Liver injury induces intra-nuclear metabolic changes and histone hyper-acetylation. Nuclear (A) acetyl-CoA, (B) lactate, and (C) nHDAC activity in livers harvested 6 h after the injection of either saline or CD95-Ab (n = 3 per group). (D) Western blotting for acetylated histone H3 (H3K9) and H4 (H4K5) on livers harvested 6 h after the injections of either saline or CD95-Ab. Histone H3 and β-actin were used as loading controls. Each line corresponds to an independent mouse. (E) Affinity purification-liquid chromatography tandem-mass spectrometry of liver proteins enriched by immunoprecipitation with acetyl lysine-specific antibody revealed 13 proteins with fold-change >2 in CD95-Ab vs. saline liver samples (n = 5 per group). (F) Venn diagram including the 751 genes upregulated in livers of mice injected with CD95-Ab and the H3K9Ac ChIP-seq data on eight-week-old mouse livers in ENCODE showing a high degree of overlap (Hypergeometric test; p value: 9.643501e−58). (G) Chart generated using custom annotation scripts shows that response to external stimulus including inflammatory and defense response processes, and cytokine-cytokine receptor interaction pathways were enriched among the 467 genes overlapping between the two groups according to KEGG pathways. Means ± SDs are shown; t test; *p <0.05. Ab, antibody; nHDAC, nuclear histone deacetylase. (This figure appears in colour on the web.)