ArticlePLoS genetics2011
A new isoform of the histone demethylase JMJD2A/KDM4A is required for skeletal muscle differentiation.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 72 citations in OpenAlex.
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- The Functions and Regulatory Mechanisms of Histone Modifications in Skeletal Muscle Development and Disease.International journal of molecular sciences · 2025Review
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- Epigenetic control of skeletal muscle atrophy.Cellular & molecular biology letters · 2024Review
- Oncogenic Cells of Renal Embryonic Lineage Sensitive to the Small-Molecule Inhibitor QC6352 Display Depletion of KDM4 Levels and Disruption of Ribosome Biogenesis.Molecular cancer therapeutics · 2024Article
- The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities.Genes & diseases · 2024Review
- Lysine methylation signaling in skeletal muscle biology: from myogenesis to clinical insights.The Biochemical journal · 2023Review
- SET domain containing 2 (SETD2) influences metabolism and alternative splicing during myogenesis.The FEBS journal · 2022Article
- Recent Advances with KDM4 Inhibitors and Potential Applications.Journal of medicinal chemistry · 2022Review
- Epigenetic Control of Muscle Stem Cells: Focus on Histone Lysine Demethylases.Frontiers in cell and developmental biology · 2022Review
- SUV39H2 controls trophoblast stem cell fate.Biochimica et biophysica acta. General subjects · 2021Article
- KDM4A regulates myogenesis by demethylating H3K9me3 of myogenic regulatory factors.Cell death & disease · 2021Article
- Article
- Epigenetic modifications in muscle regeneration and progression of Duchenne muscular dystrophy.Clinical epigenetics · 2021Review
- Histone demethylase JMJD2B/KDM4B regulates transcriptional program via distinctive epigenetic targets and protein interactors for the maintenance of trophoblast stem cells.Scientific reports · 2021Article
- Epigenetic regulation of satellite cell fate during skeletal muscle regeneration.Skeletal muscle · 2021Review
- KDM4 Involvement in Breast Cancer and Possible Therapeutic Approaches.Frontiers in oncology · 2021Review
- Histone Lysine Methylation and Long Non-Coding RNA: The New Target Players in Skeletal Muscle Cell Regeneration.Frontiers in cell and developmental biology · 2021Review
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In proliferating myoblasts, muscle specific genes are silenced by epigenetic modifications at their promoters, including histone H3K9 methylation. Derepression of the promoter of the gene encoding the myogenic factor myogenin (Myog) is key for initiation of muscle differentiation. The mechanism of H3K9 demethylation at the Myog promoter is unclear, however. Here, we identify an isoform of the histone demethylase JMJD2A/KDM4A that lacks the N-terminal demethylase domain (ΔN-JMJD2A). The amount of ΔN-JMJD2A increases during differentiation of C2C12 myoblasts into myotubes. Genome-wide expression profiling and exon-specific siRNA knockdown indicate that, in contrast to the full-length protein, ΔN-JMJD2A is necessary for myotube formation and muscle-specific gene expression. Moreover, ΔN-JMJD2A promotes MyoD-induced conversion of NIH3T3 cells into muscle cells. ChIP-on-chip analysis indicates that ΔN-JMJD2A binds to genes mainly involved in transcriptional control and that this binding is linked to gene activation. ΔN-JMJD2A is recruited to the Myog promoter at the onset of differentiation. This binding is essential to promote the demethylation of H3K9me2 and H3K9me3. We conclude that induction of the ΔN-JMJD2A isoform is crucial for muscle differentiation: by directing the removal of repressive chromatin marks at the Myog promoter, it promotes transcriptional activation of the Myog gene and thus contributes to initiation of muscle-specific gene expression.
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