Chromosome Archae-tecture: Conserved principles of chromosome organization

项目摘要 细胞内DNA的三维组织对于适当和及时的 执行基因表达程序。实验方法的最新进展使得 以前所未有的分辨率阐明细菌和真核生物染色体的构象。 细菌染色体被组织成局部折叠的单位和染色体臂， 通过SMC蛋白的作用，复制是并行的。与此相反，后生动物具有大规模的 结构域沿着染色体的线性顺序，这些分为两种不同的类型，专门与 形成两种不同的高阶隔室。到目前为止，基本上还不知道 在生命的第三个领域，染色体的构造。的许多方面 古细菌和真核生物的信息处理（DNA复制，基因转录）机制是 基本上与细菌相关且不同。这是尽管古生菌的原核性质， 与细菌的形态相似，并且存在简单的环状染色体，如在许多细菌中。 引人注目的是，初步数据显示，硫化叶菌属极端嗜热古菌的染色体， 与真核生物一样，与细菌不同，具有大规模的结构域结构， 组织成两个不同的类别的隔间。这一挑衅性的观察表明， 染色体组织的基本逻辑可能早于古细菌和真核生物谱系的分歧。 初步数据将被扩展，以提供一个高分辨率的4-D路线图的动态结构， 古细菌基因组一种新的SMC相关蛋白参与协调基因组及其 将使用遗传和生物化学方法的组合在体内和体外研究其作用。 最后，细胞基因表达程序和染色体之间相互作用的因果关系 架构将被确定。 作为一个整体，这项工作将利用一个独特的和简单的模型系统来阐明机制， 控制基因组高级组织的保守原则的进化。

PROJECT SUMMARY The three-dimensional organization of DNA within cells is of profound importance for the appropriate and timely execution of gene expression programs. Recent advances in experimental approaches have allowed the elucidation of the conformation of chromosomes of bacteria and eukaryotes with unprecedented resolution. Bacterial chromosomes are organized into locally folded units and chromosome arms either side of the origin of replication are juxtaposed processively by the action of SMC proteins. In contrast, metazoa have large-scale domains along the linear order of the chromosome, these fall into two distinct types that exclusively associate to form two distinct classes of higher-order compartment. To date, essentially nothing is known about the conformation of chromosomes from organisms in the third domain of life, the Archaea. Many aspects of the information processing (DNA replication, gene transcription) machineries of archaea and eukaryotes are fundamentally related and distinct from those of bacteria. This is despite the prokaryotic nature of archaea, their morphological similarities to bacteria and the presence of simple circular chromosomes, as in many bacteria. Strikingly, preliminary data reveal that the chromosomes of hyperthermophilic archaea of the genus Sulfolobus, like eukaryotes, and distinct from bacteria, possess a large-scale domain architecture with higher-order organization into two distinct classes of compartment. This provocative observation suggests that the fundamental logic of chromosome organization may predate the bifurcation of archaeal and eukaryotic lineages. The preliminary data will be extended to provide a high-resolution 4-D roadmap of the dynamic structure of the archaeal genome. A novel SMC-related protein is implicated in coordinating the structure of the genome and its role will be investigated both in vivo and in vitro using a combination of genetic and biochemical approaches. Finally, the causality of the interplay between the cellular gene expression program and chromosome architecture will be determined. Taken as a whole, this work will exploit a unique and simple model system to elucidate the mechanisms and evolution of the conserved principles governing the higher-order organization of genomes.