Otto-Warburg-Laboratory, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Berlin, Germany.
Transcription. 2022 Feb-Jun;13(1-3):70-81. doi: 10.1080/21541264.2022.2108302. Epub 2022 Sep 1.
Transcription elongation by RNA polymerase II (Pol II) has emerged as a regulatory hub in gene expression. A key control point occurs during early transcription elongation when Pol II pauses in the promoter-proximal region at the majority of genes in mammalian cells and at a large set of genes in . An increasing number of -acting factors have been linked to promoter-proximal pausing. Some factors help to establish the pause, whereas others are required for the release of Pol II into productive elongation. A dysfunction of this elongation control point leads to aberrant gene expression and can contribute to disease development. The BET bromodomain protein BRD4 has been implicated in elongation control. However, only recently direct BRD4-specific functions in Pol II transcription elongation have been uncovered. This mainly became possible with technological advances that allow selective and rapid ablation of BRD4 in cells along with the availability of approaches that capture the immediate consequences on nascent transcription. This review sheds light on the experimental breakthroughs that led to the emerging view of BRD4 as a general regulator of transcription elongation.
RNA 聚合酶 II（Pol II）的转录延伸已成为基因表达的调控中心。在早期转录延伸过程中，当 Pol II 在哺乳动物细胞中大多数基因的启动子近端区域以及大量基因中暂停时，就会出现一个关键的控制点。越来越多的转录延伸因子与启动子近端暂停有关。一些因子有助于建立暂停，而另一些因子则需要 Pol II 进入有效的延伸。这个延伸控制点的功能障碍会导致异常的基因表达，并可能导致疾病的发展。BET 溴结构域蛋白 BRD4 被认为与延伸控制有关。然而，直到最近，BRD4 在 Pol II 转录延伸中的直接特异性功能才被揭示。这主要得益于技术的进步，这些技术允许在细胞中选择性和快速地消除 BRD4，同时还提供了捕捉新生转录的直接后果的方法。这篇综述介绍了导致 BRD4 作为转录延伸的通用调节剂的新兴观点的实验突破。
