Logo of embojLink to Publisher's site
EMBO J. 1995 Feb 15; 14(4): 779–790.
PMCID: PMC398143

The Aspergillus PacC zinc finger transcription factor mediates regulation of both acid- and alkaline-expressed genes by ambient pH.


The pH regulation of gene expression in Aspergillus nidulans is mediated by pacC, whose 678 residue-derived protein contains three putative Cys2His2 zinc fingers. Ten pacCc mutations mimicking growth at alkaline pH remove between 100 and 214 C-terminal residues, including a highly acidic region containing an acidic glutamine repeat. Nine pacC+/- mutations mimicking acidic growth conditions remove between 299 and 505 C-terminal residues. Deletion of the entire pacC coding region mimics acidity but leads additionally to poor growth and conidiation. A PacC fusion protein binds DNA with the core consensus GCCARG. At alkaline ambient pH, PacC activates transcription of alkaline-expressed genes (including pacC itself) and represses transcription of acid-expressed genes. pacCc mutations obviate the need for pH signal transduction.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Arst HN, Jr, Bignell E, Tilburn J. Two new genes involved in signalling ambient pH in Aspergillus nidulans. Mol Gen Genet. 1994 Dec 15;245(6):787–790. [PubMed]
  • Aufauvre-Brown A, Tang CM, Holden DW. Detection of gene-disruption events in Aspergillus transformants by polymerase chain reaction direct from conidiospores. Curr Genet. 1993 Jul-Aug;24(1-2):177–178. [PubMed]
  • Bailey CR, Penfold HA, Arst HN., Jr Cis-dominant regulatory mutations affecting the expression of GABA permease in Aspergillus nidulans. Mol Gen Genet. 1979 Jan 16;169(1):79–83. [PubMed]
  • Boulikas T. Putative nuclear localization signals (NLS) in protein transcription factors. J Cell Biochem. 1994 May;55(1):32–58. [PubMed]
  • Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. [PubMed]
  • Buxton FP, Radford A. Cloning of the structural gene for orotidine 5'-phosphate carboxylase of Neurospora crassa by expression in Escherichia coli. Mol Gen Genet. 1983;190(3):403–405. [PubMed]
  • Caddick MX, Brownlee AG, Arst HN., Jr Regulation of gene expression by pH of the growth medium in Aspergillus nidulans. Mol Gen Genet. 1986 May;203(2):346–353. [PubMed]
  • Cavener DR, Ray SC. Eukaryotic start and stop translation sites. Nucleic Acids Res. 1991 Jun 25;19(12):3185–3192. [PMC free article] [PubMed]
  • Cove DJ. The induction and repression of nitrate reductase in the fungus Aspergillus nidulans. Biochim Biophys Acta. 1966 Jan 11;113(1):51–56. [PubMed]
  • Espeso EA, Peñalva MA. In vitro binding of the two-finger repressor CreA to several consensus and non-consensus sites at the ipnA upstream region is context dependent. FEBS Lett. 1994 Mar 28;342(1):43–48. [PubMed]
  • Espeso EA, Tilburn J, Arst HN, Jr, Peñalva MA. pH regulation is a major determinant in expression of a fungal penicillin biosynthetic gene. EMBO J. 1993 Oct;12(10):3947–3956. [PMC free article] [PubMed]
  • Fairall L, Schwabe JW, Chapman L, Finch JT, Rhodes D. The crystal structure of a two zinc-finger peptide reveals an extension to the rules for zinc-finger/DNA recognition. Nature. 1993 Dec 2;366(6454):483–487. [PubMed]
  • Fidel S, Doonan JH, Morris NR. Aspergillus nidulans contains a single actin gene which has unique intron locations and encodes a gamma-actin. Gene. 1988 Oct 30;70(2):283–293. [PubMed]
  • Frederick GD, Rombouts P, Buxton FP. Cloning and characterisation of pepC, a gene encoding a serine protease from Aspergillus niger. Gene. 1993 Mar 15;125(1):57–64. [PubMed]
  • Han K, Manley JL. Functional domains of the Drosophila Engrailed protein. EMBO J. 1993 Jul;12(7):2723–2733. [PMC free article] [PubMed]
  • Henikoff S. Unidirectional digestion with exonuclease III in DNA sequence analysis. Methods Enzymol. 1987;155:156–165. [PubMed]
  • Irniger S, Braus GH. Saturation mutagenesis of a polyadenylation signal reveals a hexanucleotide element essential for mRNA 3' end formation in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):257–261. [PMC free article] [PubMed]
  • Jacobs GH. Determination of the base recognition positions of zinc fingers from sequence analysis. EMBO J. 1992 Dec;11(12):4507–4517. [PMC free article] [PubMed]
  • Jarai G, Buxton F. Nitrogen, carbon, and pH regulation of extracellular acidic proteases of Aspergillus niger. Curr Genet. 1994 Sep;26(3):238–244. [PubMed]
  • Johnstone IL, Hughes SG, Clutterbuck AJ. Cloning an Aspergillus nidulans developmental gene by transformation. EMBO J. 1985 May;4(5):1307–1311. [PMC free article] [PubMed]
  • Kozak M. Structural features in eukaryotic mRNAs that modulate the initiation of translation. J Biol Chem. 1991 Oct 25;266(30):19867–19870. [PubMed]
  • Kudla B, Caddick MX, Langdon T, Martinez-Rossi NM, Bennett CF, Sibley S, Davies RW, Arst HN., Jr The regulatory gene areA mediating nitrogen metabolite repression in Aspergillus nidulans. Mutations affecting specificity of gene activation alter a loop residue of a putative zinc finger. EMBO J. 1990 May;9(5):1355–1364. [PMC free article] [PubMed]
  • Kulmburg P, Mathieu M, Dowzer C, Kelly J, Felenbok B. Specific binding sites in the alcR and alcA promoters of the ethanol regulon for the CREA repressor mediating carbon catabolite repression in Aspergillus nidulans. Mol Microbiol. 1993 Mar;7(6):847–857. [PubMed]
  • Licht JD, Hanna-Rose W, Reddy JC, English MA, Ro M, Grossel M, Shaknovich R, Hansen U. Mapping and mutagenesis of the amino-terminal transcriptional repression domain of the Drosophila Krüppel protein. Mol Cell Biol. 1994 Jun;14(6):4057–4066. [PMC free article] [PubMed]
  • MacRae WD, Buxton FP, Sibley S, Garven S, Gwynne DI, Davies RW, Arst HN., Jr A phosphate-repressible acid phosphatase gene from Aspergillus niger: its cloning, sequencing and transcriptional analysis. Gene. 1988 Nov 30;71(2):339–348. [PubMed]
  • Maxam AM, Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. [PubMed]
  • McCully KS, Forbes E. The use of p-fluorophenylalanine with 'master strains' of Aspergillus nidulans for assigning genes to linkage groups. Genet Res. 1965 Nov;6(3):352–359. [PubMed]
  • Osmani SA, Pu RT, Morris NR. Mitotic induction and maintenance by overexpression of a G2-specific gene that encodes a potential protein kinase. Cell. 1988 Apr 22;53(2):237–244. [PubMed]
  • Pavletich NP, Pabo CO. Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A. Science. 1991 May 10;252(5007):809–817. [PubMed]
  • Pavletich NP, Pabo CO. Crystal structure of a five-finger GLI-DNA complex: new perspectives on zinc fingers. Science. 1993 Sep 24;261(5129):1701–1707. [PubMed]
  • Pérez-Esteban B, Orejas M, Gómez-Pardo E, Peñalva MA. Molecular characterization of a fungal secondary metabolism promoter: transcription of the Aspergillus nidulans isopenicillin N synthetase gene is modulated by upstream negative elements. Mol Microbiol. 1993 Aug;9(4):881–895. [PubMed]
  • Pinto I, Na JG, Sherman F, Hampsey M. cis- and trans-acting suppressors of a translation initiation defect at the cyc1 locus of Saccharomyces cerevisiae. Genetics. 1992 Sep;132(1):97–112. [PMC free article] [PubMed]
  • Rossi A, Arst HN., Jr Mutants of Aspergillus nidulans able to grow at extremely acidic pH acidify the medium less than wild type when grown at more moderate pH. FEMS Microbiol Lett. 1990 Jan 1;54(1-3):51–53. [PubMed]
  • Shah AJ, Tilburn J, Adlard MW, Arst HN., Jr pH regulation of penicillin production in Aspergillus nidulans. FEMS Microbiol Lett. 1991 Jan 15;61(2-3):209–212. [PubMed]
  • Su SS, Mitchell AP. Molecular characterization of the yeast meiotic regulatory gene RIM1. Nucleic Acids Res. 1993 Aug 11;21(16):3789–3797. [PMC free article] [PubMed]
  • Suárez T, Oestreicher N, Peñalva MA, Scazzocchio C. Molecular cloning of the uaY regulatory gene of Aspergillus nidulans reveals a favoured region for DNA insertions. Mol Gen Genet. 1991 Dec;230(3):369–375. [PubMed]
  • Suzuki M. SPXX, a frequent sequence motif in gene regulatory proteins. J Mol Biol. 1989 May 5;207(1):61–84. [PubMed]
  • Suzuki M, Gerstein M, Yagi N. Stereochemical basis of DNA recognition by Zn fingers. Nucleic Acids Res. 1994 Aug 25;22(16):3397–3405. [PMC free article] [PubMed]
  • Tang CM, Cohen J, Holden DW. An Aspergillus fumigatus alkaline protease mutant constructed by gene disruption is deficient in extracellular elastase activity. Mol Microbiol. 1992 Jun;6(12):1663–1671. [PubMed]
  • Tilburn J, Scazzocchio C, Taylor GG, Zabicky-Zissman JH, Lockington RA, Davies RW. Transformation by integration in Aspergillus nidulans. Gene. 1983 Dec;26(2-3):205–221. [PubMed]
  • Tilburn J, Roussel F, Scazzocchio C. Insertional inactivation and cloning of the wA gene of Aspergillus nidulans. Genetics. 1990 Sep;126(1):81–90. [PMC free article] [PubMed]
  • Tjian R, Maniatis T. Transcriptional activation: a complex puzzle with few easy pieces. Cell. 1994 Apr 8;77(1):5–8. [PubMed]
  • Tzamarias D, Struhl K. Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex. Nature. 1994 Jun 30;369(6483):758–761. [PubMed]
  • Ullah AH, Mullaney EM, Dischinger HC., Jr The complete primary structure elucidation of Aspergillus ficuum (niger), pH 6.0, optimum acid phosphatase by Edman degradation. Biochem Biophys Res Commun. 1994 Aug 30;203(1):182–189. [PubMed]
  • Wahle E, Keller W. The biochemistry of 3'-end cleavage and polyadenylation of messenger RNA precursors. Annu Rev Biochem. 1992;61:419–440. [PubMed]
  • Walsh PS, Metzger DA, Higuchi R. Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material. Biotechniques. 1991 Apr;10(4):506–513. [PubMed]
  • Zarkower D, Hodgkin J. Molecular analysis of the C. elegans sex-determining gene tra-1: a gene encoding two zinc finger proteins. Cell. 1992 Jul 24;70(2):237–249. [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links
  • Taxonomy
    Related taxonomy entry
  • Taxonomy Tree
    Taxonomy Tree

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...