Hu J, Iyer-Biswas S, Sealfon S C, Wetmur J, Jayaprakash C, Hayot F
Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA.
Biophys J. 2009 Oct 7;97(7):1984-9. doi: 10.1016/j.bpj.2009.05.067.
Interferon-beta (IFNB1) mRNA shows very large cell-to-cell variability in primary human dendritic cells infected by Newcastle disease virus, with copy numbers varying from a few to several thousands. Analysis of data from the direct measurement of the expression of this gene in its natural chromatin environment in primary human cells shows that the distribution of mRNA across cells follows a power law with an exponent close to -1, and thus encompasses a range of variation much more extensive than a Gaussian. We also investigate the single cell levels of IFNB1 mRNA induced by infection with Texas influenza A mutant viruses, which vary in their capacity to inhibit the signaling pathways responsible for activation of this gene. Here as well we observe power-law behavior for the distribution of IFNB1 mRNA, albeit over a truncated range of values, with exponents similar to the one for cells infected by Newcastle disease virus. We propose a model of stochastic enhanceosome and preinitiation complex formation that incorporates transcriptional pulsing. Analytical and numerical results show good agreement with the observed power laws, and thus support the existence of transcriptional pulsing of an unmodified, intact gene regulated by a natural stimulus.
在感染新城疫病毒的原代人树突状细胞中,干扰素-β(IFNB1)mRNA表现出非常大的细胞间变异性,拷贝数从几个到数千个不等。对该基因在原代人细胞自然染色质环境中表达的直接测量数据进行分析表明,mRNA在细胞间的分布遵循幂律,指数接近-1,因此其变化范围比高斯分布要广泛得多。我们还研究了感染德州甲型流感突变病毒后诱导的IFNB1 mRNA单细胞水平,这些病毒在抑制负责激活该基因的信号通路的能力上有所不同。在此我们同样观察到IFNB1 mRNA分布的幂律行为,尽管是在一个截断的值范围内,其指数与感染新城疫病毒的细胞相似。我们提出了一个包含转录脉冲的随机增强体和预起始复合物形成模型。分析和数值结果与观察到的幂律表现出良好的一致性,从而支持了由自然刺激调控的未修饰完整基因存在转录脉冲的观点。