ArticlePloS one2016
Cardiomyocyte-Specific Ablation of Med1 Subunit of the Mediator Complex Causes Lethal Dilated Cardiomyopathy in Mice.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 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
27 citing papers in PubMed, 36 citations in OpenAlex.
- Diet-Associated Regulation of Cardiac Metabolism: Molecular Determinants and Pathophysiological Consequences.Nutrients · 2026Review
- Med13 and Med13L: Critical redundant players in basal cardiac function and gene expression.Journal of molecular and cellular cardiology plus · 2025Article
- Mediator complex: update of key insights into transcriptional regulation of ancestral framework and its role in cardiovascular diseases.European journal of medical research · 2025Review
- Differential regulation during development, aging, and disease implies heart cell specific functions of the Mediator Complex.Journal of molecular and cellular cardiology plus · 2025Article
- Novel pathogenic variant in MED12 causing non-syndromic dilated cardiomyopathy.BMC medical genomics · 2023Article
- Med25 Limits Master Regulators That Govern Adipogenesis.International journal of molecular sciences · 2023Article
- Cardiac-Specific Expression of Cre Recombinase Leads to Age-Related Cardiac Dysfunction Associated with Tumor-like Growth of Atrial Cardiomyocyte and Ventricular Fibrosis and Ferroptosis.International journal of molecular sciences · 2023Article
- Risk prediction model construction for post myocardial infarction heart failure by blood immune B cells.Frontiers in immunology · 2023Article
- 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
- Loss of the long non-coding RNA OIP5-AS1 exacerbates heart failure in a sex-specific manner.iScience · 2021Article
- MED1 Deficiency in Macrophages Accelerates Intimal Hyperplasia via ROS Generation and Inflammation.Oxidative medicine and cellular longevity · 2021Article
- Predictive Biomarkers for Postmyocardial Infarction Heart Failure Using Machine Learning: A Secondary Analysis of a Cohort Study.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Epigenetic Reader BRD4 (Bromodomain-Containing Protein 4) Governs Nucleus-Encoded Mitochondrial Transcriptome to Regulate Cardiac Function.Circulation · 2020Article
- Stress-Induced Cyclin C Translocation Regulates Cardiac Mitochondrial Dynamics.Journal of the American Heart Association · 2020Article
- Targeting transcriptional machinery to inhibit enhancer-driven gene expression in heart failure.Heart failure reviews · 2019Review
- Disruption of cardiac Med1 inhibits RNA polymerase II promoter occupancy and promotes chromatin remodeling.American journal of physiology. Heart and circulatory physiology · 2019Article
- Non-traumatic and non-drug-induced rhabdomyolysis.Archives of medical sciences. Atherosclerotic diseases · 2019Article
- Cardiac proteomics reveals the potential mechanism of microtubule associated protein 4 phosphorylation-induced mitochondrial dysfunction.Burns & trauma · 2019Article
- MicroRNA-146a protects against myocardial ischaemia reperfusion injury by targeting Med1.Cellular & molecular biology letters · 2019Article
- Mouse Cardiac Pde1C Is a Direct Transcriptional Target of Pparα.International journal of molecular sciences · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Mediator, an evolutionarily conserved multi-protein complex consisting of about 30 subunits, is a key component of the polymerase II mediated gene transcription. Germline deletion of the Mediator subunit 1 (Med1) of the Mediator in mice results in mid-gestational embryonic lethality with developmental impairment of multiple organs including heart. Here we show that cardiomyocyte-specific deletion of Med1 in mice (csMed1-/-) during late gestational and early postnatal development by intercrossing Med1fl/fl mice to α-MyHC-Cre transgenic mice results in lethality within 10 days after weaning due to dilated cardiomyopathy-related ventricular dilation and heart failure. The csMed1-/- mouse heart manifests mitochondrial damage, increased apoptosis and interstitial fibrosis. Global gene expression analysis revealed that loss of Med1 in heart down-regulates more than 200 genes including Acadm, Cacna1s, Atp2a2, Ryr2, Pde1c, Pln, PGC1α, and PGC1β that are critical for calcium signaling, cardiac muscle contraction, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy and peroxisome proliferator-activated receptor regulated energy metabolism. Many genes essential for oxidative phosphorylation and proper mitochondrial function such as genes coding for the succinate dehydrogenase subunits of the mitochondrial complex II are also down-regulated in csMed1-/- heart contributing to myocardial injury. Data also showed up-regulation of about 180 genes including Tgfb2, Ace, Atf3, Ctgf, Angpt14, Col9a2, Wisp2, Nppa, Nppb, and Actn1 that are linked to cardiac muscle contraction, cardiac hypertrophy, cardiac fibrosis and myocardial injury. Furthermore, we demonstrate that cardiac specific deletion of Med1 in adult mice using tamoxifen-inducible Cre approach (TmcsMed1-/-), results in rapid development of cardiomyopathy and death within 4 weeks. We found that the key findings of the csMed1-/- studies described above are highly reproducible in TmcsMed1-/- mouse heart. Collectively, these observations suggest that Med1 plays a critical role in the maintenance of heart function impacting on multiple metabolic, compensatory and reparative pathways with a likely therapeutic potential in the management of heart failure.
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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.