ArticleThe Journal of clinical investigation2020
Histone methyltransferase MLL4 controls myofiber identity and muscle performance through MEF2 interaction.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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.
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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.
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Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
- Multi-Omics Insights Into the Mechanisms of Early Muscle Fiber Difference and Transformation Between Lean-Type and Chinese Indigenous Pigs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ChREBP Is Dispensable for Myofiber Type Switch but Promotes Skeletal Muscle Regeneration.Nutrients · 2026Article
- BRD4 directs myofiber identity and metabolic adaptation through CHD4 cooperation.Nature communications · 2026Article
- Sex- and skeletal muscle-specific gene expression response of histone 3 lysine 27-modifying enzymes by voluntary running in mice.Physiological reports · 2026Article
- LNC297 promotes BMSCs differentiation and alleviates BHBA-induced inhibition through the miR-145/GAS7 axis.PloS one · 2026Article
- Enhancer regulator MLL4 controls skeletal muscle metabolic efficiency by limiting AMPK-mediated fuel catabolism.Nature communications · 2025Article
- Molecular Framework of the Onset and Progression of Skeletal Muscle Aging.International journal of molecular sciences · 2025Review
- Glucose-Responsive PAGR1-Regulated Skeletal Muscle Gene Program Controls Systemic Glucose Homeostasis and Hepatic Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Epigenetic Changes Associated With Obesity-related Metabolic Comorbidities.Journal of the Endocrine Society · 2025Review
- CircGLIS3 Inhibits Intramuscular Adipogenesis and Alleviates Skeletal Muscle Fat Infiltration.Journal of cachexia, sarcopenia and muscle · 2025Article
- Large MAF transcription factors reawaken evolutionarily dormant fast-glycolytic type IIb myofibers in human skeletal muscle.Skeletal muscle · 2025Article
- Article
- Epigenetic Mechanisms in Heart Diseases.Reviews in cardiovascular medicine · 2025Review
- Article
- Transcriptional regulation of adipocyte lipolysis by IRF2BP2.Science advances · 2025Article
- Ucp1 Ablation Improves Skeletal Muscle Glycolytic Function in Aging Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mll4 in skeletal muscle fibers maintains muscle stem cells.Skeletal muscle · 2024Article
- Functional study of theHeliyon · 2024Article
- Endurance exercise-induced histone methylation modification involved in skeletal muscle fiber type transition and mitochondrial biogenesis.Scientific reports · 2024Article
- Epigenetic control of skeletal muscle atrophy.Cellular & molecular biology letters · 2024Review
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
Skeletal muscle depends on the precise orchestration of contractile and metabolic gene expression programs to direct fiber-type specification and to ensure muscle performance. Exactly how such fiber type-specific patterns of gene expression are established and maintained remains unclear, however. Here, we demonstrate that histone monomethyl transferase MLL4 (KMT2D), an enhancer regulator enriched in slow myofibers, plays a critical role in controlling muscle fiber identity as well as muscle performance. Skeletal muscle-specific ablation of MLL4 in mice resulted in downregulation of the slow oxidative myofiber gene program, decreased numbers of type I myofibers, and diminished mitochondrial respiration, which caused reductions in muscle fatty acid utilization and endurance capacity during exercise. Genome-wide ChIP-Seq and mRNA-Seq analyses revealed that MLL4 directly binds to enhancers and functions as a coactivator of the myocyte enhancer factor 2 (MEF2) to activate transcription of slow oxidative myofiber genes. Importantly, we also found that the MLL4 regulatory circuit is associated with muscle fiber-type remodeling in humans. Thus, our results uncover a pivotal role for MLL4 in specifying structural and metabolic identities of myofibers that govern muscle performance. These findings provide therapeutic opportunities for enhancing muscle fitness to combat a variety of metabolic and muscular diseases.
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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.