Altendorfer Elisabeth, Mundlos Stefan, Mayer Andreas
Otto-Warburg-Laboratory, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Development and Disease group, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Nat Struct Mol Biol. 2025 Apr;32(4):598-606. doi: 10.1038/s41594-025-01523-7. Epub 2025 Apr 11.
How enhancers communicate with their target genes to influence transcription is an unresolved question of fundamental importance. Current models of the mechanism of enhancer-target gene or enhancer-promoter (E-P) communication are transcription-factor-centric and underappreciate major findings, including that enhancers are themselves transcribed by RNA polymerase II, which correlates with enhancer activity. In this Perspective, we posit that enhancer transcription and its products, enhancer RNAs, are elementary components of enhancer-gene communication. Specifically, we discuss the possibility that transcription at enhancers and at their cognate genes are linked and that this coupling is at the basis of how enhancers communicate with their targets. This model of transcriptional coupling between enhancers and their target genes is supported by growing experimental evidence and represents a synthesis of recent key discoveries.
增强子如何与它们的靶基因进行通信以影响转录，这是一个尚未解决但具有根本重要性的问题。当前关于增强子-靶基因或增强子-启动子（E-P）通信机制的模型是以转录因子为中心的，并且没有充分重视一些主要发现，包括增强子本身由RNA聚合酶II转录，这与增强子活性相关。在本观点文章中，我们假定增强子转录及其产物，即增强子RNA，是增强子-基因通信的基本组成部分。具体而言，我们讨论了增强子及其同源基因处的转录是相互关联的可能性，并且这种偶联是增强子与其靶标进行通信的基础。增强子与其靶基因之间的这种转录偶联模型得到了越来越多实验证据的支持，并且代表了近期关键发现的综合。
