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

• Published in: Nature communications 2017-08, Vol.8 (1), p.255-16, Article 255
• Main Authors: Vihervaara, Anniina, Mahat, Dig Bijay, Guertin, Michael J., Chu, Tinyi, Danko, Charles G., Lis, John T., Sistonen, Lea
• Format: Article
• Language: English
• Subjects: 631/208/200; 631/337/100/101; 631/337/100/2285; 631/80/86/2366; Acetylation; Cell Line; Chromatin; Enhancer Elements, Genetic; Enhancers; Gene expression; Gene Expression Regulation; Heat shock; Heat shock factors; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Heat-Shock Response; HSF1 protein; Humanities and Social Sciences; Humans; multidisciplinary; Promoter Regions, Genetic; Promoters; Psychological stress; RNA polymerase; Science; Science (multidisciplinary); Stress, Physiological; Transcription; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-00151-0

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.