Center for Theoretical Biological Physics, University of California at San Diego, La Jolla, CA 92093-0374, USA.
Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4016-21. doi: 10.1073/pnas.0915138107. Epub 2010 Feb 16.
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.
最近的研究表明,基因组上存在许多非功能转录因子结合位点。虽然这些“诱饵”位点与启动子区域竞争转录因子的结合,但它们也可能保护这些蛋白质免受降解。我们表明,在完美保护的极限下,即结合的转录因子永远不会被降解,非功能结合位点的竞争效应完全被降低降解获得的稳定性所抵消。我们考察了一个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。我们通过数学构建一个具有有效参数的单个基因,来模拟具有添加诱饵位点的基因的行为,从而对该系统有一个直观的了解。类比于多体系统中的 dressed particles,我们将这种描述称为“准基因”。我们发现,保护型诱饵通过减少转录因子之间的相关性来缓冲噪声,特别是在转录因子爆发产生的情况下。我们表明,添加保护型诱饵会导致基因表达水平接近从确定性质量作用模型预测的水平。最后,我们表明,保护型诱饵会减小表现出双稳性的参数空间区域的大小。