ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2009
The deacetylase HDAC4 controls myocyte enhancing factor-2-dependent structural gene expression in response to neural activity.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 85 citations in OpenAlex.
- Pronounced effects of acute endurance exercise on gene expression in resting and exercising human skeletal muscle.PloS one · 2012Trial
- CtBP1 sustains activity-dependent muscle properties and dampens synaptic, contractile and metabolic changes triggered by denervation.Skeletal muscle · 2026Article
- Epigenetic control of skeletal muscle atrophy.Cellular & molecular biology letters · 2024Review
- CaMKIIβ deregulation contributes to neuromuscular junction destabilization in Myotonic Dystrophy type I.Skeletal muscle · 2024Article
- Article
- Structural insights into the HDAC4-MEF2A-DNA complex and its implication in long-range transcriptional regulation.Nucleic acids research · 2024Article
- Identification of a muscle-specific isoform of VMA21 as a potent actor in X-linked myopathy with excessive autophagy pathogenesis.Human molecular genetics · 2023Article
- HDAC4 Knockdown Alleviates Denervation-Induced Muscle Atrophy by Inhibiting Myogenin-Dependent Atrogene Activation.Frontiers in cellular neuroscience · 2021Article
- Molecular Mechanisms of Skeletal Muscle Hypertrophy.Journal of neuromuscular diseases · 2021Review
- MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease.Acta neuropathologica · 2020Article
- MEF2c-Dependent Downregulation of Myocilin Mediates Cancer-Induced Muscle Wasting and Associates with Cachexia in Patients with Cancer.Cancer research · 2020Article
- The first year.Acta neuropathologica · 2020Article
- The TOR Pathway at the Neuromuscular Junction: More Than a Metabolic Player?Frontiers in molecular neuroscience · 2020Review
- The Enigmatic Canal-Associated Neurons RegulateGenetics · 2019Article
- mTORC1 and PKB/Akt control the muscle response to denervation by regulating autophagy and HDAC4.Nature communications · 2019Article
- Signal Exchange through Extracellular Vesicles in Neuromuscular Junction Establishment and Maintenance: From Physiology to Pathology.International journal of molecular sciences · 2019Review
- miR-378a-3p promotes differentiation and inhibits proliferation of myoblasts by targeting HDAC4 in skeletal muscle development.RNA biology · 2016Article
- G9a inhibits MEF2C activity to control sarcomere assembly.Scientific reports · 2016Article
- Properties of skeletal muscle in the teleost Sternopygus macrurus are unaffected by short-term electrical inactivity.Physiological genomics · 2016Article
- Long-Term Memory in Drosophila Is Influenced by Histone Deacetylase HDAC4 Interacting with SUMO-Conjugating Enzyme Ubc9.Genetics · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Histone deacetylase 4 (HDAC4) binds and inhibits activation of the critical muscle transcription factor myocyte enhancer factor-2 (MEF2). However, the physiological significance of the HDAC4-MEF2 complex in skeletal muscle has not been established. Here we show that in skeletal muscle, HDAC4 is a critical modulator of MEF2-dependent structural and contractile gene expression in response to neural activity. We present evidence that loss of neural input leads to concomitant nuclear accumulation of HDAC4 and transcriptional reduction of MEF2-regulated gene expression. Cell-based assays show that HDAC4 represses structural gene expression via direct binding to AT-rich MEF2 response elements. Notably, using both surgical denervation and the neuromuscular disease amyotrophic lateral sclerosis (ALS) model, we found that elevated levels of HDAC4 are required for efficient repression of MEF2-dependent structural gene expression, indicating a link between the pathological induction of HDAC4 and subsequent MEF2 target gene suppression. Supporting this supposition, we show that ectopic expression of HDAC4 in muscle fibers is sufficient to induce muscle damage in mice. Our study identifies HDAC4 as an activity-dependent regulator of MEF2 function and suggests that activation of HDAC4 in response to chronically reduced neural activity suppresses MEF2-dependent gene expression and contributes to progressive muscle dysfunction observed in neuromuscular 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.