Control and signal processing by transcriptional interference
Control and signal processing by transcriptional interference
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DOI：
10.1038/msb.2009.61
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发表时间：
2009-08-01
影响因子：
9.9
通讯作者：
Becskei, Attila
中科院分区：
文献类型：
--
作者：
Buetti-Dinh, Antoine;Ungricht, Rosemarie;Becskei, Attila
转录激活剂可以通过干扰另一种激活剂启动的转录来抑制基因表达。转录干扰越来越被认为是基因表达的调控机制。两种拮抗作用的激活剂接收到的信号通过沿着 DNA 的聚合酶运输而结合。我们在酵母中设计了双控制遗传系统来系统地探索这种拮抗作用。上游激活剂的拮抗作用具有竞争性抑制的特征，而下游激活剂则非竞争性抑制基因表达。当基因表达被微弱诱导时，拮抗激活剂可以产生积极作用，甚至可以引发反常激活。转录的平衡和非平衡模型揭示了干扰转换信号的机制，并揭示了激活剂的自我拮抗模仿前馈循环的行为。事实上，合成电路会产生钟形响应，因此表达的诱导仅限于输入信号的狭窄范围。识别保守的干扰调控原理将有助于预测基因在基因组背景下的转录反应。分子系统生物学5：300； 2009 年 8 月 18 日在线发布； doi：10.1038/msb.2009.61
A transcriptional activator can suppress gene expression by interfering with transcription initiated by another activator. Transcriptional interference has been increasingly recognized as a regulatory mechanism of gene expression. The signals received by the two antagonistically acting activators are combined by the polymerase trafficking along the DNA. We have designed a dual-control genetic system in yeast to explore this antagonism systematically. Antagonism by an upstream activator bears the hallmarks of competitive inhibition, whereas a downstream activator inhibits gene expression non-competitively. When gene expression is induced weakly, the antagonistic activator can have a positive effect and can even trigger paradoxical activation. Equilibrium and non-equilibrium models of transcription shed light on the mechanism by which interference converts signals, and reveals that self-antagonism of activators imitates the behavior of feed-forward loops. Indeed, a synthetic circuit generates a bell-shaped response, so that the induction of expression is limited to a narrow range of the input signal. The identification of conserved regulatory principles of interference will help to predict the transcriptional response of genes in their genomic context. Molecular Systems Biology 5: 300; published online 18 August 2009; doi: 10.1038/msb.2009.61