Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA and Core-Laboratory, College of Medicine, Korea University, Seoul 136-701, Republic of Korea.
Nucleic Acids Res. 2013 Sep;41(17):8126-34. doi: 10.1093/nar/gkt597. Epub 2013 Jul 10.
In eukaryotic cells, gene expression is mediated by enhancer activation of RNA polymerase at distant promoters. Recently, distinctions between enhancers and promoters have been blurred by the discovery that enhancers are associated with RNA polymerase and are sites of RNA synthesis. Here, we present an analysis of the insulin-like growth factor 2/H19 muscle enhancer. This enhancer includes a short conserved core element that is organized into chromatin typical of mammalian enhancers, binds tissue-specific transcription factors and functions on its own in vitro to activate promoter transcription. However, in a chromosomal context, this element is not sufficient to activate distant promoters. Instead, enhancer function also requires transcription in cis of a long non-coding RNA, Nctc1. Thus, the insulin-like growth factor 2/H19 enhancer is an active transcriptional complex whose own transcription is essential to its function.
在真核细胞中,基因表达是通过增强子激活 RNA 聚合酶在遥远的启动子上实现的。最近,通过发现增强子与 RNA 聚合酶相关,并且是 RNA 合成的位点,增强子和启动子之间的区别已经变得模糊。在这里,我们对胰岛素样生长因子 2/H19 肌肉增强子进行了分析。该增强子包含一个短的保守核心元件,该元件组织成典型的哺乳动物增强子的染色质,结合组织特异性转录因子,并在体外自身发挥作用以激活启动子转录。然而,在染色体环境中,该元件不足以激活遥远的启动子。相反,增强子功能还需要长非编码 RNA Nctc1 的顺式转录。因此,胰岛素样生长因子 2/H19 增强子是一个活跃的转录复合物,其自身的转录对于其功能至关重要。