ArticleNature chemical biology2025
Reversible histone deacetylase activity catalyzes lysine acylation.
Article in Nature chemical biology, 2025. 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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Who cites it
15 citing papers in PubMed.
- Ketogenic diet attenuates Müller cell activation and retinal neuroinflammation in autoimmune glaucoma through acetylation‑mediated FOXO signalling.International journal of molecular medicine · 2026Article
- Secondary-Amine Relay Enables Lysine-Directed Multicomponent Functionalization of Peptides.JACS Au · 2026Article
- Beyond acetylation: Evaluating the emerging biology of lysine acylation.Cell chemical biology · 2026Review
- Quinazolinone and Phthalazinone Inhibitors of the HDAC6/Ubiquitin Protein-Protein Interaction.Chembiochem : a European journal of chemical biology · 2026Article
- Chemical biology tools for studying histone post-translational modifications.Cell chemical biology · 2026Review
- The Expanding Landscape of ADP-Ribosylation: Protein, DNA, RNA, and Mitochondrial Regulation.Chemical research in toxicology · 2026Review
- Review
- Intermittent Fasting Enhances Genome Integrity and Cytoprotective Pathways via (BHB) β-Hydroxybutyrate Signaling and Chromatin Remodeling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Beyond hyperglycemia: histone modification-mediated epigenetic dysregulation in diabetic retinopathy and nephropathy.Diabetology & metabolic syndrome · 2026Review
- Quinazolinone and Phthalazinone Inhibitors of the HDAC6/Ubiquitin Protein-Protein Interaction.bioRxiv : the preprint server for biology · 2025Article
- Class I histone deacetylases catalyze lysine lactylation.The Journal of biological chemistry · 2025Article
- Article
- Sorbate induces lysine sorbylation through noncanonical activities of class I HDACs to regulate the expression of inflammation genes.Science advances · 2025Article
- From ketogenic metabolism to targeted therapeutics: current advances in β-hydroxybutyrylation.Frontiers in immunology · 2025Review
- The Roles of White Adipose Tissue and Liver NADPH in Dietary Restriction-Induced Longevity.Antioxidants (Basel, Switzerland) · 2024Review
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12 authors.
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Abstract
The dynamic modification of proteins by many metabolites suggests an intimate link between energy metabolism and post-translational modifications (PTMs). For instance, starvation and low-carbohydrate diets lead to the accumulation of β-hydroxybutyrate (BHB), whose blood concentrations can reach millimolar levels, concomitant with the accumulation of lysine β-hydroxybutyrylation (Kbhb) of proteins. Here we report that class I histone deacetylases (HDACs) unexpectedly catalyze the formation of Kbhb. Through mutational analysis, we show a shared reliance on key active site amino acids for classical deacetylation and noncanonical HDAC-catalyzed β-hydroxybutyrylation. On the basis of these data, we propose that HDACs catalyze a condensation reaction between the free amine group on lysine and the BHB carboxylic acid, thereby generating an amide bond. This reversible HDAC activity is not limited to BHB and extends to multiple short-chain fatty acids, representing a novel mechanism of PTM deposition relevant to metabolically sensitive proteome modifications.
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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.