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 () and Lea Sistonen ()
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Anniina Vihervaara: Åbo Akademi University
Dig Bijay Mahat: Cornell University
Michael J. Guertin: University of Virginia
Tinyi Chu: Cornell University
Charles G. Danko: Cornell University
John T. Lis: Cornell University
Lea Sistonen: Åbo Akademi University

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00151-0

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