Transcriptional control of nmrA by the bZIP transcription factor MeaB reveals a new level of nitrogen regulation in Aspergillus nidulans.

Fungi can use a diverse range of nitrogen sources. Some nitrogen sources sustain a rapid growth rate and are used in preference to less readily metabolized nitrogen sources. The mechanisms involved in this control of nitrogen utilization have been studied in the model filamentous ascomycete, Aspergillus nidulans. The GATA transcription factor AreA is necessary for the expression of nitrogen-catabolic permeases and enzymes. AreA activity is controlled by multiple mechanisms including regulated areA transcript levels and regulated AreA nuclear export. During nitrogen sufficiency, AreA activation is also prevented by the co-repressor NmrA. We have investigated nitrogen signalling to NmrA. NmrA overexpression prevents AreA function irrespective of the nitrogen status. The mRNA levels of areA and nmrA are inversely regulated, suggesting that the relative levels of AreA and NmrA are critical in determining AreA activation. The bZIP transcription factor MeaB was found to activate nmrA expression and a conserved element, TTGCACCAT, bound by MeaB in vitro is present in the promoters of NmrA homologues in other filamentous ascomycetes. Expression of meaB was not strongly regulated suggesting that transcriptional activation by MeaB is modulated by the nitrogen status. This work highlights a new level of complexity in the regulation of nitrogen catabolism.