ArticleGenome medicine2019
TCF21 and AP-1 interact through epigenetic modifications to regulate coronary artery disease gene expression.
Article in Genome medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- FHL5 Controls Vascular Disease-Associated Gene Programs in Smooth Muscle Cells.Circulation research · 2023Pooled it
- Vascular smooth muscle cell state trajectories mediate molecular mechanisms of coronary disease risk.Nature communications · 2026Article
- Tcf21 modulates fibroblast activation and promotes cardiac fibrosis after injury via Pdgfrb signaling.Scientific reports · 2025Article
- Persistent Activation of Endothelial Cells is Linked to Thrombosis and Inflammation in Cerebral Cavernous Malformation Disease.bioRxiv : the preprint server for biology · 2025Article
- Article
- Abundant repressor binding sites in human enhancers are associated with the fine-tuning of gene regulation.iScience · 2025Article
- Susceptibility ofHeliyon · 2024Article
- Transcription factor Tcf21 modulates urinary bladder size and differentiation.Development, growth & differentiation · 2024Article
- Article
- AP-1 signaling modulates cardiac fibroblast stress responses.Journal of cell science · 2023Article
- Klotho/FGF23 Axis Regulates Cardiomyocyte Apoptosis and Cytokine Release through ERK/MAPK Pathway.Cardiovascular toxicology · 2023Article
- Review
- Intrapericardial long non-coding RNA-Tcf21 antisense RNA inducing demethylation administration promotes cardiac repair.European heart journal · 2023Article
- Discovery of Transacting Long Noncoding RNAs That Regulate Smooth Muscle Cell Phenotype.Circulation research · 2023Article
- Etiologic Puzzle of Coronary Artery Disease: How Important Is Genetic Component?Life (Basel, Switzerland) · 2022Review
- Metabolic control of progenitor cell propagation during Drosophila tracheal remodeling.Nature communications · 2022Article
- A systematic comparison of FOSL1, FOSL2 and BATF-mediated transcriptional regulation during early human Th17 differentiation.Nucleic acids research · 2022Article
- Regulated interaction of ID2 with the anaphase-promoting complex links progression through mitosis with reactivation of cell-type-specific transcription.Nature communications · 2022Article
- Post-Transcriptional Regulation of Molecular Determinants during Cardiogenesis.International journal of molecular sciences · 2022Review
- Functional noncoding SNPs in human endothelial cells fine-map vascular trait associations.Genome research · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundGenome-wide association studies have identified over 160 loci that are associated with coronary artery disease. As with other complex human diseases, risk in coronary disease loci is determined primarily by altered expression of the causal gene, due to variation in binding of transcription factors and chromatin-modifying proteins that directly regulate the transcriptional apparatus. We have previously identified a coronary disease network downstream of the disease-associated transcription factor TCF21, and in work reported here extends these studies to investigate the mechanisms by which it interacts with the AP-1 transcription complex to regulate local epigenetic effects in these downstream coronary disease loci.
methodsGenomic studies, including chromatin immunoprecipitation sequencing, RNA sequencing, and protein-protein interaction studies, were performed in human coronary artery smooth muscle cells.
resultsWe show here that TCF21 and JUN regulate expression of two presumptive causal coronary disease genes, SMAD3 and CDKN2B-AS1, in part by interactions with histone deacetylases and acetyltransferases. Genome-wide TCF21 and JUN binding is jointly localized and particularly enriched in coronary disease loci where they broadly modulate H3K27Ac and chromatin state changes linked to disease-related processes in vascular cells. Heterozygosity at coronary disease causal variation, or genome editing of these variants, is associated with decreased binding of both JUN and TCF21 and loss of expression in cis, supporting a transcriptional mechanism for disease risk.
conclusionsThese data show that the known chromatin remodeling and pioneer functions of AP-1 are a pervasive aspect of epigenetic control of transcription, and thus, the risk in coronary disease-associated loci, and that interaction of AP-1 with TCF21 to control epigenetic features, contributes to the genetic risk in loci where they co-localize.
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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 Socratic graph.