Biology Reference
In-Depth Information
These sequences are only six to twenty nucleotides long, and numer-
ous copies of them are present in the genome, such that many inter-
actions may occur.
Hox
genes are an illustration of this situation as they determine
several stages of embryonic development. The transcription factors
they encode activate numerous genes implicated in differentiation in
the early embryo stage or in the limbs of vertebrates and insects.
These proteins do not however show any specificity in their binding
to DNA. The sequences they recognise are only six nucleotides long
and are therefore very frequent in the genome (Gehring
et al
., 1994).
As a result of this, they are capable of binding with any gene
20
in vitro
whereas they only bind with a limited number of genes
in vivo
(Carr and Biggin, 1999; Biggin, 2001).
In weaker interactions transcription factors also recognise what
are called 'degenerate' sequences, which only differ from the
sequences of maximum affinity by one or more nucleotides. These
degenerate sequences are also repeated many times in the genomes
of multicellular organisms, thus increasing the possibilities of inter-
action (Zhang
et al
., 2006; Bendall
et al
., 1993).
There are even more spectacular examples. MeCp2 represses the
activity of the genes recognising the methylated CG dinucleotide.
This target is present 40 million times in a mammalian genome
whereas there are only a million MeCp2 molecules (Nan
et al.
, 1997).
Thus, as with protein-protein interactions for signal transduc-
tion, there is a huge number of potential protein-DNA interactions.
4.1.5
Overall non-specificity of protein networks
The previous examples of non-specificity were obtained from
studying individual proteins. If each stage in every domain of cell
physiology is subject to similar multiplicity, the total number of
combinations of possible interactions for a whole cell must be enor-
mous. This has now been verified experimentally. Networks of inter-
actions between proteins have indeed been studied globally in
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Or with the regulator regions of these genes.
