A THREE-DIMENSIONAL MODEL OF THE YEAST GENOME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在DNA序列和染色质传递的信息之上是更高的顺序 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。间期染色体不是随机定位在细胞核内的，而是 取而代之的是采用首选构象。完全不同的DNA元素在功能上共存于 为转录和DNA复制定义的聚集体或“工厂”。在萌芽酵母中， 果蝇和许多其他真核生物的染色体采用Rabl构型，有手臂 从纺锤体极体附近的着丝粒延伸到与纺锤体相邻的端粒 核包膜。尽管如此，染色体的拓扑和空间关系 人们对此仍然知之甚少。在这里，我们开发了一种全局捕获内部和内部的方法 染色体的相互作用，并将其应用于生成千碱基分辨率的地图 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，并确定新的特征。广泛性 观察到单个染色体的区域和更高级别的折叠。第12号染色体 显示出惊人的构象，暗示核仁是一种强大的屏障 两端DNA序列之间的相互作用。染色体间的接触是固定的 通过着丝粒和包括转移RNA基因之间的相互作用，在早期的起源中 DNA复制和发生染色体断裂点的位置之间。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.