Glucocorticoid Receptor Binding Induces Rapid and Prolonged Large-Scale Chromatin Decompaction at Multiple Target Loci
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,...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-12-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717317059 |
| _version_ | 1819156815559000064 |
|---|---|
| author | Alasdair W. Jubb Shelagh Boyle David A. Hume Wendy A. Bickmore |
| author_facet | Alasdair W. Jubb Shelagh Boyle David A. Hume Wendy A. Bickmore |
| author_sort | Alasdair W. Jubb |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T15:58:52Z |
| format | Article |
| id | doaj.art-4d8026b630494dbf963e12d13a560c15 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T15:58:52Z |
| publishDate | 2017-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4d8026b630494dbf963e12d13a560c152022-12-21T18:20:43ZengElsevierCell Reports2211-12472017-12-0121113022303110.1016/j.celrep.2017.11.053Glucocorticoid Receptor Binding Induces Rapid and Prolonged Large-Scale Chromatin Decompaction at Multiple Target LociAlasdair W. Jubb0Shelagh Boyle1David A. Hume2Wendy A. Bickmore3MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, The University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UKMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, The University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UKThe Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UKMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, The University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UKGlucocorticoids 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.http://www.sciencedirect.com/science/article/pii/S2211124717317059chromatin remodelingfluorescence in situ hybridizationglucocorticoid receptormacrophageenhancer |
| spellingShingle | Alasdair W. Jubb Shelagh Boyle David A. Hume Wendy A. Bickmore Glucocorticoid Receptor Binding Induces Rapid and Prolonged Large-Scale Chromatin Decompaction at Multiple Target Loci Cell Reports chromatin remodeling fluorescence in situ hybridization glucocorticoid receptor macrophage enhancer |
| title | Glucocorticoid Receptor Binding Induces Rapid and Prolonged Large-Scale Chromatin Decompaction at Multiple Target Loci |
| title_full | Glucocorticoid Receptor Binding Induces Rapid and Prolonged Large-Scale Chromatin Decompaction at Multiple Target Loci |
| title_fullStr | Glucocorticoid Receptor Binding Induces Rapid and Prolonged Large-Scale Chromatin Decompaction at Multiple Target Loci |
| title_full_unstemmed | Glucocorticoid Receptor Binding Induces Rapid and Prolonged Large-Scale Chromatin Decompaction at Multiple Target Loci |
| title_short | Glucocorticoid Receptor Binding Induces Rapid and Prolonged Large-Scale Chromatin Decompaction at Multiple Target Loci |
| title_sort | glucocorticoid receptor binding induces rapid and prolonged large scale chromatin decompaction at multiple target loci |
| topic | chromatin remodeling fluorescence in situ hybridization glucocorticoid receptor macrophage enhancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717317059 |
| work_keys_str_mv | AT alasdairwjubb glucocorticoidreceptorbindinginducesrapidandprolongedlargescalechromatindecompactionatmultipletargetloci AT shelaghboyle glucocorticoidreceptorbindinginducesrapidandprolongedlargescalechromatindecompactionatmultipletargetloci AT davidahume glucocorticoidreceptorbindinginducesrapidandprolongedlargescalechromatindecompactionatmultipletargetloci AT wendyabickmore glucocorticoidreceptorbindinginducesrapidandprolongedlargescalechromatindecompactionatmultipletargetloci |