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

Pathophysiological stresses, such as those encountered during cancer progression and 193! neurodegeneration, are often sustained or repeated. To be able to investigate how repeatedly 194! encountered stress affects gene and enhancer transcription, we moved from stress-sensitive MEFs 195! to human K562 erythroleukemia cells. K562 cells are a patient-derived cancer cell line (Lozzio 196! and Lozzio, 1975; Koeffler and Kolde, 1980) , known to tolerate extended heat treatments and 197! develop thermotolerance (Mivecchi, 1989; . We preconditioned K562 198! cells with a series of heat shocks, giving a total nine 1-hour heat treatments during three 199! consecutive days, and allowed for a 48-hour recovery before measuring transcriptional response 200! to an additional single heat shock ( Figure 3A ). It is important to note that K562 cells proliferated 201! ! ! 9! throughout the six days of preconditioning, recovery and additional heat shock ( Figure S3A