Transcriptional response to stress is pre-wired by promoter and enhancer architecture

Anniina Vihervaara, Dig Bijay Mahat, Michael J Guertin, Tinyi Chu, Charles G Danko, John T Lis, Lea Sistonen

Research output: Contribution to journalArticleScientificpeer-review


Programs of gene expression are executed by a battery of transcription factors that coordinate divergent transcription from a pair of tightly linked core initiation regions of promoters and enhancers. Here, to investigate how divergent transcription is reprogrammed upon stress, we measured nascent RNA synthesis at nucleotide-resolution, and profiled histone H4 acetylation in human cells. Our results globally show that the release of promoter-proximal paused RNA polymerase into elongation functions as a critical switch at which a gene's response to stress is determined. Highly transcribed and highly inducible genes display strong transcriptional directionality and selective assembly of general transcription factors on the core sense promoter. Heat-induced transcription at enhancers, instead, correlates with prior binding of cell-type, sequence-specific transcription factors. Activated Heat Shock Factor 1 (HSF1) binds to transcription-primed promoters and enhancers, and CTCF-occupied, non-transcribed chromatin. These results reveal chromatin architectural features that orient transcription at divergent regulatory elements and prime transcriptional responses genome-wide.Heat Shock Factor 1 (HSF1) is a regulator of stress-induced transcription. Here, the authors investigate changes to transcription and chromatin organization upon stress and find that activated HSF1 binds to transcription-primed promoters and enhancers, and to CTCF occupied, untranscribed chromatin.

Original languageEnglish
Pages (from-to)255
JournalNature Communications
Issue number1
Publication statusPublished - 15 Aug 2017
MoE publication typeA1 Journal article-refereed


  • Acetylation
  • Cell Line
  • Enhancer Elements, Genetic
  • Gene Expression Regulation
  • Heat-Shock Proteins/genetics
  • Heat-Shock Response
  • Humans
  • Promoter Regions, Genetic
  • Stress, Physiological
  • Transcription Factors/genetics
  • Transcription, Genetic


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