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tracted from control and treated cells and the two mRNAs are labeled with two
uorescent dyes. The mRNA is then hybridized onto a microarray and scanning
allows recording the uorescent signal associated to each gene. The procedure is
intrinsically noisy so that it is common practice to do the entire process in paral-
lel for at least two-three replicates, even more if it is possible. By repeating the
protocol it is possible to obtain time dependent changes in gene expression.
When promoters respond to a single specic TF there is a direct correspondence
between the regulatory and the coexpression networks; the rst example has been
reported by Maas and Clark in the sixties to describe the genetic and regulatory
properties of the genes of Arginine biosynthesis (for a review see [29]). In the bac-
terium E. coli arg genes are scattered over the chromosome, but they are expressed
together when required thanks to the action of the ArgR TF. The dependency of
the expression level from ArgR is illustrated by the presence, upstream of these
genes, of a conserved motif called ARG box (e.g. see [30]).
However, this simple arrangement of a promoter characterizes a small fraction
of genes, e.g. see Fig. 2.3, and, especially in eucaryotes, TFs very often cooperate/
compete for a promoter giving rise to combinatorial regulation.
Fig. 2.3. a) The crpp1 promoter, upstream of the E. coli gene encoding CRP (catabolite repressor
protein), a global regulator, showing the presence of two types of binding sites: 4 are specic for
the protein Fis, another global regulator which exerts a negative control on crp expression, and 2
are binding targets of CRP itself, which moreover exerts a dual control on its own transcription
rate. b) The known interaction network of E. coli where the two master regulators CRP and Fis
are indicated.
