Functional Genomics Analysis of the Yeast Iron Responsive Transcription Factor Aft1 Reveals Iron-Independent Functions

ABSTRACT: The Saccharomyces cerevisiae transcription factor Aft1 is activated in iron-deficient cells to induce the expression of iron regulon genes, which coordinate the increase of iron uptake and remodel cellular metabolism to survive low iron conditions. In addition, Aft1 has been implicated in numerous cellular processes including cell cycle progression and chromosome stability; however it is unclear if all cellular effects of Aft1 are mediated through iron homeostasis. To further investigate the cellular processes impacted by Aft1 using genome-wide synthetic lethal and synthetic dosage lethal screens, we identified greater than 70 deletion mutants that are sensitive to perturbations in AFT1 levels. Our genetic network reveals that Aft1 impacts a diverse range of cellular processes, including the RIM101 pH pathway, cell wall stability, DNA damage, protein transport, chromosome stability and mitochondrial function. Surprisingly, only a subset of mutants identified are sensitive to iron fluctuations or display genetic interactions with mutants of iron regulon genes AFT2 or FET3. We demonstrate that Aft1 works in parallel with the RIM101 pH pathway and the role of Aft1 in cell wall structure and DNA damage repair is mediated by iron. In contrast, we show that the role of Aft1 in chromosome maintenance is independent of its iron regulatory role and that alterations in iron levels do not impact chromosome loss rates. Our study clearly demonstrates a novel iron-independent role for Aft1. For this experiment 4 samples (2 reference and 2 test samples), consisting of 3 biological reps were hybridized. Cy3 one-color labelling was used for each sample.

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Linda Harris 

PROVIDER: E-GEOD-20531 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress