毒力的表观遗传调控和核糖体蛋白基因的转录涉及隐球菌中的 YEATS 家族蛋白,FEMS Yeast Research

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毒力的表观遗传调控和核糖体蛋白基因的转录涉及隐球菌中的 YEATS 家族蛋白
FEMS Yeast Research ( IF 2.4 ) Pub Date : 2021-01-13 , DOI: 10.1093/femsyr/foab001
Chenxi Li ₁ , Shaonan Hou ₁ , Xiaoyu Ma ₁ , Jiajia Li ₁ , Liang Huo ₁ , Ping Zhang ₁ , Xiaoran Hao ₁ , Xudong Zhu ₁

Affiliation

组蛋白上的表观遗传标记或翻译后修饰在真核生物的基因表达中具有重要的调节作用。致病性酵母隐球菌中基因表达的表观遗传调控在很大程度上仍未确定。YEATS 结构域蛋白是组蛋白中巴豆酰化赖氨酸残基的读取器。在这里，我们报道了单拷贝基因推测编码叶芝域蛋白（Yst1）中的鉴定Ç。去隐孢子虫。为了定义其功能，我们使用 CRISPR-Cas9 编辑创建了一个突变菌株yst1Δ。yst1Δ表现出表型缺陷，例如，它在 1.3 M NaCl 或 KCl 存在下对渗透压力过敏。此外，它对 1% 刚果红过敏，表明细胞壁存在缺陷。有趣的是，RNA-seq 数据显示 Yst1p 对编码核糖体蛋白的基因的表达至关重要，也就是说，大多数在yst1Δ中表达的 mRNA 水平显着低于野生型菌株。突变株对低温和抗核糖体药物过敏，我们推测这是由于核糖体功能受损。此外，yst1Δ菌株对大蜡螟的毒力较低. 这些结果通常表明，作为组蛋白修饰阅读器的 Yst1 可能是该人类病原体转录组的关键协调者。Yst1 可能是新型抗真菌药物的潜在靶点，这可能会导致隐球菌病临床治疗的重大进展。

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Epigenetic regulation of virulence and the transcription of ribosomal protein genes involves a YEATS family protein in Cryptococcus deneoformans

Epigenetic marks or post-translational modifications on histones have important regulatory roles in gene expression in eukaryotic organisms. The epigenetic regulation of gene expression in the pathogenic yeast Cryptococcus deneoformans remains largely undetermined. The YEATS domain proteins are readers of crotonylated lysine residues in histones. Here, we reported the identification of a single-copy gene putatively coding for a YEATS domain protein (Yst1) in C. deneoformans. To define its function, we created a mutant strain, yst1Δ, using CRISPR-Cas9 editing. yst1Δ exhibited defects in phenotype, for instance, it was hypersensitive to osmotic stress in the presence of 1.3 M NaCl or KCl. Furthermore, it was hypersensitive to 1% Congo red, suggesting defects in the cell wall. Interestingly, RNA-seq data revealed that Yst1p was critical for the expression of genes encoding the ribosomal proteins, that is, most were expressed with significantly lower levels of mRNA in yst1Δ than in the wild-type strain. The mutant strain was hypersensitive to low temperature and anti-ribosomal drugs, which we putatively attribute to the impairment in ribosomal function. In addition, the yst1Δ strain was less virulent to Galleria mellonella. These results generally suggest that Yst1, as a histone modification reader, might be a key coordinator of the transcriptome of this human pathogen. Yst1 could be a potential target for novel antifungal drugs, which might lead to significant developments in the clinical treatment of cryptococcosis.

更新日期：2021-03-05

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