Conversion of graded to binary response in an activator-repressor system

TL;DR

This paper models a gene regulatory network with activator and repressor molecules, deriving an exact analytical expression that explains how gene expression responses can be graded or binary depending on inducer levels.

Contribution

It provides an exact analytical solution for the steady-state protein distribution in a gene network with mutually exclusive activator and repressor binding.

Findings

Response is graded with activators alone.

Response is graded at low and high inducer levels with both molecules.

Response becomes binary at intermediate inducer levels.

Abstract

Appropriate regulation of gene expression is essential to ensure that protein synthesis occurs in a selective manner. The control of transcription is the most dominant type of regulation mediated by a complex of molecules such as transcription factors. In general, regulatory molecules are of two types: activator and repressor. Activators promote the initiation of transcription whereas repressors inhibit transcription. In many cases, they regulate the gene transcription on binding the promoter mutually exclusively and the observed gene expression response is either graded or binary. In experiments, the gene expression response is quantified by the amount of proteins produced on varying the concentration of an external inducer molecules in the cell. In this paper, we study a gene regulatory network where activators and repressors both bind the same promoter mutually exclusively. The network is modeled by assuming that the gene can be in three possible states: repressed, unregulated and active. An exact analytical expression for the steady-state probability distribution of protein levels is then derived. The exact result helps to explain the experimental observations that in the presence of activator molecules the response is graded at all inducer levels whereas in the presence of both activator and repressor molecules, the response is graded at low and high inducer levels and binary at an intermediate inducer level.