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Cell-context dependent TCF/LEF expression and function: alternative tales of repression, de-repression and activation
Catherine D Mao1, Stephen W Byers
1Department of Clinical Sciences, College of Health Sciences and Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA. cdmao2@uky.edu
Critical Reviews in Eukaryotic Gene Expression
|November 25, 2011
Summary
The T-cell factor/lymphoid enhancer factor (TCF/LEF) family regulates cell fate via Wnt signaling. Specific TCF/LEF variants, generated by alternative splicing, fine-tune this process and interact with other transcription factors.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Wnt signaling is crucial for cell specification and tissue homeostasis.
- T-cell factor/lymphoid enhancer factor (TCF/LEF) proteins mediate Wnt signaling by binding DNA and switching transcription from repression to activation.
- Mammalian TCF/LEF family members (TCF7, TCF7L1, TCF7L2, LEF1) and their variants exhibit differential DNA binding, repression, and activation capabilities.
Purpose of the Study:
- To review the evidence linking TCF/LEF variant expression and function to cell lineage and state.
- To explore the role of p53 and nuclear receptors in modulating TCF/LEF activity.
Main Methods:
- Literature review of studies on Wnt signaling, TCF/LEF family, and related transcription factors.
- Analysis of mechanisms generating TCF/LEF variants, including alternative promoters and splicing.
- Examination of interactions between TCF/LEF, p53, and nuclear receptors.
Main Results:
- TCF/LEF variants are generated through alternative promoters, exon cassettes, and splicing, creating diverse functional domains.
- The expression and function of TCF/LEF variants are interdependent with cell lineage and cell state.
- p53 and nuclear receptors may fine-tune the Wnt signaling pathway by modulating TCF/LEF repression and activation potentials.
Conclusions:
- TCF/LEF variant diversity is essential for precise Wnt signal regulation during development and homeostasis.
- Interactions with other transcription factors like p53 and nuclear receptors add another layer of complexity to Wnt pathway control.
- Understanding TCF/LEF variant dynamics is key to comprehending cell fate determination and tissue regulation.
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