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Series GSE21725 Query DataSets for GSE21725
Status Public on Oct 01, 2010
Title Global analysis of the impact of environmental perturbation on cis-regulation of gene expression: DEX, 24hr
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Genetic variants altering cis-regulation of normal gene expression (cis-eQTLs) have been extensively mapped in human cells and tissues, but the extent to which environmental perturbation influences such traits has not been studied to date. We carried out large-scale induction experiments using primary human bone cells derived from 113 unrelated donors of Swedish origin harvested under 18 different conditions (seven treatments, two vehicles, each assessed at two time points). The treatments with the largest impact on the transcriptome, verified on two independent expression arrays, included BMP-2 (t=2h), dexamethasone (DEX) (t=24h), and PGE2 (t=24h). Using these treatments, we performed expression profiling for 18,144 RefSeq transcripts applying biological replicates of the complete study cohort (ntotal=782) and combined it with genome-wide SNP-genotyping data in order to map treatment-specific cis-eQTLs. We found that 93% of cis-eQTLs at 1% FDR were replicated in at least one additional treatment and in fact, on average only 1.4% of the cis-eQTLs were considered as treatment-specific at high confidence. The relative invariability of cis-regulation following perturbation was reiterated independently by genome-wide allelic expression tests where only a small proportion of variance could be attributed to treatment, though treatment-specific cis-regulatory effects were 2-6-fold more abundant among up-or downregulated genes. We further followed-up and validated the DEX-specific cis-regulation of the MYO6 and TNC loci and found top cis-regulatory variants located 180 and 250kb upstream of the transcription start sites, respectively. Our results suggest that, as opposed to tissue-specificity of cis-eQTLs, the interaction between cellular environment and cis-variants are relatively rare (~1.5%), but that detection of such specific interactions can be achieved by combination of functional genomic tools.
 
Overall design Total RNA from cultured trabecular bone cells obtained from ~100 unrelated Caucasian donors treated under multiple different conditions and timepoints. Each sample represented by two or three biological replicates.

This dataset includes samples treated with dexamethasone (DEX) for 24 hours.
 
Contributor(s) Grundberg E, Adoue V, Kwan T, Ge B, Duan QL, Lam KC, Koka V, Kindmark A, Weiss ST, Tantisira K, Mallmin H, Johns T, Shoubridge EA, Ljunggren O, Raby BA, Nilsson O, Pastinen T
Citation(s) 21283786
Submission date May 06, 2010
Last update date Jan 18, 2013
Contact name Elin Grundberg
Organization name McGill University
Street address 740 Dr Penfield Avenue
City Montreal
ZIP/Postal code H3A1A4
Country Canada
 
Platforms (1)
GPL6104 Illumina humanRef-8 v2.0 expression beadchip
Samples (242)
GSM535234 Human_osteoblast_sample_#506rep2_DEX_treated_24h
GSM535235 Human_osteoblast_sample_#506rep3_DEX_treated_24h
GSM535236 Human_osteoblast_sample_#507rep1_DEX_treated_24h
This SubSeries is part of SuperSeries:
GSE21728 Global analysis of the impact of environmental perturbation on cis-regulation of gene expression
Relations
BioProject PRJNA129375

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
GSE21725_RAW.tar 3.4 Mb (http)(custom) TAR
GSE21725_non-normalized.txt.gz 32.3 Mb (ftp)(http) TXT
Processed data included within Sample table
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