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

To examine whether the faster release of Pol II into productive elongation served as a general 152! mechanism for accelerated induction, we compared transcription programs upon heat shock 153! between unconditioned and preconditioned cells. The instant 12.5-minute heat shock showed the 154! highest variation in gene expression due to preconditioning ( Figure S2A ), which supports 155! observations from individual genes that preconditioning with a single heat shock primarily 156! affected the onset of the transcriptional response (Figure 2B-C; Figure S2B ). Noteworthy is that 157! these changes in nascent RNA synthesis, as measured at the steps of initiation, pause-release and 158! ongoing elongation, can only be detected with assays that directly track engaged Pol II complexes 159! Figure S2A ). This pattern of engaged Pol II molecules demonstrated faster progression of 169! Pol II from initiation into elongation in the daughters of heat-shocked cells. Importantly, we did 170! not detect preconditioning to accelerate heat responsiveness of genes that were instantly activated 171! already in unconditioned cells ( Figure S2C ). Neither was kinetics of the classical heat shock 172! genes changed ( Figure S2D ). Consequently, preconditioning with a single heat shock did not 173! globally reduce response time, but primed an additional set of genes for a rapid heat-induction. 174!