ArticleDiabetologia2011
An alternative polyadenylation signal in TCF7L2 generates isoforms that inhibit T cell factor/lymphoid-enhancer factor (TCF/LEF)-dependent target genes.
Article in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Alternative cleavage and polyadenylation: key regulatory mechanisms in health and disease.RNA biology · 2025Review
- IPScan: Detecting novel intronic PolyAdenylation events with RNA-seq data.PLoS computational biology · 2025Article
- Repurposing celecoxib for colorectal cancer targeting via pH-triggered ultra-elastic nanovesicles: Pronounced efficacy through up-regulation of Wnt/β-catenin pathway in DMH-induced tumorigenesis.International journal of pharmaceutics: X · 2024Article
- 3'aQTL-atlas: an atlas of 3'UTR alternative polyadenylation quantitative trait loci across human normal tissues.Nucleic acids research · 2022Article
- An atlas of alternative polyadenylation quantitative trait loci contributing to complex trait and disease heritability.Nature genetics · 2021Article
- Scientific Advances in Diabetes: The Impact of the Innovative Medicines Initiative.Frontiers in medicine · 2021Review
- Emerging Roles of RNA 3'-end Cleavage and Polyadenylation in Pathogenesis, Diagnosis and Therapy of Human Disorders.Biomolecules · 2020Review
- Genetic interaction effects reveal lipid-metabolic and inflammatory pathways underlying common metabolic disease risks.BMC medical genomics · 2018Article
- CFIm25 inhibits hepatocellular carcinoma metastasis by suppressing the p38 and JNK/c-Jun signaling pathways.Oncotarget · 2018Article
- Alternative Polyadenylation in Human Diseases.Endocrinology and metabolism (Seoul, Korea) · 2017Review
- Pancreatic alpha cell-selective deletion of Tcf7l2 impairs glucagon secretion and counter-regulatory responses to hypoglycaemia in mice.Diabetologia · 2017Article
- Current understanding and dispute on the function of the Wnt signaling pathway effector TCF7L2 in hepatic gluconeogenesis.Genes & diseases · 2016Review
- Analysis of VEGFA Variants and Changes in VEGF Levels Underscores the Contribution of VEGF to Polycystic Ovary Syndrome.PloS one · 2016Article
- The expression of dominant negative TCF7L2 in pancreatic beta cells during the embryonic stage causes impaired glucose homeostasis.Molecular metabolism · 2015Article
- Alternative human liver transcripts of TCF7L2 bind to the gluconeogenesis regulator HNF4α at the protein level.Diabetologia · 2014Article
- TCF7L2 in mouse pancreatic beta cells plays a crucial role in glucose homeostasis by regulating beta cell mass.Diabetologia · 2014Article
- Implications of polyadenylation in health and disease.Nucleus (Austin, Tex.) · 2014Review
- Physiological role of β-catenin/TCF signaling in neurons of the adult brain.Neurochemical research · 2013Review
- The Wnt signaling pathway effector TCF7L2 controls gut and brain proglucagon gene expression and glucose homeostasis.Diabetes · 2013Article
- Alterations in polyadenylation and its implications for endocrine disease.Frontiers in endocrinology · 2013Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors.
Funding
Abstract
aims/hypothesisIntronic single nucleotide polymorphisms within the transcription factor 7-like 2 (TCF7L2) gene are associated with risk of type 2 diabetes. It is widely hypothesised that the predisposing variation is involved in cis-regulation of TCF7L2 activity. The aim of this study was to seek evidence for the existence of novel TCF7L2 isoforms encoded within the type 2 diabetes-associated genomic region.
methodsWe searched expressed sequence tag (EST) databases for novel TCF7L2 transcripts and sought to validate the function and integrity of any isoforms found using a combination of RT-PCR, western blotting and reporter gene techniques.
resultsAnalysis of EST databases suggested the presence of an alternative polyadenylation site located in intron 4 of TCF7L2. We used 3' rapid amplification of cDNA ends and real-time PCR to validate the integrity of this polyadenylation signal and show its wide use across human tissues. Western blotting results are consistent with the use of this polyadenylation signal to generate novel protein isoforms. The alternative polyadenylation signal results in the production of isoforms that retain the β-catenin binding domain but do not possess the high-mobility group box DNA-binding domain. Promoter-reporter gene assays suggest that these isoforms inhibit TCF7L2-dependent target genes by sequestering β-catenin. CONCLUSIONS/
interpretationWe have identified a novel polyadenylation signal within TCF7L2 that can result in the production of isoforms that act to repress TCF/LEF-dependent target genes. These findings may provide new insights into the association of TCF7L2 with susceptibility to type 2 diabetes.
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