Nuclear Matrix Structure and Genomic Function

核基质结构和基因组功能

• 批准号: 7076217
• 负责人: Ronald Berezney
• 金额: $ 36.68万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-09-30 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7076217
• 关键词: DNA replication; bioimaging /biomedical imaging; cell component structure /function; cell cycle; chromatin; digital imaging; genetic transcription; nuclear matrix; three dimensional imaging /topography

DESCRIPTION (provided by applicant): A new view of the cell nucleus has emerged based on the functional dynamics of nuclear architecture. The striking structural preservation of a variety of genomic processes on the nuclear matrix provides an important approach for correlating nuclear form and function. In situ labeling coupled with three dimensional microscopy and computer imaging techniques reveal that DNA replication and transcription sites are organized into higher order units or "zones" in the cell nucleus. The dynamic interplay and "rezoning" of replication and transcription regions during the cell cycle may form the structural basis for the elaborate global coordination of replicational and transcriptional programs in the mammalian cell. As one basis for this functional organization, the genome is arranged into discrete chromosome territories in the interphase nucleus. With these previous studies as a background we propose the following specific aims: 1. Further development of multi-dimensional computer imaging approaches to 3-D microscopy. 2. Elucidate the 3-D spatio-temporal properties of DNA replication and transcription sites for genes replicating in early S-phase. 3. Study the 3-D arrangement of chromosome territories in the cell nucleus. 4. Investigate the dynamics of chromatin domains and their 3-D arrangement in living cells.

描述（由申请人提供）：基于核结构的功能动力学，出现了细胞核的新观点。核基质上各种基因组过程的惊人结构保存为关联核形式和功能提供了重要方法。原位标记结合三维显微镜和计算机成像技术揭示了 DNA 复制和转录位点在细胞核中组织成更高阶的单元或“区域”。细胞周期中复制和转录区域的动态相互作用和“重新分区”可能构成哺乳动物细胞中复制和转录程序的精细全局协调的结构基础。作为这种功能组织的基础，基因组被排列成间期核中离散的染色体区域。以这些先前的研究为背景，我们提出以下具体目标： 1. 进一步开发 3D 显微镜的多维计算机成像方法。 2. 阐明早期S期基因复制的DNA复制和转录位点的3-D时空特性。 3. 研究细胞核中染色体区域的 3-D 排列。 4. 研究活细胞中染色质结构域的动态及其 3-D 排列。