Despite the widespread use of glucocorticoids (GCs), their anti-inflammatory effects are not understood mechanistically. Numerous investigations have examined the effects of glucocorticoid receptor (GR) activation prior to inflammatory challenges. However, clinical situations are emulated by a GC intervention initiated in the midst of rampant inflammatory responses. To characterize the effects of a late GC treatment, we profiled macrophage transcriptional and chromatinscapes with Dexamethasone (Dex) treatment before or after stimulation by lipopolysaccharide (LPS). The late activation of GR had a similar gene-expression profile as from GR pre-activation, while ameliorating the disruption of metabolic genes. Chromatin occupancy of GR was not predictive of Dex-regulated gene expression, contradicting the "trans-repression by tethering" model. Rather, GR activation resulted in genome-wide blockade of NF-κB interaction with chromatin and directly induced inhibitors of NF-κB and AP-1. Our investigation using GC treatments with clinically relevant timing highlights mechanisms underlying GR actions for modulating the "inflamed epigenome."
Pubmed ID: 28801231 RIS Download
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Software that uses ellipses to automatically draw accurate area-proportional Venn diagrams for 3-set data. It generates an exact diagram for most of the cases, and when it fails, the best diagram obtained through the hill climbing search is displayed, together with the inaccuracy values for each region.
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View all literature mentionsThis unknown targets Rho-GDI
View all literature mentionsThis polyclonal targets p38 MAPK
View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis polyclonal targets RELA
View all literature mentionsThis polyclonal targets NFKBIA
View all literature mentionsThis monoclonal targets Glucocorticoid Receptor
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal targets NFkB p65 antibody - ChIP Grade
View all literature mentionsThis polyclonal targets HNRNPL
View all literature mentionsThis monoclonal targets Mapk14
View all literature mentions