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首页> 外文期刊>Genomics >Enhancer jungles establish robust tissue-specific regulatory control in the human genome
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Enhancer jungles establish robust tissue-specific regulatory control in the human genome

机译：增强者丛林在人类基因组中建立了稳健的组织特异性调节控制

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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.
机译：越来越多的研究表明，通过对环境和遗传扰动的缓冲基因表达，功能冗余的增强剂可以保护开发。在这里，我们在人B淋巴细胞细胞中识别出在人B淋巴细胞细胞中的过度增强剂（增强子丛林或EJS）的簇。我们发现EJS倾向于与参与免疫系统反应的激活的基因相关联。虽然跨越多个基因，但EJ内的增强剂倾向于彼此协作，用于调节单个基因。 EJ增强剂中的偶型转录因子结合位点（TFBS）的就业可以保护靶基因的组成增强剂之间的异质型TFBS。与常规增强剂（RES）相比，EJ增强剂在较弱的选择性压力下演变，大约35％的EJS在小鼠基因组中没有正交学。在GM12878中，这些人体特异性EJ似乎调节与自适应免疫系统反应相关的基因，而保守的EJS与先天免疫有关。与保守的EJS相比，最近获得的人类EJ与靶基因表达的较高水平相关，从而促进了在进化过程中对生物体的环境适应。简而言之，EJS的存在是赋予关键谱系基因强大的监管控制的共同监管体系结构。

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