RT Journal
A1 Stavreva, Diana A.
A1 Coulon, Antoine
A1 Baek, Songjoon
A1 Sung, Myong-Hee
A1 John, Sam
A1 Stixova, Lenka
A1 Tesikova, Martina
A1 Hakim, Ofir
A1 Miranda, Tina
A1 Hawkins, Mary
A1 Stamatoyannopoulos, John A.
A1 Chow, Carson C.
A1 Hager, Gordon L.
T1 Dynamics of chromatin accessibility and long-range interactions in response to glucocorticoid pulsing
JF Genome Research 
JO Genome Research 
YR 2015 
FD June 01 
VO 25 
IS 6 
SP 845 
OP 857 
DO 10.1101/gr.184168.114 
UL http://genome.cshlp.org/content/25/6/845.abstract 
AB Although physiological steroid levels are often pulsatile (ultradian), the genomic effects of this pulsatility are poorly understood. By utilizing glucocorticoid receptor (GR) signaling as a model system, we uncovered striking spatiotemporal relationships between receptor loading, lifetimes of the DNase I hypersensitivity sites (DHSs), long-range interactions, and gene regulation. We found that hormone-induced DHSs were enriched within ±50 kb of GR-responsive genes and displayed a broad spectrum of lifetimes upon hormone withdrawal. These lifetimes dictate the strength of the DHS interactions with gene targets and contribute to gene regulation from a distance. Our results demonstrate that pulsatile and constant hormone stimulations induce unique, treatment-specific patterns of gene and regulatory element activation. These modes of activation have implications for corticosteroid function in vivo and for steroid therapies in various clinical settings.