expression is 2-4 fold upregulated during Fe limited conditions (Colangelo and Guerinot, 2004; Jakoby et al., 2004). When
Fe is present however, FIT is only transcriptionally
induced upon the application of cycloheximide (CHX), an inhibitor of protein
biosynthesis. As speculated by Meiser et al., 2011, an unknown repressor might
prevent FIT expression, which
responds to the Fe status and also underlies a turnover control. By the
application of CHX, this repressor is not present anymore and, therefore, the
repression of FIT does not take place.
This raises the question, which positive regulator accounts for removal of the
repressor to initiate gene transcription under Fe deprived conditions (Meiser et al., 2011; Meiser and Bauer, 2012). Interestingly,
FIT gene expression is reduced in the
EMS mutant fru-C497T, which contains
a premature stop codon, hence impeding a correct protein translation of FIT (Jakoby et al., 2004). Together with the finding of a
decreased promotor activity under Fe limited conditions in the fit-3 mutant expressing a promoter pFIT-GUS construct, it becomes obvious
that FIT protein has a positive influence on its own promoter activity (Wang et al., 2007).
Recently, it was shown, that the Fe deficiency-responsive bHLH039 also promotes
FIT expression (Naranjo-Arcos et al., 2017). Hence,
both bHLH proteins could account for the unknown regulator.
More factors are known to enhance FIT expression, such as nitric oxide (NO), which accumulates in
response to Fe deficiency (Graziano and Lamattina, 2007; Chen et al., 2010;
Garcia et al., 2011; Meiser et al., 2011). NO
positively regulates the expression of the 14-3-3 protein GENERAL REGULATORY
FACTOR11 (GRF11), which in turn promotes FIT
expression (Yang et al., 2013).
Hormones can, directly or indirectly, influence the post-transcriptional
regulation of FIT as well. This
control is very complex due to the fact that different hormones share signaling
pathways which engage with each other, leading to hormonal crosstalk (Kohli et al., 2013).
Also, hormones, as well as small molecules, can influence their
synthesis in a reciprocal way, thereby controlling their mutual accumulation,
such as NO, ethylene and auxin (Romera et al., 2011). Fe limitation promotes gene
expression of several enzymes needed for ethylene synthesis and hence leads to
an accumulation of the hormone (Romera and Alcántara, 2004; Romera et al., 2006;
Garcia et al., 2010).
Ethylene promotes FIT gene
expression, most probably through the feed-forward cycle of FIT protein on its
promoter activity (Jakoby et al., 2004; Lucena et al., 2006; Wang et
al., 2007; Garcia et al., 2010; Lingam et al., 2011).
Accumulated auxin in roots in response to Fe deficiency acts upstream of NO
which became evident after analyzing a large set of respective auxin and NO
mutants. Presumably, a Fe deficiency-caused increase in root sucrose level
mediates auxin-signaling which causes the regulation of Fe uptake via NO (Chen et al., 2010; Meiser et al., 2011; Lin et al.,
Repression of FIT translational
activity by the application of jasmonate and cytokinins was demonstrated. However,
it does not account for the repression of FIT target gene expression (Séguéla et al., 2008; Maurer et al., 2011).
RNA polymerase II (RNA POL II) CARBOXYL-TERMINAL
DOMAIN PHOSPHATASE-LIKE 1 (CPL1) is inhibiting FIT and subgroup Ib BHLH gene
expression (Aksoy 2013). CPL1 interacts with REGULATOR OF CBF GENE EXPRESSION 3
(RCF3), which also affects the transcript abundance of FIT and additional Fe homeostasis genes (Jeong et al., 2013).