PMID- 24013422 OWN - NLM STAT- MEDLINE DCOM- 20140418 LR - 20211021 IS - 1551-4005 (Electronic) IS - 1538-4101 (Print) IS - 1551-4005 (Linking) VI - 12 IP - 19 DP - 2013 Oct 1 TI - Measurement and modeling of transcriptional noise in the cell cycle regulatory network. PG - 3203-18 LID - 10.4161/cc.26257 [doi] AB - 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. FAU - Ball, David A AU - Ball DA AD - Virginia Bioinformatics Institute; Virginia Tech; Blacksburg, VA USA. FAU - Adames, Neil R AU - Adames NR FAU - Reischmann, Nadine AU - Reischmann N FAU - Barik, Debashis AU - Barik D FAU - Franck, Christopher T AU - Franck CT FAU - Tyson, John J AU - Tyson JJ FAU - Peccoud, Jean AU - Peccoud J LA - eng GR - R01 GM078989/GM/NIGMS NIH HHS/United States GR - R01 GM095955/GM/NIGMS NIH HHS/United States GR - R01-GM078989/GM/NIGMS NIH HHS/United States GR - R01-GM095955/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130904 PL - United States TA - Cell Cycle JT - Cell cycle (Georgetown, Tex.) JID - 101137841 RN - 0 (CLN2 protein, S cerevisiae) RN - 0 (Cyclins) RN - 0 (RNA, Messenger) RN - 0 (Saccharomyces cerevisiae Proteins) SB - IM MH - Cell Cycle Checkpoints MH - Cyclins/genetics/metabolism MH - Gene Regulatory Networks MH - In Situ Hybridization, Fluorescence MH - *Models, Biological MH - RNA, Messenger/metabolism MH - Saccharomyces cerevisiae/genetics/metabolism MH - Saccharomyces cerevisiae Proteins/genetics/metabolism MH - Transcription, Genetic PMC - PMC3865016 OTO - NOTNLM OT - Saccharomycescerevisiae OT - cell cycle OT - gene expression noise OT - single mRNA FISH OT - stochastic modeling EDAT- 2013/09/10 06:00 MHDA- 2014/04/20 06:00 PMCR- 2013/09/04 CRDT- 2013/09/10 06:00 PHST- 2013/09/10 06:00 [entrez] PHST- 2013/09/10 06:00 [pubmed] PHST- 2014/04/20 06:00 [medline] PHST- 2013/09/04 00:00 [pmc-release] AID - 26257 [pii] AID - 2013CC4972R [pii] AID - 10.4161/cc.26257 [doi] PST - ppublish SO - Cell Cycle. 2013 Oct 1;12(19):3203-18. doi: 10.4161/cc.26257. Epub 2013 Sep 4.