The glucocorticoid receptor: rapid exchange with regulatory sites in living cells
Abstract
Steroid receptors bind to site-specific response elements in chromatin and modulate gene expression in a hormone-dependent fashion. With the use of a tandem array of mouse mammary tumor virus reporter elements and a form of glucocorticoid receptor labeled with green fluorescent protein, targeting of the receptor to response elements in live mouse cells was observed. Photobleaching experiments provide direct evidence that the hormone-occupied receptor undergoes rapid exchange between chromatin and the nucleoplasmic compartment. Thus, the interaction of regulatory proteins with target sites in chromatin is a more dynamic process than previously believed.
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Once in the nucleus, liganded glucocorticoid receptors do not bind DNA stably but constantly shuttle between the nucleoplasm and glucocorticoid-responsive elements.
“Once in the nucleus, liganded GRs do not bind to DNA in a stable manner. They rather constantly shuttle between the nucleoplasm and GC-responsive elements (GRE) located in the promoter or enhancer regions of GC-responsive genes (80, 81).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [80]
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- Authors
- McNally, J. G., Müller, W. G., Walker, D., Wolford, R., & Hager, G. L.
- Affiliations
- National Institutes of Health (US)
- Laboratory of Receptor Biology and Gene Expression, Building 41, Room B602, National Cancer Institute, Bethesda, MD 20892–5055, USA.
- Corresponding author
- McNally, James G.
- Hager, Gordon L.
- Venue
- Science
- Published
- 2000-02-18
- Volume
- 287
- Issue
- 5456
- Pages
- 1262-1265
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2096594220
- Cited by
- 802
- References
- 32
- Citations by year
- 2026: 17 · 2025: 13 · 2024: 11 · 2023: 13 · 2022: 16 · 2021: 21 · 2020: 17 · 2019: 13 · 2018: 15 · 2017: 24 · 2016: 28 · 2015: 27 · 2014: 29 · 2013: 31 · 2012: 20
- FWCI
- 35.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Keywords
- glucocorticoid receptor, chromatin, response elements, nucleoplasm, photobleaching, green fluorescent protein tagging, chromatin dynamics, transcriptional regulation
- MeSH terms
- Animals, Binding Sites, Cell Line, Transformed, Cell Nucleus, Chromatin, Dexamethasone, Ligands, Luminescent Proteins, Mammary Tumor Virus, Mouse, Microscopy, Fluorescence, Nucleosomes, Receptors, Glucocorticoid, In Situ Hybridization, Fluorescence, Microscopy, Confocal, Terminal Repeat Sequences, Response Elements, Green Fluorescent Proteins, Mice
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