Kent Fungal Group, School of Biosciences, University of Kent, Canterbury, Kent, United Kingdom.
Department of Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel.
mBio. 2019 Jul 23;10(4):e01376-19. doi: 10.1128/mBio.01376-19.
Eukaryotic genomes are packaged into chromatin structures that play pivotal roles in regulating all DNA-associated processes. Histone posttranslational modifications modulate chromatin structure and function, leading to rapid regulation of gene expression and genome stability, key steps in environmental adaptation. , a prevalent fungal pathogen in humans, can rapidly adapt and thrive in diverse host niches. The contribution of chromatin to biology is largely unexplored. Here, we generated the first comprehensive chromatin profile of histone modifications (histone H3 trimethylated on lysine 4 [H3K4me], histone H3 acetylated on lysine 9 [H3K9Ac], acetylated lysine 16 on histone H4 [H4K16Ac], and γH2A) across the genome and investigated its relationship to gene expression by harnessing genome-wide sequencing approaches. We demonstrated that gene-rich nonrepetitive regions are packaged into canonical euchromatin in association with histone modifications that mirror their transcriptional activity. In contrast, repetitive regions are assembled into distinct chromatin states; subtelomeric regions and the ribosomal DNA (rDNA) locus are assembled into heterochromatin, while major repeat sequences and transposons are packaged in chromatin that bears features of euchromatin and heterochromatin. Genome-wide mapping of γH2A, a marker of genome instability, identified potential recombination-prone genomic loci. Finally, we present the first quantitative chromatin profiling in to delineate the role of the chromatin modifiers Sir2 and Set1 in controlling chromatin structure and gene expression. This report presents the first genome-wide chromatin profiling of histone modifications associated with the genome. These epigenomic maps provide an invaluable resource to understand the contribution of chromatin to biology and identify aspects of chromatin organization that differ from that of other yeasts. The fungus is an opportunistic pathogen that normally lives on the human body without causing any harm. However, is also a dangerous pathogen responsible for millions of infections annually. is such a successful pathogen because it can adapt to and thrive in different environments. Chemical modifications of chromatin, the structure that packages DNA into cells, can allow environmental adaptation by regulating gene expression and genome organization. Surprisingly, the contribution of chromatin modification to biology is still largely unknown. For the first time, we analyzed chromatin modifications on a genome-wide basis. We demonstrate that specific chromatin states are associated with distinct regions of the genome and identify the roles of the chromatin modifiers Sir2 and Set1 in shaping chromatin and gene expression.
真核生物基因组被包装成染色质结构，这些结构在调节所有与 DNA 相关的过程中起着关键作用。组蛋白的翻译后修饰调节染色质结构和功能，导致基因表达和基因组稳定性的快速调节，这是环境适应的关键步骤。白色念珠菌是一种常见的人类真菌病原体，能够迅速适应和在各种宿主小生境中茁壮成长。染色质对白色念珠菌生物学的贡献在很大程度上尚未被探索。在这里，我们生成了第一个关于组蛋白修饰（组蛋白 H3 赖氨酸 4 三甲基化 [H3K4me]、组蛋白 H3 赖氨酸 9 乙酰化 [H3K9Ac]、组蛋白 H4 赖氨酸 16 乙酰化 [H4K16Ac]和 γH2A）的全基因组染色质图谱，并通过利用全基因组测序方法研究了其与基因表达的关系。我们证明了富含基因的非重复区域与反映其转录活性的组蛋白修饰一起被包装成典型的常染色质。相比之下，重复区域被组装成不同的染色质状态；端粒区域和核糖体 DNA（rDNA）位点被组装成异染色质，而主要重复序列和转座子则被包装成具有常染色质和异染色质特征的染色质。全基因组 γH2A 作图，一种基因组不稳定性的标记，确定了潜在的易重组基因组位点。最后，我们介绍了白色念珠菌中染色质修饰的第一个定量染色质图谱，以描绘染色质修饰物 Sir2 和 Set1 对控制染色质结构和基因表达的作用。本报告介绍了与白色念珠菌基因组相关的组蛋白修饰的第一个全基因组染色质图谱。这些表观基因组图谱为了解染色质对白色念珠菌生物学的贡献提供了宝贵的资源，并确定了白色念珠菌染色质组织与其他酵母不同的方面。真菌白色念珠菌通常生活在人体上而不会造成任何伤害，是一种机会性病原体。然而，白色念珠菌也是一种危险的病原体，每年导致数百万人感染。白色念珠菌是一种如此成功的病原体，因为它可以适应和在不同的环境中茁壮成长。染色质的化学修饰，即将 DNA 包装到细胞中的结构，可以通过调节基因表达和基因组组织来实现环境适应。令人惊讶的是，染色质修饰对白色念珠菌生物学的贡献在很大程度上仍然未知。我们首次在全基因组范围内分析了白色念珠菌的染色质修饰。我们证明了特定的染色质状态与白色念珠菌基因组的不同区域相关，并确定了染色质修饰物 Sir2 和 Set1 在塑造白色念珠菌染色质和基因表达中的作用。
