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Dynamics of chromatin accessibility and long-range interactions in response to glucocorticoid pulsing
DA. Stavreva, A. Coulon, S. Baek, MH. Sung, S. John, L. Stixova, M. Tesikova, O. Hakim, T. Miranda, M. Hawkins, JA. Stamatoyannopoulos, CC. Chow, GL. Hager,
Language English Country United States
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 1991 to 6 months ago
Freely Accessible Science Journals
from 1991-08-01 to 1 year ago
PubMed Central
from 1997 to 6 months ago
Europe PubMed Central
from 1997 to 6 months ago
Open Access Digital Library
from 1991-08-01
Open Access Digital Library
from 1991-08-01
PubMed
25677181
DOI
10.1101/gr.184168.114
Knihovny.cz E-resources
- MeSH
- Cell Line MeSH
- Chromatin genetics metabolism MeSH
- Chromatin Immunoprecipitation MeSH
- Deoxyribonuclease I genetics metabolism MeSH
- Glucocorticoids pharmacology MeSH
- Membrane Proteins genetics metabolism MeSH
- Mice MeSH
- Receptors, Glucocorticoid genetics metabolism MeSH
- Gene Expression Regulation MeSH
- Response Elements * MeSH
- Sequence Analysis, DNA MeSH
- Carrier Proteins genetics metabolism MeSH
- Protein Binding MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
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.
Department of Biosciences University of Oslo 0316 Oslo Norway
Department of Genome Sciences University of Washington Seattle Washington 98195 USA
Laboratory of Genome Integrity National Cancer Institute NIH Bethesda Maryland 20892 USA
The Mina and Everard Goodman Faculty of Life Sciences Bar Ilan University Ramat Gan 5290002 Israel
References provided by Crossref.org
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