E-GEOD-44248 - Genetic, functional and molecular features of glucocorticoid receptor binding (expression)

Status
Released on 1 April 2013, last updated on 2 June 2014
Organism
Homo sapiens
Samples (96)
Array (1)
Protocols (103)
Description
Glucocorticoids (GCs) are key mediators of stress response and are widely used as pharmacological agents to treat immune diseases, such as asthma and inflammatory bowel disease, and certain types of cancer. GCs act mainly by activating the GC receptor (GR), which interacts with other transcription factors to regulate gene expression. Here, we combined different functional genomics approaches to gain molecular insights into the mechanisms of action of GC. By profiling the transcriptional response to GC over time in 4 Yoruba (YRI) and 4 Tuscans (TSI) lymphoblastoid cell lines (LCLs), we suggest that the transcriptional response to GC is variable not only in time, but also in direction (positive or negative) depending on the presence of specific interacting TFs. Accordingly, when we performed ChIP-seq for GR and NF-kB in two YRI LCLs treated with GC or with vehicle control, we observed that features of GR binding sites differ for up- and down-regulated genes. Finally, we show that eQTLs that affect expression patterns only in the presence of GC are 1.9-fold more likely to occur in GR binding sites, compared to eQTLs that affect expression only in its absence. Our results indicate that genetic variation at GR and interacting transcription factors binding sites influences variability in gene expression, and attest to the power of combining different functional genomic approaches. Total RNA obtained from lymphoblastoid cell lines treated with either dexamethasone or EtOH (vehicle for dexamethasone) for 2, 4, 8, 12, 16, or 24 hours.
Experiment type
transcription profiling by array 
Contacts
Joseph C Maranville <jcmaranville@uchicago.edu>, Allison L Richards, Anna Di Rienzo, David B Witonsky, Francesca Luca, Matthew Stephens
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-44248.idf.txt
Sample and data relationshipE-GEOD-44248.sdrf.txt
Processed data (1)E-GEOD-44248.processed.1.zip
Array designA-MEXP-1171.adf.txt
Links