ArticleMolecular and cellular biology2011
Differential role of Nkx2-5 in activation of the atrial natriuretic factor gene in the developing versus failing heart.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Global Evaluation of Congenital Heart Disease-Associated Non-Coding Variants.Research square · 2026Article
- Congenital heart disease missense mutations in the TBX5 DNA-binding domain alter thermal stability and DNA-binding affinity.G3 (Bethesda, Md.) · 2025Article
- Prioritizing cardiovascular disease-associated variants altering NKX2-5 and TBX5 binding through an integrative computational approach.The Journal of biological chemistry · 2023Article
- A network medicine approach to study comorbidities in heart failure with preserved ejection fraction.BMC medicine · 2023Article
- Unfolding the genotype-to-phenotype black box of cardiovascular diseases through cross-scale modeling.iScience · 2022Article
- The role and molecular mechanism of epigenetics in cardiac hypertrophy.Heart failure reviews · 2021Review
- Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part.Scientific reports · 2021Article
- Imprinting aberrations of SNRPN, ZAC1 and INPP5F genes involved in the pathogenesis of congenital heart disease with extracardiac malformations.Journal of cellular and molecular medicine · 2020Article
- Extracellular Matrix Disparities in anFrontiers in cardiovascular medicine · 2020Article
- Genetic and epigenetic regulation of cardiomyocytes in development, regeneration and disease.Development (Cambridge, England) · 2018Review
- NKX2-5 regulates human cardiomyogenesis via a HEY2 dependent transcriptional network.Nature communications · 2018Article
- Structure and function of the Nppa-Nppb cluster locus during heart development and disease.Cellular and molecular life sciences : CMLS · 2018Review
- Analysis of region specific gene expression patterns in the heart and systemic responses after experimental myocardial ischemia.Oncotarget · 2017Article
- Myocardial plasticity: cardiac development, regeneration and disease.Current opinion in genetics & development · 2016Review
- Acute heart failure with cardiomyocyte atrophy induced in adult mice by ablation of cardiac myosin light chain kinase.Cardiovascular research · 2016Article
- A mouse model of human congenital heart disease: high incidence of diverse cardiac anomalies and ventricular noncompaction produced by heterozygous Nkx2-5 homeodomain missense mutation.Circulation. Cardiovascular genetics · 2014Article
- Pleiotropic and isoform-specific functions for Pitx2 in superior colliculus and hypothalamic neuronal development.Molecular and cellular neurosciences · 2013Article
- Identification of HMX1 target genes: a predictive promoter model approach.Molecular vision · 2013Article
- Regulation of chromatin structure in the cardiovascular system.Circulation journal : official journal of the Japanese Circulation Society · 2013Review
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Atrial natriuretic factor (ANF) is abundantly expressed in atrial cardiomyocytes throughout ontogeny and in ventricular cardiomyocytes in the developing heart. However, during cardiac failure and hypertrophy, ANF expression can reappear in adult ventricular cardiomyocytes. The transcription factor Nkx2-5 is one of the major transactivators of the ANF gene in the developing heart. We identified Nkx2-5 binding at three 5' regulatory elements (kb -34, -31, and -21) and at the proximal ANF promoter by ChIP assay using neonatal mouse cardiomyocytes. 3C analysis revealed close proximity between the distal elements and the promoter region. A 5.8-kb fragment consisting of these elements transactivated a reporter gene in vivo recapitulating endogenous ANF expression, which was markedly reduced in tamoxifen-inducible Nkx2-5 gene knockout mice. However, expression of a reporter gene was increased and expanded toward the outer compact layer in the absence of the transcription repressor Hey2, similar to endogenous ANF expression. Functional Nkx2-5 and Hey2 binding sites separated by 59 bp were identified in the -34 kb element in neonatal cardiomyocytes. In adult hearts, this fragment did not respond to pressure overload, and ANF was induced in the absence of Nkx2-5. These results demonstrate that Nkx2-5 and its responsive cis-regulatory DNA elements are essential for ANF expression selectively in the developing heart.
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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.