Previous Article | Next Article 
Eukaryotic Cell, June 2009, p. 806-820, Vol. 8, No. 6
1535-9778/09/$08.00+0 doi:10.1128/EC.00002-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Identification of the Candida albicans Cap1p Regulon 
,
Sadri Znaidi,1
Katherine S. Barker,2,3
Sandra Weber,1
Anne-Marie Alarco,1,
Teresa T. Liu,2,3
Geneviève Boucher,1
P. David Rogers,2,3 and
Martine Raymond1,4*
Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec, Canada H3T 1J4,1 Departments of Clinical Pharmacy, Pharmaceutical Sciences, Molecular Sciences, and Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee 38163,2 Children's Foundation Research Center of Memphis, Le Bonheur Children's Medical Center, Memphis, Tennessee 38103,3 Department of Biochemistry, Université de Montréal, Montreal, Quebec, Canada H3T 1J44
Received 2 January 2009/ Accepted 14 April 2009
Cap1p, a transcription factor of the basic region leucine zipper family, regulates the oxidative stress response (OSR) in Candida albicans. Alteration of its C-terminal cysteine-rich domain (CRD) results in Cap1p nuclear retention and transcriptional activation. To better understand the function of Cap1p in C. albicans, we used genome-wide location profiling (chromatin immunoprecipitation-on-chip) to identify its transcriptional targets in vivo. A triple-hemagglutinin (HA3) epitope was introduced at the C terminus of wild-type Cap1p (Cap1p-HA3) or hyperactive Cap1p with an altered CRD (Cap1p-CSE-HA3). Location profiling using whole-genome oligonucleotide tiling microarrays identified 89 targets bound by Cap1p-HA3 or Cap1p-CSE-HA3 (the binding ratio was at least twofold; P 
0.01). Strikingly, Cap1p binding was detected not only at the promoter region of its target genes but also at their 3' ends and within their open reading frames, suggesting that Cap1p may associate with the transcriptional or chromatin remodeling machinery to exert its activity. Overrepresented functional groups of the Cap1p targets (P 0.02) included 11 genes involved in the OSR (CAP1, GLR1, TRX1, SOD1, CAT1, and others), 13 genes involved in response to drugs (PDR16, MDR1, FLU1, YCF1, FCR1, and others), 4 genes involved in phospholipid transport (PDR16, GIT1, RTA2, and orf19.932), and 3 genes involved in the regulation of nitrogen utilization (GST3, orf19.2693, and orf19.3121), suggesting that Cap1p has other cellular functions in addition to the OSR. Bioinformatic analyses of the bound sequences suggest that Cap1p recognizes the DNA motif 5'-MTKASTMA. Finally, transcriptome analyses showed that increased expression generally accompanies Cap1p binding at its targets, indicating that Cap1p functions as a transcriptional activator.
* Corresponding author. Mailing address: Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7. Phone: (514) 343-6746. Fax: (514) 343-6843. E-mail: martine.raymond{at}umontreal.ca
Published ahead of print on 24 April 2009.
Supplemental material for this article may be found at http://ec.asm.org/.
Present address: Génome Québec, Montréal, Quebec, Canada H3B 1S6.
Eukaryotic Cell, June 2009, p. 806-820, Vol. 8, No. 6
1535-9778/09/$08.00+0 doi:10.1128/EC.00002-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»