Abduction and asylum in the lives of transcription factors
Abduction and asylum in the lives of transcription factors
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DOI：
10.1073/pnas.0915138107
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发表时间：
2010-03-02
影响因子：
11.1
通讯作者：
Wolynes, Peter G.
中科院分区：
文献类型：
--
作者：
Burger, Anat;Walczak, Aleksandra M.;Wolynes, Peter G.
最近的研究表明，有许多非功能性转录因子结合位点沿着基因组。虽然这些“诱饵”位点与启动子区域竞争转录因子的结合，但它们也可以保护这些蛋白质免于降解。我们表明，在完美的保护，其中绑定的转录因子从来没有降解的限制，非功能性结合位点的竞争效应是完全抵消了从减少降解获得的稳定性。我们研究了自调节基因对转录因子总数的响应，以量化转录因子竞争的后果。我们表明，可以通过数学方法构建具有有效参数的单个基因来获得对该系统的直觉，这些参数可以重现具有添加诱饵位点的基因的行为。类似于多体系统中的缀饰粒子，我们称这种描述为“准基因"。“我们发现，保护性诱饵通过减少转录因子之间的相关性来缓冲噪音，特别是在突发转录因子产生的情况下。我们发现，除了保护性诱饵网站的基因表达水平的方法，从确定性的大规模行动模型预测。最后，我们表明，保护诱饵网站的参数空间，表现出双稳态的区域的大小减少。
Recent studies suggest that there are many nonfunctional transcription factor binding sites along a genome. Although these "decoy" sites compete with the promoter region for binding of transcription factors, they may also protect these proteins from degradation. We show that in the limit of perfect protection, where bound transcription factors are never degraded, the competitive effect of nonfunctional binding sites is completely canceled out by the stability gained from reduced degradation. We examine the response of an autoregulated gene to the total number of transcription factors to quantify the consequences of competition for transcription factors. We show that intuition about this system can be gained by mathematically constructing a single gene with effective parameters that reproduce the behavior of a gene with added decoy sites. In analogy to dressed particles in many-body systems we term this description a "quasi gene." We find that protective decoys buffer against noise by reducing correlations between transcription factors, specifically in the case of production of transcription factors in bursts. We show that the addition of protective decoy sites causes the level of gene expression to approach that predicted from deterministic mass action models. Finally, we show that protective decoy sites decrease the size of the region of parameter space that exhibits bistability.