Laboratory of Receptor Biology and Gene Expression, Building 41, B602, 41 Library Drive, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cell. 2011 Aug 19;146(4):544-54. doi: 10.1016/j.cell.2011.07.006. Epub 2011 Aug 11.
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.
糖皮质激素受体（GR）与其他真核转录因子一样，通过与染色质化 DNA 反应元件相互作用来调节基因表达。活细胞中的光漂白实验表明，受体在几秒钟的时间内与 DNA 短暂相互作用，并预测反应元件的平均占有率可能较低。在这里，我们表明，一种受体在糖皮质激素反应元件（GRE）上的结合不会降低另一种受体变体在相同 GRE 上的稳定结合。数学模拟使用较短的 GR/GRE 居留时间和 DNA 结合事件之间较长的时间来重现这种非竞争性状态。在 GR 结合导致染色质可及性增加的许多基因组位点上，变体受体的同时稳定结合水平实际上增加了，这种现象称为辅助加载。时空稀疏的转录因子-DNA 相互作用诱导局部染色质重排，导致二级调节因子的短暂结合。
