On the Control of Gene Expression

The control theory of metabolic pathways has become fairly complete (reviewed in Kacser & Porteous, 1987; Kell & Westerhoff, 1986; Westerhoff & Van Dam, 1987; Wester-hoff, 1989ab; see also numerous chapters in this book, especially Chapter 3 by Porteous). However, it discusses control at a single level, i.e., that of metabolic pathways, without taking the variability of gene expression explicitly into account. In metabolic control theory, protein concentrations can only be reset by interventions. This type of control analysis is useful for understanding principles of metabolic control, and for understanding metabolic changes that are too quick or in too limited a metabolic system to involve changes in gene expression. Because variations in gene expression are ubiquitous and clearly implicated in metabolic regulation, it is of interest to see how the principles of metabolic control change if variable gene expression is taken into account. In this chapter we present a first attempt to extend metabolic control theory to variable gene expression. We also discuss two experimental situations in which we have analysed such control and make explicit where regulation differs from control.

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