Noise in eukaryotic gene expression.
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.
Blake
William J
WJ
Center for BioDynamics, Center for Advanced Biotechnology, Bioinformatics Program, and Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, Massachusetts 02215, USA.
KAErn
Mads
M
Cantor
Charles R
CR
Collins
J J
JJ
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
D012331:RNA, Fungal; D012333:RNA, Messenger