Yan Chao, Wu Shuyang, Pocetti Christopher, Bai Lu
Department of Biochemistry and Molecular Biology, University Park, Pennsylvania 16802, USA.
Center for Eukaryotic Gene Regulation, University Park, Pennsylvania 16802, USA.
Nat Commun. 2016 Mar 24;7:11099. doi: 10.1038/ncomms11099.
Cell-to-cell variability (noise) is an important feature of gene expression that impacts cell fitness and development. The regulatory mechanism of this variability is not fully understood. Here we investigate the effect on gene expression noise in divergent gene pairs (DGPs). We generated reporters driven by divergent promoters, rearranged their gene order, and probed their expressions using time-lapse fluorescence microscopy and single-molecule fluorescence in situ hybridization (smFISH). We show that two genes in a co-regulated DGP have higher expression covariance compared with the separate, tandem and convergent configurations, and this higher covariance is caused by more synchronized firing of the divergent transcriptions. For differentially regulated DGPs, the regulatory signal of one gene can stochastically 'leak' to the other, causing increased gene expression noise. We propose that the DGPs' function in limiting or promoting gene expression noise may enhance or compromise cell fitness, providing an explanation for the conservation pattern of DGPs.
细胞间变异性（噪声）是基因表达的一个重要特征，它影响细胞适应性和发育。这种变异性的调控机制尚未完全了解。在这里，我们研究了对不同基因对（DGP）中基因表达噪声的影响。我们构建了由不同启动子驱动的报告基因，重新排列它们的基因顺序，并使用延时荧光显微镜和单分子荧光原位杂交（smFISH）检测它们的表达。我们发现，与单独、串联和会聚构型相比，共同调控的DGP中的两个基因具有更高的表达协方差，并且这种更高的协方差是由不同转录的更同步激发引起的。对于差异调控的DGP，一个基因的调控信号可能会随机“泄漏”到另一个基因，导致基因表达噪声增加。我们提出，DGP在限制或促进基因表达噪声方面的功能可能增强或损害细胞适应性，这为DGP的保守模式提供了解释。
