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Nat Commun. 2017 Aug 15;8(1):255. doi: 10.1038/s41467-017-00151-0.

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

Author information

1
Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, 20520, Finland.
2
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, 14853, USA.
3
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, 22908, USA.
4
Department of Biomedical Sciences, The Baker Institute for Animal Health, Cornell University, Ithaca, New York, 14853, USA.
5
Graduate Field of Computational Biology, Cornell University, Ithaca, New York, 14853, USA.
6
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, 14853, USA. jtl10@cornell.edu.
7
Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, 20520, Finland. lea.sistonen@abo.fi.

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.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.

PMID:
28811569
PMCID:
PMC5557961
DOI:
10.1038/s41467-017-00151-0
[Indexed for MEDLINE]
Free PMC Article

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