A three-dimensional model of the yeast genome.
A three-dimensional model of the yeast genome.
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在DNA序列和染色质传递的信息之上，是包含部分染色体、整个染色体甚至整个基因组的高阶结构。间期染色体在细胞核内并不是随机的，而是采用优先的构象。不同的DNA元件共定位到功能定义的聚集体或“工厂”中，用于转录和DNA复制。在芽殖酵母、果蝇和许多其他真核生物中，染色体采用Rabl构型，臂从邻近纺锤体极体的着丝粒延伸到邻接核膜的端粒。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内和染色体间的相互作用，并将其应用于产生一个地图，在酿酒酵母的单倍体基因组的内切酶分辨率。该图谱概括了基因组组织的已知特征，从而验证了该方法，并确定了新的特征。观察到单个染色体的广泛区域和更高级折叠。染色体XII呈现出一种引人注目的构象，暗示核仁是两端DNA序列之间相互作用的强大屏障。染色体间的接触由着丝粒锚定，包括tRNA基因之间、早期DNA复制起点之间以及染色体断裂点发生的位点之间的相互作用。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真核基因组的形式和功能之间的接口一瞥。
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 tRNA 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.
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