转录因子对的DNA依赖形成改变了它们的结合特异性
Arttu Jolma1, Yimeng Yin1, Kazuhiro R Nitta1
1Department of Biosciences and Nutrition, Karolinska Institutet, SE 141 83, Sweden.
Nature
|November 10, 2015
概括
研究人员确定了转录因子 (TF) 在DNA上如何协作. 他们发现了新的TF对和控制基因表达的DNA动机,
科学领域:
- 分子生物学
- 遗传学
- 生物信息学
背景情况:
- 基因表达主要由与特定DNA序列结合的转录因子 (TFs) 调节.
- 多个TF与附近的DNA基因的合作结合对于精确的基因表达特异性至关重要.
- 缺少DNA结合TF之间的相互作用的系统表征.
研究的目的:
- 系统地识别具有合作DNA结合的TF对.
- 描述这些合作TF相互作用的首选间距和方向.
- 阐明基因调节中的TF-TF合作性的结构基础.
主要方法:
- 通过指数式丰富 (CAP-SELEX) 使用连续亲和力净化系统演化来分析9400个TF-TF-DNA相互作用.
- 进行了结构分析,包括MEIS1和DLX3复合物的新结晶学.
- 分析了单个TF识别图案与复合图案的重叠和特征.
主要成果:
- 发现了315种新的TF-TF相互作用和618种以前未被描述的异构DNA基因.
- 在不同TF结构家族中观察到散乱的合作性.
- 发现DNA主要介导TF-TF相互作用,通常涉及显著的模式重叠以形成复合站点.
结论:
- 这项研究显著扩大了已知的合作TF相互作用及其识别动机.
- DNA积极参与调解TF协作,塑造基因调控词汇.
- 这些发现为了解复杂的基因调节网络提供了基础.
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