ArticleMolecular cell2024
Acetyl-CoA production by Mediator-bound 2-ketoacid dehydrogenases boosts de novo histone acetylation and is regulated by nitric oxide.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Nitric oxide-driven Warburg reprogramming at the NOS2-COX2 axis: An integrative engine of cancer hallmarks.Redox biology · 2026Review
- Article
- Spatial architecture of immunometabolism: Mitochondrial‑organelle interfaces in immune signaling (Review).International journal of molecular medicine · 2026Review
- Defective branched-chain amino acid catabolism promotes pulmonary fibrosis by inducing apoptosis resistance of myofibroblasts in mice.Cell communication and signaling : CCS · 2026Article
- Hallmarks of nuclear metabolism: implications for genome integrity, nuclear signaling, and therapeutic targeting.npj metabolic health and disease · 2026Review
- Reciprocal control of metabolic and chromatin regulators improves rice tolerance to heat.Nature communications · 2025Article
- TCA-cycle metabolites in the nucleus: drivers of chromatin and epigenetic control.BMC biology · 2025Review
- Dendritic cells: understanding ontogeny, subsets, functions, and their clinical applications.Molecular biomedicine · 2025Review
- ACSS2 coupled with KAT7 regulates histone β-hydroxybutyrylation to enhance transcription.Science advances · 2025Article
- Palmitic Acid Induces Dynamic Time-Dependent Alterations in HDACs, Neuronal Chromatin Acetylation, and Gene Expression.Neurochemical research · 2025Article
- Mechanisms of metabolism-coupled protein modifications.Nature chemical biology · 2025Review
- A narrative review of epigenetic marker in H3K27ac and its emerging potential as a therapeutic target in cancer.Epigenomics · 2025Review
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- The role and regulatory mechanisms of the TCA cycle in early embryonic development.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
Histone-modifying enzymes depend on the availability of cofactors, with acetyl-coenzyme A (CoA) being required for histone acetyltransferase (HAT) activity. The discovery that mitochondrial acyl-CoA-producing enzymes translocate to the nucleus suggests that high concentrations of locally synthesized metabolites may impact acylation of histones and other nuclear substrates, thereby controlling gene expression. Here, we show that 2-ketoacid dehydrogenases are stably associated with the Mediator complex, thus providing a local supply of acetyl-CoA and increasing the generation of hyper-acetylated histone tails. Nitric oxide (NO), which is produced in large amounts in lipopolysaccharide-stimulated macrophages, inhibited the activity of Mediator-associated 2-ketoacid dehydrogenases. Elevation of NO levels and the disruption of Mediator complex integrity both affected de novo histone acetylation within a shared set of genomic regions. Our findings indicate that the local supply of acetyl-CoA generated by 2-ketoacid dehydrogenases bound to Mediator is required to maximize acetylation of histone tails at sites of elevated HAT activity.
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Registered trials
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