Glucocorticoid Receptor Binding Induces Rapid and Prolonged Large-Scale Chromatin Decompaction at Multiple Target Loci

Publication date: 12 December 2017
Source:Cell Reports, Volume 21, Issue 11
Author(s): Alasdair W. Jubb, Shelagh Boyle, David A. Hume, Wendy A. Bickmore
Glucocorticoids act by binding to the glucocorticoid receptor (GR), which binds to specific motifs within enhancers of target genes to activate transcription. Previous studies have suggested that GRs can promote interactions between gene promoters and distal elements within target loci. In contrast, we demonstrate here that glucocorticoid addition to mouse bone-marrow-derived macrophages produces very rapid chromatin unfolding detectable by fluorescence in situ hybridization (FISH) at loci associated with GR binding. Rapid chromatin decompaction was generally not dependent on transcription at those loci that are known to be inducible in both mouse and human macrophages and was sustained for up to 5 days following ligand removal. Chromatin decompaction was not dependent upon persistent GR binding, which decayed fully after 24 hr. We suggest that sustained large-scale chromatin reorganization forms an important part of the response to glucocorticoid and might contribute to glucocorticoid sensitivity and resistance.

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Teaser

Glucocorticoids are important anti-inflammatory therapeutics. Jubb at al. find that treating primary macrophages with glucocorticoid induces rapid and persistent chromatin reorganization at genes that respond in both mice and humans. Higher-order chromatin structure at these core loci may be involved in the glucocorticoid response and be relevant to resistance.


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