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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Voss, TC; Schiltz, RL; Sung, M-H; Yen, PM; Stamatoyannopoulos, JA; Biddie, SC; Johnson, TA; Miranda, TB; John, S; Hager, GL

Published Date

  • August 19, 2011

Published In

Volume / Issue

  • 146 / 4

Start / End Page

  • 544 - 554

PubMed ID

  • 21835447

Pubmed Central ID

  • 21835447

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2011.07.006

Language

  • eng

Conference Location

  • United States