The reprogramming of the molecular machinery caused mainly by transcriptional regulation, coordinates different cellular processes as the cells move from one physiological state to another. Since this is the key to the evolutionary success of any organism, it is not surprising that a significant part of its genetic endowment is devoted to regulatory functions. When the yeast shifts from the most preferred carbon source glucose to galactose, there is a large increase in the synthesis of GAL gene products, without affecting their fermentative lifestyles. Obviously, during this transition, yeast has to make compensatory changes in the pattern of gene expression to coordinate the metabolism of galactose with several other cellular processes, especially energy metabolism. One of the obvious changes is the derepression of many functions repressed by glucose, especially mitochondrial biogenesis . Recently, the genome-wide analysis has identified genes previously not suspected to be induced in the presence of galactose, emphasizing the importance of the need for multiple pathways to integrate various cellular functions. The study of the use of galactose by Saccharomyces cerevisiae provides a convenient experimental system to investigate the network of gene interaction that leads to the exquisite coordination between the different cellular processes.
Iron is essential for the survival of eukaryotic cells but toxic at higher concentrations. In yeast, iron levels are tightly regulated by the transcriptional activators Aft1 and Aft2 (activators of ferrous transport), which activate iron uptake genes when iron levels are low. We present the first crystal structure of Aft2 bound to DNA and we demonstrate that Aft2 detects cellular iron levels through direct binding of [2Fe-2S] -cluster, which promotes Aft2 dimerization and deactivation of regulated genes. We further demonstrate that Aft2 acquires a [2Fe-2S] group of glutaredoxin-3 and the Fc repressor of activation-2, two [2Fe-2S] binding proteins with homologues in the higher eukaryotes. This study reveals the molecular mechanism of the Aft family of iron regulatory proteins and emphasizes the importance of the Fe-S groups in the detection of cellular iron in eukaryotes.