Analysis of chromatin dynamics during glucocorticoid receptor activation

Mol Cell Biol. 2012 May;32(10):1805-17. doi: 10.1128/MCB.06206-11. Epub 2012 Mar 26.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Binding Sites
  • Cell Line, Tumor
  • Chromatin / chemistry
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly
  • Formaldehyde
  • Humans
  • Ligands
  • Protein Binding
  • Receptors, Glucocorticoid / metabolism*
  • Response Elements / physiology

Substances

  • Chromatin
  • Ligands
  • Receptors, Glucocorticoid
  • Formaldehyde