Creation of an anti-inflammatory GR cistrome by TLR4 signaling. Mus musculus

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 NF-κB 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. Overall design: Total RNA was obtained from primary bone marrow-derived mouse macrophages treated overnight with EtOH or 1 uM Dexamethasone, unstimulated or stimulated with LPS. Two seperate experiments were performed (at 3 hr and 6 hr LPS-treatment timepoints).