Control of stochasticity in eukaryotic gene expression.
Noise, or random fluctuations, in gene expression may produce variability in cellular behavior. To measure the noise intrinsic to eukaryotic gene expression, we quantified the differences in expression of two alleles in a diploid cell. We found that such noise is gene-specific and not dependent on the regulatory pathway or absolute rate of expression. We propose a model in which the balance between promoter activation and transcription influences the variability in messenger RNA levels. To confirm the predictions of our model, we identified both cis- and trans-acting mutations that alter the noise of gene expression. These mutations suggest that noise is an evolvable trait that can be optimized to balance fidelity and diversity in eukaryotic gene expression.
Raser
Jonathan M
JM
Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California-San Francisco (UCSF), 600 16th Street, Room S472D, San Francisco, CA 94143-2240, USA.
O'Shea
Erin K
EK
D000135:Acid Phosphatase; D000483:Alleles; D001426:Bacterial Proteins / Q000096:biosynthesis; D002352:Carrier Proteins / Q000235:genetics; D002453:Cell Cycle; D002843:Chromatin / Q000378:metabolism; D005434:Flow Cytometry; D005453:Fluorescence; D015870:Gene Expression; D005800:Genes, Fungal; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000096:biosynthesis; D008957:Models, Genetic; D009154:Mutation; D011401:Promoter Regions, Genetic; D028081:Proton-Phosphate Symporters / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D013269:Stochastic Processes; D016385:TATA Box; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D001426:Bacterial Proteins; D002352:Carrier Proteins; D002843:Chromatin; D008164:Luminescent Proteins; C105495:PHO84 protein, S cerevisiae; D028081:Proton-Phosphate Symporters; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C026989:thiamine-binding protein; C054562:yellow fluorescent protein, Bacteria; D049452:Green Fluorescent Proteins; D000135:Acid Phosphatase; C488913:PHO3 protein, S cerevisiae; C488916:PHO5 protein, S cerevisiae