Nanoscale structure and dynamics of nucleosome arrays assembled on DNA templates with physiologically relevant sequences

具有生理相关序列的 DNA 模板上组装的核小体阵列的纳米级结构和动力学

• 批准号: 2123637
• 负责人: Yuri Lyubchenko
• 金额: $ 65万
• 依托单位: University of Nebraska Medical Center
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2123637&HistoricalAwards=false
• 关键词: Nanoscale; structure; dynamics; nucleosome; arrays

Chromatin dynamics define how chromatin assembles into higher order structures and its function. However, molecular details of the assembly mechanism remain unexplained, including the role of DNA sequence in chromatin organization, specifically the interactions of nucleosomes. The research will address this gap in knowledge by examining the effects of DNA sequence on the interplay between chromatin structure, dynamics and function. This project also facilitates integration of scientific and technological advances in graduate and undergraduate student education. For example, the concepts of DNA and single molecule biophysics are incorporated into a biophysical chemistry course, and the research offers training opportunities for students at all levels in the university. The PI is also a member of the state EPSCoR committee and participates in the Young Nebraska Scientists (YNS) program that provides STEM enrichment activities for middle and high school students.Interaction between nucleosomes is a fundamental property that defines the assembly and function of chromatin. The central hypothesis examined in this project is that DNA sequence is a critical factor in the interactions between nucleosomes and their assembly into higher order structures. Nanoscale structural studies will be conducted by single-molecule high-speed atomic force microscopy (AFM) to address the role of DNA sequence in canonical nucleosome interactions, in the conformational dynamics of centromere nucleosomes, and in the assembly of higher order structures of canonical and centromere nucleosome arrays. The outcomes will advance the knowledge of chromatin structure and dynamics at different levels of organization and yield new insights into function.This project is jointly funded by the Genetic Mechanisms and Molecular Biophysics programs of the Molecular and Cellular Biosciences Division in the Biological Sciences Directorate.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.

染色质动力学定义了染色质如何组装成更高级的结构及其功能。然而，组装机制的分子细节仍然无法解释，包括DNA序列在染色质组织中的作用，特别是核小体的相互作用。该研究将通过检查DNA序列对染色质结构，动力学和功能之间相互作用的影响来解决这一知识差距。该项目还有助于将科学和技术进步纳入研究生和本科生教育。例如，DNA和单分子生物物理学的概念被纳入生物物理化学课程，研究为大学各级学生提供培训机会。PI也是州EPSCoR委员会的成员，并参加了内布拉斯加州青年科学家（YNS）计划，该计划为初中和高中学生提供STEM丰富活动。核小体之间的相互作用是定义染色质组装和功能的基本属性。在这个项目中检验的中心假设是，DNA序列是核小体之间的相互作用和它们组装成更高级结构的关键因素。纳米尺度的结构研究将通过单分子高速原子力显微镜（AFM）进行，以解决DNA序列在典型的核小体相互作用中的作用，在着丝粒核小体的构象动力学，以及在组装的更高阶结构的典型和着丝粒核小体阵列。该项目由生物科学理事会分子和细胞生物科学部的遗传机制和分子生物物理学项目共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值进行评估，被认为值得支持和更广泛的影响审查标准。

项目成果

Beyond Sequence: Internucleosomal Interactions Dominate Array Assembly

• DOI: 10.1021/acs.jpcb.2c05321
• 发表时间: 2022-12-14
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY B
• 影响因子: 3.3
• 作者: Wang，Yaqing;Stormberg，Tommy;Lyubchenko，Yuri L.
• 通讯作者: Lyubchenko，Yuri L.