Biophys J. 2010 Apr 21;98(8):L32-4. doi: 10.1016/j.bpj.2010.03.001.
Analysis of noise in gene expression has proven a powerful approach for analyzing gene regulatory architecture. To probe the regulatory mechanisms controlling expression of HIV-1, we analyze noise in gene-expression from HIV-1's long terminal repeat (LTR) promoter at different HIV-1 integration sites across the human genome. Flow cytometry analysis of GFP expression from the HIV-1 LTR shows high variability (noise) at each integration site. Notably, the measured noise levels are inconsistent with constitutive gene expression models. Instead, quantification of expression noise indicates that HIV-1 gene expression occurs through randomly timed bursts of activity from the LTR and that each burst generates an average of 2-10 mRNA transcripts before the promoter returns to an inactive state. These data indicate that transcriptional bursting can generate high variability in HIV-1 early gene products, which may critically influence the viral fate-decision between active replication and proviral latency.
基因表达噪声分析已被证明是分析基因调控结构的一种有力方法。为了研究控制 HIV-1 表达的调控机制，我们分析了 HIV-1 基因组中不同整合位点的长末端重复（LTR）启动子的基因表达噪声。来自 HIV-1 LTR 的 GFP 表达的流式细胞术分析显示，每个整合位点的表达都具有很高的可变性（噪声）。值得注意的是，所测量的噪声水平与组成型基因表达模型不一致。相反，对表达噪声的定量分析表明，HIV-1 基因表达是通过 LTR 的随机定时活性爆发进行的，每个爆发在启动子返回到非活动状态之前平均产生 2-10 个 mRNA 转录本。这些数据表明，转录爆发可以在 HIV-1 早期基因产物中产生高度的可变性，这可能会对病毒在活跃复制和前病毒潜伏之间的命运决策产生关键影响。
