ArticleGenes & development2011
DOT1L regulates dystrophin expression and is critical for cardiac function.
Article in Genes & development, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
90 citing papers in PubMed, 152 citations in OpenAlex.
- Review
- Cardiac epigenome in heart development and disease.Nature reviews. Cardiology · 2026Review
- Epigenetics, Modifiers, and Molecular Noise: Rethinking Pathophysiology in Dilated and Hypertrophic Cardiomyopathies.International journal of molecular sciences · 2026Review
- Loss of DOT1L disrupts neuronal transcription and leads to a neurodevelopmental disorder.Brain : a journal of neurology · 2026Article
- Methylation-centric epigenetic regulation in dilated cardiomyopathy: mechanisms, metabolic interplay, and translational potential.Frontiers in cardiovascular medicine · 2026Review
- Epigenetic regulation of cardiac physiology and pathophysiology: biological sex matters.The journal of cardiovascular aging · 2026Article
- Orphan Nuclear Receptor NR4A1 Promotes Proliferation and Osteogenic Differentiation of Valvular Interstitial Cells through Activation of CCND2.International journal of biological sciences · 2026Article
- Epigenetic Mechanisms in Heart Diseases.Reviews in cardiovascular medicine · 2025Review
- Loss of DOT1L disrupts neuronal transcription, behavior, and leads to a neurodevelopmental disorder.medRxiv : the preprint server for health sciences · 2025Article
- DOT1L Mediates Stem Cell Maintenance and Represents a Therapeutic Vulnerability in Cancer.Cancer research · 2025Review
- Putative Epigenetic Regulator microRNAs (epi-miRNAs) and Their Predicted Targets in High-Fat Diet-Induced Cardiac Dysfunction: An In Silico Analysis in Obese Rats.International journal of molecular sciences · 2025Article
- Review
- The role of the gut microbiota in the onset and progression of heart failure: insights into epigenetic mechanisms and aging.Clinical epigenetics · 2024Review
- Epigenetic regulation of sex dimorphism in cardiovascular health.Canadian journal of physiology and pharmacology · 2024Review
- DOT1-like histone lysine methyltransferase is critical for adult vessel maintenance and functions.Animal bioscience · 2024Article
- DOT1L-mediated RAP80 methylation promotes BRCA1 recruitment to elicit DNA repair.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Epigenetic control of skeletal muscle atrophy.Cellular & molecular biology letters · 2024Review
- Hallmarks of cardiovascular ageing.Nature reviews. Cardiology · 2023Review
- The effect of ITLN1, XCL2 and DOT1L variants on knee osteoarthritis risk in the Han population.Archives of orthopaedic and trauma surgery · 2023Article
- The Roles of Histone Lysine Methyltransferases in Heart Development and Disease.Journal of cardiovascular development and disease · 2023Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Histone methylation plays an important role in regulating gene expression. One such methylation occurs at Lys 79 of histone H3 (H3K79) and is catalyzed by the yeast DOT1 (disruptor of telomeric silencing) and its mammalian homolog, DOT1L. Previous studies have demonstrated that germline disruption of Dot1L in mice resulted in embryonic lethality. Here we report that cardiac-specific knockout of Dot1L results in increased mortality rate with chamber dilation, increased cardiomyocyte cell death, systolic dysfunction, and conduction abnormalities. These phenotypes mimic those exhibited in patients with dilated cardiomyopathy (DCM). Mechanistic studies reveal that DOT1L performs its function in cardiomyocytes through regulating Dystrophin (Dmd) transcription and, consequently, stability of the Dystrophin-glycoprotein complex important for cardiomyocyte viability. Importantly, expression of a miniDmd can largely rescue the DCM phenotypes, indicating that Dmd is a major target mediating DOT1L function in cardiomyocytes. Interestingly, analysis of available gene expression data sets indicates that DOT1L is down-regulated in idiopathic DCM patient samples compared with normal controls. Therefore, our study not only establishes a critical role for DOT1L-mediated H3K79 methylation in cardiomyocyte function, but also reveals the mechanism underlying the role of DOT1L in DCM. In addition, our study may open new avenues for the diagnosis and treatment of human heart disease.
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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.