Transcriptional response to stress is pre-wired by promoter and enhancer architecture
Open accessAbstract
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.
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The capacity of an expressed TF to interact with an enhancer may depend on the chromatin state of the region, which is a function of a cell's present state and developmental history.
“But even this generality is complicated by the fact that the capacity of an expressed TF to interact with an enhancer may depend on the chromatin state of the region in which the enhancer resides100, which is in turn a function not only of a cell’s present state but also its developmental history.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [100]
The Results (‘Lineage-specific factors prime enhancer activation’; page unavailable) link enhancer responsiveness to pre-existing lineage-specific factors, supporting a role for cellular context. But the Results (‘HSF1 binding and histone acetylation at untranscribed loci’; page unavailable) say closed chromatin did not prevent HSF1 binding. The paper therefore does not establish that chromatin state limits a TF’s capacity to interact with an enhancer, and it does not directly examine developmental history. (LLM, conf=0.82)
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- Authors
- Vihervaara, A., Mahat, D. B., Guertin, M. J., Chu, T., Danko, C. G., Lis, J. T., & Sistonen, L.
- Affiliations
- Åbo Akademi University (FI)
- Cornell University (US)
- University of Virginia (US)
- Corresponding author
- Lis, John T.
- Sistonen, Lea
- ORCID
- Venue
- Nature Communications
- Published
- 2017-08-15
- Volume
- 8
- Issue
- 1
- Pages
- 255-255
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5557961
- OpenAlex
- W2743018412
- Cited by
- 164
- References
- 81
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 9 · 2023: 14 · 2022: 24 · 2021: 29 · 2020: 25 · 2019: 15 · 2018: 14 · 2017: 1
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Åbo Akademi University Research Portal (submittedVersion)
- Funders
- Magnus Ehrnroothin Säätiö
- Sigrid Juséliuksen Säätiö
- Åbo Akademi
- National Institutes of Health (GM25232)
- National Institute of General Medical Sciences (R01GM025232)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- divergent transcription, promoter architecture, enhancer architecture, histone H4 acetylation, RNA polymerase pausing, heat shock factor 1, CTCF, chromatin organization, transcriptional reprogramming, heat shock response
- MeSH terms
- Acetylation, Cell Line, Enhancer Elements, Genetic, Gene Expression Regulation, Heat-Shock Proteins, Humans, Promoter Regions, Genetic, Stress, Physiological, Transcription Factors, Transcription, Genetic, Heat-Shock Response
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