title: Promoter architecture dictates cell-to-cell variability in gene expression.
abstract: Variability in gene expression among genetically identical cells has emerged as a central preoccupation in the study of gene regulation; however, a divide exists between the predictions of molecular models of prokaryotic transcriptional regulation and genome-wide experimental studies suggesting that this variability is indifferent to the underlying regulatory architecture. We constructed a set of promoters in Escherichia coli in which promoter strength, transcription factor binding strength, and transcription factor copy numbers are systematically varied, and used messenger RNA (mRNA) fluorescence in situ hybridization to observe how these changes affected variability in gene expression. Our parameter-free models predicted the observed variability; hence, the molecular details of transcription dictate variability in mRNA expression, and transcriptional noise is specifically tunable and thus represents an evolutionarily accessible phenotypic parameter.
authors.affiliation: Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Jones
authors.affiliation: Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA. Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Brewster
authors.affiliation: Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA. Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. phillips@pboc.caltech.edu.
authors.forename: Rob
authors.initials: R
authors.lastname: Phillips
mesh_terms: D002477:Cells / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D018628:Gene Dosage; D005786:Gene Expression Regulation; D014644:Genetic Variation; D017403:In Situ Hybridization; D007700:Kinetics; D056968:Lac Repressors / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D056968:Lac Repressors; D012333:RNA, Messenger; D012321:DNA-Directed RNA Polymerases