Genome architectures revealed by tethered chromosome conformation capture and population-based modeling.

Genome architectures revealed by tethered chromosome conformation capture and population-based modeling.
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DOI:
10.1038/nbt.2057
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发表时间:
2011-12-25
影响因子:
46.9
通讯作者:
--
中科院分区:
工程技术1区
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我们开发了拴系构象捕获(TCC),这是一种染色质相互作用的全基因组制图方法。通过固相连接,TCC大大提高了信噪比,从而能够详细分析染色体间的相互作用。我们在每条染色体中确定了一组区域,主要介导染色体间相互作用。这些区域具有高转录活性,表明它们的相互作用是由转录工厂介导的。这些区域中的每一个都以一种不分青红皂白的方式与基因组中许多其他这样的区域相互作用,部分原因是伙伴的可及性。因此,很可能在不同的细胞中存在不同的相互作用组合。为了适应这种可变性,我们开发了一种计算方法,将TCC数据转化为三维基因组结构群体中的物理染色质接触。对所得群体的统计分析表明,染色体间相互作用的不分青红皂白的特性与人类基因组众所周知的结构特征是一致的。
We developed Tethered Conformation Capture (TCC), a method for genome-wide mapping of chromatin interactions. By implementing solid-phase ligation, TCC substantially enhanced the signal-to-noise ratio and thus, enabled a detailed analysis of inter-chromosomal interactions. We identified a group of regions in each chromosome that predominantly mediate inter-chromosomal interactions. These regions are marked by high transcriptional activity, suggesting that their interactions are mediated by transcription factories. Each of these regions interacts with numerous other such regions throughout the genome in an indiscriminate fashion, partly driven by the accessibility of the partners. Therefore, it is likely that a different combination of interactions is present in different cells. Accommodating this variability, we developed a computational method to translate the TCC data into physical chromatin contacts in a population of three-dimensional genome structures. Statistical analysis of the resulting population demonstrates that the indiscriminate properties of inter-chromosomal interactions is consistent with the well-known architectural features of the human genome.
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