The Aspergillus nidulans CREA protein mediates glucose repression of the ethanol regulon at various levels through competition with the ALCR-specific transactivator.

Abstract

Carbon catabolite repression in Aspergillus nidulans is mediated by a negative‐acting protein coded by the creA gene. We have investigated how CREA controls the expression of the ethanol regulon genes. CREA is a major component of the control of this regulon. Its presence in the cell results in a permanent, albeit partial, repression of the alc genes under all physiological growth conditions, even when the fungus is grown on carbon sources considered to be non‐repressing. A crucial step in the control processes is the repression of the positive‐acting specific regulatory gene alcR, by the binding of CREA on its cognate target sites on the alcR promoter. The removal of one of these targets, URSA, results in a 50% derepression of the alcR gene. Furthermore, the presence of this sequence contributes directly to the low alcR expression under nonrepressing conditions and reduces alcR promoter function by at least 100‐fold. CREA acts both on the regulatory gene alcR and directly on the two structural genes alcA and aldA, as glucose repression of the latter genes occurs in strains where alcR transcription is driven by a strong constitutive and derepressed promoter. In vivo and in vitro competition experiments show that CREA acts by competing directly with the binding of the ALCR activator for the same region of the alcR promoter, a region which encompasses overlapping targets for both regulatory proteins. These data are consistent with a model in which the activating and repressing regulatory proteins compete to regulate expression of the ethanol regulon genes.

Regulation of transcription of cellulases- and hemicellulases-encoding genes in Aspergillus niger and Hypocrea jecorina (Trichoderma reesei)

“…A similar mechanism has been shown for the regulation of the alcA gene of A. niger, where the transcriptional activator AlcR competes with CreA for the corresponding, partially overlapping binding sites (e.g. Marmorstein et al 1992;Marmorstein and Harrison 1994;Mathieu and Felenbok 1994;Narendja et al 1999). …”

Induction of extracellular β-galactosidase (Bga1) formation by d-galactose in Hypocrea jecorina is mediated by galactitol

“…Interference of carbon catabolite regulation with gene expression at multiple regulatory levels is not unknown in fungi, and such 'double-lock mechanisms' have already been reported in A. nidulans for alcA regulation (Mathieu & Felenbok, 1994) and b-galactosidase formation (Fekete et al, 2002), and also in Aspergillus niger for xylanase biosynthesis (de Vries et al, 1999b). Chemostat-type continuous cultivations (Ilyés et al, 2004;Karaffa et al, 2006;Pakula et al, 2005) are a useful means to investigate such interfering mechanisms.…”

Crel, the carbon catabolite repressor protein from Trichoderma reesei

“…Unlike MIG1, however, CreA contains an additional domain downstream of the zinc-finger, which has been reported to bear high similarity to S. cerevisiae RGR1 [8,9], and whose function is unknown. Since its cloning and sequencing, molecular evidence has been presented for an involvement of CreA in the catabolite repression of transcription of genes involved in proline utilization [7], ethanol metabolism [10,11] and polysaccharide hydrolysis [12] in A. nidulans.Nothing is known as yet on the mechanism of carbon catabolite repression in other fungi. The filamentous fungus Trichoderma reesei is an industrially important producer of several extracellular enzymes, including a highly active cellulase [13] and hemicellulase enzyme system [14].…”