Epigenetic regulation of virulence and the transcription of ribosomal protein genes involves a YEATS family protein in Cryptococcus deneoformans.
Epigenetic regulation of virulence and the transcription of ribosomal protein genes involves a YEATS family protein in Cryptococcus deneoformans.
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DOI：
10.1093/femsyr/foab001
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发表时间：
2021-01
影响因子：
3.2
通讯作者：
Chenxi Li;Shaonan Hou;Xiaoyu Ma;Jiajia Li;Liang Huo;Ping Zhang;Xiaoran Hao;Xudong Zhu
中科院分区：
文献类型：
--
作者：
Chenxi Li;Shaonan Hou;Xiaoyu Ma;Jiajia Li;Liang Huo;Ping Zhang;Xiaoran Hao;Xudong Zhu
组蛋白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控作用。致病性酵母菌隐球菌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卡器。在这里，我们报道了在C. deneformans中鉴定了一个单拷贝基因，据推测编码YEATS结构域蛋白（Yst1）。为了定义它的功能，我们使用CRISPR-Cas9编辑技术创建了一个突变株yst1Δ。yst1Δ在表型上存在缺陷，如在1.3 M NaCl或KCl存在下对渗透胁迫敏感。此外，它对1%刚果红过敏，表明细胞壁有缺陷。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，即yst1Δ中大多数mRNA的表达水平显著低于野生型菌株。该突变株对低温和抗核糖体药物过敏，推测其可能与核糖体功能受损有关。此外，yst1Δ菌株对mellonella的毒力较弱。这些结果一般表明，Yst1作为组蛋白修饰阅读器，可能是该人类病原体转录组的关键协调者。Yst1可能成为新型抗真菌药物的潜在靶点，这可能导致隐球菌病临床治疗的重大发展。
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.