Cited by 307Genomics and Chromatin DynamicsDiffusion and Search DynamicsChromatin Remodeling and Cancer

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Dynamic Exchange at Regulatory Elements during Chromatin Remodeling Underlies Assisted Loading Mechanism

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Voss, Ty C., Schiltz, R. Louis, Sung, Myong-Hee, Yen, Paul M., Stamatoyannopoulos, John A., Biddie, Simon C., Johnson, Thomas A., Miranda, Tina B., John, Sam, Hager, Gordon L.·2011·Cell

DOI 10.1016/j.cell.2011.07.006PMC PMC3210475

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Abstract

The glucocorticoid receptor (GR), like other eukaryotic transcription factors, regulates gene expression by interacting with chromatinized DNA response elements. Photobleaching experiments in living cells indicate that receptors transiently interact with DNA on the time scale of seconds and predict that the response elements may be sparsely occupied on average. Here, we show that the binding of one receptor at the glucocorticoid response element (GRE) does not reduce the steady-state binding of another receptor variant to the same GRE. Mathematical simulations reproduce this noncompetitive state using short GR/GRE residency times and relatively long times between DNA binding events. At many genomic sites where GR binding causes increased chromatin accessibility, concurrent steady-state binding levels for the variant receptor are actually increased, a phenomenon termed assisted loading. Temporally sparse transcription factor-DNA interactions induce local chromatin reorganization, resulting in transient access for binding of secondary regulatory factors.

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Authors: Voss, T. C., Schiltz, R. L., Sung, M.-H., Yen, P. M., Stamatoyannopoulos, J. A., Biddie, S. C., Johnson, T. A., Miranda, T. B., John, S., & Hager, G. L.
Affiliations: National Institutes of Health (US)
National University of Singapore (SG)
University of Washington (US)
Corresponding author: Hager, Gordon L.
ORCID: Voss, Ty C.
Schiltz, R. Louis
Sung, Myong-Hee
Yen, Paul M.
Stamatoyannopoulos, John A.
Biddie, Simon C.
Johnson, Thomas A.
Miranda, Tina B.
Hager, Gordon L.
Venue: Cell
Publisher: Elsevier BV
Published: 2011-08
Volume: 146
Issue: 4
Pages: 544-554
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2011.07.006
PMC: PMC3210475
OpenAlex: W1963958393
Cited by: 307
References: 42
Citations by year: 2026: 5 · 2025: 10 · 2024: 11 · 2023: 11 · 2022: 16 · 2021: 20 · 2020: 17 · 2019: 23 · 2018: 33 · 2017: 23 · 2016: 29 · 2015: 23 · 2014: 25 · 2013: 26 · 2012: 29
FWCI: 11.18
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 716 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Cancer Institute (ZIABC005450)
Topics: 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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: glucocorticoid receptor, glucocorticoid response element, transcription factor-DNA binding, chromatin accessibility, chromatin remodeling, receptor isoforms, photobleaching, transcriptional regulation
MeSH terms: Adenosine Triphosphate, Animals, Mammary Tumor Virus, Mouse, Models, Biological, Monte Carlo Method, Nucleosomes, Receptors, Estrogen, Receptors, Glucocorticoid, Regulatory Sequences, Nucleic Acid, Transcription Factors, Response Elements, Chromatin Assembly and Disassembly, Cell Line, Tumor, Mice

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Dynamic Exchange at Regulatory Elements during Chromatin Remodeling Underlies Assisted Loading Mechanism

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