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Title: Transcriptional responses of mouse BMM and TEPM to lipopolysaccharide (LPS)      
dateReleased:
03-28-2012
description:
Evolutionary change in gene expression is generally considered to be a major driver of phenotypic differences between species. We investigated innate immune diversification by analyzing inter-species differences in the transcriptional responses of primary human and mouse macrophages to the TLR4 agonist, LPS. Using a custom platform permitting cross-species interrogation coupled with deep sequencing of mRNA 5’ ends, we identified extensive divergence in LPS-regulated orthologous gene expression between humans and mice (24% of orthologs, ). Divergently regulated (DR) orthologs were enriched for genes encoding cellular “inputs” such as cell surface receptors (e.g. TLR6, IL-7Rα), and functional “outputs” such as inflammatory cytokines/chemokines (e.g. CCL20, CXCL13). Conversely, intracellular signaling components linking inputs to outputs were typically concordantly regulated. DR genes were associated with a large dynamic range of gene expression, and specific promoter architectural features (TATA box enrichment, CpG island depletion). Surprisingly, regulatory divergence was also associated with enhanced inter-species promoter conservation. Thus, the genes controlled by complex, highly conserved promoters that facilitate dynamic regulation are also the most susceptible to evolutionary change. Mouse macrophages (bone marrow-derived macrophages, BMM and thioglycollate-elicited peritoneal macrophages, TEPM) were stimulated with the TLR4 agonist, lipopolysaccharide, over a time course (0, 2, 6, 24h) and analysed in biological triplicate on a custom-designed, focused microarray.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-19490
refinement:
raw
alternateIdentifiers:
19490
keywords:
functional genomics
dateModified:
06-27-2012
availability:
available
types:
gene expression
name:
Mus musculus
ID:
A-GEOD-9802
name:
Transcriptional responses of mouse BMM and TEPM to lipopolysaccharide (LPS)
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-19490/E-GEOD-19490.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-19490/E-GEOD-19490.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19490
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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