Abstract
Histone acetylation, which is critical for transcriptional regulation and various biological processes in eukaryotes, is a reversible dynamic process regulated by HATs and HDACs. This study determined the function of 6 histone acetyltransferases (HATs) (Gcn5, RTT109, Elp3, Sas3, Sas2, Nat3) and 6 histone deacetylases (HDACs) (Hos2, Rpd3, Hda1, Hos3, Hst2, Sir2) in the phytopathogenic fungus Alternaria alternata by analyzing targeted gene deletion mutants. Our data provide evidence that HATs and HDACs are both required for mycelium growth, cell development and pathogenicity as many gene deletion mutants (ΔGcn5, ΔRTT109, ΔElp3, ΔSas3, ΔNat3, ΔHos2, and ΔRpd3) displayed reduced growth, conidiation or virulence at varying degrees. In addition, HATs and HDACs are involved in the resistance to multiple stresses such as oxidative stress (Sas3, Gcn5, Elp3, RTT109, Hos2), osmotic stress (Sas3, Gcn5, RTT109, Hos2), cell wall-targeting agents (Sas3, Gcn5, Hos2), and fungicide (Gcn5, Hos2). ΔGcn5, ΔSas3, and ΔHos2 displayed severe growth defects on sole carbon source medium suggesting a vital role of HATs and HDACs in carbon source utilization. More SNPs were generated in ΔGcn5 in comparison to wild-type when they were exposed to ultraviolet ray. Moreover, ΔRTT109, ΔGcn5, and ΔHos2 showed severe defects in resistance to DNA-damaging agents, indicating the critical role of HATs and HDACs in DNA damage repair. These phenotypes correlated well with the differentially expressed genes in ΔGcn5 and ΔHos2 that are essential for carbon sources metabolism, DNA damage repair, ROS detoxification, and asexual development. Furthermore, Gcn5 is required for the acetylation of H3K4. Overall, our study provides genetic evidence to define the central role of HATs and HDACs in the pathological and biological functions of A. alternata.
Highlights
The fundamental structural subunit of the chromatin is the nucleosome, which consists of approximately 200 bp of DNA wrapped around an octamer of core histone proteins H2A, H2B, H3, and H4 (Kornberg and Lorch, 1999)
Mapping these histone acetyltransferases (HATs) and histone deacetylases (HDACs) to chromosomes revealed that all 13 genes are localized in the essential chromosomes, whereas no HATs or HDACs were identified in conditionally dispensable chromosomes (CDC) (Supplementary Figure 1)
Histone acetylation, which is important for multiple cellular processes, occurs in different organisms ranging from fungi to mammals, and the acetylation level manifested by HATs and HDACs dynamically changes over time during development and differentiation (Lee and Workman, 2007; Kong et al, 2018)
Summary
The fundamental structural subunit of the chromatin is the nucleosome, which consists of approximately 200 bp of DNA wrapped around an octamer of core histone proteins H2A, H2B, H3, and H4 (Kornberg and Lorch, 1999). The reversible acetylation of specific lysine residues in N-terminal tails of core histones is maintained by histone acetyltransferases (HATs) and histone deacetylases (HDACs) and has been found to play a pivotal role in chromatin-regulated DNA events, such as DNA replication, damage repair, recombination, and gene expression in eukaryotes (Lee and Workman, 2007; Yang and Seto, 2008). H3K56ac regulates expression homeostasis and resistance to DNA-damaging agents (Masumoto et al, 2005; Ozdemir et al, 2005; Han et al, 2007; Voichek et al, 2016) Both Sas and Esa belong to MYST family, which function as the subunits of Nucleosome Acetyltransferase of histone H3 (NuA3) and H4 (NuA4) complexes, respectively (Lee and Workman, 2007). Yeast Sir acts as anti-aging gene required for cellular lifespan regulation by caloric restriction (Lin et al, 2000; Dang et al, 2009)
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