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Creation of an anti-inflammatory GR cistrome by TLR4 signaling

ABSTRACT: An unresolved molecular paradox is how the glucocorticoid receptor (GR) activates some genes while potently repressing others. We carried out genome-wide localization and expression profiling experiments in primary bone marrow-derived mouse macrophages treated with Dexamethasone in the presence or absence of LPS. Unexpectedly, we find that the anti-inflammatory GR cistrome, which is principally composed of 'canonical' GREs colocalizing with NFkB and AP-1 co-enriched with the myeloid lineage factors C/EBP and Pu.1, is shaped by TLR4-directed chromatin dynamics, suggesting that context rather than sequence may be a critical determinant of function. Identification of GR, cJun, NFkB(p65) binding sites in primary bone-marrow derived macrophages unstimulated and LPS-stimulated (3hrs) that were untreated or pre-treated with Dexamethasone for 16 hrs

ORGANISM(S): Mus musculus

SUBMITTER: Ruth Yu

PROVIDER: E-GEOD-31796 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Insights into negative regulation by the glucocorticoid receptor from genome-wide profiling of inflammatory cistromes.

Uhlenhaut N Henriette NH Barish Grant D GD Yu Ruth T RT Downes Michael M Karunasiri Malith M Liddle Christopher C Schwalie Petra P Hübner Norbert N Evans Ronald M RM

Molecular cell 20121115 1

How the glucocorticoid receptor (GR) activates some genes while potently repressing others remains an open question. There are three current models for suppression: transrepression via GR tethering to AP-1/NF-κB sites, direct GR association with inhibitory elements (nGREs), and GR recruitment of the corepressor GRIP1. To gain insights into GR suppression, we used genomic analyses and genome-wide profiling of GR, p65, and c-Jun in LPS-stimulated macrophages. We show that GR mediates both activati ...[more]

PMID: 23159735

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