Biomedical Engineering Reference
In-Depth Information
bind DNA without phosphorylation of the protein. They also reported that
mutation of the casein kinase II target consensus sequence in CREI resulted
in loss of phosphorylation of CREI, loss of DNA binding and gain of carbon
catabolite derepression, which strongly support the role of casein kinase II
in activating CREI for DNA binding (Cziferszky et al. 2002).
Investigation of the early events that lead to the triggering of carbon
catabolite repression in
A. nidulans
has shown that all monosaccharides,
irrespective of whether they are considered repressing or derepressing,
resulted in an immediate increase in
creA
mRNA levels when added to
a carbon-starved culture of
A. nidulans
(Strauss et al. 1999). Repressing
monosaccharides such as glucose and fructose triggered a subsequent down
regulation of
creA
gene expression that was not observed in the presence
of derepressing monosaccharides (L-arabinose). This down regulation, or
autoregulation, is dependent on two CREA binding sites, which are located
around -560 bp in the
creA
promoter. The formation of this CREA-DNA
complex was dependent on the formation of glucose-6-phosphate and “de
novo” protein synthesis. The high
creA
expression that was observed under
carbon-derepressing conditions such as, in the presence of L-arabinose, did
not result in conversion of its gene product to a functional CREA protein
(Strauss et al. 1999).
Based on work conducted to date, repression of gene expression by CREI
requires translocation to the nucleus, phosphorylation of a serine residue
and DNA-binding through two zinc fi nger structures (Vautard-Mey et al.
1999, Vautard-Mey and Fevre 2000, Cziferszky et al. 2002). However, it is
not clear what type of repression mechanism is used by CREI i.e. classic
repression (repression by exclusion), co-repression or repression by histone
deacetylation involving dedicated histone acetylases. It is possible that
CREI mediates repression through the exclusion of activating factors due to
the close proximity of certain functional CREI binding sites and functional
binding sites for activating factors. For example, in the
T. reesei xyn1
promoter two functional CREI binding sites are located just downstream
of a functional binding site for the activating factor, Xyr1 (Rauscher et al.
2006). Indeed, it is also possible that CREI functions as a co-repressor as
the
Tr. reesei cbh1
promoter contains two
in vivo
functional CREI binding
sites and eight
in vitro
functional ACEI binding sites (Ilmen et al. 1996a,
Saloheimo et al. 2000). However, it is most likely that CREI is the dominant
repressor of
cbh1
gene expression in
T. reesei
(Aro et al. 2003). CREI has been
shown to participate in the positioning of nucleosomes on the
Tr. reesei cbh2
promoter under inducing and repressing conditions but does not directly
regulate expression of the
cbh2
gene (Zeilinger et al. 2003). Based on these
results, it is possible that CREI may also function in chromatin organisation
via histone modifi cation.
