Chromosome Archae-tecture: Conserved principles of chromosome organization

染色体古结构：染色体组织的保守原理

基本信息

批准号：
10524035
负责人：
Stephen David Bell
金额：
$ 31.06万
依托单位：
TRUSTEES OF INDIANA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-12-02 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10524035
关键词：
3-Dimensional Archaea Archaeal Genome Architecture Bacteria Bacterial Chromosomes Binding Biochemical Biological Models Carbon Cells ChIP-seq Chromosome Arm Chromosome Structures Chromosomes Complex DNA DNA biosynthesis DNA replication origin Dactinomycin Data Dominant-Negative Mutation Etiology Eukaryota Evolution Exhibits Experimental Genetics Fluorescent in Situ Hybridization Gene Expression Gene Expression Profile Genes Genetic Genetic Transcription Genome Growth Higher Order Chromatin Structure In Vitro Intercistronic Region Investigation Knock-out Life Logic Maintenance Molecular Conformation Morphology Nature Organism Orthologous Gene Phase Phenotype Play Population Process Prokaryotic Cells Property Protein Family Proteins Recombinant Proteins Regulation Replication Initiation Replication Origin Resolution Role Shapes Side Source Structure Sulfolobus Sulfolobus acidocaldarius System Testing Validation Work chromosome conformation capture comparative condensin experimental study falls gene induction hyperthermophile in vivo information processing inhibitor member mutant novel programs protein distribution transcriptional reprogramming

项目摘要

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.

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允许阐明具有前所未有的分辨率的细菌和真核生物染色体的构象。细菌染色体被组织成本地折叠的单元，染色体臂的起源两侧复制是通过SMC蛋白的作用进行过程并置的。相比之下，后生动物有大规模沿着染色体的线性顺序域的域，它们属于两种不同类型，它们仅与形成两个不同类别的高阶隔室。迄今为止，本质上什么都不知道从生命的第三个领域，古细菌中生物的染色体的构象。许多方面信息处理（DNA复制，基因转录）古细菌和真核生物的机械是从根本上相关并与细菌不同。尽管古细菌具有原始性质，但他们还是与许多细菌一样，与细菌的形态相似性和简单的圆形染色体的存在。引人注目的是，初步数据表明，硫属属的高素古细菌的染色体，像真核生物一样，与细菌不同，具有高阶的大规模结构组织分为两个不同的隔间类别。这个挑衅性的观察表明染色体组织的基本逻辑可能早于古细胞和真核血统的分叉。初步数据将扩展，以提供高分辨率的4-D路线图古细胞基因组。一种新型与SMC相关的蛋白质与协调基因组及其结构有关将使用遗传和生化方法的组合对角色进行体内和体外研究。最后，细胞基因表达程序与染色体之间的相互作用的因果关系将确定架构。总体而言，这项工作将利用独特而简单的模型系统来阐明机制和控制基因组高阶组织的保守原则的演变。