Simpson Querrey Center for Epigenetics and the Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Nat Rev Mol Cell Biol. 2018 Jul;19(7):464-478. doi: 10.1038/s41580-018-0010-5.
The dynamic regulation of transcription elongation by RNA polymerase II (Pol II) is an integral part of the implementation of gene expression programmes during development. In most metazoans, the majority of transcribed genes exhibit transient pausing of Pol II at promoter-proximal regions, and the release of Pol II into gene bodies is controlled by many regulatory factors that respond to environmental and developmental cues. Misregulation of the elongation stage of transcription is implicated in cancer and other human diseases, suggesting that mechanistic understanding of transcription elongation control is therapeutically relevant. In this Review, we discuss the features, establishment and maintenance of Pol II pausing, the transition into productive elongation, the control of transcription elongation by enhancers and by factors of other cellular processes, such as topoisomerases and poly(ADP-ribose) polymerases (PARPs), and the potential of therapeutic targeting of the elongation stage of transcription by Pol II.
RNA 聚合酶 II（Pol II）转录延伸的动态调控是发育过程中基因表达程序实施的一个组成部分。在大多数后生动物中，大多数转录基因在启动子近端区域表现出 Pol II 的瞬时暂停，Pol II 进入基因体的释放由许多调节因子控制，这些调节因子对环境和发育信号做出反应。转录延伸阶段的调控失常与癌症和其他人类疾病有关，这表明对转录延伸控制的机制理解具有治疗相关性。在这篇综述中，我们讨论了 Pol II 暂停的特征、建立和维持、进入生产性延伸的转变、增强子和拓扑异构酶和多（ADP-核糖）聚合酶（PARPs）等其他细胞过程因子对转录延伸的控制，以及通过 Pol II 对转录延伸阶段进行治疗靶向的潜力。
