Genome-wide Analysis of Gene Expression Regulated by the Calcineurin/Crz1p Signaling Pathway in Saccharomyces cerevisiae

Yoshimoto, Hiroyuki; Saltsman, Kirstie; Gasch, Audrey P.; Li, Hong Xia; Ogawa, Nobuo; Botstein, David; Brown, Patrick O.; Cyert, Martha S.

doi:10.1074/jbc.m202718200

Cited by 404Fungal and yeast genetics researchSignaling Pathways in DiseaseBacterial Genetics and Biotechnology

Genome-wide Analysis of Gene Expression Regulated by the Calcineurin/Crz1p Signaling Pathway in Saccharomyces cerevisiae

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Yoshimoto, Hiroyuki, Saltsman, Kirstie, Gasch, Audrey P., Li, Hong Xia, Ogawa, Nobuo, Botstein, David, Brown, Patrick O., Cyert, Martha S.·2002·Journal of Biological Chemistry

DOI 10.1074/jbc.m202718200

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Abstract

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 and is implicated in tolerance to azoles in both S. cerevisiae and C. albicans.
“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]
ScCrz1 is the main effector mediating all known calcineurin-dependent transcriptional changes in S. cerevisiae.
“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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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.
ORCID: Yoshimoto, Hiroyuki
Gasch, Audrey P.
Botstein, David
Brown, Patrick O.
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)
DOI: 10.1074/jbc.m202718200
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6663 d)
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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Genome-wide Analysis of Gene Expression Regulated by the Calcineurin/Crz1p Signaling Pathway in Saccharomyces cerevisiae

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