An increasing number of studies suggest that functionally redundant enhancers safeguard development via buffering gene expression against environmental and genetic perturbations. Here, we identified over-represented clusters of enhancers (enhancer jungles or EJs) in human B lymphoblastoid cells. We found that EJs tend to associate with genes involved in the activation of the immune system response. Although spanning multiple genes, the enhancers within an EJ tend to collaborate with each other on regulating a single gene. The employment of homotypic transcription factor binding sites (TFBSs) in EJ enhancers and heterotypic TFBSs between constituent enhancers within an EJ may safeguard a robust transcriptional output of the target gene. EJ enhancers evolve under a weaker selective pressure compared to regular enhancers (REs), and approximately 35% of EJs do not have orthologues in the mouse genome. In GM12878, these human-specific EJs appear to regulate genes associated with the adaptive immune system response, while the conserved EJs are associated with innate immunity. Recently acquired human EJs are associated with the higher level of target gene expression compared with conserved EJs, thus facilitating the environmental adaptation of the organism during evolution. In short, the existence of EJs is a common regulatory architecture conferring a robust regulatory control for key lineage genes.

越来越多的研究表明，功能上多余的增强子可以通过缓冲基因表达来抵抗环境和遗传干扰来保护发育。在这里，我们确定了人类B淋巴母细胞中增强子（增强子丛林或EJs）的过度代表簇。我们发现EJs往往与参与激活免疫系统反应的基因相关联。尽管跨越多个基因，但EJ内的增强子往往在调节单个基因上相互协作。EJ增强子中同型转录因子结合位点（TFBS）的使用以及EJ内组成增强子之间的异型TFBS的使用可以保障目标基因的强劲转录输出。与常规增强剂（RE）相比，EJ增强剂在较弱的选择压力下进化，大约35％的EJ在小鼠基因组中没有直向同源物。在GM12878中，这些人类特异性EJ似乎调节与适应性免疫系统反应相关的基因，而保守的EJ与先天免疫相关。与保守的EJ相比，最近获得的人类EJ与更高水平的靶基因表达相关，从而促进了生物在进化过程中的环境适应性。简而言之，EJ的存在是一种常见的调节架构，可为关键谱系基因提供强大的调节控制。与保守的EJ相比，最近获得的人类EJ与更高水平的靶标基因表达相关，因此有利于生物体在进化过程中的环境适应性。简而言之，EJ的存在是一种常见的调节架构，可为关键谱系基因提供强大的调节控制。与保守的EJ相比，最近获得的人类EJ与更高水平的靶标基因表达相关，因此有利于生物体在进化过程中的环境适应性。简而言之，EJ的存在是一种常见的调节架构，可为关键谱系基因提供强大的调节控制。