Stress-Induced Transcriptional Memory Accelerates Promoter-Proximal Pause-Release and Decelerates Termination over Mitotic Divisions

Anniina Vihervaara; Dig Bijay Mahat; Samu V. Himanen; Malin A.H. Blom; John T. Lis; Lea Sistonen

The ability of a cell to rapidly and robustly restore its cell type-specific transcription after heat 362! shock is mechanistically explained by the genome-wide control of promoter-proximal Pol II 363! pause-release. An important consequence of repressing thousands of genes by preventing the 364! release of Pol II from their promoter-proximal regions is its rapid reversibility; a simple re-365! activation of the pause-release can restore productive gene transcription genome-wide without 366! extensive chromatin remodeling. In this regard, Pol II pausing can be considered as one form of a 367! which is unlikely to cause permanent or long-lasting damage to the cell, did not change the basal 386! transcription, but it increased Pol II pausing ( Figure 1 ). Moreover, a single heat shock accelerated 387! heat-induced transcription in the daughter cells by allowing more efficient progression of Pol II 388! through the pause-region (Figure 2 ). This faster responsiveness without a change in the basal 389! transcription mechanistically explains how cells can retain a memory of previously encountered 390! stress to prepare their daughter cells for protection against proteotoxicity (Figure 7) . 391!