Dataset Information

Positive autoregulation of cI is a dispensable feature of the phage lambda gene regulatory circuitry.

ABSTRACT: Complex gene regulatory circuits contain many features that are likely to contribute to their operation. It is unclear, however, whether all these features are necessary for proper circuit behavior or whether certain ones are refinements that make the circuit work better but are dispensable for qualitatively normal behavior. We have addressed this question using the phage lambda regulatory circuit, which can persist in two stable states, the lytic state and the lysogenic state. In the lysogenic state, the CI repressor positively regulates its own expression by stimulating transcription from the P(RM) promoter. We tested whether this feature is an essential part of the regulatory circuitry. Several phages with a cI mutation preventing positive autoregulation and an up mutation in the P(RM) promoter showed near-normal behavior. We conclude that positive autoregulation is not necessary for proper operation of the lambda circuitry and speculate that it serves a partially redundant function of stabilizing a bistable circuit, a form of redundancy we term "circuit-level redundancy." We discuss our findings in the context of a two-stage model for evolution and elaboration of regulatory circuits from simpler to more complex forms.

SUBMITTER: Michalowski CB

PROVIDER: S-EPMC1236637 | biostudies-literature | 2005 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Positive autoregulation of cI is a dispensable feature of the phage lambda gene regulatory circuitry.

Michalowski Christine B CB Little John W JW

Journal of bacteriology 20050901 18

Complex gene regulatory circuits contain many features that are likely to contribute to their operation. It is unclear, however, whether all these features are necessary for proper circuit behavior or whether certain ones are refinements that make the circuit work better but are dispensable for qualitatively normal behavior. We have addressed this question using the phage lambda regulatory circuit, which can persist in two stable states, the lytic state and the lysogenic state. In the lysogenic ...[more]

PMID: 16159777

Similar Datasets

Project description:BackgroundGene regulatory networks can be modelled in various ways depending on the level of detail required and biological questions addressed. One of the earliest formalisms used for modeling is a Boolean network, although these models cannot describe most temporal aspects of a biological system. Differential equation models have also been used to model gene regulatory networks, but these frameworks tend to be too detailed for large models and many quantitative parameters might not be deducible in practice. Hybrid models bridge the gap between these two model classes - these are useful when concentration changes are important while the information about precise concentrations and binding site affinities is partial.ResultsIn this paper we study the stable behaviours of phage λ via a hybrid system based model. We identify wild type and mutant behaviours that arise for various orderings of binding site affinities. We propose experiments for detecting these behaviours: we suggest several ways of altering binding affinities with either mutations or genome rearrangements to achieve modified behaviours. The feasibility of these experiments is assessed. The interplay between the qualitative aspects of a network, e.g. network topology, and quantitative parameters, e.g. growth and degradation rates of proteins, is demonstrated. We also provide a software for exploring all feasible states of a hybrid system model and identifying all attractors.ConclusionsThe behaviours of phage λ are determined mainly by the topology of this network and by the mutual order of binding affinities. Exact affinities and growth and degradation rates of proteins fine tune the system. We show that only two stable behaviours are possible for phage λ if the main constraints of λ switch are preserved - these behaviours correspond to lysis and lysogeny. We identify several variants of both lysis and lysogeny - one wild type and one modified behaviour for each. We elucidate the necessary constraints for binding site affinities to achieve both wild type lysis and lysogeny. Our software is applicable to a wide range of biological models described as a hybrid system.

Dataset Information

Positive autoregulation of cI is a dispensable feature of the phage lambda gene regulatory circuitry.

Publications

Positive autoregulation of cI is a dispensable feature of the phage lambda gene regulatory circuitry.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets