316

23

Regulatory Networks

whereww is an element of the weight matrix (23.1),script upper FF is a nonlinear transfer function

(e.g., an exponential function),xx is an external input (e.g., a delay), and the negative

term at the extreme right represents degradation. The Boolean network approach

lends itself to elegant, compact descriptions that can easily be extended to hundreds

of genes.

Boolean logic is now being drawn into the fold of synthetic biology, which has

somewhat evolved from its original aim of creating life de novo from inorganic start-

ing materials to a new focus of engineering logic circuits into (bacterial) genomes to

create an information processor. The imports are environmental signals, the program

is encoded by the DNA, and the processor is the transcriptional regulatory network

acting on promoters controlling their target genes; the ultimate output is a change in

phenotype via changed expression of proteins.

Problem. Devise a NOT gate from an operon-like set of genes (see Sect. 23.3). What

other gates could be realized? ¹²

23.3 A Simple Example—Operons

In prokaryotes, and possibly some eukaryotes, genes are organized in operons. As

already discussed in Chap. 14, an operon comprises a promoter sequence control-

ling the expression of several genes (positioned successively downstream from the

promoter), whose products may be successive enzymes in a metabolic pathway. ¹³

In most of the eukaryotes investigated hitherto, a similar but less clearly delineated

arrangement also exists: The same transcription factor may control the expression of

several genes, which may, however, be quite distant from each other along the DNA,

indeed even on different chromosomes.

The lac operon (part of the DNA of E. coli) consists of consecutive repressor

gene, promoter, operator, and lactose-metabolizing gene sequences. In the absence

of lactose, the repressor protein binds to the operator sequence and prevents the RNA

polymerase from transcribing the genes (of which there are three, translated into:

permease, a protein that helps to transport lactose into the cell;betaβ-galactosidase, which

is involved in the process of breaking down lactose by splitting off galactose, which

is further broken down into glucose; and galactoside transacetylase, also involved

in the metabolism of lactose, which it breaks down into its two monosaccharide

components, glucose and galactose, the latter being then further broken down by

other enzymes). Allolactose, a by-product of lactose metabolism, is able to bind

to the repressor, changing its conformation and preventing it from binding to the

operator sequence, whereupon the RNA polymerase is no longer prevented from

12 After tackling the problem, look at Wang et al. (2011) and Stanton et al. (2014) for actual

experimental work on this problem.

13 Groups of operons controlled by a single transcription factor are called regulons; groups of

regulons are called modulons.