Global view of enhancer-promoter interactome in human cells
Global view of enhancer-promoter interactome in human cells
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DOI：
10.1073/pnas.1320308111
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发表时间：
2014-05-27
影响因子：
11.1
通讯作者：
Tan, Kai
中科院分区：
文献类型：
--
作者：
He, Bing;Chen, Changya;Tan, Kai
与之相关的各种基因组标记极大地促进了增强子的定位。然而，我们的工具箱中几乎没有可用的工具来连接增强子和它们的目标启动子，这阻碍了对增强子-启动子(EP)相互作用的机械性理解。我们开发和表征了多个基因组特征来区分真正的EP对和非相互作用的对。我们将这些特征集成到EP交互的概率预测中。多个验证实验表明，与最先进的方法相比，该方法有了显著的改进。对12种细胞类型的EP相互作用的系统分析揭示了EP相互作用的几个全球特征：(I)更大比例的EP相互作用是细胞类型特有的，而不是增强子；(Ii)由多个增强子控制的启动子具有更高的组织特异性，但调节增强子的保守性较差；(Iii)粘附素通过不依赖于CTCF的染色质环在调节组织特异性EP相互作用中发挥作用。我们的方法提出了一种系统而有效的策略来破译EP通信的潜在机制。
Enhancer mapping has been greatly facilitated by various genomic marks associated with it. However, little is available in our tool-box to link enhancers with their target promoters, hampering mechanistic understanding of enhancer-promoter (EP) interaction. We develop and characterize multiple genomic features for distinguishing true EP pairs from noninteracting pairs. We integrate these features into a probabilistic predictor for EP interactions. Multiple validation experiments demonstrate a significant improvement over state-of-the-art approaches. Systematic analyses of EP interactions across 12 cell types reveal several global features of EP interactions: (i) a larger fraction of EP interactions are cell type specific than enhancers; (ii) promoters controlled by multiple enhancers have higher tissue specificity, but the regulating enhancers are less conserved; (iii) cohesin plays a role in mediating tissue-specific EP interactions via chromatin looping in a CTCF-independent manner. Our approach presents a systematic and effective strategy to decipher the mechanisms underlying EP communication.