HSF1-dependent and -independent Regulation of the Mammalian in Vivo Heat Shock Response and Its Impairment in Huntington's Disease Mouse Models

Overview

Journal Sci Rep

Specialty Science

Date 2017 Oct 4

PMID 28970536

Citations 19

Authors

Andreas Neueder

Theresa A Gipson

Sophie Batterton

Hayley J Lazell

Pamela P Farshim

Paolo Paganetti

David E Housman

Gillian P Bates

Affiliations

Soon will be listed here.

Abstract

The heat shock response (HSR) is a mechanism to cope with proteotoxic stress by inducing the expression of molecular chaperones and other heat shock response genes. The HSR is evolutionarily well conserved and has been widely studied in bacteria, cell lines and lower eukaryotic model organisms. However, mechanistic insights into the HSR in higher eukaryotes, in particular in mammals, are limited. We have developed an in vivo heat shock protocol to analyze the HSR in mice and dissected heat shock factor 1 (HSF1)-dependent and -independent pathways. Whilst the induction of proteostasis-related genes was dependent on HSF1, the regulation of circadian function related genes, indicating that the circadian clock oscillators have been reset, was independent of its presence. Furthermore, we demonstrate that the in vivo HSR is impaired in mouse models of Huntington's disease but we were unable to corroborate the general repression of transcription that follows a heat shock in lower eukaryotes.

Citing Articles

Elucidation of Site-Specific Ubiquitination on Chaperones in Response to Mutant Huntingtin.

Panda P, Sarohi V, Basak T, Kasturi P Cell Mol Neurobiol. 2023; 44(1):3.

PMID: 38102300 PMC: 11407140. DOI: 10.1007/s10571-023-01446-1.

Mutant-Huntingtin Molecular Pathways Elucidate New Targets for Drug Repurposing.

Makeeva V, Dyrkheeva N, Lavrik O, Zakian S, Malakhova A Int J Mol Sci. 2023; 24(23).

PMID: 38069121 PMC: 10706709. DOI: 10.3390/ijms242316798.

HSF1 and Its Role in Huntington's Disease Pathology.

Kim H, Gomez-Pastor R Adv Exp Med Biol. 2022; 1410:35-95.

PMID: 36396925 DOI: 10.1007/5584_2022_742.

Heat shock factor HSF1 regulates BDNF gene promoters upon acute stress in the hippocampus, together with pCREB.

Franks H, Wang R, Li M, Wang B, Wildmann A, Ortyl T J Neurochem. 2022; 165(2):131-148.

PMID: 36227087 PMC: 10097844. DOI: 10.1111/jnc.15707.

Molecular Pathophysiological Mechanisms in Huntington's Disease.

Jurcau A Biomedicines. 2022; 10(6).

PMID: 35740453 PMC: 9219859. DOI: 10.3390/biomedicines10061432.

References

Solis E, Pandey J, Zheng X, Jin D, Gupta P, Airoldi E . Defining the Essential Function of Yeast Hsf1 Reveals a Compact Transcriptional Program for Maintaining Eukaryotic Proteostasis. Mol Cell. 2016; 63(1):60-71. PMC: 4938784. DOI: 10.1016/j.molcel.2016.05.014. View

Labbadia J, Cunliffe H, Weiss A, Katsyuba E, Sathasivam K, Seredenina T . Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease. J Clin Invest. 2011; 121(8):3306-19. PMC: 3148745. DOI: 10.1172/JCI57413. View

Mendillo M, Santagata S, Koeva M, Bell G, Hu R, Tamimi R . HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers. Cell. 2012; 150(3):549-62. PMC: 3438889. DOI: 10.1016/j.cell.2012.06.031. View

Mortola J . Gender and the circadian pattern of body temperature in normoxia and hypoxia. Respir Physiol Neurobiol. 2016; 245:4-12. DOI: 10.1016/j.resp.2016.11.002. View

Kwon S, Zhang Y, Matthias P . The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response. Genes Dev. 2007; 21(24):3381-94. PMC: 2113037. DOI: 10.1101/gad.461107. View

Ernst J, Kellis M . Discovery and characterization of chromatin states for systematic annotation of the human genome. Nat Biotechnol. 2010; 28(8):817-25. PMC: 2919626. DOI: 10.1038/nbt.1662. View

Neueder A, Achilli F, Moussaoui S, Bates G . Novel isoforms of heat shock transcription factor 1, HSF1γα and HSF1γβ, regulate chaperone protein gene transcription. J Biol Chem. 2014; 289(29):19894-906. PMC: 4106310. DOI: 10.1074/jbc.M114.570739. View

Labbadia J, Morimoto R . The biology of proteostasis in aging and disease. Annu Rev Biochem. 2015; 84:435-64. PMC: 4539002. DOI: 10.1146/annurev-biochem-060614-033955. View

Moffitt H, McPhail G, Woodman B, Hobbs C, Bates G . Formation of polyglutamine inclusions in a wide range of non-CNS tissues in the HdhQ150 knock-in mouse model of Huntington's disease. PLoS One. 2009; 4(11):e8025. PMC: 2778556. DOI: 10.1371/journal.pone.0008025. View

10.

Leak R . Heat shock proteins in neurodegenerative disorders and aging. J Cell Commun Signal. 2014; 8(4):293-310. PMC: 4390795. DOI: 10.1007/s12079-014-0243-9. View

11.

Buhr E, Yoo S, Takahashi J . Temperature as a universal resetting cue for mammalian circadian oscillators. Science. 2010; 330(6002):379-85. PMC: 3625727. DOI: 10.1126/science.1195262. View

12.

Sasi B, Sonawane P, Gupta V, Sahu B, Mahapatra N . Coordinated transcriptional regulation of Hspa1a gene by multiple transcription factors: crucial roles for HSF-1, NF-Y, NF-κB, and CREB. J Mol Biol. 2013; 426(1):116-35. DOI: 10.1016/j.jmb.2013.09.008. View

13.

Chatr-Aryamontri A, Breitkreutz B, Oughtred R, Boucher L, Heinicke S, Chen D . The BioGRID interaction database: 2015 update. Nucleic Acids Res. 2014; 43(Database issue):D470-8. PMC: 4383984. DOI: 10.1093/nar/gku1204. View

14.

Busse M, Hughes G, Wiles C, Rosser A . Use of hand-held dynamometry in the evaluation of lower limb muscle strength in people with Huntington's disease. J Neurol. 2008; 255(10):1534-40. DOI: 10.1007/s00415-008-0964-x. View

15.

Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C . Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell. 1996; 87(3):493-506. DOI: 10.1016/s0092-8674(00)81369-0. View

16.

Tamaru T, Hattori M, Honda K, Benjamin I, Ozawa T, Takamatsu K . Synchronization of circadian Per2 rhythms and HSF1-BMAL1:CLOCK interaction in mouse fibroblasts after short-term heat shock pulse. PLoS One. 2011; 6(9):e24521. PMC: 3168500. DOI: 10.1371/journal.pone.0024521. View

17.

Shirasaki D, Greiner E, Al-Ramahi I, Gray M, Boontheung P, Geschwind D . Network organization of the huntingtin proteomic interactome in mammalian brain. Neuron. 2012; 75(1):41-57. PMC: 3432264. DOI: 10.1016/j.neuron.2012.05.024. View

18.

Lin C, Chien W, Cearley J, JACKSON W, Crouse A, Ren S . Neurological abnormalities in a knock-in mouse model of Huntington's disease. Hum Mol Genet. 2001; 10(2):137-44. DOI: 10.1093/hmg/10.2.137. View

19.

Zheng X, Krakowiak J, Patel N, Beyzavi A, Ezike J, Khalil A . Dynamic control of Hsf1 during heat shock by a chaperone switch and phosphorylation. Elife. 2016; 5. PMC: 5127643. DOI: 10.7554/eLife.18638. View

20.

de Thonel A, Le Mouel A, Mezger V . Transcriptional regulation of small HSP-HSF1 and beyond. Int J Biochem Cell Biol. 2012; 44(10):1593-612. DOI: 10.1016/j.biocel.2012.06.012. View