Global roles of Ssn6 in Tup1- and Nrg1-dependent gene regulation in the fungal pathogen, Candida albicans

Susana Garcia-Sanchez, Abigail L. Mavor, Claire L. Russell, Silvia Argimon, Paul Dennison, Brice Patrick Enjalbert, Alistair J. P. Brown

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Abstract

In budding yeast, Tup1 and Ssn6/Cyc8 form a corepressor that regulates a large number of genes. This Tup1-Ssn6 corepressor appears to be conserved from yeast to man. In the pathogenic fungus Candida albicans, Tup1 regulates cellular morphogenesis, phenotypic switching, and metabolism, but the role of Ssn6 remains unclear. We show that there are clear differences in the morphological and invasive phenotypes of C. albicans ssn6 and tup1 mutants. Unlike Tup1, Ssn6 depletion promoted morphological events reminiscent of phenotypic switching rather than filamentous growth. Transcript profiling revealed minimal overlap between the Ssn6 and Tup1 regulons. Hypha-specific genes, which are repressed by Tup1 and Nrg1, were not derepressed in ssn6 cells under the conditions studied. In contrast, the phase specific gene WH11 was derepressed in ssn6 cells, but not in tup1 or nrg1 cells. Hence Ssn6 and Tup1 play distinct roles in C. albicans. Nevertheless, both Ssn6 and Tup1 were required for the Nrg1-mediated repression of an artificial NRE promoter, and lexA-Nrg1 mediated repression in the C. albicans one-hybrid system. These observations are explained in models that are generally consistent with the Tup1-Ssn6 paradigm in budding yeast.

Original languageEnglish
Pages (from-to)2913-2925
Number of pages12
JournalMolecular Biology of the Cell
Volume16
Issue number6
Early online date6 Apr 2005
DOIs
Publication statusPublished - 1 Jun 2005

Keywords

  • transcriptional co-repressor
  • amino-acid starvation
  • saccharomyces-cerevisiae
  • hyphal morphogenesis
  • protein complex
  • in-vivo
  • yeast
  • TUP1
  • expression
  • SSN6-TUP1

Cite this

Global roles of Ssn6 in Tup1- and Nrg1-dependent gene regulation in the fungal pathogen, Candida albicans. / Garcia-Sanchez, Susana; Mavor, Abigail L. ; Russell, Claire L.; Argimon, Silvia; Dennison, Paul; Enjalbert, Brice Patrick; Brown, Alistair J. P.

In: Molecular Biology of the Cell, Vol. 16, No. 6, 01.06.2005, p. 2913-2925.

Research output: Contribution to journalArticle

Garcia-Sanchez, S, Mavor, AL, Russell, CL, Argimon, S, Dennison, P, Enjalbert, BP & Brown, AJP 2005, 'Global roles of Ssn6 in Tup1- and Nrg1-dependent gene regulation in the fungal pathogen, Candida albicans', Molecular Biology of the Cell, vol. 16, no. 6, pp. 2913-2925. https://doi.org/10.1091/MBC.E05-01-0071
Garcia-Sanchez, Susana ; Mavor, Abigail L. ; Russell, Claire L. ; Argimon, Silvia ; Dennison, Paul ; Enjalbert, Brice Patrick ; Brown, Alistair J. P. / Global roles of Ssn6 in Tup1- and Nrg1-dependent gene regulation in the fungal pathogen, Candida albicans. In: Molecular Biology of the Cell. 2005 ; Vol. 16, No. 6. pp. 2913-2925.
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abstract = "In budding yeast, Tup1 and Ssn6/Cyc8 form a corepressor that regulates a large number of genes. This Tup1-Ssn6 corepressor appears to be conserved from yeast to man. In the pathogenic fungus Candida albicans, Tup1 regulates cellular morphogenesis, phenotypic switching, and metabolism, but the role of Ssn6 remains unclear. We show that there are clear differences in the morphological and invasive phenotypes of C. albicans ssn6 and tup1 mutants. Unlike Tup1, Ssn6 depletion promoted morphological events reminiscent of phenotypic switching rather than filamentous growth. Transcript profiling revealed minimal overlap between the Ssn6 and Tup1 regulons. Hypha-specific genes, which are repressed by Tup1 and Nrg1, were not derepressed in ssn6 cells under the conditions studied. In contrast, the phase specific gene WH11 was derepressed in ssn6 cells, but not in tup1 or nrg1 cells. Hence Ssn6 and Tup1 play distinct roles in C. albicans. Nevertheless, both Ssn6 and Tup1 were required for the Nrg1-mediated repression of an artificial NRE promoter, and lexA-Nrg1 mediated repression in the C. albicans one-hybrid system. These observations are explained in models that are generally consistent with the Tup1-Ssn6 paradigm in budding yeast.",
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AU - Argimon, Silvia

AU - Dennison, Paul

AU - Enjalbert, Brice Patrick

AU - Brown, Alistair J. P.

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AB - In budding yeast, Tup1 and Ssn6/Cyc8 form a corepressor that regulates a large number of genes. This Tup1-Ssn6 corepressor appears to be conserved from yeast to man. In the pathogenic fungus Candida albicans, Tup1 regulates cellular morphogenesis, phenotypic switching, and metabolism, but the role of Ssn6 remains unclear. We show that there are clear differences in the morphological and invasive phenotypes of C. albicans ssn6 and tup1 mutants. Unlike Tup1, Ssn6 depletion promoted morphological events reminiscent of phenotypic switching rather than filamentous growth. Transcript profiling revealed minimal overlap between the Ssn6 and Tup1 regulons. Hypha-specific genes, which are repressed by Tup1 and Nrg1, were not derepressed in ssn6 cells under the conditions studied. In contrast, the phase specific gene WH11 was derepressed in ssn6 cells, but not in tup1 or nrg1 cells. Hence Ssn6 and Tup1 play distinct roles in C. albicans. Nevertheless, both Ssn6 and Tup1 were required for the Nrg1-mediated repression of an artificial NRE promoter, and lexA-Nrg1 mediated repression in the C. albicans one-hybrid system. These observations are explained in models that are generally consistent with the Tup1-Ssn6 paradigm in budding yeast.

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KW - TUP1

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