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

Authors
  • Li, Chenxi1
  • Hou, Shaonan1
  • Ma, Xiaoyu1
  • Li, Jiajia1
  • Huo, Liang1
  • Zhang, Ping1
  • Hao, Xiaoran1
  • Zhu, Xudong1
  • 1 Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, Institute of Biochemistry and Molecular Biology, College of Life Sciences, Beijing Normal University (CLS-BNU), Beijing 100875, PR China. , (China)
Type
Published Article
Journal
FEMS Yeast Research
Publisher
Oxford University Press
Publication Date
Mar 04, 2021
Volume
21
Issue
1
Identifiers
DOI: 10.1093/femsyr/foab001
PMID: 33440003
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. © The Author(s) 2021. Published by Oxford University Press on behalf of FEMS.

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