Nature:芽殖酵母基因组的三维立体图

2010-05-20 00:00 · sunny

芽殖酵母细胞核中染色体的三维构形已从一个分辨率为千碱基对的染色体内和染色体间相互作用图被确定,而这些相互作用则是通过高通过量染色体捕捉方法识别出的。 其基因组总体形状像一个荷花(睡莲),有32个染色体臂从由细胞核一个极上簇集的“着丝点”所形成的根部伸出。这个3D图(它是一个忽略


芽殖酵母细胞核中染色体的三维构形已从一个分辨率为千碱基对的染色体内和染色体间相互作用图被确定,而这些相互作用则是通过高通过量染色体捕捉方法识别出的。

其基因组总体形状像一个荷花(睡莲),有32个染色体臂从由细胞核一个极上簇集的“着丝点”所形成的根部伸出。这个3D图(它是一个忽略了染色体动态性质的快照)让人们首次有机会以高分辨率一睹一个真核基因组的架构,它凸显了即便是这样简单的一种生物的基因组的三维复杂性。进一步的研究工作应能揭示决定这一结构的DNA序列所遵循的普遍组织原则。>

原文出处:

Nature doi:10.1038/nature08973

A three-dimensional model of the yeast genome

Zhijun Duan1,2,6, Mirela Andronescu3,6, Kevin Schutz4, Sean McIlwain3, Yoo Jung Kim1,2, Choli Lee3, Jay Shendure3, Stanley Fields2,3,5, C. Anthony Blau1,2,3 " William S. Noble3

Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98195-8056, USA

Department of Medicine, University of Washington Seattle, Washington 98195-8056, USA

Department of Genome Sciences, University of Washington, Seattle, Washington 98195-5065, USA

Graduate Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington 98195-5065, USA

Howard Hughes Medical Institute

These authors contributed equally to this work.

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 genomes1, 2, 3. Interphase chromosomes are not positioned randomly within the nucleus, but instead adopt preferred conformations4, 5, 6, 7. Disparate DNA elements co-localize into functionally defined aggregates or ‘factories’ for transcription8 and DNA replication9. 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 envelope10, 11, 12. 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.

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