How does chromatin structure influence nuclear localization of chromosomes and genome stability?

染色质结构如何影响染色体的核定位和基因组稳定性？

• 批准号: 426366823
• 负责人: Dr. Mareike Möller
• 金额: --
• 依托单位: Department of Biochemistry and Biophysics
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/426366823?language=en
• 关键词: How; does; chromatin; structure; influence

Genome stability is essential to maintain cellular viability and function. However, a high degree of genome variation and instability is often found in cells associated to disease (e.g. cancer cells) or organisms that are rapidly evolving in response to changing environmental conditions. Based on previous studies on genome diversity and the presence of certain histone modifications in highly divergent regions, I hypothesize that histone marks, especially H3K27me3, contribute to the observed variability by promoting genome instability. With this project, I want to determine how heterochromatin distribution contributes to genome instability by influencing nuclear interaction of chromatin and the occurrence of DNA damage in a comparative study of the filamentous fungal model organisms Zymoseptoria tritici, Fusarium graminearum, and Neurospora crassa. I will analyze the distribution of heterochromatin histone marks H3K9me3, H3K27me3, H3K36me3, and H4K20me3 in wildtype and deletion mutants of the respective histone-methyltransferases in the three species. Using ChIP-sequencing, detection of double-strand breaks and chromosome conformation capture, I will be able to determine heterochromatin dynamics and their influence on genome stability and nuclear chromatin interactions. This project will gain important novel insights into the role of chromatin organization and dynamics for genome stability and genome evolution in different species. These findings will be especially relevant to understand mechanisms of DNA instability in organisms or cells that exhibit a high degree of genome instability and variability such as plant, animal, or human pathogens, as well as cancer cells.

基因组稳定性对于维持细胞活力和功能至关重要。然而，在与疾病相关的细胞（例如癌细胞）或响应于变化的环境条件而快速进化的生物体中经常发现高度的基因组变异和不稳定性。基于以前的研究基因组多样性和存在的某些组蛋白修饰在高度分化的地区，我假设组蛋白标记，特别是H3K27me3，有助于通过促进基因组的不稳定性观察到的变异性。 在这个项目中，我想确定异染色质分布如何通过影响染色质的核相互作用和丝状真菌模式生物Zymoseptoria trivonium，Fusarium graminearum和Neurospora crassa的比较研究中DNA损伤的发生来影响基因组的不稳定性。我将分析异染色质组蛋白标记H3K9me3，H3K27me3，H3K36me3，和H4K20me3在野生型和缺失突变体的相应组蛋白甲基转移酶在三个物种的分布。使用ChIP测序，检测双链断裂和染色体构象捕获，我将能够确定异染色质动力学及其对基因组稳定性和核染色质相互作用的影响。该项目将获得重要的新的见解染色质组织和动态的基因组稳定性和基因组进化在不同物种中的作用。这些发现将特别有助于了解生物体或细胞中DNA不稳定性的机制，这些生物体或细胞表现出高度的基因组不稳定性和变异性，如植物，动物或人类病原体以及癌细胞。