Switching off: The phenotypic transition to the uninduced state of the lactose uptake pathway.

Details

Serval ID
serval:BIB_3D5D4B742C7C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Switching off: The phenotypic transition to the uninduced state of the lactose uptake pathway.
Journal
Biophysical journal
Author(s)
Bhogale P.M., Sorg R.A., Veening J.W., Berg J.
ISSN
1542-0086 (Electronic)
ISSN-L
0006-3495
Publication state
Published
Issued date
18/01/2022
Peer-reviewed
Oui
Volume
121
Number
2
Pages
183-192
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
The lactose uptake pathway of E. coli is a paradigmatic example of multistability in gene regulatory circuits. In the induced state of the lac pathway, the genes comprising the lac operon are transcribed, leading to the production of proteins that import and metabolize lactose. In the uninduced state, a stable repressor-DNA loop frequently blocks the transcription of the lac genes. Transitions from one phenotypic state to the other are driven by fluctuations, which arise from the random timing of the binding of ligands and proteins. This stochasticity affects transcription and translation, and ultimately molecular copy numbers. Our aim is to understand the transition from the induced to the uninduced state of the lac operon. We use a detailed computational model to show that repressor-operator binding and unbinding, fluctuations in the total number of repressors, and inducer-repressor binding and unbinding all play a role in this transition. Based on the timescales on which these processes operate, we construct a minimal model of the transition to the uninduced state and compare the results with simulations and experimental observations. The induced state turns out to be very stable, with a transition rate to the uninduced state lower than 2×10 <sup>-9</sup> per minute. In contrast to the transition to the induced state, the transition to the uninduced state is well described in terms of a 2D diffusive system crossing a barrier, with the diffusion rates emerging from a model of repressor unbinding.
Pubmed
Web of science
Create date
04/01/2022 9:34
Last modification date
27/04/2022 6:37
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