Aix-Marseille University, INSERM, TAGC, UMR 1090, Marseille, France.
INSERM, UMR 967, CEA/DRF/iRCM, Laboratory of Molecular Hematopoiesis, Université Paris-Diderot, Université Paris-Saclay, Fontenay-aux-Roses, France.
Nat Genet. 2017 Jul;49(7):1073-1081. doi: 10.1038/ng.3884. Epub 2017 Jun 5.
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.
哺乳动物的基因表达是通过启动子和基因远端调控区域（称为增强子）的组合精确调控的。有几项研究表明，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程度以及它们是否实际上起到调节远端基因表达的作用仍然难以捉摸。在这里，我们利用高通量增强子报告基因检测，揭示了一组具有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在其天然基因座中参与了远端基因表达的顺式调控。我们的研究结果对理解正常发育和疾病中的复杂基因调控具有重要意义。
