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

Reversing from a differentiated to pluripotent cell, instead, requires specific transcription factors 350! that push the cell up the energy landscape, which rarely occurs in nature (Gurdon et al., 1958; 351! Takahashi and Yamanaka 2006) . In this study, we showed that after genome-wide 352! reprogramming of transcription by heat shock, cells robustly return to their cell type-specific 353! transcription program within hours of recovery ( Figure 1 ). In Waddington's landscape, the heat-354! induced reprogramming of thousands of genes would be analogous with the cell transiently 355! occupying a near-by valley, but during recovery, returning to its cell type-specific basal 356! transcription program without acquiring new functions or committing to differentiation. This 357! rapidly reprogrammed and precisely recovered transcription of genes and enhancers highlights 358! the plasticity of transcription program, and implies that the transcriptional heat shock response is 359! truly transient.