Genome-wide characterization of mammalian promoters with distal enhancer functions
Genome-wide characterization of mammalian promoters with distal enhancer functions
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DOI：
10.1038/ng.3884
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发表时间：
2017-07-01
期刊：
影响因子：
30.8
通讯作者：
Spicuglia, Salvatore
中科院分区：
文献类型：
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作者：
Dao, Lan T. M.;Galindo-Albarran, Ariel O.;Spicuglia, Salvatore
哺乳动物中的基因表达是由启动子和基因远端调节区（称为增强子）的组合精确调节的。一些研究表明一些启动子可能具有增强子功能。然而，这种类型的启动子的范围以及它们是否确实起到调节远端基因表达的作用仍然难以捉摸。在这里，通过利用高通量增强子报告基因测定，我们揭示了一组显示增强子活性的哺乳动物启动子。这些启动子具有独特的基因组和表观基因组特征，并且经常与其他基因启动子相互作用。广泛的 CRISPR-Cas9 基因组操作证明了这些启动子参与其自然位点远端基因表达的顺式调节。我们的结果对于理解正常发育和疾病中复杂的基因调控具有重要意义。
Gene expression in mammals is precisely regulated by the combination of promoters and gene-distal regulatory regions, known as enhancers. Several studies have suggested that some promoters might have enhancer functions. However, the extent of this type of promoters and whether they actually function to regulate the expression of distal genes have remained elusive. Here, by exploiting a high-throughput enhancer reporter assay, we unravel a set of mammalian promoters displaying enhancer activity. These promoters have distinct genomic and epigenomic features and frequently interact with other gene promoters. Extensive CRISPR-Cas9 genomic manipulation demonstrated the involvement of these promoters in the cis regulation of expression of distal genes in their natural loci. Our results have important implications for the understanding of complex gene regulation in normal development and disease.