ArticlePloS one2013
Mutations in Mll2, an H3K4 methyltransferase, result in insulin resistance and impaired glucose tolerance in mice.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 45 citations in OpenAlex.
- Histone lactylation: A key epigenetic modulator in the pathogenesis of metabolic dysfunction-associated steatohepatitis and alcoholic steatohepatitis.World journal of hepatology · 2025Review
- Molecular Framework of the Onset and Progression of Skeletal Muscle Aging.International journal of molecular sciences · 2025Review
- trithorax is an essential regulator of cardiac Hox gene expression and anterior-posterior patterning of the Drosophila embryonic heart tube.Biology open · 2025Article
- Clinical and pathological characteristics of metabolic dysfunction-associated steatotic liver disease and the key role of epigenetic regulation: implications for molecular mechanism and treatment.Therapeutic advances in endocrinology and metabolism · 2025Review
- Free amino acids accelerate the time-dependent inactivation of rat liver nucleotide pyrophosphatase/phosphodiesterase Enpp3 elicited by EDTA.Amino acids · 2024Article
- Roles of Lysine Methylation in Glucose and Lipid Metabolism: Functions, Regulatory Mechanisms, and Therapeutic Implications.Biomolecules · 2024Review
- Unraveling the relationship between histone methylation and nonalcoholic fatty liver disease.World journal of hepatology · 2024Review
- KMT2 Family of H3K4 Methyltransferases: Enzymatic Activity-dependent and -independent Functions.Journal of molecular biology · 2024Review
- Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- Histone Modifications in NAFLD: Mechanisms and Potential Therapy.International journal of molecular sciences · 2023Review
- Epigenetic modifications in pancreas development, diabetes, and therapeutics.Medicinal research reviews · 2022Review
- Diabetes mellitus and insulin resistance associated with Kabuki syndrome-A case report and literature review.Clinical case reports · 2022Article
- Metabolic and Epigenetic Regulation by Estrogen in Adipocytes.Frontiers in endocrinology · 2022Review
- Histone Methylation Related Therapeutic Challenge in Cardiovascular Diseases.Frontiers in cardiovascular medicine · 2021Review
- Epigenetics and Beyond: Targeting Histone Methylation to Treat Type 2 Diabetes Mellitus.Frontiers in pharmacology · 2021Review
- Epigenetics of Hepatic Insulin Resistance.Frontiers in endocrinology · 2021Review
- Epigenetic Regulation of Adipogenesis in Development of Metabolic Syndrome.Frontiers in cell and developmental biology · 2020Review
- Update on KMT2B-Related Dystonia.Current neurology and neuroscience reports · 2019Review
- The Lysine Demethylase KDM5B Regulates Islet Function and Glucose Homeostasis.Journal of diabetes research · 2019Article
- Epigenetics of metabolic syndrome.Physiological genomics · 2018Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
We employed a random mutagenesis approach to identify novel monogenic determinants of type 2 diabetes. Here we show that haplo-insufficiency of the histone methyltransferase myeloid-lineage leukemia (Mll2/Wbp7) gene causes type 2 diabetes in the mouse. We have shown that mice heterozygous for two separate mutations in the SET domain of Mll2 or heterozygous Mll2 knockout mice were hyperglycaemic, hyperinsulinaemic and developed non-alcoholic fatty liver disease. Consistent with previous Mll2 knockout studies, mice homozygous for either ENU mutation (or compound heterozygotes) died during embryonic development at 9.5-14.5 days post coitum. Heterozygous deletion of Mll2 induced in the adult mouse results in a normal phenotype suggesting that changes in chromatin methylation during development result in the adult phenotype. Mll2 has been shown to regulate a small subset of genes, a number of which Neurod1, Enpp1, Slc27a2, and Plcxd1 are downregulated in adult mutant mice. Our results demonstrate that histone H3K4 methyltransferase Mll2 is a component of the genetic regulation necessary for glucose homeostasis, resulting in a specific disease pattern linking chromatin modification with causes and progression of type 2 diabetes, providing a basis for its further understanding at the molecular level.
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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.