Cells experience a progressive decline in function and lifespan, accompanied by epigenetic changes. Here, we show that intracellular BCAA (icBCAA) homeostasis is regulated by histone H3K4 and H3K121 in budding yeast. Using a comprehensive H3/H4 mutant library, we identified residues essential for lifespan maintenance linked to BCAA metabolism. Among these, H3K4A/R and H3K121A mutations led to significant transcriptional changes in genes involved in BCAA biosynthesis and catabolism, accompanied by abnormally elevated icBCAA levels. Consistent with the upregulation of BAT1, ILV6, and ADH1 genes in the H3K121A mutant, chromatin immunoprecipitation revealed increased H3K4me3 at their promoters. The genetic perturbation of BAT1 and BAT2 restored icBCAA balance and partially rescued lifespan defects in H3K4 or H3K121 mutants. Additionally, H3K4 and H3K121 mutations affected lifespan regulation through TORC1 signaling. Our findings suggest that the epigenetic control of BCAA metabolism, specifically through the modification of histone residues, contributes to maintaining metabolic homeostasis and replicative lifespan.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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| Evidence ID | Analyze ID | File | Description |
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