ArticleCirculation2024
A Genomic Link From Heart Failure to Atrial Fibrillation Risk: FOG2 Modulates a TBX5/GATA4-Dependent Atrial Gene Regulatory Network.
Article in Circulation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 9 citations in OpenAlex.
- Phenotyping and hierarchical clustering in genetically unresolved DSD identifies distinct multisystem clinical subgroups-a DSDgene study.Journal of the Endocrine Society · 2026Article
- Epigenetics in Atrial Fibrillation: Molecular Mechanisms and Therapeutic Avenues.Reviews in cardiovascular medicine · 2026Review
- Rare TruncatingGenes · 2026Article
- Epigenetic and chromatin remodeling mechanisms across cardiomyopathies: a comprehensive review.Epigenetics & chromatin · 2026Review
- Prioritizing Discovery and Advancements in Arrhythmia Therapies: NIH/NHLBI Workshop.JACC. Clinical electrophysiology · 2026Review
- Gene-gene interactions between a LMNA variant and common polymorphisms drive early-onset atrial fibrillation.Nature communications · 2026Article
- Metamorphosis and lncRNAs: A Close Relationship.Genesis (New York, N.Y. : 2000) · 2026Review
- Enhancer Dynamics for Gene Regulation in the Cardiovascular System.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- A reduced TBX5-dependent gene regulatory network links atrial fibrillation and heart failure.Nature cardiovascular research · 2026Article
- A precision medicine approach to interpret a GATA4 genetic variant in a paediatric patient with congenital heart disease.Human genomics · 2026Article
- ID2 attenuates post-MI ventricular arrhythmias by targeting GATA4 suppression to preserve mitochondrial function and NaOpen medicine (Warsaw, Poland) · 2026Article
- Consequences of Right Heart Disease for Cardiac Electrophysiology and Arrhythmias: Cellular and Structural Mechanisms.CJC open · 2025Review
- Targeting senescence and GATA4 in age-related cardiovascular disease: a comprehensive approach.Biogerontology · 2025Review
- Bioinformatics analysis of the expression of potential common genes and immune-related genes between atrial fibrillation and chronic kidney disease.Frontiers in cardiovascular medicine · 2025Article
- Single-nuclei transcriptomics reveals TBX5-dependent targets in a patient with Holt-Oram syndrome.The Journal of clinical investigation · 2024Article
- [Intrinsic steady-state pattern of mouse cardiac electrophysiology: analysis using a characterized quantitative electrocardiogram strategy].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Genetic and Molecular Underpinnings of Atrial Fibrillation.NPJ cardiovascular health · 2024Article
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Authors and funding
26 authors at 11 institutions in 4 countries.
Funding
Abstract
backgroundThe relationship between heart failure (HF) and atrial fibrillation (AF) is clear, with up to half of patients with HF progressing to AF. The pathophysiological basis of AF in the context of HF is presumed to result from atrial remodeling. Upregulation of the transcription factor FOG2 (friend of GATA2; encoded by
methodsFOG2 expression was assessed in human atria. The effect of adult-specific FOG2 overexpression in the mouse heart was evaluated by whole animal electrophysiology, in vivo organ electrophysiology, cellular electrophysiology, calcium flux, mouse genetic interactions, gene expression, and genomic function, including a novel approach for defining functional transcription factor interactions based on overlapping effects on enhancer noncoding transcription.
resultsFOG2 is significantly upregulated in the human atria during HF. Adult cardiomyocyte-specific FOG2 overexpression in mice caused primary spontaneous AF before the development of HF or atrial remodeling. FOG2 overexpression generated arrhythmia substrate and trigger in cardiomyocytes, including calcium cycling defects. We found that FOG2 repressed atrial gene expression promoted by TBX5. FOG2 bound a subset of GATA4 and TBX5 co-bound genomic locations, defining a shared atrial gene regulatory network. FOG2 repressed TBX5-dependent transcription from a subset of co-bound enhancers, including a conserved enhancer at the
conclusionsTranscriptional changes in the atria observed in human HF directly antagonize the atrial rhythm gene regulatory network, providing a genomic link between HF and AF risk independent of atrial remodeling.
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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.