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Vol. 16, Issue 6, 2913-2925, June 2005

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Global Roles of Ssn6 in Tup1- and Nrg1-dependent Gene Regulation in the Fungal Pathogen, Candida albicans

Susana García-Sánchez ^*, Abigail L. Mavor , Claire L. Russell, Silvia Argimon, Paul Dennison , Brice Enjalbert, and Alistair J.P. Brown

Aberdeen Fungal Group, School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, United Kingdom

Submitted January 26, 2005; Revised March 25, 2005; Accepted March 30, 2005
Monitoring Editor: Thomas Fox

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.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

^* Present address: Department of Biotechnology, Basque Institute for Agricultural Research and Development, PO Box 46, 01080 Vitoria-Gasteiz, Spain

Present address: Robert Koch-Institut, Nordufer 20, D-13353 Berlin, Germany

Present address: Centre for Biomolecular Sciences, University of St. Andrews, St. Andrews KY16 9ST, United Kingdom

Address correspondence to: Alistair J.P. Brown (Al.Brown{at}abdn.ac.uk).

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