Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel
Journal cover image

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

Publication ,  Journal Article
Vockley, CM; D'Ippolito, AM; McDowell, IC; Majoros, WH; Safi, A; Song, L; Crawford, GE; Reddy, TE
Published in: Cell
August 25, 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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

August 25, 2016

Volume

166

Issue

5

Start / End Page

1269 / 1281.e19

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factors
  • Response Elements
  • Receptors, Glucocorticoid
  • Protein Binding
  • Humans
  • Glucocorticoids
  • Genome, Human
  • Genes, Reporter
  • Dexamethasone
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Vockley, C. M., D’Ippolito, A. M., McDowell, I. C., Majoros, W. H., Safi, A., Song, L., … Reddy, T. E. (2016). Direct GR Binding Sites Potentiate Clusters of TF Binding across the Human Genome. Cell, 166(5), 1269-1281.e19. https://doi.org/10.1016/j.cell.2016.07.049
Vockley, Christopher M., Anthony M. D’Ippolito, Ian C. McDowell, William H. Majoros, Alexias Safi, Lingyun Song, Gregory E. Crawford, and Timothy E. Reddy. “Direct GR Binding Sites Potentiate Clusters of TF Binding across the Human Genome.Cell 166, no. 5 (August 25, 2016): 1269-1281.e19. https://doi.org/10.1016/j.cell.2016.07.049.
Vockley CM, D’Ippolito AM, McDowell IC, Majoros WH, Safi A, Song L, et al. Direct GR Binding Sites Potentiate Clusters of TF Binding across the Human Genome. Cell. 2016 Aug 25;166(5):1269-1281.e19.
Vockley, Christopher M., et al. “Direct GR Binding Sites Potentiate Clusters of TF Binding across the Human Genome.Cell, vol. 166, no. 5, Aug. 2016, pp. 1269-1281.e19. Pubmed, doi:10.1016/j.cell.2016.07.049.
Vockley CM, D’Ippolito AM, McDowell IC, Majoros WH, Safi A, Song L, Crawford GE, Reddy TE. Direct GR Binding Sites Potentiate Clusters of TF Binding across the Human Genome. Cell. 2016 Aug 25;166(5):1269-1281.e19.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

August 25, 2016

Volume

166

Issue

5

Start / End Page

1269 / 1281.e19

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factors
  • Response Elements
  • Receptors, Glucocorticoid
  • Protein Binding
  • Humans
  • Glucocorticoids
  • Genome, Human
  • Genes, Reporter
  • Dexamethasone