Tissue function and homeostasis reflect the gene expression signature by which the combination of ubiquitous and tissue-specific genes contribute to the tissue maintenance and stimuli-responsive function. Enhancers are central to control this tissue-specific gene expression pattern. Here, we explore the correlation between the genomic location of enhancers and their role in tissue-specific gene expression. We find that enhancers showing tissue-specific activity are highly enriched in intronic regions and regulate the expression of genes involved in tissue-specific functions, whereas housekeeping genes are more often controlled by intergenic enhancers, common to many tissues. Notably, an intergenic-to-intronic active enhancers continuum is observed in the transition from developmental to adult stages: the most differentiated tissues present higher rates of intronic enhancers, whereas the lowest rates are observed in embryonic stem cells. Altogether, our results suggest that the genomic location of active enhancers is key for the tissue-specific control of gene expression.

中文翻译：

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具有组织特异性活性的增强子在内含子区域中富集

组织功能和体内平衡反映了普遍存在的和组织特异性基因的组合有助于组织维持和刺激响应功能的基因表达特征。增强子是控制这种组织特异性基因表达模式的核心。在这里，我们探讨了增强子的基因组位置与其在组织特异性基因表达中的作用之间的相关性。我们发现显示组织特异性活性的增强子在内含子区域高度富集并调节与组织特异性功能相关的基因的表达，而管家基因更经常受基因间增强子控制，这在许多组织中都很常见。值得注意的是，在从发育阶段到成年阶段的过渡过程中观察到基因间到内含子的活性增强子连续体：分化程度最高的组织具有较高的内含子增强子比率，而在胚胎干细胞中观察到的比率最低。总之，我们的结果表明，活性增强子的基因组位置是组织特异性控制基因表达的关键。