ArticleProceedings of the National Academy of Sciences of the United States of America2019
2-hydroxyglutarate inhibits MyoD-mediated differentiation by preventing H3K9 demethylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Meta-analysis of whole-genome gene expression datasets assessing the effects of IDH1 and IDH2 mutations in isogenic disease models.Scientific reports · 2022Pooled it
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- Mitochondrial ATP production promotes T cell differentiation and function by regulating chromatin accessibility.bioRxiv : the preprint server for biology · 2026Article
- Nuclear-localized metabolic enzymes: emerging key players in tumor epigenetic regulation.Molecular and cellular biochemistry · 2025Review
- Review
- Oncogenic IDH1Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Isocitrate Dehydrogenase Mutations in Cancer: Mechanisms of Transformation and Metabolic Liability.Cold Spring Harbor perspectives in medicine · 2024Review
- Identification of mIDH1 R132C/S280F Inhibitors from Natural Products by Integrated Molecular Docking, Pharmacophore Modeling and Molecular Dynamics Simulations.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Metabolic regulation of the hallmarks of stem cell biology.Cell stem cell · 2024Review
- 2-Hydroxyglutarate modulates histone methylation at specific loci and alters gene expression via Rph1 inhibition.Life science alliance · 2024Article
- Review
- Methionine availability influences essential H3K36me3 dynamics during cell differentiation.bioRxiv : the preprint server for biology · 2023Article
- The curious case of IDH mutant acute myeloid leukaemia: biochemistry and therapeutic approaches.Biochemical Society transactions · 2023Review
- Oncogenic IDH mutations increase heterochromatin-related replication stress without impacting homologous recombination.Molecular cell · 2023Article
- Review
- Renal oncometabolite L-2-hydroxyglutarate imposes a block in kidney tubulogenesis: Evidence for an epigenetic basis for the L-2HG-induced impairment of differentiation.Frontiers in endocrinology · 2022Article
- Metabolic Remodeling Impacts the Epigenetic Landscape of Dental Mesenchymal Stem Cells.Stem cells international · 2022Review
- Metabolism navigates neural cell fate in development, aging and neurodegeneration.Disease models & mechanisms · 2021Review
- Intergenerational trauma transmission is associated with brain metabotranscriptome remodeling and mitochondrial dysfunction.Communications biology · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Oncogenic IDH1/2 mutations produce 2-hydroxyglutarate (2HG), resulting in competitive inhibition of DNA and protein demethylation. IDH-mutant cancer cells show an inability to differentiate but whether 2HG accumulation is sufficient to perturb differentiation directed by lineage-specifying transcription factors is unknown. A MyoD-driven model was used to study the role of IDH mutations in the differentiation of mesenchymal cells. The presence of 2HG produced by oncogenic IDH2 blocks the ability of MyoD to drive differentiation into myotubes. DNA 5mC hypermethylation is dispensable while H3K9 hypermethylation is required for this differentiation block. IDH2-R172K mutation results in H3K9 hypermethylation and impaired accessibility at myogenic chromatin regions but does not result in genome-wide decrease in accessibility. The results demonstrate the ability of the oncometabolite 2HG to block transcription factor-mediated differentiation in a molecularly defined system.
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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.