The UPC2 Promoter in Candida albicans Contains Two cis -Acting Elements That Bind Directly to Upc2p, Resulting in Transcriptional Autoregulation

Hoot, Samantha J.; Brown, Ryan P.; Oliver, Brian G.; White, Theodore C.

doi:10.1128/ec.00130-10

Cited by 25Fungal and yeast genetics researchAntifungal resistance and susceptibilityGenomics and Chromatin Dynamics

The UPC2 Promoter in Candida albicans Contains Two cis -Acting Elements That Bind Directly to Upc2p, Resulting in Transcriptional Autoregulation

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Hoot, Samantha J., Brown, Ryan P., Oliver, Brian G., White, Theodore C.·2010·Eukaryotic Cell

DOI 10.1128/ec.00130-10PMC PMC2937341

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Abstract

In Candida albicans , ergosterol biosynthetic genes, including ERG11 , which encodes the target of azole antifungal drugs, are regulated by the transcriptional regulator Upc2p. To initially characterize the promoter of the UPC2 gene, 5′ rapid amplification of cDNA ends was used to identify two transcriptional initiation sites upstream of the ATG codon. The regions within the UPC2 promoter required for azole regulation of the UPC2 promoter were then identified using nested deletions fused to a luciferase reporter which were tested for azole inducibility in wild-type (WT) and upc2 Δ /upc2 Δ strains. Two distinct regions important for azole induction were identified: a Upc2p-dependent region (UDR) between bp −450 and −350 upstream of the ATG codon and a Upc2p-independent region (UIR) between bp −350 and −250 upstream of the ATG codon. Within the UDR, loss or mutation of the sterol response element (SRE), so named because of homology to the Saccharomyces cerevisiae Upc2p binding site, resulted in a decrease in both basal and induced expression in the WT strain but did not affect azole inducibility in the upc2 Δ/ upc2 Δ deletion strain. Gel shift analyses using the DNA binding domain of Upc2p confirmed binding of the protein to two SRE-related sequences within the UPC2 promoter, with strongest binding to the UDR SRE. Detailed gel shift analyses of the UDR SRE shows that Upc2p binds to a bipartite element within the UPC2 promoter, including the previously identified SRE and a new, adjacent element, the short direct repeat (SDR), with partial homology to the SRE.

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In response to azoles, Upc2p has the ability of transcriptional self-regulation.
“In response to azoles, Upc2p has the ability of transcriptional self-regulation.”
From The synthesis, regulation, and functions of sterols inCandida albicans: Well-known but still lots to learn (2016) · cites this paper as [57]

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cis -Acting Elements within the Candida albicans ERG11 Promoter Mediate the Azole Response through Transcription Factor Upc2p
Oliver, B. G., Song, J. L., Choiniere, J. H., & White, T. C. (2007) · Eukaryotic Cell · doi:10.1128/ec.00331-06 · Cited by 53 · see citing works
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Candida albicans UPC2 is transcriptionally induced in response to antifungal drugs and anaerobicity through Upc2p-dependent and -independent mechanisms
Hoot, S. J., Oliver, B. G. G., & White, T. C. (2008) · Microbiology · doi:10.1099/mic.0.2008/017475-0 · Cited by 39 · see citing works
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Candida albicans UPC2 is transcriptionally induced in response to antifungal drugs and anaerobicity through Upc2p-dependent and -independent mechanisms
Hoot, S. J., Oliver, B. G. G., & White, T. C. (2008) · Microbiology · doi:10.1099/mic.0.2008/017475-0 · Cited by 39 · see citing works
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Genomewide Location Analysis of Candida albicans Upc2p, a Regulator of Sterol Metabolism and Azole Drug Resistance
Znaidi, S., Weber, S., Zin Al-Abdin, O., Bomme, P., Saidane, S., Drouin, S., Lemieux, S., De Deken, X., Robert, F., & Raymond, M. (2008) · Eukaryotic Cell · doi:10.1128/ec.00070-08 · Cited by 119 · see citing works
cis -Acting Elements within the Candida albicans ERG11 Promoter Mediate the Azole Response through Transcription Factor Upc2p
Oliver, B. G., Song, J. L., Choiniere, J. H., & White, T. C. (2007) · Eukaryotic Cell · doi:10.1128/ec.00331-06 · Cited by 53 · see citing works
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Candida albicans Zinc Cluster Protein Upc2p Confers Resistance to Antifungal Drugs and Is an Activator of Ergosterol Biosynthetic Genes
MacPherson, S., Akache, B., Weber, S., De Deken, X., Raymond, M., & Turcotte, B. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.5.1745-1752.2005 · Cited by 238 · see citing works
Role of Candida albicans Transcription Factor Upc2p in Drug Resistance and Sterol Metabolism
Silver, P. M., Oliver, B. G., & White, T. C. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.6.1391-1397.2004 · Cited by 216 · see citing works
Self-citation

Authors: Hoot, S. J., Brown, R. P., Oliver, B. G., & White, T. C.
Affiliations: Center for Infectious Disease Research (US)
Corresponding author: White, Theodore C.
ORCID: Oliver, Brian G.
White, Theodore C.
Venue: Eukaryotic Cell
Publisher: American Society for Microbiology
Published: 2010-09
Volume: 9
Issue: 9
Pages: 1354-1362
ISSN: 1535-9778 (ISSN-L)
1535-9786
DOI: 10.1128/ec.00130-10
PMC: PMC2937341
OpenAlex: W2108846692
Cited by: 25
References: 21
Citations by year: 2025: 1 · 2024: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 1 · 2014: 1 · 2013: 4
FWCI: 1.04
Type: journal article
Language: en
Open access: diamond
doi.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Eukaryotic Cell (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Dental and Craniofacial Research (R01DE011367, R01DE017078, R01 DE-11367, R01 DE 14161, R01DE014161)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: Candida albicans, sterol response element, cis-regulatory elements, transcriptional autoregulation, ERG11, ergosterol biosynthesis, transcription start sites
MeSH terms: Base Sequence, Candida albicans, Fungal Proteins, Molecular Sequence Data, Promoter Regions, Genetic, Protein Binding, Transcription, Genetic, Trans-Activators, Gene Expression Regulation, Fungal, Response Elements

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The UPC2 Promoter in Candida albicans Contains Two cis -Acting Elements That Bind Directly to Upc2p, Resulting in Transcriptional Autoregulation

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