Fig. 6: Histone hyper-acetylation affects central carbon metabolism.
a Global metabolome analysis of cells of the indicated genotypes cultured in synthetic complete medium with normal glucose. Replicates were clustered by centered log2 metabolite intensities (n = 5–6 independent replicate cultures). b Classification of altered metabolites in sml1Δrad53Δ vs sml1Δ cells by HHT2 dependence and super-pathway. Alterations in glycolysis and TCA cycle are depicted. Significances were calculated by SAM (FDR < 0.1). c Jitter plots of total Ac-CoA levels from metabolomics data. The indicated genotypes are normalized by the average of the internal sml1Δ control strain. The mean values are represented by black bars. Significances were calculated by Kruskal–Wallis rank sum test (psml1Δrad53Δhht2Δ_sml1Δrad53Δ_sml1Δ = 0.0041), followed by Mann–Whitney test (two-sided) with Benjamini–Hochberg correction (psml1Δrad53Δ_vs_sml1Δ = 0.0043, psml1Δrad53Δhht2Δ_vs_sml1Δrad53Δ = 0.0043), or by Mann–Whitney test (psml1Δspt21S276A_vs_sml1Δ = 0.0022). n = 5 (sml1Δrad53Δhht2Δ) or 6 (other genotypes) independent culture replicates. d Heat map representing fatty-acid alterations from metabolomics data in cells with the indicated experimental vs control genotypes. Asterisks indicate significant alterations by SAM analysis (FDR < 0.1, q values are listed in Supplementary Table 4). e Heat map representing fatty-acid sterol synthesis and TCA cycle intermediate alterations from metabolomics data in cells with the indicated experimental vs control genotypes or conditions. Asterisks indicate significant alterations by SAM analysis (FDR < 0.1, q values are listed in Supplementary Table 5). f 107 cells/mL were serially diluted (1:6), spotted on YP plates with 0.01% glucose, with or without acetate, and grown for 2d. D glucose, DR glucose restriction (0.04% in liquid media), EtOH ethanol; Aux Auxin; tc tetracycline; Ac-CoA acetyl-coenzyme A; G6P glucose 6-phosphate; F6P fructose 6-phosphate; F1,6P2 fructose 1,6-bisphosphate; GA3P glyceraldehyde 3-phosphate; DHAP dihydroxyacetone phosphate; G1,3P2 1,3-bisphosphoglycerate; 3PG 3-phosphoglycerate; 2PG 2-phosphoglycerate; PEP phosphoenolpyruvate; FA fatty acids, 6PGA 6-phosphogluconate; R5P ribose 5-phosphate; HMG-CoA hydroxymethylglutaryl-Coenzyme A, TCA tricarboxylic acid. **p < 0.01, ***p < 0.001.
