ArticleThe EMBO journal1997
The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors.
Article in The EMBO journal, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 200 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
200 citing papers in PubMed, 670 citations in OpenAlex.
- Genotype-Dependent Effects of Mechanical Stretch and GATA4-Targeted Compound 3i-1262 in Cardiomyopathy Patient-Derived hiPSC-Cardiomyocytes.Basic & clinical pharmacology & toxicology · 2026Article
- A three-dimensional spatial transcriptome atlas reconstructs early organogenesis in primate Carnegie stages 9 and 10 embryos.Nature cell biology · 2026Article
- SAM68 is a multifunctional post-transcriptional regulator of cardiomyocyte differentiation.Nucleic acids research · 2026Article
- Application of Prenatal Whole Exome Sequencing for Congenital Heart Anomalies.International journal of molecular sciences · 2026Review
- Procollagen IIA mediates positive feedback control of the mouse cardiogenic transcriptional network.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- NKX2-5 congenital heart disease mutations show diverse loss and gain of epigenomic, biochemical and chromatin search functions underpinning pathogenicity.bioRxiv : the preprint server for biology · 2025Article
- Esketamine induces embryonic and cardiac malformation through regulating the nkx2.5 and gata4 in zebrafish.Scientific reports · 2025Article
- Review
- Laminin-derived peptide drives the cardiomyogenic potential and cardiac cells functionality.Frontiers in bioengineering and biotechnology · 2025Article
- Sall4 and Gata4 induce cardiac fibroblast transition towards a partially multipotent state with cardiogenic potential.Scientific reports · 2024Article
- Epigenetic Regulation of Mammalian Cardiomyocyte Development.Epigenomes · 2024Review
- Affinity chromatography reveals direct binding of the GATA4-NKX2-5 interaction inhibitor (3i-1000) with GATA4.Scientific reports · 2024Article
- SomaticExperimental and therapeutic medicine · 2024Article
- Rare genomic copy number variants implicate new candidate genes for bicuspid aortic valve.PloS one · 2024Article
- Article
- Human Genetics of Truncus Arteriosus.Advances in experimental medicine and biology · 2024Review
- Gene editing and cardiac disease modelling for the interpretation of genetic variants of uncertain significance in congenital heart disease.Stem cell research & therapy · 2023Article
- Uncovering the Genetic Basis of Congenital Heart Disease: Recent Advancements and Implications for Clinical Management.CJC pediatric and congenital heart disease · 2023Review
- The multi-lineage transcription factor ISL1 controls cardiomyocyte cell fate through interaction with NKX2.5.Stem cell reports · 2023Article
140 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The tissue-restricted GATA-4 transcription factor and Nkx2-5 homeodomain protein are two early markers of precardiac cells. Both are essential for heart formation, but neither can initiate cardiogenesis. Overexpression of GATA-4 or Nkx2-5 enhances cardiac development in committed precursors, suggesting each interacts with a cardiac cofactor. We tested whether GATA-4 and Nkx2-5 are cofactors for each other by using transcription and binding assays with the cardiac atrial natriuretic factor (ANF) promoter_the only known target for Nkx2-5. Co-expression of GATA-4 and Nkx2-5 resulted in synergistic activation of the ANF promoter in heterologous cells. The synergy involves physical Nkx2-5-GATA-4 interaction, seen in vitro and in vivo, which maps to the C-terminal zinc finger of GATA-4 and a C-terminus extension; similarly, a C-terminally extended homeodomain of Nkx2-5 is required for GATA-4 binding. Structure/function studies suggest that binding of GATA-4 to the C-terminus autorepressive domain of Nkx2-5 may induce a conformational change that unmasks Nkx2-5 activation domains. GATA-6 cannot substitute for GATA-4 for interaction with Nkx2-5. This interaction may impart functional specificity to GATA factors and provide cooperative crosstalk between two pathways critical for early cardiogenesis. Given the co-expression of GATA proteins and NK2 class members in other tissues, the GATA/Nkx partnership may represent a paradigm for transcription factor interaction during organogenesis.
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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.