Reconstruction of enhancer-target networks in 935 samples of human primary cells, tissues and cell lines
Reconstruction of enhancer-target networks in 935 samples of human primary cells, tissues and cell lines
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DOI：
10.1038/ng.3950
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发表时间：
2017-10-01
期刊：
影响因子：
30.8
通讯作者：
Yip, Kevin Y.
中科院分区：
文献类型：
--
作者：
Cao, Qin;Anyansi, Christine;Yip, Kevin Y.
我们提出了一种新的方法来确定特定细胞和组织中转录增强子的靶基因。它结合了许多样本的全局趋势和样本特定信息，并考虑了多种增强剂的联合作用。我们的方法优于现有的方法预测增强子的靶基因在看不见的样品，独立的实验数据进行评估。需要几种类型的输入数据，我们能够应用我们的方法来重建935个样本的人类原代细胞，组织和细胞系，这构成了迄今为止最大的一组增强子-靶标网络的增强子-靶标网络。来自不同样本的这些网络的相似性紧密遵循它们的细胞和组织谱系。我们发现了增强子的三种主要的共调控模式，并发现防御相关基因往往同时受到不同转录因子结合的多个增强子的调控。我们还确定了差异甲基化的增强子在肝细胞癌（HCC）和实验证实其改变肝癌相关基因的调节。
We propose a new method for determining the target genes of transcriptional enhancers in specific cells and tissues. It combines global trends across many samples and sample-specific information, and considers the joint effect of multiple enhancers. Our method outperforms existing methods when predicting the target genes of enhancers in unseen samples, as evaluated by independent experimental data. Requiring few types of input data, we are able to apply our method to reconstruct the enhancer-target networks in 935 samples of human primary cells, tissues and cell lines, which constitute by far the largest set of enhancer-target networks. The similarity of these networks from different samples closely follows their cell and tissue lineages. We discover three major coregulation modes of enhancers and find defense-related genes often simultaneously regulated by multiple enhancers bound by different transcription factors. We also identify differentially methylated enhancers in hepatocellular carcinoma (HCC) and experimentally confirm their altered regulation of HCC-related genes.