Point mutation of H3/H4 histones affects acetic acid tolerance in Saccharomyces cerevisiae

• Effects of histone H3/H4 mutations on yeast acetic acid tolerance were examined.
• Effects of histone H3/H4 mutations on yeast acetic acid tolerance were examined.
• Six histone H3/H4 acetic acid-resistant mutants in yeast were identified.
• Improved ethanol fermentation under acetic acid stress using histone H3/H4 mutants.
• Transcriptome analysis of histone H3/H4 mutants in response to acetic acid stress.

The molecular mechanism of acetic acid tolerance in yeast remains unclear despite of its importance for efficient cellulosic ethanol production. In this study, we examined the effects of histone H3/H4 point mutations on yeast acetic acid tolerance by comprehensively screening a histone H3/H4 mutant library. A total of 24 histone H3/H4 mutants (six acetic acid resistant and 18 sensitive) were identified. Compared to the wild-type strain, the histone acetic acid-resistant mutants exhibited improved ethanol fermentation performance under acetic acid stress. Genome-wide transcriptome analysis revealed that changes in the gene expression in the acetic acid-resistant mutants H3 K37A and H4 K16Q were mainly related to energy production, antioxidative stress. Our results provide novel insights into yeast acetic acid tolerance on the basis of histone, and suggest a novel approach to improve ethanol production by altering the histone H3/H4 sequences.