Dynamic and complex transcription factor binding during an inducible response in yeast
Dynamic and complex transcription factor binding during an inducible response in yeast
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DOI：
10.1101/gad.1781909
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发表时间：
2009-06-01
影响因子：
10.5
通讯作者：
Snyder, Michael
中科院分区：
文献类型：
--
作者：
Ni, Li;Bruce, Can;Snyder, Michael
复杂的生物学过程通常至少部分地通过转录因子与其靶标的结合来调节。最近，已经做出了相当大的努力来分析相关因子与它们所调节的一系列靶点的结合，从而生成调节电路图。然而，对于大多数研究，结合的动力学没有被分析，因此，事件的时间顺序和发生的机制知之甚少。我们在全球范围内详细分析了几个关键因素的结合的时间顺序，参与酵母的盐响应，他们的靶基因。对Yap4和Sko 1与其靶基因结合的分析揭示了结合模式的多个时间类别：（1）恒定结合，（2）快速诱导，（3）缓慢诱导，和（4）瞬时诱导。这些结果表明，个别转录因子可以有多种结合模式，并帮助确定在真核基因调控中使用的不同类型的时间结合模式。为了进一步研究这些结合模式，我们还分析了与渗透调节有关的其他七个关键转录因子的结合，包括Hot1，Msn1，Msn2，Msn4，Skn7和Yap6，并发现不同因子在其基因靶点之间存在显著的共关联。此外，几个关键因素的结合与不同类别的Yap4和Sko1结合模式和不同类型的基因相关。基因表达研究揭示了Yap4，Sko1和其他转录因子结合模式与不同基因表达模式的关联。结合和表达信息的整合和分析揭示了一个复杂的动态和分层电路，其中转录因子的特定组合在离散时间靶向不同的基因组，以协调快速和重要的生物反应。
Complex biological processes are often regulated, at least in part, by the binding of transcription factors to their targets. Recently, considerable effort has been made to analyze the binding of relevant factors to the suite of targets they regulate, thereby generating a regulatory circuit map. However, for most studies the dynamics of binding have not been analyzed, and thus the temporal order of events and mechanisms by which this occurs are poorly understood. We globally analyzed in detail the temporal order of binding of several key factors involved in the salt response of yeast to their target genes. Analysis of Yap4 and Sko1 binding to their target genes revealed multiple temporal classes of binding patterns: (1) constant binding, (2) rapid induction, (3) slow induction, and (4) transient induction. These results demonstrate that individual transcription factors can have multiple binding patterns and help define the different types of temporal binding patterns used in eukaryotic gene regulation. To investigate these binding patterns further, we also analyzed the binding of seven other key transcription factors implicated in osmotic regulation, including Hot1, Msn1, Msn2, Msn4, Skn7, and Yap6, and found significant coassociation among the different factors at their gene targets. Moreover, the binding of several key factors was correlated with distinct classes of Yap4- and Sko1-binding patterns and with distinct types of genes. Gene expression studies revealed association of Yap4, Sko1, and other transcription factor-binding patterns with different gene expression patterns. The integration and analysis of binding and expression information reveals a complex dynamic and hierarchical circuit in which specific combinations of transcription factors target distinct sets of genes at discrete times to coordinate a rapid and important biological response.