Computer Laboratory, Cambridge University, Cambridge, UK.
Mol Syst Biol. 2010 Nov 2;6:426. doi: 10.1038/msb.2010.79.
A prime goal in systems biology is the comprehensive use of existing high-throughput genomic datasets to gain a better understanding of chromatin organization and genome function. In this report, we use chromatin immunoprecipitation (ChIP) data that map protein-binding sites on the genome, and Hi-C data that map interactions between DNA fragments in the genome in an integrative approach. We first reanalyzed the contact map of the human genome as determined with Hi-C and found that long-range interactions are highly nonrandom; the same DNA fragments are often found interacting together. We then show using ChIP data that these interactions can be explained by the action of the CCCTC-binding factor (CTCF). These CTCF-mediated interactions are found both within chromosomes and in between different chromosomes. This makes CTCF a major organizer of both the structure of the chromosomal fiber within each individual chromosome and of the chromosome territories within the cell nucleus.
系统生物学的主要目标是全面利用现有的高通量基因组数据集，以更好地了解染色质组织和基因组功能。在本报告中，我们使用染色质免疫沉淀 (ChIP) 数据来绘制基因组上蛋白质结合位点的图谱，并使用 Hi-C 数据来绘制基因组中 DNA 片段之间相互作用的图谱，我们采用了一种整合的方法。我们首先重新分析了用 Hi-C 方法确定的人类基因组的接触图谱，发现长程相互作用高度非随机；通常发现相同的 DNA 片段相互作用。然后，我们使用 ChIP 数据表明，这些相互作用可以通过 CCCTC 结合因子 (CTCF) 的作用来解释。这些 CTCF 介导的相互作用不仅存在于染色体内部，也存在于不同染色体之间。这使得 CTCF 成为每个染色体内部的染色体纤维结构以及细胞核内染色体区室的主要组织者。
