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| Status |
Public on Jun 19, 2012 |
| Title |
Polyglutamine expanded huntingtin dramatically alters the genome-wide binding of HSF1 (ChIP-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
In Huntington’s disease (HD), polyglutamine expansions in the huntingtin (Htt) protein cause subtle changes in cellular functions that, over-time, lead to neurodegeneration and death. Studies have indicated that activation of the heat shock response can reduce many of the effects of mutant Htt in disease models, suggesting that the heat shock response is impaired in the disease. To understand the basis for this impairment, we have used genome-wide chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) to examine the effects of mutant Htt on the master regulator of the heat shock response, HSF1. We find that, under normal conditions, HSF1 function is highly similar in cells carrying either wild-type or mutant Htt. However, polyQ-expanded Htt severely blunts the HSF1-mediated stress response. Surprisingly, we find that the HSF1 targets most affected upon stress are not directly associated with proteostasis, but with cytoskeletal binding, focal adhesion and GTPase activity. Our data raise the intriguing hypothesis that the accumulated damage from life-long impairment in these stress responses may contribute significantly to the etiology of Huntington's disease.
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| Overall design |
ChIP-Seq experiments for HSF-1 were performed in striatal cells that express either wild-type or mutant Htt using ChIP-Seq technology under normal (33°C) and heat shock (42°C for six hours) conditions. The cells were crosslinked with 1% formaldehyde and immunoprecipitated using antibody sc-9144 (Santa Cruz Biotech) for HSF-1. Sequencing was performed using the Illumina Genome Analyzer II.
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| Contributor(s) |
Riva L, Koeva M, Yildirim F, Pirhaji L, Dinesh D, Mazor TL, Duennwald MM, Fraenkel E |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
May 16, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Laura Riva |
| E-mail(s) |
lriva@mit.edu
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| Organization name |
MIT
|
| Department |
Biological Engineering
|
| Lab |
Fraenkel Lab
|
| Street address |
77 Massachusetts Avenue
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02139 |
| Country |
USA |
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| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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| Samples (6)
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| GSM931693 |
HSF1 STHdhQ7/Q7 no treatment ChIP-seq |
| GSM931694 |
HSF1 STHdhQ111/Q111 no treatment ChIP-seq |
| GSM931695 |
HSF1 STHdhQ7/Q7 Heat Shock ChIP-seq |
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| This SubSeries is part of SuperSeries: |
| GSE38002 |
Polyglutamine expanded huntingtin dramatically alters the genome-wide binding of HSF1 |
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| Relations |
| BioProject |
PRJNA167041 |
| SRA |
SRP013215 |
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