ArticleNucleic acids research2012
Intrinsic properties of Tcf1 and Tcf4 splice variants determine cell-type-specific Wnt/β-catenin target gene expression.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Distinct differentiation trajectories leave lasting impacts on gene regulation and function of V2a neurons.Nature communications · 2026Article
- WNT-mediating TCF/LEF transcription factor gene expression in early human pluripotency and cell lineages differs from the rodent paradigm.Journal of cell science · 2025Article
- The mechanism of low molecular weight fucoidan-incorporated nanofiber scaffolds inhibiting oral leukoplakia via SR-A/Wnt signal axis.Frontiers in pharmacology · 2024Article
- The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Long non-coding RNAs (LncRNAs), viral oncogenomics, and aberrant splicing events: therapeutics implications.American journal of cancer research · 2021Review
- Wnt/β-Catenin Signaling Promotes Differentiation of Ischemia-Activated Adult Neural Stem/Progenitor Cells to Neuronal Precursors.Frontiers in neuroscience · 2021Article
- Roles of long non-coding RNAs in the hallmarks of glioma.Oncology letters · 2020Review
- β-Catenin mutations as determinants of hepatoblastoma phenotypes in mice.The Journal of biological chemistry · 2019Article
- Msx1 loss suppresses formation of the ectopic crypts developed in the Apc-deficient small intestinal epithelium.Scientific reports · 2019Article
- Tcf7L2 is essential for neurogenesis in the developing mouse neocortex.Neural development · 2018Article
- Sp5 negatively regulates the proliferation of HCT116 cells by upregulating the transcription of p27.Oncology letters · 2018Article
- Review
- Review
- Hedgehog inhibits β-catenin activity in synovial joint development and osteoarthritis.The Journal of clinical investigation · 2016Article
- Alternative splicing within the Wnt signaling pathway: role in cancer development.Cellular oncology (Dordrecht, Netherlands) · 2016Review
- SNAIL1 combines competitive displacement of ASCL2 and epigenetic mechanisms to rapidly silence the EPHB3 tumor suppressor in colorectal cancer.Molecular oncology · 2015Article
- Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways.Frontiers in genetics · 2015Article
- The TCF C-clamp DNA binding domain expands the Wnt transcriptome via alternative target recognition.Nucleic acids research · 2014Article
- Bipartite recognition of DNA by TCF/Pangolin is remarkably flexible and contributes to transcriptional responsiveness and tissue specificity of wingless signaling.PLoS genetics · 2014Article
- Structure-function analysis of the C-clamp of TCF/Pangolin in Wnt/ß-catenin signaling.PloS one · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-cell factor (Tcf)/lymphoid-enhancer factor (Lef) proteins are a structurally diverse family of deoxyribonucleic acid-binding proteins that have essential nuclear functions in Wnt/β-catenin signalling. Expression of Wnt/β-catenin target genes is highly dependent on context, but the precise role of Tcf/Lef family members in the generation and maintenance of cell-type-specific Wnt/β-catenin responses is unknown. Herein, we show that induction of a subset of Wnt/β-catenin targets in embryonic stem cells depends on Tcf1 and Tcf4, whereas other co-expressed Tcf/Lef family members cannot induce these targets. The Tcf1/Tcf4-dependent gene responses to Wnt are primarily if not exclusively mediated by C-clamp-containing Tcf1E and Tcf4E splice variants. A combined knockdown of Tcf1/Tcf4 abrogates Wnt-inducible transcription but does not affect the active chromatin conformation of their targets. Thus, the transcriptionally poised state of Wnt/β-catenin targets is maintained independent of Tcf/Lef proteins. Conversely, ectopically overexpressed Tcf1E cannot invade silent chromatin and fails to initiate expression of inactive Wnt/β-catenin targets even if repressive chromatin modifications are abolished. The observed non-redundant functions of Tcf1/Tcf4 isoforms in acute transcriptional activation demonstrated that the cell-type-specific complement of Tcf/Lef proteins is a critical determinant of context-dependent Wnt/β-catenin responses. Moreover, the apparent inability to cope with chromatin uncovers an intrinsic property of Tcf/Lef proteins that prevents false ectopic induction and ensures spatiotemporal stability of Wnt/β-catenin target gene expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.