Conservation and divergence in Toll-like receptor 4-regulated gene expression in primary human versus mouse macrophages.

ABSTRACT: 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 interspecies differences in the transcriptional responses of primary human and mouse macrophages to the Toll-like receptor (TLR)-4 agonist lipopolysaccharide (LPS). By 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 orthologues were identified as "divergently regulated"). We further demonstrate concordant regulation of human-specific LPS target genes in primary pig macrophages. Divergently regulated orthologues were enriched for genes en

SUBMITTER: Schroder K 

PROVIDER: S-EPMC3341041 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature