title: Analysis of chromatin dynamics during glucocorticoid receptor activation.
abstract: Steroid hormone receptors initiate a genetic program tightly regulated by the chromatin environment of the responsive regions. Using the glucocorticoid receptor (GR) as a model factor for transcriptional initiation, we classified chromatin structure through formaldehyde-assisted isolation of regulatory elements (FAIRE). We looked at dynamic changes in FAIRE signals during GR activation specifically at regions of receptor interaction. We found a distribution of GR-responsive regions with diverse responses to activation and chromatin modulation. The majority of GR binding regions demonstrate increases in FAIRE signal in response to ligand. However, the majority GR-responsive regions shared a similar FAIRE signal in the basal chromatin state, suggesting a common chromatin structure for GR recruitment. Supporting this notion, global FAIRE sequencing (seq) data indicated an enrichment of signal surrounding the GR binding site prior to activation. Brg-1 knockdown showed response element-specific effects of ATPase-dependent chromatin remodeling. FAIRE induction was universally decreased by Brg-1 depletion, but to varying degrees in a target specific manner. Taken together, these data suggest classes of nuclear receptor response regions that react to activation through different chromatin regulatory events and identify a chromatin structure that classifies the majority of response elements tested.
authors.affiliation: Chromatin and Gene Expression Group, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Burd
authors.forename: James M
authors.initials: JM
authors.lastname: Ward
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Crusselle-Davis
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kissling
authors.forename: Dhiral
authors.initials: D
authors.lastname: Phadke
authors.forename: Ruchir R
authors.initials: RR
authors.lastname: Shah
authors.forename: Trevor K
authors.initials: TK
authors.lastname: Archer
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D005557:Formaldehyde; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology
chemical_list: D002843:Chromatin; D008024:Ligands; D011965:Receptors, Glucocorticoid; D005557:Formaldehyde