ArticleBMC biology2015
Long-range regulatory interactions at the 4q25 atrial fibrillation risk locus involve PITX2c and ENPEP.
Article in BMC biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 63 citations in OpenAlex.
- Epigenetics in Atrial Fibrillation: Molecular Mechanisms and Therapeutic Avenues.Reviews in cardiovascular medicine · 2026Review
- Single-Nucleotide Polymorphisms,International journal of molecular sciences · 2025Review
- Efficient and accurate framework for genome-wide gene-environment interaction analysis in large-scale biobanks.Nature communications · 2025Article
- PITX2 deficiency leads to atrial mitochondrial dysfunction.Cardiovascular research · 2024Article
- TAD boundary deletion causes PITX2-related cardiac electrical and structural defects.Nature communications · 2024Article
- Intergenic sequences harboring potential enhancer elements contribute to Axenfeld-Rieger syndrome by regulating PITX2.JCI insight · 2024Article
- Review
- The dynamics of three-dimensional chromatin organization and phase separation in cell fate transitions and diseases.Cell regeneration (London, England) · 2022Review
- Identification of atrial-enriched lncRNA Walras linked to cardiomyocyte cytoarchitecture and atrial fibrillation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Identification of candidate miRNA biomarkers correlated with the prognosis of cell carcinoma and endocervical adenocarcinoma via integrated bioinformatics analysis.American journal of translational research · 2022Article
- Basic Research Approaches to Evaluate Cardiac Arrhythmia in Heart Failure and Beyond.Frontiers in physiology · 2022Review
- Genomic enhancers in cardiac development and disease.Nature reviews. Cardiology · 2022Review
- A novel transgenic Cre allele to label mouse cardiac conduction system.Developmental biology · 2021Article
- Understanding PITX2-Dependent Atrial Fibrillation Mechanisms through Computational Models.International journal of molecular sciences · 2021Review
- Three-dimensional chromatin organization in cardiac development and disease.Journal of molecular and cellular cardiology · 2021Review
- In Silico Assessment of Class I Antiarrhythmic Drug Effects onInternational journal of molecular sciences · 2021Article
- Heat shock proteins and small nucleolar RNAs are dysregulated in a Drosophila model for feline hypertrophic cardiomyopathy.G3 (Bethesda, Md.) · 2021Article
- Article
- Big Data and Atrial Fibrillation: Current Understanding and New Opportunities.Journal of cardiovascular translational research · 2020Review
- Genetics and Epigenetics of Atrial Fibrillation.International journal of molecular sciences · 2020Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecent genome-wide association studies have uncovered genomic loci that underlie an increased risk for atrial fibrillation, the major cardiac arrhythmia in humans. The most significant locus is located in a gene desert at 4q25, approximately 170 kilobases upstream of PITX2, which codes for a transcription factor involved in embryonic left-right asymmetry and cardiac development. However, how this genomic region functionally and structurally relates to PITX2 and atrial fibrillation is unknown.
resultsTo characterise its function, we tested genomic fragments from 4q25 for transcriptional activity in a mouse atrial cardiomyocyte cell line and in transgenic mouse embryos, identifying a non-tissue-specific potentiator regulatory element. Chromosome conformation capture revealed that this region physically interacts with the promoter of the cardiac specific isoform of Pitx2. Surprisingly, this regulatory region also interacts with the promoter of the next neighbouring gene, Enpep, which we show to be expressed in regions of the developing mouse heart essential for cardiac electrical activity.
conclusionsOur data suggest that de-regulation of both PITX2 and ENPEP could contribute to an increased risk of atrial fibrillation in carriers of disease-associated variants, and show the challenges that we face in the functional analysis of genome-wide disease associations.
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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.