转录因子家族中的DNA特异性的进化产生了一种新的基因调节模块
Alesia N McKeown1, Jamie T Bridgham1, Dave W Anderson1
1Institute of Ecology and Evolution, University of Oregon, Eugene, OR 97403, USA.
Cell
|September 27, 2014
概括
在类固醇激素受体中研究了转录因子DNA结合特异性的演变. 关键突变削弱了祖先的DNA结合,同时实现了新的序列识别,揭示了特异性进化的负面决定因素.
科学领域:
- 分子生物学分子生物学
- 进化生物学 进化生物学
- 生物化学 生物化学
背景情况:
- 转录因子 (TF) 通过结合特定的DNA序列来调节基因网络.
- 了解TF DNA结合特异性的演变对于破译基因调节至关重要.
- 类固醇激素受体 (SR) 家族为研究TF进化提供了一个模型.
研究的目的:
- 研究如何在类固醇激素受体 (SR) 家族内多样化DNA识别.
- 阐明了新型TF DNA结合特异性的演化背后的分子机制.
主要方法:
- 遗传学分析来追踪进化的历史.
- 生物化学测试用于测量DNA结合亲和力和特异性.
- 生物物理技术探测TF和DNA之间的分子相互作用.
主要成果:
- 在SR基因拷贝中的三个特定突变削弱了与祖先雌激素反应元素 (ERE) 的结合.
- 这些突变同时增强了与新类固醇反应元素 (SREs) 的结合.
- 负决定因素 (不利的相互作用) 和允许的替代对改变的DNA选择性和结合亲和力至关重要.
结论:
- 对DNA结合的负决定因素在TF序列选择性中起着重要作用.
- 新型TF DNA结合特异性的演化可以在不破坏祖先调节模块的情况下发生.
- 这项研究阐明了TF DNA结合和连接体特异性的共同进化机制.
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