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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 01, 2009 |
| Title |
Analysis of the Heat Shock Response in Mouse Liver Reveals Transcriptional Dependence on the Nuclear Receptor PPARα |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα) regulates responses to chemical or physical stress in part by altering expression of genes involved in proteome maintenance. Many of these genes are also transcriptionally regulated by heat shock (HS) through activation by HS factor-1 (HSF1). We hypothesized that there are interactions on a genetic level between PPARα and the HS response mediated by HSF1. Wild-type and PPARα-null mice were exposed to HS, the PPARα agonist WY-14,643 (WY), or both; gene and protein expression was examined in the livers of the mice 4 or 24 hrs after HS. Gene expression profiling identified a number of Hsp family members that were altered similarly in both mouse strains. However, most of the targets of HS did not overlap between strains. A subset of genes was shown by microarray and RT-PCR to be regulated by HS in a PPARα-dependent manner. HS also down-regulated a large set of mitochondrial genes specifically in PPARα-null mice that are known targets of PPARg co-activator 1 (PGC-1) family members. Pretreatment of PPARα-null mice with WY increased expression of PGC-1b and target genes and prevented the down-regulation of the mitochondrial genes by HS. A comparison of HS genes regulated in our dataset with those identified in wild-type and HSF1-null mouse embryonic fibroblasts indicated that although many HS genes are regulated independently of both PPARα and HSF1, a number require both factors for HS responsiveness. These findings demonstrate that the PPARα genotype has a dramatic effect on the transcriptional targets of HS and support an expanded role for PPARα in the regulation of proteome maintenance genes after exposure to diverse forms of environmental stress including HS.
Keywords: Gene Expresssion-Heat shock
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| Overall design |
total 24 samples, 3 per group, for controls and treated.
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| Contributor(s) |
Vallanat B, Anderson SP, Brown-Borg HM, Ren H, Kersten S, Jonnalagadda S, Srinivasan R, Corton JC |
| Citation(s) |
20059764 |
| Submission date |
Feb 17, 2009 |
| Last update date |
Feb 18, 2018 |
| Contact name |
beena vallanat |
| E-mail(s) |
vallanat.beena@epa.gov
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| Organization name |
EPA
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| Street address |
109 Tw Alexanser Dr
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| City |
Research Triangle Park |
| ZIP/Postal code |
27711 |
| Country |
USA |
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| Platforms (1) |
| GPL81 |
[MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA111933 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE14869_RAW.tar |
180.3 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
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