Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Nature. 2013 Jun 27;498(7455):516-20. doi: 10.1038/nature12210. Epub 2013 Jun 2.
The functional importance of gene enhancers in regulated gene expression is well established. In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation. Here we report that in human breast cancer cells 17β-oestradiol (E2)-bound oestrogen receptor α (ER-α) causes a global increase in eRNA transcription on enhancers adjacent to E2-upregulated coding genes. These induced eRNAs, as functional transcripts, seem to exert important roles for the observed ligand-dependent induction of target coding genes, increasing the strength of specific enhancer-promoter looping initiated by ER-α binding. Cohesin, present on many ER-α-regulated enhancers even before ligand treatment, apparently contributes to E2-dependent gene activation, at least in part by stabilizing E2/ER-α/eRNA-induced enhancer-promoter looping. Our data indicate that eRNAs are likely to have important functions in many regulated programs of gene transcription.
基因增强子在调控基因表达中的功能重要性已得到充分证实。除了哺乳动物细胞中长链非编码 RNA（lncRNA）的广泛转录外，双向 ncRNA 也在增强子上转录，因此被称为增强子 RNA（eRNA）。然而，这些 eRNA 是否具有功能，还是仅仅反映了增强子的激活，仍然不清楚。在这里，我们报告在人类乳腺癌细胞中，17β-雌二醇（E2）结合的雌激素受体 α（ER-α）导致邻近 E2 上调编码基因的增强子上的 eRNA 转录全局增加。这些诱导的 eRNA 作为功能性转录本，似乎对观察到的配体依赖性靶编码基因诱导发挥重要作用，增加了由 ER-α 结合起始的特定增强子-启动子环的强度。即使在配体处理之前，黏合蛋白也存在于许多 ER-α 调控的增强子上，显然有助于 E2 依赖性基因激活，至少部分原因是通过稳定 E2/ER-α/eRNA 诱导的增强子-启动子环。我们的数据表明，eRNA 可能在许多受调控的基因转录程序中具有重要功能。
