A THREE-DIMENSIONAL MODEL OF THE YEAST GENOME

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在DNA序列和染色质传递的信息之上， 包括部分染色体，整个染色体，甚至整个染色体的结构， 基因组间期染色体并不是随机定位在细胞核内，而是 而是采用优选构象。不同的DNA元件在功能上共定位于 用于转录和DNA复制的定义的聚集体或“工厂”。在芽殖酵母中， 果蝇和许多其他真核生物的染色体采用Rabl构型， 从邻近纺锤体极体的着丝粒延伸到邻接纺锤体的端粒， 核膜尽管如此，染色体的拓扑结构和空间关系 仍然知之甚少。在这里，我们开发了一种方法来全局捕获帧内和帧间， 染色体的相互作用，并应用它来生成一个地图，在内切酶分辨率的 酿酒酵母的单倍体基因组。这张地图概括了 基因组组织，从而验证该方法，并识别新的特征。广泛 观察到单个染色体的区域和更高阶折叠。染色体XII 表现出一种引人注目的构象，暗示核仁是一个强大的屏障， DNA序列两端的相互作用。染色体间接触锚定 包括转移RNA基因之间的相互作用，在早期的起源中， DNA复制和染色体断裂点发生的位点之间。最后我们 构建了酵母基因组的三维模型。我们的发现提供了一个一瞥 真核生物基因组的形式和功能之间的界面。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Layered on top of information conveyed by DNA sequence and chromatin are higher order structures that encompass portions of chromosomes, entire chromosomes, and even whole genomes. Interphase chromosomes are not positioned randomly within the nucleus, but instead adopt preferred conformations. Disparate DNA elements co-localize into functionally defined aggregates or "factories" for transcription and DNA replication. In budding yeast, Drosophila and many other eukaryotes, chromosomes adopt a Rabl configuration, with arms extending from centromeres adjacent to the spindle pole body to telomeres that abut the nuclear envelope. Nonetheless, the topologies and spatial relationships of chromosomes remain poorly understood. Here we developed a method to globally capture intra- and inter- chromosomal interactions, and applied it to generate a map at kilobase resolution of the haploid genome of Saccharomyces cerevisiae. The map recapitulates known features of genome organization, thereby validating the method, and identifies new features. Extensive regional and higher order folding of individual chromosomes is observed. Chromosome XII exhibits a striking conformation that implicates the nucleolus as a formidable barrier to interaction between DNA sequences at either end. Inter-chromosomal contacts are anchored by centromeres and include interactions among transfer RNA genes, among origins of early DNA replication and among sites where chromosomal breakpoints occur. Finally, we constructed a three-dimensional model of the yeast genome. Our findings provide a glimpse of the interface between the form and function of a eukaryotic genome.