Information Technology Reference
In-Depth Information
Fig. 2.1. The transcription regulatory network of the JUN TF in human. Only direct JUN targets
and TFs coregulating genes with JUN are shown.
2.2. Regulatory Networks
Living cells are endowed with specic sensory and signalling systems to obtain and
transmit information from their environment in order to adjust cellular metabolism,
growth, and development to environmental alterations. Such molecular communi-
cations can be triggered by small molecules (i.e. nutrients, ions, drugs), and by
physical parameters (i.e. temperature and pressure). Moreover, there are several
systems that continuously monitor the intracellular milieu, e.g. energetic charge
and redox state, and accordingly modulate cell physiology. Similarly, the extremely
dierent cell types in higher eukaryotes are the results of expression pattern dif-
ferences, as well as cellular proliferation and dierentiation, that are controlled by
regulatory circuits giving origin to space- and time-dependent activation patterns.
Several systems directly modulate the response to extra- and intra-cellular sig-
nals; one of the most important acts on the rate of transcription of a gene [2{9].
The genetic basis for the dynamic expression prole of each gene resides in part
within its promoter and in part within the many other segments of the genome that
encode transcription factors (TF) which are able to recognize specic promoter se-
quences. TFs interact with promoters and cis-regulatory modules, and, within such
elements TFs are able to bind specic elements (TF binding sites). The genome of
the unicellular yeast Saccharomyces cerevisiae encodes200 predicted TFs [10],
which is3% of all protein-coding genes; the relatively simple metazoan nema-
tode Caenorhabditis elegans contains 934 predicted TFs (5% of all protein-coding
genes [11]); humans may devote up to 10% of their coding potential to regulatory
TFs, in agreement with a positive correlation between the fraction of TF-encoding
genes in a genome and the complexity of an organism. Determining the binding
