Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C
Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C
复制标题
DOI：
10.1038/ng.3286
复制
发表时间：
2015-06-01
期刊：
影响因子：
30.8
通讯作者：
Osborne, Cameron S.
中科院分区：
文献类型：
--
作者：
Mifsud, Borbala;Tavares-Cadete, Filipe;Osborne, Cameron S.
大基因组中的转录控制通常需要远端DNA元件（例如增强子和靶启动子）之间的成环相互作用。目前的染色体构象捕获技术不能提供足够高的分辨率来询问基因组规模上的这些调控相互作用。在这里，我们使用捕获Hi-C（CHi-C），一种适应性的基因组构象测定，来检查2种人类血细胞类型中近22，000个启动子的长程相互作用。我们确定了超过160万个共享和细胞类型限制的相互作用，跨越启动子和远端基因座之间的数百个酶。转录活性基因与增强子样元件接触，而转录非活性基因与以前未表征的元件相互作用，这些元件由可能作为长距离沉默器的抑制特征标记。最后，我们发现，相互作用的基因座富含疾病相关的SNP，这表明远端突变可能会破坏相关基因的调控。这项研究提供了新的见解和可访问的工具，解剖正常和异常基因调控的调控相互作用。
Transcriptional control in large genomes often requires looping interactions between distal DNA elements, such as enhancers and target promoters. Current chromosome conformation capture techniques do not offer sufficiently high resolution to interrogate these regulatory interactions on a genomic scale. Here we use Capture Hi-C (CHi-C), an adapted genome conformation assay, to examine the long-range interactions of almost 22,000 promoters in 2 human blood cell types. We identify over 1.6 million shared and cell type restricted interactions spanning hundreds of kilobases between promoters and distal loci. Transcriptionally active genes contact enhancer-like elements, whereas transcriptionally inactive genes interact with previously uncharacterized elements marked by repressive features that may act as long-range silencers. Finally, we show that interacting loci are enriched for disease-associated SNPs, suggesting how distal mutations may disrupt the regulation of relevant genes. This study provides new insights and accessible tools to dissect the regulatory interactions that underlie normal and aberrant gene regulation.