A heat shock–responsive lncRNA Heat acts as a HSF1-directed transcriptional brake via m6A modification

Long noncoding RNAs (lncRNAs) are key regulators of gene expression in diverse cellular contexts and biological processes. Given the surprising range of shapes and sizes, how distinct lncRNAs achieve functional specificity remains incompletely understood. Here, we identified a heat shock–inducible lncRNA, Heat, in mouse cells that acts as a transcriptional brake to restrain stress gene expression. Functional characterization reveals that Heat directly binds to heat shock transcription factor 1 (HSF1), thereby targeting stress genes in a trans-acting manner. Intriguingly, Heat is heavily methylated in the form of m6A. Although dispensable for HSF1 binding, Heat methylation is required for silencing stress genes to attenuate heat shock response. Consistently, m6A depletion results in prolonged activation of stress genes. Furthermore, Heat mediates these effects via the nuclear m6A reader YTHDC1, forming a transcriptional silencing complex for stress genes. Our study reveals a crucial role of nuclear epitranscriptome in the transcriptional regulation of heat shock response.

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The heat shock response: A case study of chromatin dynamics in gene regulation

Biochemistry and Cell Biology ◽

10.1139/bcb-2012-0075 ◽

2013 ◽

Vol 91 (1) ◽

pp. 42-48 ◽

Cited By ~ 11

Author(s):

Sheila S. Teves ◽

Steven Henikoff

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Heat Shock ◽

Heat Shock Response ◽

Control Of Gene Expression ◽

Pol Ii ◽

Chromatin Dynamics ◽

Regulatory Processes ◽

Shock Response ◽

Rate Limiting

Recent studies in transcriptional regulation using the Drosophila heat shock response system have elucidated many of the dynamic regulatory processes that govern transcriptional activation and repression. The classic view that the control of gene expression occurs at the point of RNA polymerase II (Pol II) recruitment is now giving way to a more complex outlook of gene regulation. Promoter chromatin dynamics coordinate with transcription factor binding to maintain the promoters of active genes accessible. For a large number of genes, the rate-limiting step in Pol II progression occurs during its initial elongation, where Pol II transcribes 30–50 bp and pauses for further signals. These paused genes have unique genic chromatin architecture and dynamics compared with genes where Pol II recruitment is rate limiting for expression. Further elongation of Pol II along the gene causes nucleosome turnover, a continuous process of eviction and replacement, which suggests a potential mechanism for Pol II transit along a nucleosomal template. In this review, we highlight recent insights into transcription regulation of the heat shock response and discuss how the dynamic regulatory processes involved at each transcriptional stage help to generate faithful yet highly responsive gene expression.

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Allograft injury mediated by reactive oxygen species: from conserved proteins of Drosophila to acute and chronic rejection of human transplants. Part II: Role of reactive oxygen species in the induction of the heat shock response as a regulator of innate

Transplantation Reviews ◽

10.1053/trre.2003.2 ◽

2003 ◽

Vol 17 (1) ◽

pp. 31-44 ◽

Cited By ~ 12

Author(s):

Walter Land

Keyword(s):

Reactive Oxygen Species ◽

Heat Shock ◽

Heat Shock Response ◽

Chronic Rejection ◽

Reactive Oxygen ◽

Oxygen Species ◽

Shock Response

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Ubiquitin gene expression in Dictyostelium is induced by heat and cold shock, cadmium, and inhibitors of protein synthesis

Journal of Cell Science ◽

10.1242/jcs.90.1.51 ◽

1988 ◽

Vol 90 (1) ◽

pp. 51-58 ◽

Cited By ~ 1

Author(s):

A. Muller-Taubenberger ◽

J. Hagmann ◽

A. Noegel ◽

G. Gerisch

Keyword(s):

Gene Expression ◽

Protein Synthesis ◽

Heat Shock ◽

Differential Expression ◽

Dictyostelium Discoideum ◽

Heat Shock Response ◽

Cold Shock ◽

Multifunctional Protein ◽

Cadmium Treatment ◽

Shock Response

Ubiquitin is a highly conserved, multifunctional protein, which is implicated in the heat-shock response of eukaryotes. The differential expression of the multiple ubiquitin genes in Dictyostelium discoideum was investigated under various stress conditions. Growing D. discoideum cells express four major ubiquitin transcripts of sizes varying from 0.6 to 1.9 kb. Upon heat shock three additional ubiquitin mRNAs of 0.9, 1.2 and 1.4 kb accumulate within 30 min. The same three transcripts are expressed in response to cold shock or cadmium treatment. Inhibition of protein synthesis by cycloheximide leads to a particularly strong accumulation of the larger ubiquitin transcripts, which code for polyubiquitins. Possible mechanisms regulating the expression of ubiquitin transcripts upon heat shock and other stresses are discussed.

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Thermal acclimation alters both basal heat shock protein gene expression and the heat shock response in juvenile lake whitefish (Coregonus clupeaformis)

Journal of Thermal Biology ◽

10.1016/j.jtherbio.2021.103185 ◽

2022 ◽

pp. 103185

Author(s):

Lori A. Manzon ◽

Megan A. Zak ◽

Matthew Agee ◽

Douglas R. Boreham ◽

Joanna Y. Wilson ◽

...

Keyword(s):

Gene Expression ◽

Heat Shock ◽

Heat Shock Protein ◽

Heat Shock Response ◽

Protein Gene ◽

Thermal Acclimation ◽

Coregonus Clupeaformis ◽

Lake Whitefish ◽

Heat Shock Protein Gene ◽

Shock Response

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Thermal acclimation changes DNA-binding activity of heat shock factor 1(HSF1) in the gobyGillichthys mirabilis: implications for plasticity in the heat-shock response in natural populations

Journal of Experimental Biology ◽

10.1242/jeb.205.20.3231 ◽

2002 ◽

Vol 205 (20) ◽

pp. 3231-3240 ◽

Cited By ~ 6

Author(s):

Bradley A. Buckley ◽

Gretchen E. Hofmann

Keyword(s):

Gene Expression ◽

Heat Shock ◽

Heat Shock Response ◽

Environmental Control ◽

Heat Shock Factor ◽

Thermal Acclimation ◽

Model Systems ◽

Threshold Temperature ◽

Heat Shock Factor 1 ◽

Shock Response

SUMMARYThe intracellular build-up of thermally damaged proteins following exposure to heat stress results in the synthesis of a family of evolutionarily conserved proteins called heat shock proteins (Hsps) that act as molecular chaperones, protecting the cell against the aggregation of denatured proteins. The transcriptional regulation of heat shock genes by heat shock factor 1(HSF1) has been extensively studied in model systems, but little research has focused on the role HSF1 plays in Hsp gene expression in eurythermal organisms from broadly fluctuating thermal environments. The threshold temperature for Hsp induction in these organisms shifts with the recent thermal history of the individual but the mechanism by which this plasticity in Hsp induction temperature is achieved is unknown. We examined the effect of thermal acclimation on the heat-activation of HSF1 in the eurythermal teleost Gillichthys mirabilis. After a 5-week acclimation period (at 13, 21 or 28°C) the temperature of HSF1 activation was positively correlated with acclimation temperature. HSF1 activation peaked at 27°C in fish acclimated to 13°C, at 33°C in the 21°C group, and at 36°C in the 28°C group. Concentrations of both HSF1 and Hsp70 in the 28°C group were significantly higher than in the colder acclimated fish. Plasticity in HSF1 activation may be important to the adjustable nature of the heat shock response in eurythermal organisms and the environmental control of Hsp gene expression.

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