ArticleJCI insight2017
MED12 regulates a transcriptional network of calcium-handling genes in the heart.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 31 citations in OpenAlex.
- Maternal Med12 safeguards trophoblast pluripotency and placental development.Biology of reproduction · 2026Article
- Chasing the Ghost Proteome in the Dark Matter.Molecular & cellular proteomics : MCP · 2025Review
- Med13 and Med13L: Critical redundant players in basal cardiac function and gene expression.Journal of molecular and cellular cardiology plus · 2025Article
- MED12 dysregulation: insights into cancer and therapeutic resistance.Naunyn-Schmiedeberg's archives of pharmacology · 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
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Hypoxia-responsive zinc finger E-box-binding homeobox 2 (ZEB2) regulates a network of calcium-handling genes in the injured heart.Cardiovascular research · 2024Article
- Novel insights into the phenotypic spectrum and pathogenesis of Hardikar syndrome.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Temporal regulation of the Mediator complex during muscle proliferation, differentiation, regeneration, aging, and disease.Frontiers in cell and developmental biology · 2024Article
- Novel pathogenic variant in MED12 causing non-syndromic dilated cardiomyopathy.BMC medical genomics · 2023Article
- Genetically Engineered Mice Unveil In Vivo Roles of the Mediator Complex.International journal of molecular sciences · 2023Review
- Article
- Comparing the epigenetic landscape in myonuclei purified with a PCM1 antibody from a fast/glycolytic and a slow/oxidative muscle.PLoS genetics · 2021Article
- Integrative analysis reveals essential mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) in paroxysmal and persistent atrial fibrillation patients.Anatolian journal of cardiology · 2021Article
- Transcriptome analysis reveals key pathways that vary in patients with paroxysmal and persistent atrial fibrillation.Experimental and therapeutic medicine · 2021Article
- Epigenetic Reader BRD4 (Bromodomain-Containing Protein 4) Governs Nucleus-Encoded Mitochondrial Transcriptome to Regulate Cardiac Function.Circulation · 2020Article
- Calcineurin Aβ-Specific Anchoring Confers Isoform-Specific Compartmentation and Function in Pathological Cardiac Myocyte Hypertrophy.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
- Regulation of cardiac transcription by thyroid hormone and Med13.Journal of molecular and cellular cardiology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The Mediator complex regulates gene transcription by linking basal transcriptional machinery with DNA-bound transcription factors. The activity of the Mediator complex is mainly controlled by a kinase submodule that is composed of 4 proteins, including MED12. Although ubiquitously expressed, Mediator subunits can differentially regulate gene expression in a tissue-specific manner. Here, we report that MED12 is required for normal cardiac function, such that mice with conditional cardiac-specific deletion of MED12 display progressive dilated cardiomyopathy. Loss of MED12 perturbs expression of calcium-handling genes in the heart, consequently altering calcium cycling in cardiomyocytes and disrupting cardiac electrical activity. We identified transcription factors that regulate expression of calcium-handling genes that are downregulated in the heart in the absence of MED12, and we found that MED12 localizes to transcription factor consensus sequences within calcium-handling genes. We showed that MED12 interacts with one such transcription factor, MEF2, in cardiomyocytes and that MED12 and MEF2 co-occupy promoters of calcium-handling genes. Furthermore, we demonstrated that MED12 enhances MEF2 transcriptional activity and that overexpression of both increases expression of calcium-handling genes in cardiomyocytes. Our data support a role for MED12 as a coordinator of transcription through MEF2 and other transcription factors. We conclude that MED12 is a regulator of a network of calcium-handling genes, consequently mediating contractility in the mammalian heart.
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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.