Journal
GENOME RESEARCH
Volume 25, Issue 6, Pages 845-857Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.184168.114
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Funding
- Center for Cancer Research
- National Institute of Diabetes and Digestive and Kidney Diseases
- federal funds from the National Cancer Institute, National Institutes of Health [HHSN261200800001E]
- OPVK project [CZ.1.07/2.3.00/30.0030]
- National Institutes of Health
- National Cancer Institute
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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.
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