HSF1-dependent and -independent regulation of the mammalian in vivo heat shock response and its impairment in Huntington's disease mouse models

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. Howe...

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Main Authors: Neueder, Andreas, Gipson, Theresa A., Batterton, Sophie, Lazell, Hayley J., Farshim, Pamela P., Paganetti, Paolo, Bates, Gillian P., Wasylenko, Theresa Anne, Housman, David E
Other Authors: Koch Institute for Integrative Cancer Research at MIT
Format: Article
Published: Nature Publishing Group 2018
Online Access:http://hdl.handle.net/1721.1/115201
https://orcid.org/0000-0002-0524-5301
https://orcid.org/0000-0001-5016-0756
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author Neueder, Andreas
Gipson, Theresa A.
Batterton, Sophie
Lazell, Hayley J.
Farshim, Pamela P.
Paganetti, Paolo
Bates, Gillian P.
Wasylenko, Theresa Anne
Housman, David E
author2 Koch Institute for Integrative Cancer Research at MIT
author_facet Koch Institute for Integrative Cancer Research at MIT
Neueder, Andreas
Gipson, Theresa A.
Batterton, Sophie
Lazell, Hayley J.
Farshim, Pamela P.
Paganetti, Paolo
Bates, Gillian P.
Wasylenko, Theresa Anne
Housman, David E
author_sort Neueder, Andreas
collection MIT
description 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.
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spelling mit-1721.1/1152012022-09-23T13:31:35Z HSF1-dependent and -independent regulation of the mammalian in vivo heat shock response and its impairment in Huntington's disease mouse models Neueder, Andreas Gipson, Theresa A. Batterton, Sophie Lazell, Hayley J. Farshim, Pamela P. Paganetti, Paolo Bates, Gillian P. Wasylenko, Theresa Anne Housman, David E Koch Institute for Integrative Cancer Research at MIT Wasylenko, Theresa Anne Housman, David E 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. 2018-05-02T20:27:44Z 2018-05-02T20:27:44Z 2017-10 2017-07 2018-04-27T17:06:14Z Article http://purl.org/eprint/type/JournalArticle 2045-2322 http://hdl.handle.net/1721.1/115201 Neueder, Andreas et al. “HSF1-Dependent and -Independent Regulation of the Mammalian in Vivo Heat Shock Response and Its Impairment in Huntington’s Disease Mouse Models.” Scientific Reports 7, 1 (October 2017) © 2017 The Author(s) https://orcid.org/0000-0002-0524-5301 https://orcid.org/0000-0001-5016-0756 http://dx.doi.org/10.1038/S41598-017-12897-0 Scientific Reports Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Scientific Reports
spellingShingle Neueder, Andreas
Gipson, Theresa A.
Batterton, Sophie
Lazell, Hayley J.
Farshim, Pamela P.
Paganetti, Paolo
Bates, Gillian P.
Wasylenko, Theresa Anne
Housman, David E
HSF1-dependent and -independent regulation of the mammalian in vivo heat shock response and its impairment in Huntington's disease mouse models
title HSF1-dependent and -independent regulation of the mammalian in vivo heat shock response and its impairment in Huntington's disease mouse models
title_full HSF1-dependent and -independent regulation of the mammalian in vivo heat shock response and its impairment in Huntington's disease mouse models
title_fullStr HSF1-dependent and -independent regulation of the mammalian in vivo heat shock response and its impairment in Huntington's disease mouse models
title_full_unstemmed HSF1-dependent and -independent regulation of the mammalian in vivo heat shock response and its impairment in Huntington's disease mouse models
title_short HSF1-dependent and -independent regulation of the mammalian in vivo heat shock response and its impairment in Huntington's disease mouse models
title_sort hsf1 dependent and independent regulation of the mammalian in vivo heat shock response and its impairment in huntington s disease mouse models
url http://hdl.handle.net/1721.1/115201
https://orcid.org/0000-0002-0524-5301
https://orcid.org/0000-0001-5016-0756
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