhibit Wnt signaling, may participate in the fine tuning of TCF7/LEF1 repression/activation potentials.
authors: Department of Clinical Sciences, College of Health Sciences and Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA. cdmao2@uky.edu
authors: Catherine D
authors: CD
authors: Mao
authors: Stephen W
authors: SW
authors: Byers
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D015870:Gene Expression; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008322:Mammals / Q000196:embryology / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D051822:T Cell Transcription Factor 1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051820:TCF Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D051822:T Cell Transcription Factor 1; D051820:TCF Transcription Factors; C497576:TCF7 protein, human