Chromosome Archae-tecture: Conserved principles of chromosome organization

项目总结 DNA在细胞内的三维组织对于适当和及时地 执行基因表达程序。实验方法的最新进展使 以前所未有的分辨率阐明细菌和真核生物的染色体构象。 细菌的染色体被组织成局部折叠的单位和染色体臂 在SMC蛋白的作用下，复制是连续并列的。相比之下，后生动物有大规模的 沿着染色体的线性顺序，这些结构域分为两种不同的类型，它们专门与 形成两个截然不同的更高级别的隔间。到目前为止，人们基本上对 第三生命领域，古生代生物的染色体构象。的许多方面 古生物和真核生物的信息处理(DNA复制、基因转录)机制是 从根本上与细菌相关且不同的。尽管古生菌具有原核生物的性质，但它们的 与细菌的形态相似，并且存在简单的环形染色体，如在许多细菌中。 值得注意的是，初步数据显示，硫磺属嗜热古菌的染色体， 与真核生物一样，具有不同于细菌的大规模结构域，具有更高的阶数 组织成两个不同类别的隔间。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生物和真核生物谱系的分歧。 初步数据将被扩展，以提供高分辨率的4-D路线图，以了解 古生代基因组。一种新的SMC相关蛋白参与协调基因组和其结构 将结合遗传和生化方法，在体内和体外研究这一作用。 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而简单的模型系统来解释机制和 关于基因组高阶组织的守恒原理的进化。

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.