This Article Full Text Full Text (PDF) Other Versions of this Article: EC.00331-06v1 6/12/2231    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Google Scholar Articles by Oliver, B. G. Articles by White, T. C. PubMed PubMed Citation Articles by Oliver, B. G. Articles by White, T. C.

cis-Acting Elements within the Candida albicans ERG11 Promoter Mediate the Azole Response through Transcription Factor Upc2p

Brian G. Oliver, Jia L. Song,^, Jake H. Choiniere, and Theodore C. White^*

Department of Pathobiology, School of Public Health and Community Medicine, University of Washington, and Seattle Biomedical Research Institute, Seattle, Washington

Received 16 October 2006/ Accepted 2 October 2007

The azole antifungal drugs are used to treat infections caused by Candida albicans and other fungi. These drugs interfere with the biosynthesis of ergosterol, the major sterol in fungal cells, by inhibiting an ergosterol biosynthetic enzyme, lanosterol 14 -demethylase, encoded by the ERG11 gene. In vitro, these drugs as well as other ergosterol biosynthesis inhibitors increase ERG11 mRNA expression by activation of the ERG11 promoter. The signal for this activation most likely is the depletion of ergosterol, the end product of the pathway. To identify cis-acting regulatory elements that mediate this activation, ERG11 promoter fragments have been fused to the luciferase reporter gene from Renilla reniformis. Promoter deletions and linker scan mutations localized the region important for azole induction to a segment from bp –224 to –251 upstream of the start codon, specifically two 7-bp sequences separated by 13 bp. These sequences form an imperfect inverted repeat. The region is recognized by the transcription factor Upc2p and functions as an enhancer of transcription, as it can be placed upstream of a heterologous promoter in either direction, resulting in the azole induction of that promoter. The promoter constructs are not azole inducible in the upc2/upc2 homozygous deletion, demonstrating that Upc2p controls the azole induction of ERG11. These results identify an azole-responsive enhancer element (ARE) in the ERG11 promoter that is controlled by the Upc2p transcription factor. No other ARE is present in the promoter. Thus, this ARE and Upc2p are necessary and sufficient for azole induction of ERG11.

Published ahead of print on 19 October 2007.

B.G.O. and J.L.S. contributed equally to this work.

Present address: Brown University, Providence, RI.

Present address: Western University of Health Sciences, Pomona, CA.

This article has been cited by other articles:

• Znaidi, S., Weber, S., Zin Al-Abdin, O., Bomme, P., Saidane, S., Drouin, S., Lemieux, S., De Deken, X., Robert, F., Raymond, M. (2008). Genomewide Location Analysis of Candida albicans Upc2p, a Regulator of Sterol Metabolism and Azole Drug Resistance. Eukaryot Cell 7: 836-847 [Abstract] [Full Text]