title: Regulation of cell-to-cell variability in divergent gene expression.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University Park, Pennsylvania 16802, USA.|Center for Eukaryotic Gene Regulation, University Park, Pennsylvania 16802, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Biochemistry and Molecular Biology, University Park, Pennsylvania 16802, USA.
authors.forename: Shuyang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Physics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Pocetti
authors.affiliation: Department of Biochemistry and Molecular Biology, University Park, Pennsylvania 16802, USA.|Center for Eukaryotic Gene Regulation, University Park, Pennsylvania 16802, USA.|Department of Physics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Bai
mesh_terms: D002453:Cell Cycle; D017124:Conserved Sequence; D019143:Evolution, Molecular; D020440:Gene Duplication; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D018869:Heat-Shock Response; D017404:In Situ Hybridization, Fluorescence; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics*; D013269:Stochastic Processes; D014158:Transcription, Genetic