Identification of a Novel cis-Regulatory Element Involved in the Heat Shock Response in Caenorhabditis elegans Using Microarray Gene Expression and Computational Methods

To mitigate the deleterious effects of temperature increases on cellular organization and proteotoxicity, organisms have developed mechanisms to respond to heat stress. In eukaryotes, HSF1 is the master regulator of the heat shock transcriptional response, but the heat shock response pathway is not yet fully understood. From a forward genetic screen for suppressors of heat-shock-induced gene expression in Caenorhabditis elegans, we found a new allele of hsf-1 that alters its DNA-binding domain, and we found three additional alleles of sup-45, a previously molecularly uncharacterized genetic locus. We identified sup-45 as one of the two hitherto unknown C. elegans orthologs of the human AF4/FMR2 family proteins, which are involved in regulation of transcriptional elongation rate. We thus renamed sup-45 as affl-2 (AF4/FMR2-Like). Through RNA-seq, we demonstrated that affl-2 mutants are deficient in heat-shock-induced transcription. Additionally, affl-2 mutants have herniated intestines, while worms lacking its sole paralog (affl-1) appear wild type. AFFL-2 is a broadly expressed nuclear protein, and nuclear localization of AFFL-2 is necessary for its role in heat shock response. affl-2 and its paralog are not essential for proper HSF-1 expression and localization after heat shock, which suggests that affl-2 may function downstream of, or parallel to, hsf-1. Our characterization of affl-2 provides insights into the regulation of heat-shock-induced gene expression to protect against heat stress.

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Faculty Opinions recommendation of Regulation of the cellular heat shock response in Caenorhabditis elegans by thermosensory neurons.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1108439.564668 ◽

2008 ◽

Author(s):

Nektarios Tavernarakis

Keyword(s):

Caenorhabditis Elegans ◽

Heat Shock ◽

Heat Shock Response ◽

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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A novel assay for drug screening that utilizes the heat shock response of Caenorhabditis elegans nematodes

PLoS ONE ◽

10.1371/journal.pone.0240255 ◽

2020 ◽

Vol 15 (10) ◽

pp. e0240255

Author(s):

Chih-Hsiung Chen ◽

Rahul Patel ◽

Alessandro Bortolami ◽

Federico Sesti

Keyword(s):

Caenorhabditis Elegans ◽

Heat Shock ◽

Drug Screening ◽

Heat Shock Response ◽

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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