Regulation of zinc homeostatic genes by environmental pH in the filamentous fungus Aspergillus fumigatus.

Aspergillus fumigatus can grow over a broad range of pH values even though zinc availability is greatly conditioned by ambient pH. We have previously shown that regulation of zinc homeostatic genes in this fungus relies on the transcription factor ZafA. In addition, their expression is further modulated by the transcription factor PacC depending on ambient pH, which allows this fungus to grow in diverse types of niches, including soils and the lungs of immunosuppressed hosts. In this work we have analyzed in detail the regulation by PacC of genes zrfB and zrfC that are expressed, respectively, under acidic and alkaline zinc-limiting conditions. Thus, we provide data that extend the current model for PacC function, including the role of the full-length PacC72 protein and the PacC processed forms (PacC53 and PacC27 ) on gene expression, and describe a new mechanism for the repression of acid-expressed genes in alkaline media based on interference with the start of transcription. Moreover, we propose that the transcription of both acid- and alkaline-expressed genes under zinc-limiting conditions might also rely on a third factor (putatively Pontin/Reptin), which may be required to integrate the action of PacC and ZafA into gene specific transcriptional responses. This article is protected by copyright. All rights reserved.