ArticleNucleic acids research2024
ENL reads histone β-hydroxybutyrylation to modulate gene transcription.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Histone Post-Translational Modifications Regulating Ferroptosis: The Molecular Mechanisms and Disease Associations.Cell biochemistry and function · 2026Review
- A β-Hydroxybutyrylation-FOXM1/CENPA Axis Links Ketone-Body Metabolism to Mitotic Transcription in Basal-like Breast Cancer.International journal of molecular sciences · 2026Article
- The impact of microbial metabolites on host chromatin and epigenetic regulation.Nature metabolism · 2026Review
- Novel protein acylations in Alzheimer's disease: Molecular, mechanisms, biological significance, and diagnostic and therapeutic potentials.Journal of advanced research · 2026Review
- DeepKbhb: Context-Aware Prediction of Human Lysine β-Hydroxybutyrylation Sites.Journal of chemical information and modeling · 2026Article
- Chemical biology tools for studying histone post-translational modifications.Cell chemical biology · 2026Review
- Comprehensive Proteomics and β-Hydroxybutyrylation Profiling in Starvation-Induced Gastrocnemius Muscle Remodeling.Biology · 2026Article
- Post-translational acylation of proteins in cardiac hypertrophy.Nature reviews. Cardiology · 2025Review
- Short-chain acyl post-translational modifications in cancers: Mechanisms, roles, and therapeutic implications.Cancer communications (London, England) · 2025Review
- Reversible histone deacetylase activity catalyzes lysine acylation.Nature chemical biology · 2025Article
- Novel protein acylations in ferroptosis: decoding the regulatory roles of lactylation, crotonylation, succinylation, and β-hydroxybutyrylation.Frontiers in pharmacology · 2025Review
- From ketogenic metabolism to targeted therapeutics: current advances in β-hydroxybutyrylation.Frontiers in immunology · 2025Review
- Chromatin and transcription in Nucleic Acids Research: the first 50 years.Nucleic acids research · 2024Article
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Authors and funding
12 authors.
Funding
Abstract
Histone modifications are typically recognized by chromatin-binding protein modules (referred to as 'readers') to mediate fundamental processes such as transcription. Lysine β-hydroxybutyrylation (Kbhb) is a new type of histone mark that couples metabolism to gene expression. However, the readers that prefer histone Kbhb remain elusive. This knowledge gap should be filled in order to reveal the molecular mechanism of this epigenetic regulation. Herein, we developed a chemical proteomic approach, relying upon multivalent photoaffinity probes to capture binders of the mark, and identified ENL as a novel target of H3K9bhb. Biochemical studies and CUT&Tag analysis further suggested that ENL favorably binds to H3K9bhb, and co-localizes with it on promoter regions to modulate gene expression. Notably, disrupting the interaction between H3K9bhb and ENL via structure-based mutation led to the suppressed expression of genes such MYC that drive cell proliferation. Together, our work offered a chemoproteomics approach and identified ENL as a novel histone β-hydroxybutyrylation effector that regulates gene transcription, providing new insight into the regulation mechanism and function of histone Kbhb.
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Registered trials
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