Abstract：
As a widely distributed food-borne pathogenic fungus, Aspergillus flavus and its secondary metabolites, mainly aflatoxin B1 (AFB1), pose a great danger to humans. It is urgent to reveal the complex regulatory network of toxigenic and virulence of this fungus. The bio-function of Set9, a SET-domain-containing histone methyltransferase, is still unknown in A. flavus. By genetic engineering means, this study revealed that, through catalyzing H4K20me2 and -me3, Set9 is involved in fungal growth, reproduction, and mycotoxin production via the orthodox regulation pathway, and regulates fungal colonization on crop kernels through adjusting fungal sensitivity reactions to oxidation stress and cell wall integrity stress. Further domain deletion and point mutation inferred that the SET domain is the core element in catalyzing H4K20 methylation, and D200 site of the domain is the key amino acid in the active center of the methyltransferase. Combined with RNA-seq analysis, this study revealed that Set9 regulates the aflatoxin gene cluster by the AflR-like protein (ALP), other than traditional AflR. This study revealed the epigenetic regulation mechanism of fungal morphogenesis, secondary metabolism, and pathogenicity of A. flavus mediated by the H4K20-methyltransferase Set9, which might provide a potential new target for early prevention of contamination of A. flavus and its deadly mycotoxins.
摘要：
作为一种分布广泛的食源性病原真菌,黄曲霉及其次生代谢产物,主要是黄曲霉毒素B1（AFB1），对人类构成极大的危险。迫切需要揭示这种真菌的产毒和毒力的复杂调控网络。Set9，一种含有SET结构域的组蛋白甲基转移酶的生物功能，在A.flavus中仍然未知。通过基因工程手段,这项研究表明，通过催化H4K20me2和-me3，Set9参与真菌生长，繁殖，通过正统的调节途径产生霉菌毒素，并通过调节真菌对氧化胁迫和细胞壁完整性胁迫的敏感性反应来调节真菌在作物籽粒上的定植。进一步的结构域缺失和点突变推断SET结构域是催化H4K20甲基化的核心元件,域的D200位点是甲基转移酶活性中心的关键氨基酸。结合RNA-seq分析，这项研究表明，Set9通过AflR样蛋白（ALP）调节黄曲霉毒素基因簇，除了传统的阿弗拉。本研究揭示了真菌形态发生的表观遗传调控机制,次生代谢,和由H4K20-甲基转移酶Set9介导的黄曲霉的致病性，这可能为早期预防黄曲霉及其致命真菌毒素的污染提供潜在的新靶标。
