Contributions of low molecule number and chromosomal positioning to stochastic gene expression

The presence of low-copy-number regulators and switch-like signal propagation in regulatory networks are expected to increase noise in cellular processes. We developed a noise amplifier that detects fluctuations in the level of low-abundance mRNAs in yeast. The observed fluctuations are not due to the low number of molecules expressed from a gene per se but originate in the random, rare events of gene activation. The frequency of these events and the correlation between stochastic expressions of genes in a single cell depend on the positioning of the genes along the chromosomes. Transcriptional regulators produced by such random expression propagate noise to their target genes.

[1]  Péter Érdi,et al.  Mathematical Models of Chemical Reactions: Theory and Applications of Deterministic and Stochastic Models , 1989 .

[2]  Fluctuations and correlations in a diffusion-reaction system: Unified description of internal fluctuations and external noise. , 1992, Physical review. A, Atomic, molecular, and optical physics.

[3]  J. Peccoud,et al.  Markovian Modeling of Gene-Product Synthesis , 1995 .

[4]  P. Guptasarma,et al.  Does replication-induced transcription regulate synthesis of the myriad low copy number proteins of Escherichia coli? , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.

[5]  V. Iyer,et al.  Absolute mRNA levels and transcriptional initiation rates in Saccharomyces cerevisiae. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[6]  E. Gilson,et al.  Evidence for silencing compartments within the yeast nucleus: a role for telomere proximity and Sir protein concentration in silencer-mediated repression. , 1996, Genes & development.

[7]  D. Agard,et al.  Perturbation of Nuclear Architecture by Long-Distance Chromosome Interactions , 1996, Cell.

[8]  Wei Zhou,et al.  Characterization of the Yeast Transcriptome , 1997, Cell.

[9]  Karsten Melcher,et al.  Evidence for two modes of cooperative DNA binding in vivo that do not involve direct protein–protein interactions , 1998, Current Biology.

[10]  M. Busslinger,et al.  Independent regulation of the two Pax5 alleles during B-cell development , 1999, Nature Genetics.

[11]  K. Struhl.  Fundamentally Different Logic of Gene Regulation in Eukaryotes and Prokaryotes , 1999, Cell.

[12]  J. Tyson,et al.  Modeling the fission yeast cell cycle: quantized cycle times in wee1- cdc25Delta mutant cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[13]  H. Xu,et al.  Gal80‐Gal80 interaction on adjacent Gal4p binding sites is required for complete GAL gene repression , 2001, The EMBO journal.

[14]  D. Martin,et al.  Transcriptional enhancers--on/off gene regulation as an adaptation to silencing in higher eukaryotic nuclei. , 2001, Trends in genetics : TIG.

[15]  B. Séraphin,et al.  Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion , 2001, The EMBO journal.

[16]  Steven Henikoff,et al.  Modulation of a Transcription Factor Counteracts Heterochromatic Gene Silencing in Drosophila , 2001, Cell.

[17]  L. Breeden,et al.  Conserved homeodomain proteins interact with MADS box protein Mcm1 to restrict ECB-dependent transcription to the M/G1 phase of the cell cycle. , 2002, Genes & development.

[18]  C. Rao,et al.  Control, exploitation and tolerance of intracellular noise , 2002, Nature.

[19]  M. Holland,et al.  Transcript Abundance in Yeast Varies over Six Orders of Magnitude* , 2002, The Journal of Biological Chemistry.

[20]  Etienne Schwob,et al.  The yeast CDK inhibitor Sic1 prevents genomic instability by promoting replication origin licensing in late G(1). , 2002, Molecular cell.

[21]  J. Hasty,et al.  Synthetic gene network for entraining and amplifying cellular oscillations. , 2002, Physical review letters.

[22]  E. O’Shea,et al.  Global analysis of protein expression in yeast , 2003, Nature.

[23]  Farren J. Isaacs,et al.  Prediction and measurement of an autoregulatory genetic module , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Jeffrey A. Magee,et al.  Haploinsufficiency at the Nkx3.1 locus. A paradigm for stochastic, dosage-sensitive gene regulation during tumor initiation. , 2003, Cancer cell.

[25]  Tom Misteli,et al.  Spatial proximity of translocation-prone gene loci in human lymphomas , 2003, Nature Genetics.

[26]  Mads Kærn,et al.  Noise in eukaryotic gene expression , 2003, Nature.

[27]  J. Paulsson.  Summing up the noise in gene networks , 2004, Nature.

[28]  Peter S Swain,et al.  Efficient attenuation of stochasticity in gene expression through post-transcriptional control. , 2004, Journal of molecular biology.

[29]  Jason R. Pirone,et al.  Fluctuations in transcription factor binding can explain the graded and binary responses observed in inducible gene expression. , 2004, Journal of theoretical biology.

[30]  Katherine C. Chen,et al.  Cycling without the Cyclosome: Modeling a Yeast Strain Lacking the APC , 2004, Cell cycle.

[31]  S. Basu,et al.  Spatiotemporal control of gene expression with pulse-generating networks. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Nicola J. Rinaldi,et al.  Transcriptional regulatory code of a eukaryotic genome , 2004, Nature.

[33]  C. Pál,et al.  The evolutionary dynamics of eukaryotic gene order , 2004, Nature Reviews Genetics.

[34]  M. Thattai,et al.  Stochastic Gene Expression in Fluctuating Environments , 2004, Genetics.

[35]  J. Widom,et al.  Nucleosomes facilitate their own invasion , 2004, Nature Structural &Molecular Biology.

[36]  Cameron S. Osborne,et al.  Active genes dynamically colocalize to shared sites of ongoing transcription , 2004, Nature Genetics.

[37]  Pamela A. Silver,et al.  Genome-Wide Localization of the Nuclear Transport Machinery Couples Transcriptional Status and Nuclear Organization , 2004, Cell.

[38]  B. Pugh,et al.  Identification and Distinct Regulation of Yeast TATA Box-Containing Genes , 2004, Cell.

[39]  J. Raser,et al.  Control of Stochasticity in Eukaryotic Gene Expression , 2004, Science.

[40]  Alexander van Oudenaarden,et al.  Amplitude control of cell-cycle waves by nuclear import , 2004, Nature Cell Biology.

[41]  P. Swain,et al.  Gene Regulation at the Single-Cell Level , 2005, Science.

[42]  Tom Misteli,et al.  Concepts in nuclear architecture , 2005, BioEssays : news and reviews in molecular, cellular and developmental biology.

[43]  B. Andrews,et al.  Reverse recruitment : The Nup 84 nuclear pore subcomplex mediates Rap 1 Gcr 1 Gcr 2 transcriptional activation , 2005 .

[44]  R. Weiss,et al.  Ultrasensitivity and noise propagation in a synthetic transcriptional cascade. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[45]  D. Whitmore,et al.  Imaging of single light-responsive clock cells reveals fluctuating free-running periods , 2005, Nature Cell Biology.

[46]  K. Fujimoto,et al.  Noisy signal amplification in ultrasensitive signal transduction. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[47]  A. Oudenaarden,et al.  Enhancement of cellular memory by reducing stochastic transitions , 2005, Nature.

[48]  A. van Oudenaarden,et al.  Noise Propagation in Gene Networks , 2005, Science.

[49]  B. Andrews,et al.  Reverse recruitment: the Nup84 nuclear pore subcomplex mediates Rap1/Gcr1/Gcr2 transcriptional activation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[50]  James E. Ferrell,et al.  A positive-feedback-based bistable ‘memory module’ that governs a cell fate decision , 2007, Nature.

[51]  Jeffrey W. Smith,et al.  Stochastic Gene Expression in a Single Cell , 2022 .