title: Nucleosomal promoter variation generates gene expression noise.
abstract: Gene product molecule numbers fluctuate over time and between cells, confounding deterministic expectations. The molecular origins of this noise of gene expression remain unknown. Recent EM analysis of single PHO5 gene molecules of yeast indicated that promoter molecules stochastically assume alternative nucleosome configurations at steady state, including the fully nucleosomal and nucleosome-free configuration. Given that distinct configurations are unequally conducive to transcription, the nucleosomal variation of promoter molecules may constitute a source of gene expression noise. This notion, however, implies an untested conjecture, namely that the nucleosomal variation arises de novo or intrinsically (i.e., that it cannot be explained as the result of the promoter's deterministic response to variation in its molecular surroundings). Here, we show--by microscopically analyzing the nucleosome configurations of two juxtaposed physically linked PHO5 promoter copies--that the configurational variation, indeed, is intrinsically stochastic and thus, a cause of gene expression noise rather than its effect.
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA 95064.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Brown
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA 95064 hboeger@ucsc.edu.
authors.forename: Hinrich
authors.initials: H
authors.lastname: Boeger
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D014644:Genetic Variation; D008854:Microscopy, Electron; D008954:Models, Biological; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000235:genetics* / Q000648:ultrastructure; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D013269:Stochastic Processes
chemical_list: D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D000135:Acid Phosphatase; C488916:PHO5 protein, S cerevisiae
keywords: PHO5; chromatin; gene expression noise; transcription