在染色体重塑过程中,调节元件的动态交换是辅助加载机制的基础
Ty C Voss1, R Louis Schiltz, Myong-Hee Sung
1Laboratory of Receptor Biology and Gene Expression, Building 41, B602, 41 Library Drive, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cell
|August 13, 2011
概括
葡萄糖皮质体受体 (GR) 与DNA的结合是暂时的,允许多个受体在没有竞争的情况下结合同一位点. 这种稀疏的结合促进了染色质的重组,并辅助了其他因素的加载.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 细胞生物学 细胞生物学
背景情况:
- 细胞转录因子,包括葡萄糖皮质体受体 (GR),通过与DNA的相互作用来调节基因表达.
- 之前的光漂白实验表明,GR在几秒钟的尺度上短暂地与DNA结合,这意味着响应元素的占用率很低.
研究的目的:
- 在DNA反应元素中研究葡萄糖皮质体受体 (GR) 的结合动力学.
- 为了确定GR结合是否会影响同一部位的其他受体变体的稳定状态结合.
主要方法:
- 在活细胞中对受体结合的实验分析.
- 数学模拟模型转录因子-DNA相互作用和居住时间.
主要成果:
- 一个GR的结合不会阻碍另一种GR变体与相同的葡萄皮质醇反应元件 (GRE) 的稳定状态结合.
- 数学模型支持非竞争性结合,其特点是短的GR/GRE居住时间和罕见的DNA结合事件.
- 结合GR可以增加染色质的可访问性,导致变异性受体的结合增强,这种现象被称为"辅助加载".
结论:
- 稀有,短暂的转录因子-DNA相互作用可以诱导染色质重组.
- 这种重组促进了二次调节因子的暂时访问,影响了基因表达调节.
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