人类基因的内在动力学揭示了表达异质性的基础
Joseph Rodriguez1, Gang Ren2, Christopher R Day1
1Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD, USA.
Cell
|December 18, 2018
概括
人类的基因表达是由于可变的不活跃时期而不是稳定的状态而引起的. 这项研究将基因调节,染色体结构和细胞对雌激素信号的反应联系起来.
科学领域:
- 分子生物学
- 基因组学
- 细胞生物学
背景情况:
- 甲基动物转录调节涉及增强剂和促进剂之间的长距离基因组接触.
- 大多数基因表现出偶尔的RNA合成,称为转录性爆发.
研究的目的:
- 研究基因接触,转录爆发和动态基因调节之间的关系.
- 使用活细胞成像和染色体构成捕获来剖析对雌激素敏感的TFF1基因的内源调节.
主要方法:
- 活细胞RNA成像用于监测内源基因转录动态.
- 分析三维基因组结构的高温测量.
- 数学建模以关联转录,染色体结构和信号传感.
主要成果:
- 对TFF1基因观察到短暂的活跃转录周期和可变的不活跃周期 (分钟至天).
- 证明不活性时间的异质性解释了基因表达噪声和蛋白质水平分布.
- 显示TFF1高度诱导,但表现出动态的转录突发.
结论:
- 基因表达"噪音"来自动态转录变异,而不是稳定的生物状态.
- 细胞对雌激素等信号的反应涉及转录突发的动态调节.
- 数学模型可以将染色体结构,基因活动和信号诱导的转录动态联系起来.
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