Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland; Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA; Department of Gene Technology, Science for Life Laboratory, KTH Royal Institute of Technology, 17165 Stockholm, Sweden.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Mol Cell. 2021 Apr 15;81(8):1715-1731.e6. doi: 10.1016/j.molcel.2021.03.007. Epub 2021 Mar 29.
Heat shock instantly reprograms transcription. Whether gene and enhancer transcription fully recover from stress and whether stress establishes a memory by provoking transcription regulation that persists through mitosis remained unknown. Here, we measured nascent transcription and chromatin accessibility in unconditioned cells and in the daughters of stress-exposed cells. Tracking transcription genome-wide at nucleotide-resolution revealed that cells precisely restored RNA polymerase II (Pol II) distribution at gene bodies and enhancers upon recovery from stress. However, a single heat exposure in embryonic fibroblasts primed a faster gene induction in their daughter cells by increasing promoter-proximal Pol II pausing and by accelerating the pause release. In K562 erythroleukemia cells, repeated stress refined basal and heat-induced transcription over mitotic division and decelerated termination-coupled pre-mRNA processing. The slower termination retained transcripts on the chromatin and reduced recycling of Pol II. These results demonstrate that heat-induced transcriptional memory acts through promoter-proximal pause release and pre-mRNA processing at transcription termination.
热休克即刻重新编程转录。基因和增强子转录是否能从压力中完全恢复，以及压力是否通过持续到有丝分裂的转录调控来建立记忆，这些仍然未知。在这里，我们在未处理的细胞和暴露于压力的细胞的子细胞中测量了新生转录和染色质可及性。在全基因组范围内跟踪转录，发现在从压力中恢复后，细胞精确地恢复了 RNA 聚合酶 II（Pol II）在基因体和增强子上的分布。然而，胚胎成纤维细胞中的单次热暴露通过增加启动子近端 Pol II 暂停和加速暂停释放，在其子细胞中预先诱导更快的基因诱导。在 K562 红细胞白血病细胞中，重复的应激通过有丝分裂分裂来优化基础和热诱导的转录，并减慢终止偶联的前体 RNA 加工。较慢的终止保留了染色质上的转录本，并减少了 Pol II 的回收。这些结果表明，热诱导的转录记忆通过启动子近端暂停释放和转录终止处的前体 RNA 加工起作用。
