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Genome-wide Analysis of Gene Expression Regulated by the Calcineurin/Crz1p Signaling Pathway in Saccharomyces cerevisiae
Open accessAbstract
In Saccharomyces cerevisiae, the Ca(2+)/calmodulin-dependent protein phosphatase, calcineurin, is activated by specific environmental conditions, including exposure to Ca(2+) and Na(+), and induces gene expression by regulating the Crz1p/Tcn1p transcription factor. We used DNA microarrays to perform a comprehensive analysis of calcineurin/Crz1p-dependent gene expression following addition of Ca(2+) (200 mm) or Na(+) (0.8 m) to yeast. 163 genes exhibited increased expression that was reduced 50% or more by calcineurin inhibition. These calcineurin-dependent genes function in signaling pathways, ion/small molecule transport, cell wall maintenance, and vesicular transport, and include many open reading frames of previously unknown function. Three distinct gene classes were defined as follows: 28 genes displayed calcineurin-dependent induction in response to Ca(2+) and Na(+), 125 showed calcineurin-dependent expression following Ca(2+) but not Na(+) addition, and 10 were regulated by calcineurin in response to Na(+) but not Ca(2+). Analysis of crz1Delta cells established Crz1p as the major effector of calcineurin-regulated gene expression in yeast. We identified the Crz1p-binding site as 5'-GNGGC(G/T)CA-3' by in vitro site selection. A similar sequence, 5'-GAGGCTG-3', was identified as a common sequence motif in the upstream regions of calcineurin/ Crz1p-dependent genes. This finding is consistent with direct regulation of these genes by Crz1p.
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“Crz1 is the key mediator of calcineurin-dependent transcriptional responses [37],[41] and is implicated in tolerance to azoles in both S. cerevisiae and C. albicans [20],[42].”
From Hsp90 Governs Echinocandin Resistance in the Pathogenic Yeast Candida albicans via Calcineurin (2009) · cites this paper as [41]
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“which, in genome-wide expression studies using DNA microarrays, has been identified as the main effector mediating all known calcineurin-dependent transcriptional changes in S. cerevisiae (Yoshimoto et al. 2002).”
From Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor (2005) · cites this paper as Yoshimoto et al. 2002
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Metadata
- Authors
- Yoshimoto, H., Saltsman, K., Gasch, A. P., Li, H. X., Ogawa, N., Botstein, D., Brown, P. O., & Cyert, M. S.
- Affiliations
- Stanford University (US)
- Stanford Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Cyert, Martha S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 277
- Issue
- 34
- Pages
- 31079-31088
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2126241360
- Cited by
- 404
- References
- 45
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 9 · 2023: 5 · 2022: 12 · 2021: 11 · 2020: 15 · 2019: 4 · 2018: 10 · 2017: 15 · 2016: 19 · 2015: 11 · 2014: 19 · 2013: 23 · 2012: 13
- FWCI
- 7.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hg000983-06)
- National Human Genome Research Institute (HG-00983)
- National Cancer Institute (CA 77097, R01CA077097)
- National Institute of General Medical Sciences (GM-48728, GM46406)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- calcineurin, transcriptional regulation, gene expression, Saccharomyces cerevisiae, calcium signaling, transcription factor binding motifs, calcineurin inhibition, cell wall maintenance, vesicle trafficking, ion transport
- MeSH terms
- Binding Sites, Calcium, DNA-Binding Proteins, Promoter Regions, Genetic, Saccharomyces cerevisiae, Sodium, Transcription Factors, Trans-Activators, Gene Expression Regulation, Fungal, DNA Methylation, Calcineurin, Response Elements, Oligonucleotide Array Sequence Analysis, Saccharomyces cerevisiae Proteins
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