Enhancers are short DNA sequences that activate their target promoter from a distance; however, increasing the genomic distance between the enhancer and the promoter decreases expression levels. Many genes are controlled by combinations of multiple enhancers, yet the interaction and cooperation of individual enhancer elements are not well understood. Here, we developed a synthetic platform in mouse embryonic stem cells that allows building complex regulatory landscapes from the bottom up. We tested the system by integrating individual enhancers at different distances and confirmed that the strength of an enhancer contributes to how strongly it is affected by increased genomic distance. Furthermore, synergy between two enhancer elements depends on the distance at which the two elements are integrated: introducing a weak enhancer between a strong enhancer and the promoter strongly increases reporter gene expression, allowing enhancers to activate from increased genomic distances.

中文翻译：

---

增强子协同性可以补偿大基因组距离上的活性损失


增强子是从远处激活其靶启动子的短 DNA 序列;然而，增加增强子和启动子之间的基因组距离会降低表达水平。许多基因由多个增强子的组合控制，但单个增强子元件的相互作用和合作尚不清楚。在这里，我们在小鼠胚胎干细胞中开发了一个合成平台，该平台允许自下而上构建复杂的调节环境。我们通过整合不同距离的单个增强子来测试该系统，并确认增强子的强度有助于其受基因组距离增加影响的强度。此外，两个增强子元件之间的协同作用取决于两个元件整合的距离：在强增强子和启动子之间引入弱增强子会强烈增加报告基因表达，从而使增强子能够从增加的基因组距离中激活。