title: Noise in eukaryotic gene expression.
abstract: Transcription in eukaryotic cells has been described as quantal, with pulses of messenger RNA produced in a probabilistic manner. This description reflects the inherently stochastic nature of gene expression, known to be a major factor in the heterogeneous response of individual cells within a clonal population to an inducing stimulus. Here we show in Saccharomyces cerevisiae that stochasticity (noise) arising from transcription contributes significantly to the level of heterogeneity within a eukaryotic clonal population, in contrast to observations in prokaryotes, and that such noise can be modulated at the translational level. We use a stochastic model of transcription initiation specific to eukaryotes to show that pulsatile mRNA production, through reinitiation, is crucial for the dependence of noise on transcriptional efficiency, highlighting a key difference between eukaryotic and prokaryotic sources of noise. Furthermore, we explore the propagation of noise in a gene cascade network and demonstrate experimentally that increased noise in the transcription of a regulatory protein leads to increased cell-cell variability in the target gene output, resulting in prolonged bistable expression states. This result has implications for the role of noise in phenotypic variation and cellular differentiation.
authors.affiliation: Center for BioDynamics, Center for Advanced Biotechnology, Bioinformatics Program, and Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, Massachusetts 02215, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Blake
authors.forename: Mads
authors.initials: M
authors.lastname: KAErn
authors.forename: Charles R
authors.initials: CR
authors.lastname: Cantor
authors.forename: J J
authors.initials: JJ
authors.lastname: Collins
mesh_terms: D002454:Cell Differentiation; D005057:Eukaryotic Cells / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics*; D008957:Models, Genetic; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics*; D013269:Stochastic Processes; D014158:Transcription, Genetic
chemical_list: D012331:RNA, Fungal; D012333:RNA, Messenger