Immunity phase-shift in defective lysogens: Non-mutational hereditary change of early regulation of λ prophage

Neubauer, Zdeněk; Calef, E.

doi:10.1016/0022-2836(70)90265-2

Cited by 73 publications

(28 citation statements)

References 29 publications

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“…Since the late 1960s, it has been known that a portion of the genome, encoding the CI and Cro repressors and the promoters they regulate (Fig. 1A), comprises a bistable switch-a gene control circuit that is able to exist stably in either of two distinct, self-sustaining regulatory states: "immune" and "anti-immune" (Eisen et al 1970;Neubauer and Calef 1970;Toman et al 1985;Svenningsen et al 2005). In the immune (CI-dominant) state, the CI protein is expressed from the lysogenic promoter P RM and binds cooperatively to two operators, O R 1 and O R 2, to repress the P R lytic promoter and thus block transcription of the cro gene.…”

mentioning

confidence: 99%

Cro’s role in the CI–Cro bistable switch is critical for λ’s transition from lysogeny to lytic development

Schubert

Dodd²,

Egan³

et al. 2007

Genes Dev.

104

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CI represses cro; Cro represses cI. This double negative feedback loop is the core of the classical CI-Cro epigenetic switch of bacteriophage . Despite the classical status of this switch, the role in development of Cro repression of the P RM promoter for CI has remained unclear. To address this, we created binding site mutations that strongly impaired Cro repression of P RM with only minimal effects on CI regulation of P RM . These mutations had little impact on development after infection but strongly inhibited the transition from lysogeny to the lytic pathway. We demonstrate that following inactivation of CI by ultraviolet treatment of lysogens, repression of P RM by Cro is needed to prevent synthesis of new CI that would otherwise significantly impede lytic development. Thus a bistable CI-Cro circuit reinforces the commitment to a developmental transition.

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mentioning

confidence: 99%

Cro’s role in the CI–Cro bistable switch is critical for λ’s transition from lysogeny to lytic development

Schubert

Dodd²,

Egan³

et al. 2007

Genes Dev.

104

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“…The action of cro was demonstrated dramatically by creating lysogens deleted for all of the phage genes except the fragment containing cI and cro. These bacteria variegated: at any given time or condition, they expressed one or the other, but not both genes (41). Just how cro manages to work contra repressor (and vice versa) soon became clear as the complete workings of the switch .…”

Section: The Biphasic Switchmentioning

confidence: 99%

The Chemistry of Regulation of Genes and Other Things

Ptashne

2014

Journal of Biological Chemistry

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“…Its rate, k x , is set to 10 −6 s −1 , implying that, on average, X will appear in the cell at approximately t = 0.5 × 10 6 s, which is half of a cell's lifetime (here set to 10 6 s). This unrealistically long lifetime provides better statistics, but one could instead follow the dynamics of cells over many generations (as done experimentally in [34]). Reaction 18 occurs at most once during a cell's lifetime.…”

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confidence: 99%

Tuning cell differentiation patterns and single cell dynamics by regulating proteins’ functionalities in a toggle switch

Dai¹,

Healy²,

Yli‐Harja³

et al. 2009

Journal of Theoretical Biology

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We investigate how the regulation of protein multi-functionalities affect the dynamics of a stochastic model of a toggle switch and the differentiation pattern of cell population regulated by the switch. We study the effects of loss of functionality in DNA-binding and repression and the involvement in differentiation pathway choice. First is shown how the patterns of cell differentiation differ, when each of these functionalities is fully non-functional. Next, tuning the fraction of non-functional proteins regarding the ability to bind DNA is shown to allow fine tuning of the switch and cell differentiation pattern dynamics. Finally, biasing the probability of functionality of the two proteins biases the dynamics of the switch and cell differentiation patterns, especially when transcription factors retain the ability to bind DNA but have lost the ability to repress gene expression. Our results suggest that, besides transcriptional and translational levels of regulation, activation of functionalities in multi-functional proteins are an important regulator of gene networks.

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Immunity phase-shift in defective lysogens: Non-mutational hereditary change of early regulation of λ prophage

Cited by 73 publications

References 29 publications

Cro’s role in the CI–Cro bistable switch is critical for λ’s transition from lysogeny to lytic development

Cro’s role in the CI–Cro bistable switch is critical for λ’s transition from lysogeny to lytic development

The Chemistry of Regulation of Genes and Other Things

Tuning cell differentiation patterns and single cell dynamics by regulating proteins’ functionalities in a toggle switch

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