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Series GSE38000 Query DataSets for GSE38000
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
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.
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.
Contributor(s) Riva L, Koeva M, Yildirim F, Pirhaji L, Dinesh D, Mazor TL, Duennwald MM, Fraenkel E
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Submission date May 16, 2012
Last update date May 15, 2019
Contact name Laura Riva
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
Platforms (1)
GPL9185 Illumina Genome Analyzer (Mus musculus)
Samples (6)
GSM931693 HSF1 STHdhQ7/Q7 no treatment ChIP-seq
GSM931694 HSF1 STHdhQ111/Q111 no treatment ChIP-seq
GSM931695 HSF1 STHdhQ7/Q7 Heat Shock ChIP-seq
This SubSeries is part of SuperSeries:
GSE38002 Polyglutamine expanded huntingtin dramatically alters the genome-wide binding of HSF1
BioProject PRJNA167041
SRA SRP013215

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE38000_RAW.tar 140.0 Kb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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