THE CREA REPRESSOR IS THE SOLE DNA-BINDING PROTEIN RESPONSIBLE FOR CARBON CATABOLITE REPRESSION OF THE ALCA GENE IN ASPERGILLUS-NIDULANS VIA ITS BINDING TO A COUPLE OF SPECIFIC SITES

Carbon catabolite repression is mediated in Aspergillus nidulans by th e negative acting protein CreA. The CreA repressor plays a major role in the control of the expression of the ale regulon, encoding proteins required for the ethanol utilization pathway. It represses directly, at the transcriptional level, the specific transacting gene alcR, the two structural genes alcA and aldA, and other ale genes in all physiol ogical growth conditions. Among the seven putative CreA sites identifi ed in the alcA promoter region, we have determined the CreA functional targets in AlcR constitutive and derepressed genetic backgrounds. Two different divergent CreA sites, of which one overlaps a functional Al cR inverted repeat site, are largely responsible for alcA repression. Totally derepressed alcA expression is achieved when these two CreA si tes are disrupted in addition to another single site, which overlaps t he functional palindromic induction target. The fact that derepression is always associated with alcA overexpression is consistent with a co mpetition model between AlcR and CreA for their cognate targets in the same region of the alcA promoter. Our results also indicate that the CreA repressor is necessary and sufficient for the total repression of the alcA gene.