The genetic architecture of the genome-wide transcriptional response to ER stress in the mouse
Transcriptomics Dataset
FAIR Metrics
0 evaluations
General Information
| Accession | GSE63756 |
| Title | The genetic architecture of the genome-wide transcriptional response to ER stress in the mouse |
| Description | Endoplasmic reticulum (ER) stress occurs when misfolded proteins accumulate in the ER. The cellular response to ER stress involves complex transcriptional and translational changes, important to the survival of the cell. ER stress is a primary cause and a modifier of many human diseases. A first step to understanding how the ER stress response impacts human disease is to determine how the transcriptional response to ER stress varies among individuals. The genetic diversity of the eight mouse Collaborative Cross (CC) founder strains allowed us to determine how genetic variation impacts the ER stress transcriptional response. We used tunicamycin, a drug commonly used to induce ER stress, to elicit an ER stress response in mouse embryonic fibroblasts (MEFs) derived from the CC founder strains and measured their transcriptional responses. We identified hundreds of genes that differed in response to ER stress across these genetically diverse strains. Strikingly, inflammatory response genes differed most between strains; major canonical ER stress response genes showed relatively invariant responses across strains. To uncover the genetic architecture underlying these strain differences in ER stress response, we measured the transcriptional response to ER stress in MEFs derived from a subset of F1 crosses between the CC founder strains. We found a unique layer of regulatory variation that is only detectable under ER stress conditions. Over 80%% of the regulatory variation under ER stress derives from cis-regulatory differences. This is the first study to characterize the genetic variation in ER stress transcriptional response in the laboratory mouse. Our findings indicate that the ER stress transcriptional response is highly variable among strains and arises from genetic variation in individual downstream response genes, rather than major signaling transcription factors. These results have important implications for understanding how genetic variation impacts the ER stress response, an important component of many human diseases. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63756 |
| Repository | Gene Expression Omnibus |
Related Datasets
GSE48159
Mapping ER genomic binding sites reveals unique genomic features and identifies EBF1 as an ER interactor [Gro-Seq]
1
GSE78285
Modeling the ESR1 tyrosine 537 mutation with CRISPR-Cas9 for mechanistic studies and evaluation of therapeutic approaches for metastatic breast cancer...
1
GSE2082
Transcription factor CHOP null mutation effect on fibroblasts subjected to ER stress: time course
21
Tools
used to analyze the dataset
Canned Analyses
generated with the dataset
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.
