Stochastic model of transcription factor-regulated gene expression
Stochastic model of transcription factor-regulated gene expression
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DOI：
10.1088/1478-3975/3/3/005
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发表时间：
2006-09-01
期刊：
影响因子：
2
通讯作者：
Bose, Indrani
中科院分区：
文献类型：
--
作者：
Karmakar, Rajesh;Bose, Indrani
我们考虑一个随机模型的转录因子（TF）调控的基因表达。该模型描述了两个基因，基因A和基因B，分别合成TF和靶基因蛋白。我们通过分析计算表明，当平均TF水平福尔斯落在剂量-反应曲线的最高敏感区域时，TF波动对靶基因蛋白水平的分布有显著影响。我们进一步研究了将基因A的拷贝数从两个减少到一个的影响。增强的TF波动产生的结果不同于那些在确定性的情况下。利用与TF和靶基因蛋白质水平相关的概率密度函数的知识来计算靶基因蛋白质水平超过阈值的概率。一个更详细的随机模型的数值模拟结果与通过解析计算得到的结果一致。这些结果的遗传性疾病单倍不足的背景下的相关性指出。肿瘤抑制基因Nkx 3.1的单倍不足的一些实验观察，解释与TF调节基因表达的随机模型的帮助。
We consider a stochastic model of transcription factor (TF)-regulated gene expression. The model describes two genes, gene A and gene B, which synthesize the TFs and the target gene proteins, respectively. We show through analytic calculations that the TF fluctuations have a significant effect on the distribution of the target gene protein levels when the mean TF level falls in the highest sensitive region of the dose-response curve. We further study the effect of reducing the copy number of gene A from two to one. The enhanced TF fluctuations yield results different from those in the deterministic case. The probability that the target gene protein level exceeds a threshold value is calculated with the knowledge of the probability density functions associated with the TF and target gene protein levels. Numerical simulation results for a more detailed stochastic model are shown to be in agreement with those obtained through analytic calculations. The relevance of these results in the context of the genetic disorder haploinsufficiency is pointed out. Some experimental observations on the haploinsufficiency of the tumour suppressor gene, Nkx 3.1, are explained with the help of the stochastic model of TF-regulated gene expression.