Phenotypic consequences of promoter-mediated transcriptional noise
Phenotypic consequences of promoter-mediated transcriptional noise
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DOI：
10.1016/j.molcel.2006.11.003
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发表时间：
2006-12-28
期刊：
影响因子：
16
通讯作者：
Collins, James J.
中科院分区：
文献类型：
--
作者：
Blake, William J.;Balazsi, Gbor;Collins, James J.
需要更全面地了解基因表达中细胞-细胞变异性的原因和影响，以阐明由此产生的表型是不利的还是赋予一些适应性优势。在这里，我们表明，受TATA盒子序列影响的基因表达变异性的增加，在环境条件急剧变化后可能是有益的。我们合理地在工程酿酒酵母GAL1启动子的TATA区域引入突变，并测量启动子响应，其特征可以是高度可变和快速或稳定和缓慢。我们通过计算说明了一个稳定的转录支架如何导致基因表达的“爆发”，从而在稳定状态下，在短暂和增加的细胞-细胞变异性中实现快速的单个细胞反应。我们通过实验验证了计算预测，即在面对急性环境压力时，由含tata的启动子实现的快速反应和增加的细胞-细胞变异性具有明显的益处。
A more complete understanding of the causes and effects of cell-cell variability in gene expression is needed to elucidate whether the resulting phenotypes are disadvantageous or confer some adaptive advantage. Here we show that increased variability in gene expression, affected by the sequence of the TATA box, can be beneficial after an acute change in environmental conditions. We rationally introduce mutations within the TATA region of an engineered Saccharomyces cerevisiae GAL1 promoter and measure promoter responses that can be characterized as being either highly variable and rapid or steady and slow. We computationally illustrate how a stable transcription scaffold can result in "bursts" of gene expression, enabling rapid individual cell responses in the transient and increased cell-cell variability at steady state. We experimentally verify computational predictions that the rapid response and increased cell-cell variability enabled by TATA-containing promoters confer a clear benefit in the face of an acute environmental stress.