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PMID: 11532939 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

NRG1, a repressor of filamentous growth in C.albicans, is down-regulated during filament induction.

The EMBO journal ·Vol. 20 ·No. 17 ·2001-09-03 ·Pages 4753-61

Braun BR, Kadosh D, Johnson AD

Abstract

In response to a variety of external signals, the fungal pathogen Candida albicans undergoes a transition between ellipsoidal single cells (blastospores) and filaments composed of elongated cells attached end-to-end. Here we identify a DNA-binding protein, Nrg1, that represses filamentous growth in Candida probably by acting through the co-repressor Tup1. nrg1 mutant cells are predominantly filamentous under non-filament-inducing conditions and their colony morphology resembles that of tup1 mutants. We also identify two filament-specific genes, ECE1 and HWP1, whose transcription is repressed by Nrg1 under non-inducing conditions. These genes constitute a subset of those under Tup1 control, providing further evidence that Nrg1 acts by recruiting Tup1 to target genes. We show that growth in serum at 37 degrees C, a potent inducer of filamentous growth, causes a reduction of NRG1 mRNA, suggesting that filamentous growth is induced by the down-regulation of NRG1. Consistent with this idea, expression of NRG1 from a non-regulated promoter partially blocks the induction of filamentous growth.

MeSH Terms
Amino Acid Sequence Binding Sites Candida/genetics,growth & development,pathogenicity Culture Media DNA-Binding Proteins Fungal Proteins/genetics,metabolism Gene Deletion Gene Expression Regulation, Fungal Membrane Glycoproteins/genetics Molecular Sequence Data Promoter Regions, Genetic Repressor Proteins/chemistry,genetics,metabolism Saccharomyces cerevisiae/genetics,growth & development Saccharomyces cerevisiae Proteins Sequence Alignment Sequence Homology, Amino Acid Transcription, Genetic Virulence Zinc Fingers
Chemicals
Culture Media DNA-Binding Proteins ECE1 protein, Candida albicans Fungal Proteins HWP1 protein, Candida albicans Membrane Glycoproteins NRG1 protein, S cerevisiae Repressor Proteins Saccharomyces cerevisiae Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Braun B R
Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143-0414, USA.
Kadosh D
Johnson A D
References (48)
48 references, click to expand
  1. The DNA binding protein Rfg1 is a repressor of filamentation in Candida albicans.
    Genetics. 2001 Apr;157(4):1503-12 PMID: 11290707
  2. The Tup1-Ssn6 general repressor is involved in repression of IME1 encoding a transcriptional activator of meiosis in Saccharomyces cerevisiae.
    Curr Genet. 1998 Apr;33(4):239-47 PMID: 9560430
  3. Repressors and upstream repressing sequences of the stress-regulated ENA1 gene in Saccharomyces cerevisiae: bZIP protein Sko1p confers HOG-dependent osmotic regulation.
    Mol Cell Biol. 1999 Jan;19(1):537-46 PMID: 9858577
  4. Identification and characterization of TUP1-regulated genes in Candida albicans.
    Genetics. 2000 Sep;156(1):31-44 PMID: 10978273
  5. Transcription factors in Candida albicans - environmental control of morphogenesis.
    Microbiology. 2000 Aug;146 ( Pt 8):1763-74 PMID: 10931884
  6. Nonfilamentous C. albicans mutants are avirulent.
    Cell. 1997 Sep 5;90(5):939-49 PMID: 9298905
  7. Pathogenesis of Candida infections.
    J Am Acad Dermatol. 1994 Sep;31(3 Pt 2):S2-5 PMID: 8077502
  8. Genomic sequencing.
    Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 PMID: 6326095
  9. The DNA replication and damage checkpoint pathways induce transcription by inhibition of the Crt1 repressor.
    Cell. 1998 Sep 4;94(5):595-605 PMID: 9741624
  10. Reduced virulence of HWP1-deficient mutants of Candida albicans and their interactions with host cells.
    Infect Immun. 2000 Apr;68(4):1997-2002 PMID: 10722594
  11. Repression by SSN6-TUP1 is directed by MIG1, a repressor/activator protein.
    Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3132-6 PMID: 7724528
  12. Candida pathogenesis: unravelling the threads of infection.
    Curr Biol. 1997 Nov 1;7(11):R691-4 PMID: 9382797
  13. Dimorphism and virulence in Candida albicans.
    Curr Opin Microbiol. 1998 Dec;1(6):687-92 PMID: 10066539
  14. Morphogenesis in Candida albicans.
    Crit Rev Microbiol. 1985;12(1):45-93 PMID: 3893894
  15. Snf1 protein kinase regulates phosphorylation of the Mig1 repressor in Saccharomyces cerevisiae.
    Mol Cell Biol. 1998 Nov;18(11):6273-80 PMID: 9774644
  16. The control of filamentous differentiation and virulence in fungi.
    Trends Cell Biol. 1998 Sep;8(9):348-53 PMID: 9728395
  17. Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi.
    EMBO J. 1997 Apr 15;16(8):1982-91 PMID: 9155024
  18. Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex.
    Nature. 1994 Jun 30;369(6483):758-61 PMID: 8008070
  19. Candida albicans: biology, genetics, and pathogenicity.
    Annu Rev Microbiol. 1985;39:579-614 PMID: 3904613
  20. Filamentous growth of Candida albicans in response to physical environmental cues and its regulation by the unique CZF1 gene.
    Mol Microbiol. 1999 Nov;34(4):651-62 PMID: 10564506
  21. Distinct TPR motifs of Cyc8 are involved in recruiting the Cyc8-Tup1 corepressor complex to differentially regulated promoters.
    Genes Dev. 1995 Apr 1;9(7):821-31 PMID: 7705659
  22. Regulatory networks controlling Candida albicans morphogenesis.
    Trends Microbiol. 1999 Aug;7(8):333-8 PMID: 10431207
  23. NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans.
    EMBO J. 2001 Sep 3;20(17):4742-52 PMID: 11532938
  24. Development of Streptococcus thermophilus lacZ as a reporter gene for Candida albicans.
    Microbiology. 2001 May;147(Pt 5):1189-95 PMID: 11320122
  25. Clinical aspects and pathogenesis of Candida infection.
    Trends Microbiol. 1998 Dec;6(12):468-70 PMID: 10036723
  26. Candida albicans hyphal formation and virulence: is there a clearly defined role?
    Trends Microbiol. 1998 Mar;6(3):92-4 PMID: 9582930
  27. Evolutionary origin of nonuniversal CUGSer codon in some Candida species as inferred from a molecular phylogeny.
    Genetics. 1995 Nov;141(3):903-7 PMID: 8582635
  28. TUP1, CPH1 and EFG1 make independent contributions to filamentation in candida albicans.
    Genetics. 2000 May;155(1):57-67 PMID: 10790384
  29. Nrg1 is a transcriptional repressor for glucose repression of STA1 gene expression in Saccharomyces cerevisiae.
    Mol Cell Biol. 1999 Mar;19(3):2044-50 PMID: 10022891
  30. Characterization of TUP1, a mediator of glucose repression in Saccharomyces cerevisiae.
    Mol Cell Biol. 1990 Dec;10(12):6500-11 PMID: 2247069
  31. Pleiotropic Mutations at the TUP1 Locus That Affect the Expression of Mating-Type-Dependent Functions in SACCHAROMYCES CEREVISIAE.
    Genetics. 1980 Apr;94(4):899-920 PMID: 17249022
  32. Developmental expression of a tandemly repeated, proline-and glutamine-rich amino acid motif on hyphal surfaces on Candida albicans.
    J Biol Chem. 1996 Mar 15;271(11):6298-305 PMID: 8626424
  33. Isogenic strain construction and gene mapping in Candida albicans.
    Genetics. 1993 Jul;134(3):717-28 PMID: 8349105
  34. Cloning and characterization of ECE1, a gene expressed in association with cell elongation of the dimorphic pathogen Candida albicans.
    Infect Immun. 1993 Sep;61(9):3648-55 PMID: 8359888
  35. RIM101-dependent and-independent pathways govern pH responses in Candida albicans.
    Mol Cell Biol. 2000 Feb;20(3):971-8 PMID: 10629054
  36. Effect of environmental pH on morphological development of Candida albicans is mediated via the PacC-related transcription factor encoded by PRR2.
    J Bacteriol. 1999 Dec;181(24):7524-30 PMID: 10601210
  37. Feasting, fasting and fermenting. Glucose sensing in yeast and other cells.
    Trends Genet. 1999 Jan;15(1):29-33 PMID: 10087931
  38. Candida albicans, the opportunist. A cellular and molecular perspective.
    J Am Podiatr Med Assoc. 1995 Feb;85(2):104-15 PMID: 7877106
  39. A model for the germ tube formation and mycelial growth form of Candida albicans.
    Sabouraudia. 1984;22(2):137-44 PMID: 6374934
  40. Turning genes off by Ssn6-Tup1: a conserved system of transcriptional repression in eukaryotes.
    Trends Biochem Sci. 2000 Jul;25(7):325-30 PMID: 10871883
  41. Regulated nuclear translocation of the Mig1 glucose repressor.
    Mol Biol Cell. 1997 Aug;8(8):1603-18 PMID: 9285828
  42. Mutational analysis of Rox1, a DNA-bending repressor of hypoxic genes in Saccharomyces cerevisiae.
    Mol Cell Biol. 1995 Nov;15(11):6109-17 PMID: 7565763
  43. Rfg1, a protein related to the Saccharomyces cerevisiae hypoxic regulator Rox1, controls filamentous growth and virulence in Candida albicans.
    Mol Cell Biol. 2001 Apr;21(7):2496-505 PMID: 11259598
  44. Characterization of three related glucose repressors and genes they regulate in Saccharomyces cerevisiae.
    Genetics. 1998 Dec;150(4):1377-91 PMID: 9832517
  45. Multiple elements and auto-repression regulate Rox1, a repressor of hypoxic genes in Saccharomyces cerevisiae.
    Genetics. 1995 Mar;139(3):1149-58 PMID: 7768429
  46. Ssn6-Tup1 is a general repressor of transcription in yeast.
    Cell. 1992 Feb 21;68(4):709-19 PMID: 1739976
  47. The Tup1-Cyc8 protein complex can shift from a transcriptional co-repressor to a transcriptional co-activator.
    J Biol Chem. 1999 Jan 1;274(1):205-10 PMID: 9867831
  48. Control of filament formation in Candida albicans by the transcriptional repressor TUP1.
    Science. 1997 Jul 4;277(5322):105-9 PMID: 9204892
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
2001-09-03
Pages
4753-61
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125265
Subset
IM
Grants
NIGMS NIH HHS · R01 GM037049 · United States
NIGMS NIH HHS · GM37049 · United States
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