title: A bistable hysteretic switch in an activator-repressor regulated restriction-modification system.
abstract: Restriction-modification (RM) systems are extremely widespread among bacteria and archaea, and are often specified by mobile genetic elements. In type II RM systems, where the restriction endonuclease (REase) and protective DNA methyltransferase (MTase) are separate proteins, a major regulatory challenge is delaying expression of the REase relative to the MTase after RM genes enter a new host cell. Basic understanding of this regulation is available for few RM systems, and detailed understanding for none. The PvuII RM system is one of a large subset in which the central regulatory role is played by an activator-repressor protein (called C, for controller). REase expression depends upon activation by C, whereas expression of the MTase does not. Thus delay of REase expression depends on the rate of C-protein accumulation. This is a nonlinear process, as C also activates transcription of its own gene. Mathematical modeling of the PvuII system led to the unexpected predictions of responsiveness to a factor not previously studied in RM system control--gene copy number--and of a hysteretic response. In this study, those predictions have been confirmed experimentally. The results may apply to many other C-regulated RM systems, and help explain their ability to spread so widely.
authors: Department of Medical Microbiology & Immunology, and Program in Bioinformatics, University of Toledo, Toledo, OH 43614, USA.
authors: Kristen
authors: K
authors: Williams
authors: Michael A
authors: MA
authors: Savageau
authors: Robert M
authors: RM
authors: Blumenthal
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D015257:DNA-Cytosine Methylases / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics*; D018628:Gene Dosage; D015964:Gene Expression Regulation, Bacterial; D007700:Kinetics; D008957:Models, Genetic; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C047084:DNA modification methylase PvuII; D015257:DNA-Cytosine Methylases; C025630:CAGCTG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific
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