Figure 2. Thermodynamic destabilization of the histone octamer correlates with lethal phenotypes in yeast.

A, Yeast strains bearing H3-H3′ interface mutations predicted to cause thermodynamic destabilization of the nucleosome are lethal. The WZY42 histone shuffle strain transformed with the wild-type or indicated H3 mutant was plated in 10-fold serial dilution on selective synthetic complete-Trp media with (right plate) or without (left plate) 5-Fluoroorotic acid (5-FOA). B, Broad analysis of growth phenotypes and their relation to predicted nucleosome stability reveal significant difference in ΔΔG between viable and lethal mutants. Box plots are shown, which represent range between 25 and 75 percentile values. Horizontal line inside the box represents the median. Whiskers correspond to values nearest to 1.5 times the interquartile range and outliers are represented as circles. P-value is obtained from two sample, single-tailed t-test. The dashed-line represents ΔΔG of 3kcal/mol, used to distinguish between stabilizing and destabilizing mutants. C, Venn diagram showing the significant overlap that exists between lethal and destabilizing mutants found in H3 and H4 for interface and buried residues. Compilation of lethal mutant results is from HistoneHits database. The numbers inside the Venn diagram refer to number of mutations belonging to the corresponding categories. D, Venn diagram showing the significant overlap that exists between viable and stabilizing mutants found in H3 and H4 for interface and buried residues. Compilation of lethal mutant results is from HistoneHits database. The numbers inside the Venn diagram refer to number of mutations belonging to the corresponding categories.