title: Measurement and modeling of transcriptional noise in the cell cycle regulatory network.
abstract: Fifty years of genetic and molecular experiments have revealed a wealth of molecular interactions involved in the control of cell division. In light of the complexity of this control system, mathematical modeling has proved useful in analyzing biochemical hypotheses that can be tested experimentally. Stochastic modeling has been especially useful in understanding the intrinsic variability of cell cycle events, but stochastic modeling has been hampered by a lack of reliable data on the absolute numbers of mRNA molecules per cell for cell cycle control genes. To fill this void, we used fluorescence in situ hybridization (FISH) to collect single molecule mRNA data for 16 cell cycle regulators in budding yeast, Saccharomyces cerevisiae. From statistical distributions of single-cell mRNA counts, we are able to extract the periodicity, timing, and magnitude of transcript abundance during the cell cycle. We used these parameters to improve a stochastic model of the cell cycle to better reflect the variability of molecular and phenotypic data on cell cycle progression in budding yeast.
authors.affiliation: Virginia Bioinformatics Institute; Virginia Tech; Blacksburg, VA USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Ball
authors.forename: Neil R
authors.initials: NR
authors.lastname: Adames
authors.forename: Nadine
authors.initials: N
authors.lastname: Reischmann
authors.forename: Debashis
authors.initials: D
authors.lastname: Barik
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Franck
authors.forename: John J
authors.initials: JJ
authors.lastname: Tyson
authors.forename: Jean
authors.initials: J
authors.lastname: Peccoud
mesh_terms: D059447:Cell Cycle Checkpoints; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D053263:Gene Regulatory Networks; D017404:In Situ Hybridization, Fluorescence; D008954:Models, Biological; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C082721:CLN2 protein, S cerevisiae; D016213:Cyclins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins
keywords: Saccharomycescerevisiae; cell cycle; gene expression noise; single mRNA FISH; stochastic modeling