Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
Medical University of Vienna, Vienna Biocenter (VBC), Vienna, Austria.
Nat Rev Mol Cell Biol. 2018 Oct;19(10):621-637. doi: 10.1038/s41580-018-0028-8.
RNA polymerase II (Pol II) core promoters are specialized DNA sequences at transcription start sites of protein-coding and non-coding genes that support the assembly of the transcription machinery and transcription initiation. They enable the highly regulated transcription of genes by selectively integrating regulatory cues from distal enhancers and their associated regulatory proteins. In this Review, we discuss the defining properties of gene core promoters, including their sequence features, chromatin architecture and transcription initiation patterns. We provide an overview of molecular mechanisms underlying the function and regulation of core promoters and their emerging functional diversity, which defines distinct transcription programmes. On the basis of the established properties of gene core promoters, we discuss transcription start sites within enhancers and integrate recent results obtained from dedicated functional assays to propose a functional model of transcription initiation. This model can explain the nature and function of transcription initiation at gene starts and at enhancers and can explain the different roles of core promoters, of Pol II and its associated factors and of the activating cues provided by enhancers and the transcription factors and cofactors they recruit.
RNA 聚合酶 II（Pol II）核心启动子是蛋白编码和非编码基因转录起始位点的特异性 DNA 序列，支持转录机器的组装和转录起始。它们通过选择性整合来自远端增强子及其相关调节蛋白的调节信号，实现基因的高度调控转录。在这篇综述中，我们讨论了基因核心启动子的定义特性，包括它们的序列特征、染色质结构和转录起始模式。我们概述了核心启动子功能和调节的分子机制及其新兴的功能多样性，这些多样性定义了不同的转录程序。基于基因核心启动子的既定特性，我们讨论了增强子内的转录起始位点，并整合了专门的功能测定中获得的最新结果，提出了转录起始的功能模型。该模型可以解释基因起始和增强子处转录起始的性质和功能，以及核心启动子、Pol II 及其相关因子以及增强子提供的激活信号和它们募集的转录因子和辅助因子的不同作用。
