anti-sigma and interacts with a third factor, SpoIIAA, which
is called anti-anti-sigma, which then triggers sporulation
(Duncan and Losick 1993).
Gene transcription by RNA polymerase is sometimes
modified by the presence of proteins that attach to DNA;
such proteins are called “transcriptional regulators*.” The
attachment of the regulator to DNA is not irreversible,
because this protein oscillates between two states, attached
or not attached, according to various physicochemical
factors. When the regulator is in a free, non-attached state,
it cannot bind to DNA, and synthesis of messengers can then
take place (Fig. 9.1).
Some transcriptional regulators are repressors*; they are
attached to the DNA as a base situation. When the metabolite or metal for which the repressor has a high affinity is
present in the cell, it attaches to the repressor, which then has
its conformation changed, reducing its affinity for the DNA
sequence, and it is then released from DNA. Other transcriptional regulators are activators*; they change their conformation as repressors do following environmental stimuli
such as the presence of a metabolite or a metal. They attach
to the DNA near the promoters* of the genes under their
control and then activate their expression. Finally, some
regulators can operate either as an activator or as a repressor.
There are about a dozen families of transcriptional
regulators identified in bacteria; among these are the
families AraC (arabinose), CRP (catabolite repressor protein), LacI (lactose), LysR (lysine biosynthesis), and MerR
(metabolism of mercury) families, whose structures and
mechanisms have been best characterized (Ma et al. 2004).
For example, the regulator Fur is a small protein of 17kD
with high affinity for iron. Its name means “ferric ion uptake
regulator” because the function that was attributed originally
to this protein was to regulate the intracellular level of Fe
(II), which is a cofactor for many enzymes such as nitrogenase, superoxide dismutase, or uptake hydrogenase. Since
free iron can generate oxidative stress through the Fenton
effect, it is necessary to closely regulate its level in the cell.
In case of low intracellular iron, there is little risk to the cell,
and the Fur protein remains attached to the upstream
sequences of genes involved in iron metabolism and oxidative stress. When the intracellular iron level rises, this iron is
recognized by the Fur protein that has a high affinity for it,
and Fur then sees its conformation changed; it then releases
the DNA sequences to which it was attached (Andrews et al.
2003). Many proteins exist that are homologous to Fur; these
proteins are derived from duplications that occurred before
the emergence of lineages such as that of the Actinobacteria
(Santos et al. 2009).
The transcriptional regulators bind to DNA through
areas of attachment to the DNA of different types; the best
known of these is the “helix-turn-helix” domain which
has two sites of interaction with the major DNA groove
(“helices”) and a hinge region (“turn”). Other known
domains are called “zinc finger domain,” “winged helix,”
or “leucine zipper.”
Some genes are under the control of several of these
transcription factors, which makes sense since they are
involved in the response to several physicochemical factors.
For example, the gene kdgN is responsible for the
synthesis of a carrier for the entry of galacturonate in the
phytopathogenic bacterium Dickeya dadantii formerly
known as Erwinia chrysanthemi (Condemine and Ghazi
2007). No less than five regulators modulate the transcription of this gene, in particular KdgR (galacturonate), PecS
(pectinase), OmpR (outer membrane protein), HNS (histone
nucleoid structuring), and CRP (catabolite repressor protein). It is thus estimated that complex regulatory networks
relate the genes and operons, thus constituting regulons*.
The different regulons are related to each other; thus, ultimately all genes of the genome interact with others in the
global network of transcriptional regulation as shown in
Fig. 9.2.
The genome sequencing programs have revealed a strong
correlation between genome size and the number of transcriptional regulators (Fig. 9.3). A strict symbiont such as
Wolbachia, whose genome has undergone a sharp reduction,
is thus dependent on its host not only for food but also for its
regulation as it has only six transcriptional regulators (Wu
et al. 2004). Conversely, Frankia bacteria that live in soil
and symbiotically in root nodules of the plant and have
Fig. 9.2 Hierarchical structure of the network that controls transcription in Escherichia coli. This network includes 1,278 factors (circles)
and 2,274 interactions (lines connecting the circles). There are nine
levels in the regulatory network, the highest ones controlling those
below. The first level at the top of the pyramid is CRP; the second is
RpoS; the third includes CspE, Ihf, and PhoB; the fourth includes CytR,
SoxR, and DnaA; and the fifth includes RpoE, HNS, and RpoN. The
self-regulatory loops are not represented in this network (Modified
from Ma et al. 2004)
298
P. Normand et al.
is called anti-anti-sigma, which then triggers sporulation
(Duncan and Losick 1993).
Gene transcription by RNA polymerase is sometimes
modified by the presence of proteins that attach to DNA;
such proteins are called “transcriptional regulators*.” The
attachment of the regulator to DNA is not irreversible,
because this protein oscillates between two states, attached
or not attached, according to various physicochemical
factors. When the regulator is in a free, non-attached state,
it cannot bind to DNA, and synthesis of messengers can then
take place (Fig. 9.1).
Some transcriptional regulators are repressors*; they are
attached to the DNA as a base situation. When the metabolite or metal for which the repressor has a high affinity is
present in the cell, it attaches to the repressor, which then has
its conformation changed, reducing its affinity for the DNA
sequence, and it is then released from DNA. Other transcriptional regulators are activators*; they change their conformation as repressors do following environmental stimuli
such as the presence of a metabolite or a metal. They attach
to the DNA near the promoters* of the genes under their
control and then activate their expression. Finally, some
regulators can operate either as an activator or as a repressor.
There are about a dozen families of transcriptional
regulators identified in bacteria; among these are the
families AraC (arabinose), CRP (catabolite repressor protein), LacI (lactose), LysR (lysine biosynthesis), and MerR
(metabolism of mercury) families, whose structures and
mechanisms have been best characterized (Ma et al. 2004).
For example, the regulator Fur is a small protein of 17kD
with high affinity for iron. Its name means “ferric ion uptake
regulator” because the function that was attributed originally
to this protein was to regulate the intracellular level of Fe
(II), which is a cofactor for many enzymes such as nitrogenase, superoxide dismutase, or uptake hydrogenase. Since
free iron can generate oxidative stress through the Fenton
effect, it is necessary to closely regulate its level in the cell.
In case of low intracellular iron, there is little risk to the cell,
and the Fur protein remains attached to the upstream
sequences of genes involved in iron metabolism and oxidative stress. When the intracellular iron level rises, this iron is
recognized by the Fur protein that has a high affinity for it,
and Fur then sees its conformation changed; it then releases
the DNA sequences to which it was attached (Andrews et al.
2003). Many proteins exist that are homologous to Fur; these
proteins are derived from duplications that occurred before
the emergence of lineages such as that of the Actinobacteria
(Santos et al. 2009).
The transcriptional regulators bind to DNA through
areas of attachment to the DNA of different types; the best
known of these is the “helix-turn-helix” domain which
has two sites of interaction with the major DNA groove
(“helices”) and a hinge region (“turn”). Other known
domains are called “zinc finger domain,” “winged helix,”
or “leucine zipper.”
Some genes are under the control of several of these
transcription factors, which makes sense since they are
involved in the response to several physicochemical factors.
For example, the gene kdgN is responsible for the
synthesis of a carrier for the entry of galacturonate in the
phytopathogenic bacterium Dickeya dadantii formerly
known as Erwinia chrysanthemi (Condemine and Ghazi
2007). No less than five regulators modulate the transcription of this gene, in particular KdgR (galacturonate), PecS
(pectinase), OmpR (outer membrane protein), HNS (histone
nucleoid structuring), and CRP (catabolite repressor protein). It is thus estimated that complex regulatory networks
relate the genes and operons, thus constituting regulons*.
The different regulons are related to each other; thus, ultimately all genes of the genome interact with others in the
global network of transcriptional regulation as shown in
Fig. 9.2.
The genome sequencing programs have revealed a strong
correlation between genome size and the number of transcriptional regulators (Fig. 9.3). A strict symbiont such as
Wolbachia, whose genome has undergone a sharp reduction,
is thus dependent on its host not only for food but also for its
regulation as it has only six transcriptional regulators (Wu
et al. 2004). Conversely, Frankia bacteria that live in soil
and symbiotically in root nodules of the plant and have
Fig. 9.2 Hierarchical structure of the network that controls transcription in Escherichia coli. This network includes 1,278 factors (circles)
and 2,274 interactions (lines connecting the circles). There are nine
levels in the regulatory network, the highest ones controlling those
below. The first level at the top of the pyramid is CRP; the second is
RpoS; the third includes CspE, Ihf, and PhoB; the fourth includes CytR,
SoxR, and DnaA; and the fifth includes RpoE, HNS, and RpoN. The
self-regulatory loops are not represented in this network (Modified
from Ma et al. 2004)
298
P. Normand et al.