Proteotoxic stress, that is, stress caused by protein misfolding and aggregation, triggers the rapid and global reprogramming of transcription at genes and enhancers. Genome-wide assays that track transcriptionally engaged RNA polymerase II (Pol II) at nucleotide resolution have provided key insights into the underlying molecular mechanisms that regulate transcriptional responses to stress. In addition, recent kinetic analyses of transcriptional control under heat stress have shown how cells ‘prewire’ and rapidly execute genome-wide changes in transcription while concurrently becoming poised for recovery. The regulation of Pol II at genes and enhancers in response to heat stress is coupled to chromatin modification and compartmentalization, as well as to co-transcriptional RNA processing. These mechanistic features seem to apply broadly to other coordinated genome-regulatory responses.

蛋白质毒性应激，即由蛋白质错误折叠和聚集引起的应激，会触发基因和增强子转录的快速和全局重编程。在核苷酸分辨率下跟踪转录参与的 RNA 聚合酶 II (Pol II) 的全基因组测定为调节转录应激反应的潜在分子机制提供了关键见解。此外，最近对热应激下转录控制的动力学分析表明，细胞如何“预接线”并快速执行全基因组转录变化，同时为恢复做好准备。响应热应激的基因和增强子上 Pol II 的调节与染色质修饰和区室化以及共转录 RNA 加工相结合。