全基因组的蛋白质-DNA结合动力学表明,转录因子功能的分子离合器
Colin R Lickwar1, Florian Mueller, Sean E Hanlon
1Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3280, USA.
Nature
|April 14, 2012
概括
转录因子结合动态,而不仅仅是占用,决定了基因功能. 快速结合周转 (跑步机) 与低基因输出相关,而长期存在会激活转录.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 对遗传信息的动态访问对于发展和环境反应至关重要.
- 传统的染色体免疫沉 (ChIP) 测量了转录因子占用率,但缺乏动态信息.
- 占用数据很难预测特定基因组位置的转录因子功能.
研究的目的:
- 测量全基因组转录因子结合动态.
- 为了将绑定动态与功能结果相关联.
- 为了研究结合周转在基因表达中的调节作用.
主要方法:
- 利用竞争ChIP (染色体免疫沉) 来评估转录因子结合动态.
- 研究了一种特定序列的Saccharomyces cerevisiae转录因子Rap1.1.
- 分析了Rap1结合动态,占用率和转录输出之间的相关性.
主要成果:
- 拉普1结合动态和占用率显示出弱相关性 (R2 = 0.14).
- 绑定动态是功能比占用更强有力的预测因素.
- 长时间的Rap1居住与转录激活相关,而快速的周转 (跑步机) 与低的转录输出相关.
结论:
- 具有相似占用率的DNA结合事件可以根据结合动态产生不同的功能结果.
- 转录因子结合周转是影响基因表达的关键调节机制.
- 一个类似于离合器的机制,涉及与核酶的竞争,可以调节结合周转率并调节转录因子功能.
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