title: Phenotypic consequences of promoter-mediated transcriptional noise.
abstract: A more complete understanding of the causes and effects of cell-cell variability in gene expression is needed to elucidate whether the resulting phenotypes are disadvantageous or confer some adaptive advantage. Here we show that increased variability in gene expression, affected by the sequence of the TATA box, can be beneficial after an acute change in environmental conditions. We rationally introduce mutations within the TATA region of an engineered Saccharomyces cerevisiae GAL1 promoter and measure promoter responses that can be characterized as being either highly variable and rapid or steady and slow. We computationally illustrate how a stable transcription scaffold can result in "bursts" of gene expression, enabling rapid individual cell responses in the transient and increased cell-cell variability at steady state. We experimentally verify computational predictions that the rapid response and increased cell-cell variability enabled by TATA-containing promoters confer a clear benefit in the face of an acute environmental stress.
authors.affiliation: Department of Biomedical Engineering, Massachusetts, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Blake
authors.forename: Gábor
authors.initials: G
authors.lastname: Balázsi
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kohanski
authors.forename: Farren J
authors.initials: FJ
authors.lastname: Isaacs
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Murphy
authors.forename: Yina
authors.initials: Y
authors.lastname: Kuang
authors.forename: Charles R
authors.initials: CR
authors.lastname: Cantor
authors.forename: David R
authors.initials: DR
authors.lastname: Walt
authors.forename: James J
authors.initials: JJ
authors.lastname: Collins
mesh_terms: D001483:Base Sequence; D003198:Computer Simulation; D015966:Gene Expression Regulation, Fungal; D018740:Genetic Heterogeneity; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D016385:TATA Box / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D029701:Saccharomyces cerevisiae Proteins