ArticleMolecular and cellular biology2008
Distinct expression and function of alternatively spliced Tbx5 isoforms in cell growth and differentiation.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- Posttranscriptional Regulation by Proteins and Noncoding RNAs.Advances in experimental medicine and biology · 2024Article
- Tbx5 maintains atrial identity in post-natal cardiomyocytes by regulating an atrial-specific enhancer network.Nature cardiovascular research · 2023Article
- Circ-sh3rf3/GATA-4/miR-29a regulatory axis in fibroblast-myofibroblast differentiation and myocardial fibrosis.Cellular and molecular life sciences : CMLS · 2023Article
- The TH1 cell lineage-determining transcription factor T-bet suppresses TH2 gene expression by redistributing GATA3 away from TH2 genes.Nucleic acids research · 2022Article
- Identification of a novel TBX5 c.755 + 1 G > A variant and related pathogenesis in a family with Holt-Oram syndrome.American journal of medical genetics. Part A · 2022Article
- Preclinical evidence for the therapeutic value of TBX5 normalization in arrhythmia control.Cardiovascular research · 2021Article
- miR-182-5p is an evolutionarily conserved Tbx5 effector that impacts cardiac development and electrical activity in zebrafish.Cellular and molecular life sciences : CMLS · 2020Article
- The oncoprotein TBX3 is controlling severity in experimental arthritis.Arthritis research & therapy · 2019Article
- Interplay between cardiac transcription factors and non-coding RNAs in predisposing to atrial fibrillation.Journal of molecular medicine (Berlin, Germany) · 2018Review
- TBX5: A Key Regulator of Heart Development.Current topics in developmental biology · 2017Review
- The Epigenetic Regulator HDAC1 Modulates Transcription of a Core Cardiogenic Program in Human Cardiac Mesenchymal Stromal Cells Through a p53-Dependent Mechanism.Stem cells (Dayton, Ohio) · 2016Article
- Myocardial transcription factors in diastolic dysfunction: clues for model systems and disease.Heart failure reviews · 2016Review
- Tetralogy of Fallot and Hypoplastic Left Heart Syndrome - Complex Clinical Phenotypes Meet Complex Genetic Networks.Current genomics · 2015Article
- Novel exons in the tbx5 gene locus generate protein isoforms with distinct expression domains and function.The Journal of biological chemistry · 2015Article
- Loss of muscleblind-like 1 results in cardiac pathology and persistence of embryonic splice isoforms.Scientific reports · 2015Article
- Forward Programming of Cardiac Stem Cells by Homogeneous Transduction with MYOCD plus TBX5.PloS one · 2015Article
- Caspase-1 cleavage of transcription factor GATA4 and regulation of cardiac cell fate.Cell death & disease · 2014Article
- Cyclin D2 is a GATA4 cofactor in cardiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- The alternative heart: impact of alternative splicing in heart disease.Journal of cardiovascular translational research · 2013Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the T-box transcription factor Tbx5 cause Holt-Oram syndrome, an autosomal dominant disease characterized by a wide spectrum of cardiac and upper limb defects with variable expressivity. Tbx5 haploinsufficiency has been suggested to be the underlying mechanism, and experimental models are consistent with a dosage-sensitive requirement for Tbx5 in heart development. Here, we report that Tbx5 levels are regulated through alternative splicing that generates, in addition to the known 518-amino-acid protein, a C-terminal truncated isoform. This shorter isoform retains the capacity to bind DNA, but its interaction with Tbx5 collaborators such as GATA-4 is altered. In vivo, the two spliced isoforms are oppositely regulated in a temporal and growth factor-dependent manner and are present in distinct DNA-binding complexes. The expression of the long isoform correlates with growth stimulation, and its reexpression in postnatal transgenic mouse hearts promotes hypertrophy. Conversely, the upregulation of the short but not the long isoform in C2C12 myoblasts leads to growth arrest and cell death. The results provide novel insight into posttranscriptional Tbx5 regulation and point to an important role not only in cell differentiation but also in cell proliferation and organ growth. The data may help analyze genotype-phenotype relations in patients with Holt-Oram syndrome.
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