title: Quantitative kinetic analysis of the bacteriophage lambda genetic network.
abstract: The lysis-lysogeny decision of bacteriophage lambda has been a paradigm for a developmental genetic network, which is composed of interlocked positive and negative feedback loops. This genetic network is capable of responding to environmental signals and to the number of infecting phages. An interplay between CI and Cro functions suggested a bistable switch model for the lysis-lysogeny decision. Here, we present a real-time picture of the execution of lytic and lysogenic pathways with unprecedented temporal resolution. We monitor, in vivo, both the level and function of the CII and Q gene regulators. These activators are cotranscribed yet control opposite developmental pathways. Conditions that favor the lysogenic response show severe delay and down-regulation of Q activity, in both CII-dependent and CII-independent ways. Whereas CII activity correlates with its protein level, Q shows a pronounced threshold before its function is observed. Our quantitative analyses suggest that by regulating CII and CIII, Cro plays a key role in the ability of the lambda genetic network to sense the difference between one and more than one phage particles infecting a cell. Thus, our results provide an improved framework to explain the longstanding puzzle of the decision process.
authors.affiliation: Department of Molecular Genetics and Biotechnology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Kobiler
authors.forename: Assaf
authors.initials: A
authors.lastname: Rokney
authors.forename: Nir
authors.initials: N
authors.lastname: Friedman
authors.forename: Donald L
authors.initials: DL
authors.lastname: Court
authors.forename: Joel
authors.initials: J
authors.lastname: Stavans
authors.forename: Amos B
authors.initials: AB
authors.lastname: Oppenheim
mesh_terms: D010582:Bacteriophage lambda / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D049452:Green Fluorescent Proteins / Q000235:genetics; D007700:Kinetics; D008242:Lysogeny / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins; D014775:Virus Activation / Q000235:genetics / Q000502:physiology
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; C066119:Q protein, Bacteriophage lambda; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C039000:cII protein, bacteriophage lambda; C016649:phage repressor proteins; D049452:Green Fluorescent Proteins
references.citation: Nat Rev Genet. 2003 Jun;4(6):471-7
references.pmid: 12776216
references.citation: J Bacteriol. 1990 Aug;172(8):4610-5
references.pmid: 2142940
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2002 May;65(5 Pt 1):051914
references.pmid: 12059600
references.citation: Science. 1995 Aug 4;269(5224):650-6
references.pmid: 7624793
references.citation: J Biol Chem. 1985 Sep 25;260(21):11838-44
references.pmid: 2931430
references.citation: Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):8972-8
references.pmid: 11481468
references.citation: Proc Natl Acad Sci U S A. 1970 Jul;66(3):855-62
references.pmid: 5269249
references.citation: Virology. 2004 Feb 20;319(2):185-9
references.pmid: 14980479
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14964-9
references.pmid: 12397182
references.citation: Genetics. 1976 May;83(1):5-10
references.pmid: 773751
references.citation: Microbiol Mol Biol Rev. 2000 Mar;64(1):69-114
references.pmid: 10704475
references.citation: Genetics. 1998 Aug;149(4):1633-48
references.pmid: 9691025
references.citation: Curr Opin Microbiol. 2003 Oct;6(5):506-11
references.pmid: 14572544
references.citation: Genes Dev. 1987 May;1(3):217-26
references.pmid: 2960589
references.citation: Proc Natl Acad Sci U S A. 1971 Sep;68(9):2185-9
references.pmid: 4943790
references.citation: Gene. 1996;173(1 Spec No):33-8
references.pmid: 8707053
references.citation: J Bacteriol. 1991 Oct;173(20):6647-9
references.pmid: 1717439
references.citation: J Struct Biol. 2004 Apr-May;146(1-2):72-8
references.pmid: 15037238
references.citation: Funct Integr Genomics. 2004 Jul;4(3):188-95
references.pmid: 14762706
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10555-60
references.pmid: 12145321
references.citation: J Bacteriol. 2000 Sep;182(18):5225-30
references.pmid: 10960109
references.citation: Microb Ecol. 2003 Aug;46(2):249-56
references.pmid: 14708749
references.citation: Biochimie. 1974;56(11-12):1517-23
references.pmid: 4619342
references.citation: J Mol Biol. 1975 Apr 5;93(2):267-88
references.pmid: 1152053
references.citation: Virology. 1957 Feb;3(1):42-61
references.pmid: 13409759
references.citation: Mol Microbiol. 2002 May;44(4):957-70
references.pmid: 12010491
references.citation: Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5217-21
references.pmid: 1828895
references.citation: Curr Opin Microbiol. 2001 Apr;4(2):201-7
references.pmid: 11282477
references.citation: Cell. 2003 Apr 18;113(2):171-82
references.pmid: 12705866
references.citation: Proc Natl Acad Sci U S A. 1985 May;82(10):3134-8
references.pmid: 3159014