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

Cell | 2016

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.

Pubmed ID: 27565349 RIS Download

Associated grants

  • Agency: NICHD NIH HHS, United States
    Id: T32 HD040372
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007754
  • Agency: NHGRI NIH HHS, United States
    Id: U01 HG007900
  • Agency: NHLBI NIH HHS, United States
    Id: F31 HL129743
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM071340
  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL111018
  • Agency: NIAID NIH HHS, United States
    Id: F31 AI124563

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