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Dynamic exchange at regulatory elements during chromatin remodeling underlies assisted loading mechanism.

Publication ,  Journal Article
Voss, TC; Schiltz, RL; Sung, M-H; Yen, PM; Stamatoyannopoulos, JA; Biddie, SC; Johnson, TA; Miranda, TB; John, S; Hager, GL
Published in: Cell
August 19, 2011

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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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

August 19, 2011

Volume

146

Issue

4

Start / End Page

544 / 554

Location

United States

Related Subject Headings

  • Transcription Factors
  • Response Elements
  • Regulatory Sequences, Nucleic Acid
  • Receptors, Glucocorticoid
  • Receptors, Estrogen
  • Nucleosomes
  • Monte Carlo Method
  • Models, Biological
  • Mice
  • Mammary Tumor Virus, Mouse
 

Citation

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Voss, T. C., Schiltz, R. L., Sung, M.-H., Yen, P. M., Stamatoyannopoulos, J. A., Biddie, S. C., … Hager, G. L. (2011). Dynamic exchange at regulatory elements during chromatin remodeling underlies assisted loading mechanism. Cell, 146(4), 544–554. https://doi.org/10.1016/j.cell.2011.07.006
Voss, Ty C., R Louis Schiltz, Myong-Hee Sung, Paul M. Yen, John A. Stamatoyannopoulos, Simon C. Biddie, Thomas A. Johnson, Tina B. Miranda, Sam John, and Gordon L. Hager. “Dynamic exchange at regulatory elements during chromatin remodeling underlies assisted loading mechanism.Cell 146, no. 4 (August 19, 2011): 544–54. https://doi.org/10.1016/j.cell.2011.07.006.
Voss TC, Schiltz RL, Sung M-H, Yen PM, Stamatoyannopoulos JA, Biddie SC, et al. Dynamic exchange at regulatory elements during chromatin remodeling underlies assisted loading mechanism. Cell. 2011 Aug 19;146(4):544–54.
Voss, Ty C., et al. “Dynamic exchange at regulatory elements during chromatin remodeling underlies assisted loading mechanism.Cell, vol. 146, no. 4, Aug. 2011, pp. 544–54. Pubmed, doi:10.1016/j.cell.2011.07.006.
Voss TC, Schiltz RL, Sung M-H, Yen PM, Stamatoyannopoulos JA, Biddie SC, Johnson TA, Miranda TB, John S, Hager GL. Dynamic exchange at regulatory elements during chromatin remodeling underlies assisted loading mechanism. Cell. 2011 Aug 19;146(4):544–554.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

August 19, 2011

Volume

146

Issue

4

Start / End Page

544 / 554

Location

United States

Related Subject Headings

  • Transcription Factors
  • Response Elements
  • Regulatory Sequences, Nucleic Acid
  • Receptors, Glucocorticoid
  • Receptors, Estrogen
  • Nucleosomes
  • Monte Carlo Method
  • Models, Biological
  • Mice
  • Mammary Tumor Virus, Mouse