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，出现了对细胞核的新观点。核基质上各种基因组过程的惊人结构保存为研究核的形态和功能提供了重要的途径。结合三维显微镜和计算机成像技术的原位标记技术表明，DNA复制和转录位点在细胞核中被组织成更高级别的单位或区域。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复杂的全球协调的结构基础。作为这种功能组织的基础之一，基因组在间期核中被排列成离散的染色体区域。在前人研究的基础上，我们提出了以下具体的研究目标：1.进一步发展计算机多维成像技术应用于三维显微镜。2.阐明S早期基因复制和转录的三维时空特性。3.研究染色体区域在细胞核内的三维排列。4.研究活细胞中染色质结构域的动态变化及其三维排列。

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.