Open AccessOn the Mechanism by which Alkaline pH Prevents Expression of an Acid-Expressed Gene
Author(s) -
Eduardo A. Espeso,
Herbert N. Arst
Publication year - 2000
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.20.10.3355-3363.2000
Subject(s) - biology , activator (genetics) , gene expression , biochemistry , permease , zinc finger , transcription factor , gene , regulation of gene expression , promoter , zinc finger transcription factor , microbiology and biotechnology , transporter
Previous work has shown that zinc finger transcription factor PacC mediates the regulation of gene expression by ambient pH in the fungusAspergillus nidulans . This regulation ensures that the syntheses of molecules functioning in the external environment, such as permeases, secreted enzymes, and exported metabolites, are tailored to the pH of the growth environment. A direct role for PacC in activating the expression of an alkaline-expressed gene has previously been demonstrated, but the mechanism by which alkaline ambient pH prevents the expression of any eukaryotic acid-expressed gene has never been reported. Here we show that a double PacC binding site in the promoter of the acid-expressedgabA gene, encoding γ-aminobutyrate (GABA) permease, overlaps the binding site for the transcriptional activator IntA, which mediates ω-amino acid induction. Using bacterially expressed fusion proteins, we have shown that PacC competes with IntA for DNA binding in vitro at this site. Thus, PacC repression of GABA permease synthesis is direct and occurs by blocking induction. A swap of IntA sites between promoters forgabA andamdS , a gene not subject to pH regulation, makesgabA expression pH independent andamdS acid expressed.