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

Autor: Alasdair W. Jubb, Shelagh Boyle, David A. Hume, Wendy A. Bickmore
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Cell Reports, Vol 21, Iss 11, Pp 3022-3031 (2017)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2017.11.053
Popis: 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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