Genome-wide expression and location analyses of the Candida albicans Tac1p regulon

Teresa T. Liu, Sadri Znaidi, Katherine S. Barker, Lijing Xu, Ramin Homayouni, Saloua Saidane, Joachim Morschhäuser, André Nantel, Martine Raymond, Phillip Rogers

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Abstract

A major mechanism of azole resistance in Candida albicans is overexpression of the genes encoding the ATP binding cassette transporters Cdr1p and Cdr2p due to gain-of-function mutations in Tac1p, a transcription factor of the zinc cluster family. To identify the Tac1p regulon, we analyzed four matched sets of clinical isolates representing the development of CDR1- and CDR2-mediated azole resistance by using gene expression profiling. We identified 31 genes that were consistently up-regulated with CDR1 and CDR2, including TAC1 itself, and 12 consistently down-regulated genes. When a resistant strain deleted for TAC1 was examined similarly, expression of almost all of these genes returned to levels similar to those in the matched azole-susceptible isolate. Using genome-wide location (ChIP-chip) analysis (a procedure combining chromatin immunoprecipitation with hybridization to DNA intergenic microarrays), we found 37 genes whose promoters were bound by Tac1p in vivo, including CDR1 and CDR2. Sequence analysis identified nine new genes whose promoters contain the previously reported Tac1p drug-responsive element (CGGN4CGG), including TAC1. In total, there were eight genes whose expression was modulated in the four azole-resistant clinical isolates in a TAC1-dependent manner and whose promoters were bound by Tac1p, qualifying them as direct Tac1p targets: CDR1, CDR2, GPX1 (putative glutathione peroxidase), LCB4 (putative sphingosine kinase), RTA3 (putative phospholipid flippase), and orf19.1887 (putative lipase), as well as IFU5 and orf19.4898 of unknown function. Our results show that Tac1p binds under nonactivating conditions to the promoters of its targets, including to its own promoter. They also suggest roles for Tac1p in regulating lipid metabolism (mobilization and trafficking) and oxidative stress response in C. albicans.

Original languageEnglish (US)
Pages (from-to)2122-2138
Number of pages17
JournalEukaryotic Cell
Volume6
Issue number11
DOIs
StatePublished - Nov 1 2007

Fingerprint

Regulon
regulon
azoles
Candida albicans
Azoles
promoter regions
Genome
genome
Genes
genes
sphingosine
gene expression
Lipid Mobilization
gene overexpression
ABC transporters
intergenic DNA
ATP-Binding Cassette Transporters
glutathione peroxidase
lipid metabolism
Chromatin Immunoprecipitation

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

Cite this

Liu, T. T., Znaidi, S., Barker, K. S., Xu, L., Homayouni, R., Saidane, S., ... Rogers, P. (2007). Genome-wide expression and location analyses of the Candida albicans Tac1p regulon. Eukaryotic Cell, 6(11), 2122-2138. https://doi.org/10.1128/EC.00327-07

Genome-wide expression and location analyses of the Candida albicans Tac1p regulon. / Liu, Teresa T.; Znaidi, Sadri; Barker, Katherine S.; Xu, Lijing; Homayouni, Ramin; Saidane, Saloua; Morschhäuser, Joachim; Nantel, André; Raymond, Martine; Rogers, Phillip.

In: Eukaryotic Cell, Vol. 6, No. 11, 01.11.2007, p. 2122-2138.

Research output: Contribution to journalArticle

Liu, TT, Znaidi, S, Barker, KS, Xu, L, Homayouni, R, Saidane, S, Morschhäuser, J, Nantel, A, Raymond, M & Rogers, P 2007, 'Genome-wide expression and location analyses of the Candida albicans Tac1p regulon', Eukaryotic Cell, vol. 6, no. 11, pp. 2122-2138. https://doi.org/10.1128/EC.00327-07
Liu TT, Znaidi S, Barker KS, Xu L, Homayouni R, Saidane S et al. Genome-wide expression and location analyses of the Candida albicans Tac1p regulon. Eukaryotic Cell. 2007 Nov 1;6(11):2122-2138. https://doi.org/10.1128/EC.00327-07
Liu, Teresa T. ; Znaidi, Sadri ; Barker, Katherine S. ; Xu, Lijing ; Homayouni, Ramin ; Saidane, Saloua ; Morschhäuser, Joachim ; Nantel, André ; Raymond, Martine ; Rogers, Phillip. / Genome-wide expression and location analyses of the Candida albicans Tac1p regulon. In: Eukaryotic Cell. 2007 ; Vol. 6, No. 11. pp. 2122-2138.
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