A high-resolution map of the three-dimensional chromatin interactome in human cells.
A high-resolution map of the three-dimensional chromatin interactome in human cells.
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DOI：
10.1038/nature12644
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发表时间：
2013-11-14
期刊：
影响因子：
64.8
通讯作者：
Ren, Bing
中科院分区：
文献类型：
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作者：
Jin, Fulai;Li, Yan;Dixon, Jesse R.;Selvaraj, Siddarth;Ye, Zhen;Lee, Ah Young;Yen, Chia-An;Schmitt, Anthony D.;Espinoza, Celso A.;Ren, Bing
人类基因组中已经注释了大量的顺式调控序列，但确定它们的靶基因仍然是一个挑战。一种策略是利用基于染色体构象捕获(3C)的技术来识别这些元件上的远程环相互作用。然而，以前的研究要么缺乏分辨率，要么缺乏覆盖面，无法实现对染色质相互作用的全基因组、公正的看法。在这里，我们报告了使用全基因组3C分析方法(Hi-C)在人成纤维细胞中产生的全面的染色质相互作用图。我们测定了100多万个5-10kb分辨率的长距离染色质相互作用，并揭示了不同类型基因组特征的染色质组织的一般原理。我们还研究了这些细胞中启动子-增强子接触对肿瘤坏死因子-α信号的影响。出乎意料的是，我们发现肿瘤坏死因子-α反应增强子在信号传递之前就已经与其目标启动子接触。这种预先存在的染色质环也存在于其他类型的细胞中，具有不同的细胞外信号，是基因诱导的有力预测因素。我们的观察表明，一旦在特定细胞类型中建立起三维染色质景观，就相当稳定，并可能以细胞特有的方式影响普遍存在的转录激活因子对靶基因的选择或激活。
A large number of cis-regulatory sequences have been annotated in the human genome, but defining their target genes remains a challenge. One strategy is to identify the long-range looping interactions at these elements with the use of chromosome conformation capture (3C) based techniques. However, previous studies lack either the resolution or coverage to permit a whole-genome, unbiased view of chromatin interactions. Here, we report a comprehensive chromatin interaction map generated in human fibroblasts using a genome-wide 3C analysis method (Hi-C). We determined over one million long-range chromatin interactions at 5–10kb resolution, and uncovered general principles of chromatin organization at different types of genomic features. We also characterized the dynamics of promoter-enhancer contacts upon TNF-α signaling in these cells. Unexpectedly, we found that TNF-α responsive enhancers are already in contact with their target promoters prior to signaling. Such pre-existing chromatin looping, which also exists in other cell types with different extra-cellular signaling, is a strong predictor of gene induction. Our observations suggest that the three-dimensional chromatin landscape, once established in a particular cell type, is rather stable and could influence the selection or activation of target genes by a ubiquitous transcription activator in a cell-specific manner.
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影响因子：
64.5
作者：
Phillips-Cremins JE;Sauria ME;Sanyal A;Gerasimova TI;Lajoie BR;Bell JS;Ong CT;Hookway TA;Guo C;Sun Y;Bland MJ;Wagstaff W;Dalton S;McDevitt TC;Sen R;Dekker J;Taylor J;Corces VG
通讯作者：
Corces VG
影响因子：
64.8
作者：
Sanyal, Amartya;Lajoie, Bryan R.;Jain, Gaurav;Dekker, Job
通讯作者：
Dekker, Job
影响因子：
44.1
作者：
Hawkins, R. David;Hon, Gary C.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
5.3
作者：
Tan, Peck Yean;Chang, Cheng Wei;Cheung, Edwin
通讯作者：
Cheung, Edwin
DOI：
10.1038/nrg3454
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
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作者：
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