Histone deacetylase HDAC3 regulates ergosterol production for oxidative stress tolerance in the entomopathogenic and endophytic fungus .

Oxidative stress is encountered by fungi in almost all niches, resulting in fungal degeneration or even death. Fungal tolerance to oxidative stress has been extensively studied, but the current understanding of the mechanisms regulating oxidative stress tolerance in fungi remains limited. The entomopathogenic and endophytic fungus encounters oxidative stress when it infects insects and develops a symbiotic relationship with plants, and we found that host reactive oxygen species (ROSs) greatly limited fungal growth in both insects and plants. We identified a histone H3 deacetylase (HDAC3) that catalyzed the deacetylation of lysine 56 of histone H3. Deleting significantly reduced the tolerance of to oxidative stress from insects and plants, thereby decreasing fungal ability to colonize the insect hemocoel and plant roots. HDAC3 achieved this by regulating the expression of three genes in the ergosterol biosynthesis pathway, which includes the lanosterol synthase gene . The deletion of or reduced the ergosterol content and impaired cell membrane integrity. This resulted in an increase in ROS accumulation in fungal cells that were thus more sensitive to oxidative stress. We further showed that HDAC3 regulated the expression of the three ergosterol biosynthesis genes in an indirect manner. Our work significantly advances insights into the epigenetic regulation of oxidative stress tolerance and the interactions between and its plant and insect hosts.IMPORTANCEOxidative stress is a common challenge encountered by fungi that have evolved sophisticated mechanisms underlying tolerance to this stress. Although fungal tolerance to oxidative stress has been extensively investigated, the current understanding of the mechanisms for fungi to regulate oxidative stress tolerance remains limited. In the model entomopathogenic and plant symbiotic fungus , we found that the histone H3 deacetylase HDAC3 regulates the production of ergosterol, an essential cell membrane component. This maintains the cell membrane integrity to resist the oxidative stress derived from the insect and plant hosts for successful infection of insects and development of symbiotic associates with plants. Our work provides significant insights into the regulation of oxidative stress tolerance in and its interactions with insects and plants.