Epigenetic inheritance in the Crenarchaeota

Crearchaeota的表观遗传

• 批准号: 2004613
• 负责人: Paul Blum
• 金额: $ 61.85万
• 依托单位: University of Nebraska-Lincoln
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2004613&HistoricalAwards=false
• 关键词: Epigenetic; inheritance; Crenarchaeota

This project addresses evolution by studying how microbes called archaea inherit biological traits through an epigenetic mechanism. Epigenetics refers to chemical modifications of DNA or of proteins bound to that DNA that cause inherited changes without modifying the order of nucleotides (sequence) of a gene. This form of heredity has significant impacts on the physiology and evolution of animals and plants but it is not known when this form of inheritance arose in evolution. This project explores the possibility that epigenetic inheritance arose first in in the archaea, which are a much more ancient lineage than eukaryotes including plants and animals. The PI will examine laboratory-adapted lineages of an archaeal species that inherit extreme resistance to acidic environments. These cells have extensive changes in gene expression that enable this acid resistance, yet they do not have any DNA sequence variations that explain this inherited trait. This project will also enable development a new investigative laboratory course module for a general microbiology course (400 students/year). The laboratory module will be adapted for use in high schools and with underserved minority students (in the U.S Department of Education Upward Bound program) and in a regional Women in Science program. SARC archaeal lines were evolved in the laboratory to select for extreme acid resistance. In some of the SARC lines, chromatin protein hypomethylation and not mutation account for inherited global changes in gene expression that are responsible for extreme acid resistance. In the proposed work, the locus-specific distribution of epigenetic marks on chromatin proteins will be determined using called site-specific chromatin immunoprecipitation-mass spectrometry. These experiments will determine whether hypomethylated archaeal chromatin proteins preferentially localize to genes within the SARC transcriptome. While the composition and epigenetic variation of chromatin protein networks have been established, the connectivity among component proteins has not. These networks are critical because they may constitute the signal transduction pathway controlling epigenetic traits. The PI will use three different techniques to elucidate how the proteins are connected in one or more networks. Finally, the PI will investigate the observation that SARC lines have a reduced mutation rate per cell division. The PI will test two competing models to clarify the mechanism underlying this trait. This work has the potential to reveal that epigenetic inheritance is an ancient mechanism for adaptation to sudden environmental changes typified by steep physiochemical gradients.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该项目通过研究称为古细菌的微生物如何通过表观遗传机制继承生物特征来解决进化问题。 表观遗传学是指DNA或与DNA结合的蛋白质的化学修饰，其引起遗传变化而不改变基因的核苷酸（序列）顺序。 这种遗传形式对动物和植物的生理和进化有重大影响，但不知道这种遗传形式何时出现在进化中。 这个项目探讨了表观遗传首先出现在古生菌中的可能性，古生菌是比包括植物和动物在内的真核生物更古老的谱系。 PI将研究一种古细菌物种的实验室适应性谱系，这些物种继承了对酸性环境的极端抵抗力。 这些细胞在基因表达上有广泛的变化，使这种耐酸性成为可能，但它们没有任何DNA序列变异来解释这种遗传特性。该项目还将为普通微生物学课程（400名学生/年）开发一个新的调查实验室课程模块。 该实验室模块将适用于高中和服务不足的少数民族学生（在美国教育部向上拓展计划）和地区妇女在科学计划。SARC古菌系在实验室中进化，以选择极端的耐酸性。 在一些SARC系中，染色质蛋白低甲基化而不是突变解释了基因表达的遗传性全局变化，这些变化是极端耐酸性的原因。 在拟议的工作中，染色质蛋白上表观遗传标记的位点特异性分布将使用所谓的位点特异性染色质免疫沉淀质谱法来确定。 这些实验将确定低甲基化古细菌染色质蛋白是否优先定位于SARC转录组内的基因。 虽然染色质蛋白质网络的组成和表观遗传变异已经建立，但组分蛋白质之间的连接还没有。 这些网络是至关重要的，因为它们可能构成控制表观遗传性状的信号转导途径。 PI将使用三种不同的技术来阐明蛋白质如何在一个或多个网络中连接。最后，PI将研究SARC系每次细胞分裂突变率降低的观察结果。 PI将测试两个相互竞争的模型，以阐明这种特征背后的机制。这项工作有可能揭示表观遗传是一种古老的机制，用于适应以陡峭的生理化学梯度为代表的突然环境变化。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。