Chromatin structures influencing the dynamics of nucleosome remodeling

染色质结构影响核小体重塑的动力学

• 批准号: 5456709
• 负责人: Professor Dr. Gernot M. Längst
• 金额: --
• 依托单位: Lehrstuhl für Biochemie III
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5456709?language=en
• 关键词: Chromatin; structures; influencing; dynamics; nucleosome

One of the persistent enigmas of gene regulation is how the chromatin organisation, which reliably packages eukaryotic DNA, can at the same time be transparent to allow access of regulatory factors. Recent years have witnessed the discovery of enzymes modifying the structure of chromatin in response to cell-internal and -external cues, rendering chromatin a highly dynamic structure. Chromatin remodeling enzymes couple ATP hydrolysis to alterations of the chromatin structure at the level of the nucleosomal-array. Post-translational modifications of the histone tails are correlated with distinct chromatin states and DNA accessibility. The recent advances in proteomic analyses revealed novel modifications in the nucleosome core, many of which are positioned at the histone-DNA interface. Little is known about the role of these modifications, but several modifications are implicated to modulate chromatin remodeling, suggesting an intimate link between histone modifications and nucleosome remodelers in modulating chromatin dynamics. However, detailed analysis and functional testing is still lacking. (i) I propose an in vivo screen, to identify histone modifications and their combinations that modulate chromatin dynamics. (ii) We want to address the mechanistical basis of chromatin dynamics. Do ATP-dependent remodeler generate accessible DNA by constantly moving nucleosomes or are they regulated complexes that required additional signals that lead to localized nucleosome remodeling? (iii) Do remodeling complexes work similarly well in different higher order structures of chromatin? Or are specialized complexes required for different compaction states of chromatin?

基因调控的持久谜团之一是可靠地包装真核 DNA 的染色质组织如何同时保持透明以允许调控因子进入。近年来，人们发现酶可以响应细胞内部和外部的信号来改变染色质的结构，从而使染色质成为高度动态的结构。染色质重塑酶将 ATP 水解与核小体阵列水平的染色质结构的改变结合起来。组蛋白尾部的翻译后修饰与不同的染色质状态和 DNA 可及性相关。蛋白质组学分析的最新进展揭示了核小体核心的新修饰，其中许多修饰位于组蛋白-DNA 界面。人们对这些修饰的作用知之甚少，但一些修饰与调节染色质重塑有关，这表明组蛋白修饰和核小体重塑因子在调节染色质动力学方面存在密切联系。然而，仍然缺乏详细的分析和功能测试。 (i) 我建议进行体内筛选，以确定调节染色质动力学的组蛋白修饰及其组合。 (ii) 我们想要解决染色质动力学的机制基础。 ATP依赖性重塑剂是否通过不断移动核小体产生可接近的DNA，或者它们是否是需要额外信号来导致局部核小体重塑的调节复合物？ (iii) 重塑复合物在染色质的不同高级结构中是否同样有效？或者染色质的不同压缩状态是否需要专门的复合物？