Regulation of cell-to-cell variability in divergent gene expression.

Chao Yan, Shuyang Wu, Christopher Pocetti, Lu Bai
Author Information
  1. Chao Yan: Department of Biochemistry and Molecular Biology, University Park, Pennsylvania 16802, USA.
  2. Shuyang Wu: Department of Biochemistry and Molecular Biology, University Park, Pennsylvania 16802, USA.
  3. Christopher Pocetti: Department of Physics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
  4. Lu Bai: Department of Biochemistry and Molecular Biology, University Park, Pennsylvania 16802, USA.

Abstract

Cell-to-cell variability (noise) is an important feature of gene expression that impacts cell fitness and development. The regulatory mechanism of this variability is not fully understood. Here we investigate the effect on gene expression noise in divergent gene pairs (DGPs). We generated reporters driven by divergent promoters, rearranged their gene order, and probed their expressions using time-lapse fluorescence microscopy and single-molecule fluorescence in situ hybridization (smFISH). We show that two genes in a co-regulated DGP have higher expression covariance compared with the separate, tandem and convergent configurations, and this higher covariance is caused by more synchronized firing of the divergent transcriptions. For differentially regulated DGPs, the regulatory signal of one gene can stochastically 'leak' to the other, causing increased gene expression noise. We propose that the DGPs' function in limiting or promoting gene expression noise may enhance or compromise cell fitness, providing an explanation for the conservation pattern of DGPs.

References

  1. Science. 2002 Aug 16;297(5584):1183-6 [PMID: 12183631]
  2. Mol Biol Cell. 2000 Dec;11(12):4241-57 [PMID: 11102521]
  3. Genome Res. 2004 Jan;14(1):62-6 [PMID: 14707170]
  4. Nature. 2004 Apr 8;428(6983):617-24 [PMID: 15004568]
  5. Nat Rev Genet. 2004 Apr;5(4):299-310 [PMID: 15131653]
  6. Genetics. 2004 May;167(1):523-30 [PMID: 15166174]
  7. PLoS Biol. 2004 Jun;2(6):e137 [PMID: 15124029]
  8. Cell. 1986 Jan 17;44(1):43-52 [PMID: 3510079]
  9. Biochim Biophys Acta. 1991 Mar 26;1088(3):327-39 [PMID: 2015297]
  10. Mol Biol Cell. 1998 Dec;9(12):3273-97 [PMID: 9843569]
  11. Mol Cell. 2005 Jun 10;18(6):735-48 [PMID: 15949447]
  12. Science. 2005 Sep 23;309(5743):2075-8 [PMID: 16123265]
  13. Science. 2005 Sep 23;309(5743):2010-3 [PMID: 16179466]
  14. Mol Cell. 2006 Jan 6;21(1):3-14 [PMID: 16387649]
  15. Nature. 2006 Jun 15;441(7095):840-6 [PMID: 16699522]
  16. Genes Dev. 2006 Aug 15;20(16):2266-78 [PMID: 16912276]
  17. PLoS Biol. 2006 Oct;4(10):e309 [PMID: 17048983]
  18. Mol Cell. 2006 Dec 28;24(6):853-65 [PMID: 17189188]
  19. Nucleic Acids Res. 2007;35(3):812-21 [PMID: 17202156]
  20. Curr Biol. 2007 Apr 17;17(8):668-77 [PMID: 17398098]
  21. PLoS One. 2008;3(1):e1468 [PMID: 18213377]
  22. Bioinformatics. 2007 Oct 15;23(20):2692-9 [PMID: 17724061]
  23. Nat Genet. 2007 Oct;39(10):1235-44 [PMID: 17873876]
  24. Trends Genet. 2008 May;24(5):207-11 [PMID: 18375009]
  25. Nat Rev Genet. 2008 Aug;9(8):583-93 [PMID: 18591982]
  26. Nat Methods. 2008 Oct;5(10):877-9 [PMID: 18806792]
  27. Cell. 2008 Oct 17;135(2):216-26 [PMID: 18957198]
  28. Nat Rev Genet. 2009 May;10(5):336-42 [PMID: 19337290]
  29. BMC Evol Biol. 2009;9:55 [PMID: 19284596]
  30. FEBS Lett. 2009 Dec 17;583(24):3999-4005 [PMID: 19878681]
  31. Cell. 2010 Apr 2;141(1):69-80 [PMID: 20371346]
  32. Dev Cell. 2010 Apr 20;18(4):544-55 [PMID: 20412770]
  33. Mol Cell Biol. 2011 Feb;31(3):557-72 [PMID: 21115727]
  34. PLoS Comput Biol. 2011 Mar;7(3):e1001100 [PMID: 21390269]
  35. Phys Rev Lett. 2011 Nov 18;107(21):218101 [PMID: 22181928]
  36. Cell. 2011 Dec 23;147(7):1484-97 [PMID: 22196726]
  37. Mol Biol Evol. 2012 Jan;29(1):71-9 [PMID: 21546358]
  38. BMC Genomics. 2012;13 Suppl 1:S11 [PMID: 22369481]
  39. Science. 2012 Apr 13;336(6078):183-7 [PMID: 22499939]
  40. BMC Genomics. 2012;13:546 [PMID: 23051624]
  41. Development. 2013 Feb 1;140(3):493-503 [PMID: 23293281]
  42. Nat Methods. 2013 Feb;10(2):119-21 [PMID: 23263691]
  43. PLoS Biol. 2013;11(4):e1001528 [PMID: 23565060]
  44. Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):14012-7 [PMID: 23836672]
  45. Nucleic Acids Res. 2014 May;42(9):5468-82 [PMID: 24598258]
  46. Science. 2014 Dec 19;346(6216):1533-6 [PMID: 25525251]
  47. Nucleic Acids Res. 2015 Sep 3;43(15):7292-305 [PMID: 26082499]
  48. Yeast. 2000 Oct;16(14):1313-23 [PMID: 11015728]
  49. Cell. 2003 Nov 26;115(5):537-49 [PMID: 14651846]

Grants

  1. R01 GM118682/NIGMS NIH HHS

MeSH Term

Cell Cycle
Conserved Sequence
Evolution, Molecular
Gene Duplication
Gene Expression Profiling
Gene Expression Regulation, Fungal
Genome, Fungal
Heat-Shock Response
In Situ Hybridization, Fluorescence
Models, Genetic
Promoter Regions, Genetic
Saccharomyces cerevisiae
Stochastic Processes
Transcription, Genetic

Word Cloud

Created with Highcharts 10.0.0geneexpressionnoisedivergentvariabilityDGPscellfitnessregulatoryfluorescencehighercovarianceCell-to-cellimportantfeatureimpactsdevelopmentmechanismfullyunderstoodinvestigateeffectpairsgeneratedreportersdrivenpromotersrearrangedorderprobedexpressionsusingtime-lapsemicroscopysingle-moleculesituhybridizationsmFISHshowtwogenesco-regulatedDGPcomparedseparatetandemconvergentconfigurationscausedsynchronizedfiringtranscriptionsdifferentiallyregulatedsignalonecanstochastically'leak'causingincreasedproposeDGPs'functionlimitingpromotingmayenhancecompromiseprovidingexplanationconservationpatternRegulationcell-to-cell

Similar Articles

Cited By