ArticleCellular and molecular gastroenterology and hepatology2021
Wilson Disease: Intersecting DNA Methylation and Histone Acetylation Regulation of Gene Expression in a Mouse Model of Hepatic Copper Accumulation.
Article in Cellular and molecular gastroenterology and hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 22 citations in OpenAlex.
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Diagnostic and Prognostic Value of Epigenetic Markers in Neurological Diseases. A Narrative Review.Cellular and molecular neurobiology · 2026Review
- Inactivation of Atp7b Copper Transporter in Intestinal Epithelial Cells Is Associated with Altered Lipid Processing and Cell Growth Machinery Independent from Hepatic Copper Accumulation and Severity of Liver Histology.The American journal of pathology · 2026Article
- NADH-Reductive Stress Induced by Dihydrolipoamide Dehydrogenase Activation Contributes to Cuproptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Recent advances in research on high-frequency mutations in the ATP7B gene associated with Wilson disease in the Chinese population: from genetic evolution to precision medicine.Frontiers in molecular biosciences · 2026Review
- Multiscale computational genomics in Wilson disease: from atomic dynamics to clinical prediction.Frontiers in genetics · 2026Review
- Experimental models of hepatic injury in Wilson disease: stage-specific mechanisms and translational applications.Frontiers in immunology · 2026Review
- Epigenetic modification of cuproptosis by non-coding RNAs in cancer drug resistance.Molecular cancer · 2025Review
- The role of dysregulated copper metabolism in diabetes and its complications: a review.Frontiers in endocrinology · 2025Review
- Comparative review of copper-associated chronic hepatitis in dogs and Wilson disease in humans.Frontiers in veterinary science · 2025Review
- Mitochondrial pathways of copper neurotoxicity: focus on mitochondrial dynamics and mitophagy.Frontiers in molecular neuroscience · 2024Review
- Therapeutic implications of impaired nuclear receptor function and dysregulated metabolism in Wilson's disease.Pharmacology & therapeutics · 2023Review
- Wilson Disease: Update on Pathophysiology and Treatment.Frontiers in cell and developmental biology · 2022Review
- Dynamic and cell-specific transport networks for intracellular copper ions.Journal of cell science · 2021Review
- Wilson Disease: Epigenetic Factors Contribute to Genetic Mutations to Affect the Disease.Cellular and molecular gastroenterology and hepatology · 2021Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsThe pathogenesis of Wilson disease (WD) involves hepatic and brain copper accumulation resulting from pathogenic variants affecting the ATP7B gene and downstream epigenetic and metabolic mechanisms. Prior methylome investigations in human WD liver and blood and in the Jackson Laboratory (Bar Harbor, ME) C3He-Atp7b
methodsWe investigated class IIa HDAC4 and HDAC5 and H3K9/H3K27 histone acetylation in tx-j mouse livers compared with C3HeB/FeJ (C3H) control in response to 3 treatments: 60% kcal fat diet, D-penicillamine (copper chelator), and choline (methyl group donor). Experiments with copper-loaded hepatoma G2 cells were conducted to validate in vivo studies.
resultsIn 9-week tx-j mice, HDAC5 levels increased significantly after 8 days of a 60% kcal fat diet compared with chow. In 24-week tx-j mice, HDAC4/5 levels were reduced 5- to 10-fold compared with C3H, likely through mechanisms involving HDAC phosphorylation. HDAC4/5 levels were affected by disease progression and accompanied by increased acetylation. D-penicillamine and choline partially restored HDAC4/5 and H3K9ac/H3K27ac to C3H levels. Integrated RNA and chromatin immunoprecipitation sequencing analyses revealed genes regulating energy metabolism and cellular stress/development, which, in turn, were regulated by histone acetylation in tx-j mice compared with C3H mice, with Pparα and Pparγ among the most relevant targets.
conclusionsThese results suggest dietary modulation of class IIa HDAC4/5, and subsequent H3K9/H3K27 acetylation/deacetylation can regulate gene expression in key metabolic pathways in the pathogenesis of WD.
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