Molecular and Cellular Biology, School of Biosciences, Sheffield Institute For Nucleic Acids, The University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
Development. 2022 Aug 15;149(16). doi: 10.1242/dev.200398. Epub 2022 Aug 30.
Enhancers confer precise spatiotemporal patterns of gene expression in response to developmental and environmental stimuli. Over the last decade, the transcription of enhancer RNAs (eRNAs) - nascent RNAs transcribed from active enhancers - has emerged as a key factor regulating enhancer activity. eRNAs are relatively short-lived RNA species that are transcribed at very high rates but also quickly degraded. Nevertheless, eRNAs are deeply intertwined within enhancer regulatory networks and are implicated in a number of transcriptional control mechanisms. Enhancers show changes in function and sequence over evolutionary time, raising questions about the relationship between enhancer sequences and eRNA function. Moreover, the vast majority of single nucleotide polymorphisms associated with human complex diseases map to the non-coding genome, with causal disease variants enriched within enhancers. In this Primer, we survey the diverse roles played by eRNAs in enhancer-dependent gene expression, evaluating different models for eRNA function. We also explore questions surrounding the genetic conservation of enhancers and how this relates to eRNA function and dysfunction.
增强子赋予基因表达精确的时空模式，以响应发育和环境刺激。在过去的十年中，增强子 RNA（eRNA）的转录——从活跃增强子转录的新生 RNA——已成为调节增强子活性的关键因素。eRNA 是相对短命的 RNA 种类，其转录速度非常快，但也很快降解。然而，eRNAs 深深交织在增强子调控网络中，并涉及许多转录控制机制。增强子在进化过程中表现出功能和序列的变化，这引发了关于增强子序列和 eRNA 功能之间关系的问题。此外，与人类复杂疾病相关的绝大多数单核苷酸多态性都映射到非编码基因组上，因果疾病变体在增强子中富集。在这篇概述中，我们调查了 eRNA 在增强子依赖的基因表达中发挥的多种作用，评估了 eRNA 功能的不同模型。我们还探讨了增强子的遗传保守性问题，以及这与 eRNA 功能和功能障碍的关系。
