Identifying transcription factor functions and targets by phenotypic activation
Identifying transcription factor functions and targets by phenotypic activation
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DOI：
10.1073/pnas.0605140103
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发表时间：
2006-08-08
影响因子：
11.1
通讯作者：
Hughes, Timothy R.
中科院分区：
文献类型：
--
作者：
Chua, Gordon;Morris, Quaid D.;Hughes, Timothy R.
映射转录调节网络很困难，因为许多转录因子（TF）仅在特定条件下被激活。我们描述了一个通用策略，用于识别由单个TF诱导的基因和途径，该途径不需要知道其正常激活线索的知识。对55种酵母TFS的微阵列分析，这些分析在过表达表明大多数引起特定生理类别中的转录基因水平上升时，这表明了生长抑制的机制。诱导的基因通常包括具有共识启动子基序的已建立的靶标和基因，如果已知，表明这些数据对于识别潜在的新靶基因和结合位点很有用。我们将序列5'-TCACGCAA鉴定为HMS1P的结合序列，HMS1P是一种阳性调节假氢生长的TF，以前没有已知的基序。此处概述的一般策略提出了一种直接发现TF活动和映射目标的方法，这些方法可以通过转基因技术适应任何生物体。
Mapping transcriptional regulatory networks is difficult because many transcription factors (TFs) are activated only under specific conditions. We describe a generic strategy for identifying genes and pathways induced by individual TFs that does not require knowledge of their normal activation cues. Microarray analysis of 55 yeast TFs that caused a growth phenotype when overexpressed showed that the majority caused increased transcript levels of genes in specific physiological categories, suggesting a mechanism for growth inhibition. Induced genes typically included established targets and genes with consensus promoter motifs, if known, indicating that these data are useful for identifying potential new target genes and binding sites. We identified the sequence 5'-TCACGCAA as a binding sequence for Hms1p, a TF that positively regulates pseudohyphal growth and previously had no known motif. The general strategy outlined here presents a straightforward approach to discovery of TF activities and mapping targets that could be adapted to any organism with transgenic technology.