The Wistar Institute, Philadelphia, Pennsylvania, USA.
Nucleic Acids Res. 2010 Dec;38(22):8164-77. doi: 10.1093/nar/gkq955. Epub 2010 Oct 28.
We have comprehensively mapped long-range associations between chromosomal regions throughout the fission yeast genome using the latest genomics approach that combines next generation sequencing and chromosome conformation capture (3C). Our relatively simple approach, referred to as enrichment of ligation products (ELP), involves digestion of the 3C sample with a 4 bp cutter and self-ligation, achieving a resolution of 20 kb. It recaptures previously characterized genome organizations and also identifies new and important interactions. We have modeled the 3D structure of the entire fission yeast genome and have explored the functional relationships between the global genome organization and transcriptional regulation. We find significant associations among highly transcribed genes. Moreover, we demonstrate that genes co-regulated during the cell cycle tend to associate with one another when activated. Remarkably, functionally defined genes derived from particular gene ontology groups tend to associate in a statistically significant manner. Those significantly associating genes frequently contain the same DNA motifs at their promoter regions, suggesting that potential transcription factors binding to these motifs are involved in defining the associations among those genes. Our study suggests the presence of a global genome organization in fission yeast that is functionally similar to the recently proposed mammalian transcription factory.
我们使用最新的基因组学方法,结合下一代测序和染色体构象捕获(3C),全面绘制了裂殖酵母基因组中染色体区域之间的长程关联。我们的方法相对简单,称为连接产物富集(ELP),包括用 4 bp 切割器消化 3C 样品和自我连接,分辨率达到 20 kb。它重新捕获了先前表征的基因组结构,并确定了新的和重要的相互作用。我们构建了整个裂殖酵母基因组的 3D 结构,并探索了全基因组组织和转录调控之间的功能关系。我们发现高度转录的基因之间存在显著的关联。此外,我们证明在细胞周期中共同调控的基因在被激活时往往彼此关联。值得注意的是,来自特定基因本体组的功能定义基因以统计上显著的方式倾向于关联。那些显著关联的基因在其启动子区域通常含有相同的 DNA 基序,这表明结合这些基序的潜在转录因子参与定义这些基因之间的关联。我们的研究表明,裂殖酵母中存在一种类似于最近提出的哺乳动物转录工厂的全基因组组织,其功能相似。