The fission yeast Schizosaccharomyces pombe responds to the deprivation of
iron by inducing the expression of the php4+ gene, which encodes a negative regulatory subunit of the heteromeric
CCAAT-binding factor. Once formed, the
Php2/3/4/5 transcription complex is required to inactivate a subset of genes encoding
iron-using
proteins. Here, we used a pan-S. pombe microarray to study the transcriptional response to
iron starvation and identified 86 genes that exhibit php4+-dependent changes on a genome-wide scale. One of these genes encodes the
iron-responsive transcriptional repressor Fep1, whose
mRNA levels were decreased
after treatment with the permeant
iron chelator 2,2'-dipyridyl. In addition, several genes encoding the components of
iron-dependent biochemical pathways, including the tricarboxylic acid cycle, mitochondrial respiration,
amino acid biosynthesis, and oxidative stress defense, were downregulated in response to
iron deficiency. Furthermore, Php4 repressed transcription when brought to a promoter using a yeast
DNA-binding domain, and
iron deprivation was required for this repression. On the other hand, Php4 was constitutively active when
glutathione levels were depleted within the cell. Based on these and previous results, we propose that
iron-dependent inactivation of Php4 is regulated at two distinct levels: first, at the transcriptional level by the
iron-responsive
GATA factor Fep1 and second, at the posttranscriptional level by a mechanism yet to be identified, which inhibits Php4-mediated repressive function when
iron is abundant.