Acetic acid is a prevalent inhibitor
in lignocellulosic
hydrolysate,
which represses microbial growth and bioproduction. Histone modification
and chromatin remodeling have been revealed to be critical for regulating
eukaryotic metabolism. However, related studies in chronic acetic
acid stress responses remain unclear. Our previous studies revealed
that overexpression of the histone H4 methyltransferase Set5p enhanced
acetic acid stress tolerance of the budding yeast Saccharomyces
cerevisiae. In this study, we examined the role of Set5p
in acetic acid stress by analyzing global protein expression. Significant
activation of intracellular protein expression under the stress was
discovered, and the functions of the differential proteins were mainly
involved in chromatin modification, signal transduction, and carbohydrate
metabolism. Notably, a substantial increase of Set5p expression was
observed in response to acetic acid stress. Functional studies demonstrated
that the restriction of the telomere capping protein Rtc3p, as well
as Ies3p and Taf14p, which are related to chromatin regulation, was
critical for yeast stress response. This study enriches the understanding
of the epigenetic regulatory mechanisms underlying yeast stress response
mediated by histone-modifying enzymes. The results also benefit the
development of robust yeast strains for lignocellulosic bioconversion.