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Expression response of human monocyte derived macrophages to dexamethasone over a 24h time series

ABSTRACT: Macrophages are amongst the major targets of glucocorticoids (GC) as therapeutic anti-inflammatory agents. Here we show that GC treatment of mouse and human macrophages initiates a cascade of induced gene expression including many anti-inflammatory genes. Inducible binding of the glucocorticoid receptor (GR) was detected at candidate enhancers in the vicinity of induced genes in both species and this was strongly associated with canonical GR binding motifs. However, the sets of inducible genes, the candidate enhancers, and the GR motifs within them, were highly-divergent between the two species.. The data cast further doubt upon the predictive value of mouse models of inflammatory disease. Four biological replicates of a 6 point 24h time series transcriptional response of human monocyte derived macrophages to dexamethasone 100nM.

ORGANISM(S): Homo sapiens

SUBMITTER: Alasdair Jubb

PROVIDER: E-GEOD-61880 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages.

Jubb Alasdair W AW Young Robert S RS Hume David A DA Bickmore Wendy A WA

Journal of immunology (Baltimore, Md. : 1950) 20151209 2

Phenotypic differences between individuals and species are controlled in part through differences in expression of a relatively conserved set of genes. Genes expressed in the immune system are subject to especially powerful selection. We have investigated the evolution of both gene expression and candidate enhancers in human and mouse macrophages exposed to glucocorticoid (GC), a regulator of innate immunity and an important therapeutic agent. Our analyses revealed a very limited overlap in the ...[more]

PMID: 26663721

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