Abstract
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.
MeSH Terms
Acid Phosphatase
Alleles
Bacterial Proteins/biosynthesis
Carrier Proteins/genetics
Cell Cycle
Chromatin/metabolism
Flow Cytometry
Fluorescence
Gene Expression
Genes, Fungal
Green Fluorescent Proteins
Luminescent Proteins/biosynthesis
Models, Genetic
Mutation
Promoter Regions, Genetic
Proton-Phosphate Symporters/genetics
RNA, Messenger/metabolism
Saccharomyces cerevisiae/genetics,physiology
Saccharomyces cerevisiae Proteins/genetics
Stochastic Processes
TATA Box
Transcription, Genetic
Transcriptional Activation
Chemicals
Bacterial Proteins
Carrier Proteins
Chromatin
Luminescent Proteins
PHO84 protein, S cerevisiae
Proton-Phosphate Symporters
RNA, Messenger
Saccharomyces cerevisiae Proteins
thiamine-binding protein
yellow fluorescent protein, Bacteria
Green Fluorescent Proteins
Acid Phosphatase
PHO3 protein, S cerevisiae
PHO5 protein, S cerevisiae
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Raser Jonathan M
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
References (21)
21 references, click to expand
-
Regulation of noise in the expression of a single gene.
Nat Genet. 2002 May;31(1):69-73
PMID: 11967532
-
Increasing the rate of chromatin remodeling and gene activation--a novel role for the histone acetyltransferase Gcn5.
EMBO J. 2001 Sep 3;20(17):4944-51
PMID: 11532958
-
Intrinsic noise in gene regulatory networks.
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8614-9
PMID: 11438714
-
Stochastic gene expression in a single cell.
Science. 2002 Aug 16;297(5584):1183-6
PMID: 12183631
-
Intrinsic and extrinsic contributions to stochasticity in gene expression.
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12795-800
PMID: 12237400
-
Haploinsufficiency at the Nkx3.1 locus. A paradigm for stochastic, dosage-sensitive gene regulation during tumor initiation.
Cancer Cell. 2003 Mar;3(3):273-83
PMID: 12676585
-
Regulation of chromatin remodeling by inositol polyphosphates.
Science. 2003 Jan 3;299(5603):114-6
PMID: 12434012
-
Control, exploitation and tolerance of intracellular noise.
Nature. 2002 Nov 14;420(6912):231-7
PMID: 12432408
-
Noise in eukaryotic gene expression.
Nature. 2003 Apr 10;422(6932):633-7
PMID: 12687005
-
Multiple mechanistically distinct functions of SAGA at the PHO5 promoter.
Mol Cell Biol. 2003 May;23(10):3468-76
PMID: 12724405
-
Nucleosomes unfold completely at a transcriptionally active promoter.
Mol Cell. 2003 Jun;11(6):1587-98
PMID: 12820971
-
Negative feedback regulation ensures the one receptor-one olfactory neuron rule in mouse.
Science. 2003 Dec 19;302(5653):2088-94
PMID: 14593185
-
Summing up the noise in gene networks.
Nature. 2004 Jan 29;427(6973):415-8
PMID: 14749823
-
Noise minimization in eukaryotic gene expression.
PLoS Biol. 2004 Jun;2(6):e137
PMID: 15124029
-
Nuclease hypersensitive regions with adjacent positioned nucleosomes mark the gene boundaries of the PHO5/PHO3 locus in yeast.
EMBO J. 1986 Oct;5(10):2681-7
PMID: 3023055
-
Role of trans-activating proteins in the generation of active chromatin at the PHO5 promoter in S. cerevisiae.
EMBO J. 1990 Aug;9(8):2523-8
PMID: 2196175
-
A stochastic model for gene induction.
J Theor Biol. 1991 Nov 21;153(2):181-94
PMID: 1787735
-
Structural and functional requirements for the chromatin transition at the PHO5 promoter in Saccharomyces cerevisiae upon PHO5 activation.
J Mol Biol. 1993 Jun 5;231(3):658-67
PMID: 8515443
-
Stochastic kinetic analysis of developmental pathway bifurcation in phage lambda-infected Escherichia coli cells.
Genetics. 1998 Aug;149(4):1633-48
PMID: 9691025
-
It's a noisy business! Genetic regulation at the nanomolar scale.
Trends Genet. 1999 Feb;15(2):65-9
PMID: 10098409
-
The product of the SNF2/SWI2 paralogue INO80 of Saccharomyces cerevisiae required for efficient expression of various yeast structural genes is part of a high-molecular-weight protein complex.
Mol Microbiol. 1999 May;32(4):741-51
PMID: 10361278