Myst family is highly conserved histone acetyltransferases in eukaryotic cells and is known to play crucial roles in various cellular processes; however, acetylation catalysed by acetyltransferases is unclear in filamentous fungi. Here, we identified two classical nonessential Myst enzymes and analysed their functions in Aspergillus flavus, which generates aflatoxin B1, one of the most carcinogenic secondary metabolites. MystA and MystB located in nuclei and cytoplasm, and mystA could acetylate H4K16ac, while mystB acetylates H3K14ac, H3K18ac and H3K23ac. Deletion mystA resulted in decreased conidiation, increased sclerotia formation and aflatoxin production. Deletion of mystB leads to significant defects in conidiation, sclerotia formation and aflatoxin production. Additionally, double-knockout mutant (ΔmystA/mystB) display a stronger and similar defect to ΔmystB mutant, indicating that mystB plays a major role in regulating development and aflatoxin production. Both mystA and mystB play important role in crop colonization. Moreover, catalytic domain MOZ and the catalytic site E199/E243 were important for the acetyltransferase function of Myst. Notably, chromatin immunoprecipitation results indicated that mystB participated in oxidative detoxification by regulating the acetylation level of H3K14, and further regulated nsdD to affect sclerotia formation and aflatoxin production. This study provides new evidences to discover the biological functions of histone acetyltransferase in A. flavus.

中文翻译：

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组蛋白乙酰转移酶 MystA 和 MystB 通过调节真菌黄曲霉的乙酰化促进形态发生和黄曲霉毒素生物合成

Myst 家族是真核细胞中高度保守的组蛋白乙酰转移酶，已知在各种细胞过程中发挥关键作用；然而，丝状真菌中乙酰转移酶催化的乙酰化作用尚不清楚。在这里，我们鉴定了两种经典的非必需 Myst 酶，并分析了它们在黄曲霉中的功能，黄曲霉产生黄曲霉毒素 B1，黄曲霉毒素 B1 是最致癌的次生代谢物之一。MystA和MystB位于细胞核和细胞质中，mystA可以乙酰化H4K16ac，而mystB可以乙酰化H3K14ac、H3K18ac和H3K23ac。删除mystA导致分生孢子减少、菌核形成和黄曲霉毒素产生增加。删除mystB导致分生孢子、菌核形成和黄曲霉毒素产生的显着缺陷。此外，双敲除突变体（ΔmystA / mystB ）表现出与ΔmystB突变体更强且相似的缺陷，表明mystB在调节发育和黄曲霉毒素产生中起主要作用。mystA和mystB在作物定植中都发挥着重要作用。此外，催化结构域 MOZ 和催化位点 E199/E243 对 Myst 的乙酰转移酶功能很重要。值得注意的是，染色质免疫沉淀结果表明mystB通过调节 H3K14 的乙酰化水平参与氧化解毒，并进一步调节nsdD影响菌核形成和黄曲霉毒素的产生。该研究为发现A中组蛋白乙酰转移酶的生物学功能提供了新的证据。黄曲霉。