Subcellular localization of Aft1 transcription factor responds to iron status in Saccharomyces cerevisiae

The Aft1 transcription factor regulates the iron regulon in response to iron availability in Saccharomyces cerevisiae. Aft1 activates a battery of genes required for iron uptake under iron-starved conditions, whereas Aft1 function is inactivated under iron-replete conditions. Previously, we have shown that iron-regulated DNA binding by Aft1 is responsible for the controlled expression of target genes. Here we show that this iron-regulated DNA binding by Aft1 is not due to the change in the total expression level of Aft1 or alteration of DNA binding activity. Rather, nuclear localization of Aft1 responds to iron status, leading to iron-regulated expression of the target genes. We identified the nuclear export signal (NES)-like sequence in the AFT1 open reading frame. Mutation of the NES-like sequence causes nuclear retention of Aft1 and the constitutive activation of Aft1 function independent of the iron status of the cells. These results suggest that the nuclear export of Aft1 is critical for ensuring iron-responsive transcriptional activation of the Aft1 regulon and that the nuclear import/export systems are involved in iron sensing by Aft1 in S. cerevisiae.