Metallosensors, the ups and downs of gene regulation

In fungal cells, transcriptional regulatory mechanisms play a central role in both the homeostatic regulation of the essential metals iron, copper and zinc and in the detoxification of heavy metal ions such as cadmium. Fungi detect changes in metal ion levels using unique metallo-regulatory factors whose activity is responsive to the cellular metal ion status. New studies have revealed that these factors not only regulate the expression of genes required for metal ion acquisition, storage or detoxification but also globally remodel metabolism to conserve metal ions or protect against metal toxicity. This review focuses on the mechanisms metallo-regulators use to up- and down-regulate gene expression.