Direct GR Binding Sites Potentiate Clusters of TF Binding across the Human Genome.

Journal Article

The glucocorticoid receptor (GR) binds the human genome at >10,000 sites but only regulates the expression of hundreds of genes. To determine the functional effect of each site, we measured the glucocorticoid (GC) responsive activity of nearly all GR binding sites (GBSs) captured using chromatin immunoprecipitation (ChIP) in A549 cells. 13% of GBSs assayed had GC-induced activity. The responsive sites were defined by direct GR binding via a GC response element (GRE) and exclusively increased reporter-gene expression. Meanwhile, most GBSs lacked GC-induced reporter activity. The non-responsive sites had epigenetic features of steady-state enhancers and clustered around direct GBSs. Together, our data support a model in which clusters of GBSs observed with ChIP-seq reflect interactions between direct and tethered GBSs over tens of kilobases. We further show that those interactions can synergistically modulate the activity of direct GBSs and may therefore play a major role in driving gene activation in response to GCs.

Full Text

Duke Authors

Cited Authors

  • Vockley, CM; D'Ippolito, AM; McDowell, IC; Majoros, WH; Safi, A; Song, L; Crawford, GE; Reddy, TE

Published Date

  • August 2016

Published In

Volume / Issue

  • 166 / 5

Start / End Page

  • 1269 - 1281.e19

PubMed ID

  • 27565349

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2016.07.049

Language

  • eng