Zhu Yun, Chen Zhao, Zhang Kai, Wang Mengchi, Medovoy David, Whitaker John W, Ding Bo, Li Nan, Zheng Lina, Wang Wei
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0359, USA.
Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093-0359, USA.
Nat Commun. 2016 Mar 10;7:10812. doi: 10.1038/ncomms10812.
The human genome is tightly packaged into chromatin whose functional output depends on both one-dimensional (1D) local chromatin states and three-dimensional (3D) genome organization. Currently, chromatin modifications and 3D genome organization are measured by distinct assays. An emerging question is whether it is possible to deduce 3D interactions by integrative analysis of 1D epigenomic data and associate 3D contacts to functionality of the interacting loci. Here we present EpiTensor, an algorithm to identify 3D spatial associations within topologically associating domains (TADs) from 1D maps of histone modifications, chromatin accessibility and RNA-seq. We demonstrate that active promoter-promoter, promoter-enhancer and enhancer-enhancer associations identified by EpiTensor are highly concordant with those detected by Hi-C, ChIA-PET and eQTL analyses at 200 bp resolution. Moreover, EpiTensor has identified a set of interaction hotspots, characterized by higher chromatin and transcriptional activity as well as enriched TF and ncRNA binding across diverse cell types, which may be critical for stabilizing the local 3D interactions.
人类基因组被紧密包装成染色质，其功能输出取决于一维（1D）局部染色质状态和三维（3D）基因组组织。目前，染色质修饰和3D基因组组织是通过不同的检测方法来测量的。一个新出现的问题是，是否有可能通过对1D表观基因组数据的综合分析来推断3D相互作用，并将3D接触与相互作用位点的功能联系起来。在这里，我们展示了EpiTensor，这是一种从组蛋白修饰、染色质可及性和RNA-seq的1D图谱中识别拓扑相关结构域（TADs）内3D空间关联的算法。我们证明，EpiTensor识别出的活跃启动子-启动子、启动子-增强子和增强子-增强子关联与Hi-C、ChIA-PET和eQTL分析在200bp分辨率下检测到的关联高度一致。此外，EpiTensor已经识别出一组相互作用热点，其特征是具有更高的染色质和转录活性，以及在不同细胞类型中富集的转录因子（TF）和非编码RNA（ncRNA）结合，这可能对稳定局部3D相互作用至关重要。
