Stress-induced transcriptional memory accelerates promoter-proximal pause release and decelerates termination over mitotic divisions.
Stress-induced transcriptional memory accelerates promoter-proximal pause release and decelerates termination over mitotic divisions.
复制标题
应激诱导的转录记忆加速启动子-近端停顿的释放，并减慢有丝分裂的终止。
DOI：
10.1016/j.molcel.2021.03.007
复制
发表时间：
2021-04-15
期刊：
影响因子：
16
通讯作者：
Sistonen L
中科院分区：
文献类型：
--
作者：
Vihervaara A;Mahat DB;Himanen SV;Blom MAH;Lis JT;Sistonen L
热休克会立即重新编写转录程序。基因和增强子转录是否从应激中完全恢复，以及应激是否通过激发转录调控而建立记忆，并持续到有丝分裂，目前尚不清楚。在这里，我们测量了非条件细胞和应激暴露细胞子代的新生转录和染色质可及性。在核苷酸分辨率下跟踪全基因组转录表明，细胞在从应激恢复时精确地恢复了RNA聚合酶II(POL II)在基因体和增强子上的分布。然而，胚胎成纤维细胞的单次热暴露通过增加启动子近端的POL II停顿和加速停顿-释放，在其子代细胞中启动了更快的基因诱导。在K562红白血病细胞中，反复应激细化了基础转录和热诱导的过度有丝分裂，并减慢了终止偶联的Pre-mRNA处理。较慢的终止保留了染色质上的转录物，减少了POL II的再循环。这些结果表明，热诱导的转录记忆是通过转录终止时启动子近端的暂停释放和mRNA的预处理来发挥作用的。热休克在基因和增强子上重新编程转录。Vihervaara等人。揭示了细胞在热暴露后精确地恢复了转录程序，并建立了对应激的转录记忆。在应激细胞的子代中，增加POL II暂停释放加速基因激活，减少转录终止减慢mRNA的处理。
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 restore 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. Heat shock reprograms transcription at genes and enhancers. Vihervaara et al. reveal that cells precisely restore transcription program after heat exposure, and that cells establish a transcriptional memory of stress. In the daughters of stressed cells, increased Pol II pause-release accelerates gene activation and reduced transcription termination decelerates mRNA processing.
登录
查看更多内容
影响因子：
2.9
作者：
Chen M;Xie S
通讯作者：
Xie S
影响因子：
16
作者：
Fujiwara T;O'Geen H;Keles S;Blahnik K;Linnemann AK;Kang YA;Choi K;Farnham PJ;Bresnick EH
通讯作者：
Bresnick EH
影响因子：
30.8
作者：
Corces, M. Ryan;Buenrostro, Jason D.;Wu, Beijing;Greenside, Peyton G.;Chan, Steven M.;Koenig, Julie L.;Snyder, Michael P.;Pritchard, Jonathan K.;Kundaje, Anshul;Gkeenleaf, William J.;Majeti, Ravindra;Chang, Howard Y.
通讯作者：
Chang, Howard Y.
影响因子：
2.5
作者：
D'Urso A;Brickner JH
通讯作者：
Brickner JH
影响因子：
10.5
作者：
Ahn, SG;Liu, PCC;Thiele, DJ
通讯作者：
Thiele, DJ