Genome Research

Dynamics of chromatin accessibility and long-range interactions in response to glucocorticoid pulsing [RESEARCH]

D. A. Stavreva, A. Coulon, S. Baek, M.-H. Sung, S. John, L. Stixova, M. Tesikova, O. Hakim, T. Miranda, M. Hawkins, J. A. Stamatoyannopoulos, C. C. Chow, G. L. Hager.

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.