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ATAC测序鉴定与人类真菌病原体氧化应激调控相关的染色质景观

ATAC-Seq Identifies Chromatin Landscapes Linked to the Regulation of Oxidative Stress in the Human Fungal Pathogen .

作者信息

Jenull Sabrina, Tscherner Michael, Mair Theresia, Kuchler Karl

机构信息

Medical University of Vienna, Center for Medical Biochemistry, Max Perutz Labs Vienna, Campus Vienna Biocenter, Dr. Bohr-Gasse 9/2, A-1030 Vienna, Austria.

出版信息

J Fungi (Basel). 2020 Sep 21;6(3):182. doi: 10.3390/jof6030182.

Abstract

Human fungal pathogens often encounter fungicidal stress upon host invasion, but they can swiftly adapt by transcriptional reprogramming that enables pathogen survival. Fungal immune evasion is tightly connected to chromatin regulation. Hence, fungal chromatin modifiers pose alternative treatment options to combat fungal infections. Here, we present an assay for transposase-accessible chromatin using sequencing (ATAC-seq) protocol adapted for the opportunistic pathogen to gain further insight into the interplay of chromatin accessibility and gene expression mounted during fungal adaptation to oxidative stress. The ATAC-seq workflow not only facilitates the robust detection of genomic regions with accessible chromatin but also allows for the precise modeling of nucleosome positions in . Importantly, the data reveal genes with altered chromatin accessibility in upstream regulatory regions, which correlate with transcriptional regulation during oxidative stress. Interestingly, many genes show increased chromatin accessibility without change in gene expression upon stress exposure. Such chromatin signatures could predict yet unknown regulatory factors under highly dynamic transcriptional control. Additionally, de novo motif analysis in genomic regions with increased chromatin accessibility upon HO treatment shows significant enrichment for Cap1 binding sites, a major factor of oxidative stress responses in . Taken together, the ATAC-seq workflow enables the identification of chromatin signatures and highlights the dynamics of regulatory mechanisms mediating environmental adaptation of .

摘要

人类真菌病原体在入侵宿主时常常会遇到杀菌压力,但它们可以通过转录重编程迅速适应,从而实现病原体的存活。真菌的免疫逃避与染色质调控密切相关。因此,真菌染色质修饰因子为对抗真菌感染提供了替代治疗选择。在此,我们提出了一种适用于机会性病原体的转座酶可及染色质测序(ATAC-seq)方案,以进一步深入了解真菌适应氧化应激过程中染色质可及性与基因表达之间的相互作用。ATAC-seq工作流程不仅有助于对具有可及染色质的基因组区域进行可靠检测,还能对核小体位置进行精确建模。重要的是,数据揭示了上游调控区域中染色质可及性发生改变的基因,这些基因与氧化应激期间的转录调控相关。有趣的是,许多基因在应激暴露后染色质可及性增加,但基因表达没有变化。这种染色质特征可能预示着在高度动态转录控制下尚未知晓的调控因子。此外,对HO处理后染色质可及性增加的基因组区域进行的从头基序分析显示,Cap1结合位点显著富集,Cap1是[具体物种]氧化应激反应的主要因子。综上所述,ATAC-seq工作流程能够识别染色质特征,并突出介导[具体物种]环境适应的调控机制的动态变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e85c/7559329/ed84d5ded1c5/jof-06-00182-g001.jpg

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