Promoter decoding of transcription factor dynamics.
Promoter decoding of transcription factor dynamics.
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转录因子动力学的启动子解码。
DOI：
10.1038/msb.2013.63
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发表时间：
2013
影响因子：
9.9
通讯作者：
Batchelor,Eric
中科院分区：
文献类型：
--
作者：
Moody,AmieD;Batchelor,Eric
“隐写术”，意思是“隐藏的文字”，是一种将秘密信息隐藏在另一条信息中的艺术。原始信息看起来只是一封信或一张照片，但拥有必要知识的人可以解码它，找到隐藏的信息。事实证明，细胞可能已经发展出一种隐写术。最近的研究表明，单个转录因子（TF）可以响应于不同的刺激而表现出不同的动力学（纳尔逊等人，2004; Tay等人，2010; Batchelor等人，2011; Hao和O 'Shea，2012），并且TF动力学可以改变靶基因激活（Tay等人，2010; Purvis等人，2012）。汉森和O 'Shea（2013）现在提供了对单个启动子如何解码特定TF动态模式以影响不同基因表达应答的见解。为了理解这一过程，作者研究了Msn 2，这是一种酵母转录因子，它以不同的动态表达模式响应不同的应激：短持续时间重复脉冲，具有剂量依赖性持续时间的单脉冲，或具有剂量依赖性幅度的单脉冲（Hao和O 'Shea，2012）。使用小分子来控制Msn 2的核易位，汉森和O 'Shea（2013）用一组30个激活曲线来激发细胞，所述激活曲线模拟天然Msn 2动力学，涵盖一系列持续时间、振幅和脉冲数。为了测量Msn 2动力学对靶基因表达的影响，他们产生了二倍体酵母菌株，其中编码YFP或CFP的基因取代了同源染色体上7个强烈激活的Msn 2靶基因的ORF。测量来自用Msn 2活化谱处理的报告菌株的荧光水平表明，启动子对持续的Msn 2核定位或脉冲的响应不同（图1）。将三态启动子模型应用于数据，作者确定了两种启动子类别：高幅度阈值，慢启动子（HS）;和低幅度阈值，快启动子（LF）。在分析的七个启动子中，三个被分类为HS启动子，三个为LF启动子，并且一个启动子是表现出两个类别的特征的杂交体。作者推测，四类启动子可能
‘Steganography,’meaning ‘concealed writing,’is the art of hiding a secret message within another message. The original message appears to be simply a letter or photograph, yet a person with the requisite knowledge can decode it to find hidden information. As it turns out, cells may have developed a form of steganography. Recent studies have shown that a single transcription factor (TF) can exhibit different dynamics in response to different stimuli (Nelson et al, 2004; Tay et al, 2010; Batchelor et al, 2011; Hao and O’Shea, 2012) and that TF dynamics can alter target gene activation (Tay et al, 2010; Purvis et al, 2012). Hansen and O’Shea (2013) now provide insight into how individual promoters can decode specific TF dynamic patterns to effect distinct gene expression responses. To understand this process, the authors studied Msn2, a yeast transcription factor that responds to different stresses with distinct dynamic expression patterns: short-duration repeated pulses, a single pulse with a dose-dependent duration, or a single pulse with a dose-dependent amplitude (Hao and O’Shea, 2012). Using a small molecule to control nuclear translocation of Msn2, Hansen and O’Shea (2013) challenged cells with a panel of 30 activation profiles simulating the natural Msn2 dynamics, covering a range of duration, amplitude, and number of pulses. To measure the effects of Msn2 dynamics on target gene expression, they generated diploid yeast strains in which genes encoding YFP or CFP replaced the ORFs on homologous chromosomes for seven strongly activated Msn2 target genes. Measuring fluorescence levels from the reporter strains treated with the Msn2 activation profiles demonstrated that promoters responded differently to either sustained Msn2 nuclear localization or pulses (Figure 1). Applying a three-state promoter model to the data, the authors identified two promoter classes: High amplitude threshold, Slow promoters (HS); and Low amplitude threshold, Fast promoters (LF). Of the seven promoters analyzed, three were classified as HS promoters, three as LF promoters, and one promoter was a hybrid that exhibited characteristics of both classes. The authors speculated that four classes of promoters might