Biology Reference
In-Depth Information
often overcome this limitation and can be used to discern functions, unravel
regulation mechanisms or identify direct targets within regulatory networks.
The first studies discerning the FurA regulon showed that this metal-
loregulator specifically bound in vitro to A/T-rich sequences of its own
promoter, while the absence of both divalent metal ions and/or reducing
conditions as well as the presence of haeme severely impaired its affinity for
DNA (
Hernández, López-Gomollón et al., 2006
;
Hernández, Peleato et al.,
2004
). Surprisingly, the expression of FurA appeared strongly enhanced in
proheterocysts and mature heterocysts, and this upregulation seemed to be
mediated by NtcA, a master regulator of nitrogen metabolism that triggers
heterocyst differentiation and nitrogen fixation in diazotrophic cyanobac-
teria (
López-Gomollón, Hernández, Wolk, Peleato, & Fillat, 2007
). These
findings represented the first evidence of FurA involvement in nitrogen
metabolism and led to further definition of a cross-talk between FurA and
NtcA, identifying overlapping genes in both regulons (
López-Gomollón,
Hernández, Pellicer et al., 2007
).
More recently, overexpression has been successfully used as an alter-
native method to gain new insights into the FurA regulatory function.
Overexpression of FurA in
Anabaena
PCC 7120 induced changes in the
transcriptional pattern of a variety of genes, leading to alterations in photo-
autotrophic growth, filament integrity, cell morphology, ultrastructure, pho-
tosynthetic function and defence against oxidative stress (
González et al.,
2010
). Although some of the effects observed under a FurA overexpression
phenotype could result from an aberrant response unrelated to the normal
function of the protein, the combination of phenotypic studies with both
transcriptional and proteomic profile variations in conjunction with FurA-
DNA interaction analyses allowed more than 20 new direct targets of this
transcriptional regulator to be identified (
González et al., 2010
,
2011
).
Of the three different Fur homologues described in
Anabaena
sp.
(
Hernández, López-Gomollón et al., 2004
), FurA is the master regu-
lator of iron homeostasis, controlling the expression of iron uptake and
the storage machinery in response to iron availability (
González A. et al.,
2012
). However, the same protein appears to have a direct regulatory role
in the transcription of several genes involved in oxidative stress defences
and redox signalling, modulating the expression of at least two peroxire-
doxins (
González et al., 2011
), thioredoxin (
López-Gomollón, Hernández,
Pellicer et al., 2007
), thioredoxin reductase (
González et al., 2011
) and DpsA-
homologues (
Hernández, Pellicer, Huang, Peleato, & Ft, 2007
). Since DNA-
binding activity of FurA is critically dependent on reducing conditions
