Nuclear Matrix Structure and Genomic Function

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核形式和功能的相关性提供了重要方法。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被组织成更高级的单元或“区域”。在细胞周期中复制和转录区域的动态相互作用和“重新分区”可能形成哺乳动物细胞中复制和转录程序的复杂全局协调的结构基础。作为这种功能组织的基础之一，基因组在间期核中排列成离散的染色体区域。以这些研究为背景，我们提出以下具体目标：1.进一步发展三维显微镜的多维计算机成像方法。2.阐明了DNA复制的三维时空特性和早期S期基因复制的转录位点。3.研究细胞核中染色体区域的三维排列。4.研究活细胞中染色质结构域及其三维排列的动力学。

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.