TY - JOUR 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 Y1 - 2015/06/01 JF - Genome Research JO - Genome Research SP - 845 EP - 857 DO - 10.1101/gr.184168.114 VL - 25 IS - 6 UR - http://genome.cshlp.org/content/25/6/845.abstract N2 - 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. ER -