Systems Biology Center, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
Cell Res. 2012 Mar;22(3):490-503. doi: 10.1038/cr.2012.15. Epub 2012 Jan 24.
Recent epigenomic studies have predicted thousands of potential enhancers in the human genome. However, there has not been systematic characterization of target promoters for these potential enhancers. Using H3K4me2 as a mark for active enhancers, we identified genome-wide EP interactions in human CD4(+) T cells. Among the 6 520 long-distance chromatin interactions, we identify 2 067 enhancers that interact with 1 619 promoters and enhance their expression. These enhancers exist in accessible chromatin regions and are associated with various histone modifications and polymerase II binding. The promoters with interacting enhancers are expressed at higher levels than those without interacting enhancers, and their expression levels are positively correlated with the number of interacting enhancers. Interestingly, interacting promoters are co-expressed in a tissue-specific manner. We also find that chromosomes are organized into multiple levels of interacting domains. Our results define a global view of EP interactions and provide a data set to further understand mechanisms of enhancer targeting and long-range chromatin organization. The Gene Expression Omnibus accession number for the raw and analyzed chromatin interaction data is GSE32677.
最近的表观基因组学研究预测了人类基因组中数千个潜在的增强子。然而，这些潜在增强子的靶启动子还没有得到系统的描述。我们使用 H3K4me2 作为活性增强子的标记，在人类 CD4(+) T 细胞中鉴定了全基因组的 EP 相互作用。在 6520 个长距离染色质相互作用中，我们确定了 2067 个增强子与 1619 个启动子相互作用并增强其表达。这些增强子存在于可及染色质区域，并与各种组蛋白修饰和聚合酶 II 结合有关。与相互作用的增强子相互作用的启动子的表达水平高于没有相互作用的增强子，并且它们的表达水平与相互作用的增强子的数量呈正相关。有趣的是，相互作用的启动子以组织特异性的方式共同表达。我们还发现染色体被组织成多个相互作用的域。我们的研究结果定义了一个全局的 EP 相互作用视图，并提供了一个数据集，以进一步了解增强子靶向和长距离染色质组织的机制。原始和分析的染色质相互作用数据的基因表达综合数据库（GEO） accession number 是 GSE32677。
