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

0446234 - BFÚ 2016 RIV US eng J - Článek v odborném periodiku
Stavreva, D. A. - Coulon, A. - Baek, S. - Sung, M.H. - John, S. - Stixová, Lenka … celkem 13 autorů
Dynamics of chromatin accessibility and long-range interactions in response to glucocorticoid pulsing.
Genome Research. Roč. 25, č. 6 (2015), s. 845-857. ISSN 1088-9051. E-ISSN 1549-5469
Grant CEP: GA MŠMT(CZ) EE2.3.30.0030
Institucionální podpora: RVO:68081707
Klíčová slova: NEUTRAL LIPID DROPLETS * DNASE-I * HYPERSENSITIVE SITES
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 11.351, rok: 2015

lthough 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.
Trvalý link: http://hdl.handle.net/11104/0248225