Mammalian heat shock response and mechanisms underlying its genome-wide transcriptional regulation
Open accessAbstract
The heat shock response (HSR) is critical for survival of all organisms. However, its scope, extent, and the molecular mechanism of regulation are poorly understood. Here we show that the genome-wide transcriptional response to heat shock in mammals is rapid and dynamic and results in induction of several hundred and repression of several thousand genes. Heat shock factor 1 (HSF1), the "master regulator" of the HSR, controls only a fraction of heat shock-induced genes and does so by increasing RNA polymerase II release from promoter-proximal pause. Notably, HSF2 does not compensate for the lack of HSF1. However, serum response factor appears to transiently induce cytoskeletal genes independently of HSF1. The pervasive repression of transcription is predominantly HSF1-independent and is mediated through reduction of RNA polymerase II pause release. Overall, mammalian cells orchestrate rapid, dynamic, and extensive changes in transcription upon heat shock that are largely modulated at pause release, and HSF1 plays a limited and specialized role.
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In invertebrates and mammals, HSF1 activates protein-folding chaperone expression in response to elevated unfolded proteins.
“In invertebrates and mammals, the transcription factor HSF1 activates expression of protein-folding chaperones in response to elevated levels of unfolded proteins (Labbadia and Morimoto, 2014; Mahat et al., 2016).”
From The Aging Epigenome (2016) · cites this paper as Mahat et al., 2016
In mammals, SRF and HSF2 contribute to the heat shock transcriptional response.
“In mammals, additional transcription factors, including SRF and HSF2, are important contributors to the transcriptional response to heat shock (Mahat et al., 2016).”
From The Aging Epigenome (2016) · cites this paper as Mahat et al., 2016
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- Authors
- Mahat, D. B., Salamanca, H. H., Duarte, F. M., Danko, C. G., & Lis, J. T.
- Affiliations
- Cornell University (US)
- Corresponding author
- Lis, John T.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 62
- Issue
- 1
- Pages
- 63-78
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC4826300
- OpenAlex
- W2306540679
- Cited by
- 426
- References
- 57
- Citations by year
- 2026: 34 · 2025: 41 · 2024: 45 · 2023: 31 · 2022: 53 · 2021: 46 · 2020: 55 · 2019: 47 · 2018: 37 · 2017: 26 · 2016: 10
- FWCI
- 20.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM025232, R01GM25232)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- heat shock response, heat shock factor 1, HSF2, serum response factor, transcriptional repression, mammalian cells, gene induction
- MeSH terms
- Heat Shock Transcription Factors, Animals, Cell Line, DNA-Binding Proteins, Fibroblasts, Gene Expression Regulation, Heat-Shock Proteins, Mammals, Promoter Regions, Genetic, RNA Polymerase II, Transcription Factors, Transcription, Genetic, Heat-Shock Response, Serum Response Factor, Mice
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