Promoter sequences regulated by the calcineurin-activated transcription factor Crz1 in the yeast ENA1 gene
Abstract
In Saccharomyces cerevisiae the transcription of the ENA1 gene is modulated by multiple transduction pathways that respond to osmotic, ionic and nutrient stresses. We have investigated the molecular mechanisms involved in ENA1 induction by the calcium-calcineurin-activated transcription factor Crzl/Tcn1. We found in the ENA1 promoter a calcium-responsive, Crzl-dependent upstream activating region (UASENA1) located between -713 bp and 826 bp relative to the translation start. This region contains two separate control elements: the upstream element (5'-GAATGGCTG-3') between -813 and -821 binds Crzlp with lower affinity and mostly contributes to basal ENA1 expression, whereas the downstream element (5'-GGGTGGCTG-3') between 727 and 719 binds Crz1p with higher affinity and is a major determinant of the induction response to calcium.
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Crz1p binds to the CDRE sequence in FKS2 and ENA1 promoters and activates expression of calcineurin-responsive genes.
“To drive this transcriptional stress response, Crz1p binds to a cognate sequence called CDRE, already identified in FKS2 and ENA1 gene promoters, and activates the expression of calcineurin-responsive genes (Stathopoulos and Cyert 1997;Mendizabal et al. 2001).”
From Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor (2005) · cites this paper as Mendizabal et al. 2001
CaCrz1p regulates transcription of a minimal CDRE-LacZ reporter carrying a target for ScCrz1p binding as upstream activating sequence.
“we show that CaCrz1p regulates transcription of a minimal CDRE-LacZ reporter which carries as upstream activating sequence a target for ScCrz1p binding (Mendizabal et al. 2001)”
From Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor (2005) · cites this paper as Mendizabal et al. 2001
Cited by
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Yoshimoto, H., Saltsman, K., Gasch, A. P., Li, H. X., Ogawa, N., Botstein, D., Brown, P. O., & Cyert, M. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202718200 · Cited by 404 · see citing works
Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections.
Steinbach, W. J., Reedy, J. L., Cramer, R. A., Perfect, J. R., & Heitman, J. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1680 · Cited by 313 · see citing works
Alkali Metal Cation Transport and Homeostasis in Yeasts
Ariño, J., Ramos, J., & Sychrová, H. (2010) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00042-09 · Cited by 292 · see citing works
Lamb, T. M., & Mitchell, A. P. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.23.2.677-686.2003 · Cited by 255 · see citing works
“Induction of ENA1 by alkaline pH has been shown to depend on the calcineurinactivated transcription factor Crz1p (32).”
Background<i>CRZ1</i> , a target of the calcineurin pathway in <i>Candida albicans</i>
Karababa, M., Valentino, E., Pardini, G., Coste, A. T., Bille, J., & Sanglard, D. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.05037.x · Cited by 231 · see citing works
“cerevisiae ENA1 gene revealed that Crz1p was able to activate ENA1 in the presence of calcium through two separate elements: one contributing to the basal expression of ENA1 (5′-GAATGGCTG-3′) with low affinity binding to Crz1p and the other one crucial for the induction response to calcium (5′-GGGTGGCTG-3′) with high…”
BackgroundSerrano, R., Ruiz, A., Bernal, D., Chambers, J. R., & Ariño, J. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.03246.x · Cited by 198 · see citing works
“This sequence contains the downstream, high-affinity Crz1-binding element identified by Mendizabal et al. (2001).”
BackgroundMethodSelf-citationSchumacher, J., Fernandez-de-Larrinoa, Í., & Tudzynski, B. (2008) · Eukaryotic Cell · doi:10.1128/ec.00426-07 · Cited by 155 · see citing works
“We propose that the suppression of the Na sensitivity by expressing Bccrz1 in crz1defective yeast cells is based on the BcCRZ1-mediated transcriptional activation of the gene ENA1, encoding the ATPdriven ion pump, which is induced and activated by toxic concentrations of Na and Li, promoting the extrusion of these ion…”
BackgroundSelf-citationFortwendel, J. R., Juvvadi, P. R., Perfect, B. Z., Rogg, L. E., Perfect, J. R., & Steinbach, W. J. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00854-09 · Cited by 153 · see citing works
Mechanisms underlying the halotolerant way of
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“P-type ATPase genes (PMC1, PMR1, and ENA1), is regulated by Crz1p in a Ca 2+ /calcineurin-dependent manner (Matheos et al., 1997; Mendizabal et al., 2001 ).”
BackgroundFunction and Regulation of the Saccharomyces cerevisiae ENA Sodium ATPase System
Ruiz, A., & Ariño, J. (2007) · Eukaryotic Cell · doi:10.1128/ec.00337-07 · Cited by 116 · see citing works
Platara, M., Ruiz, A., Serrano, R., Palomino, A., Moreno, F., & Ariño, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606483200 · Cited by 95 · see citing works
Self-citationCoordinate responses to alkaline pH stress in budding yeast
Serra‐Cardona, A., Canadell, D., & Ariño, J. (2015) · Microbial Cell · doi:10.15698/mic2015.06.205 · Cited by 91 · see citing works
“Remarkably, a very recent report highlighted that, in response to high pH stress, ENA1 and PHO89 share the same regulatory network [82] and that both proteins accumulate roughly at the same time at the plasma membrane.”
InfluentialZhang, T., Xu, Q., Sun, X., & Li, H. (2013) · Microbiological Research · doi:10.1016/j.micres.2012.11.006 · Cited by 75 · see citing works
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“MBP-Nrg1 affinity purification of Rim101(1-531).”
BackgroundMethodInfluentialSantos, M., & de Larrinoa, I. F. (2005) · Current Genetics · doi:10.1007/s00294-005-0003-8 · Cited by 78 · see citing works
“The integrative plasmids pLacZ1 and pLacZ2 containing native and mutated CDREENA1-LacZ reporters have been described elsewhere (Mendizabal et al. 2001).”
BackgroundInfluentialSelf-citationMonovalent cation transporters at the plasma membrane in yeasts
Ariño, J., Ramos, J., & Sychrová, H. (2018) · Yeast · doi:10.1002/yea.3355 · Cited by 69 · see citing works
“The ENA1 promoter contains two Crz1‐binding regions at positions −813/−821 and −727/−719, with the downstream element being the most relevant for induction of the gene in response to salt stress and high pH (Mendizabal et al., 2001; Petrezsélyová et al., 2016).”
BackgroundRuiz, A., Yenush, L., & Ariño, J. (2003) · Eukaryotic Cell · doi:10.1128/ec.2.5.937-948.2003 · Cited by 71 · see citing works
“phatases. Here we present evidence that a region containing the downstream CDRE of ENA1 ( 30 , 43) is necessary and sufficient to mimic the increased expression of the full promoter in a ppz1 mutant.”
BackgroundInfluentialHagiwara, D., Kondo, A., Fujioka, T., & Abe, K. (2008) · Current Genetics · doi:10.1007/s00294-008-0220-z · Cited by 69 · see citing works
“Similar dual regulation has been observed in S. cerevisiae ENA1, which encodes a P-type Na?-ATPase (Mendoza et al. 1994; Marquez and Serrano 1996; Mendizabal et al. 2001 ).”
Potassium and Sodium Transport in Yeast
Yenush, L. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-25304-6_8 · Cited by 66 · see citing works
Lamoth, F., Juvvadi, P. R., Gehrke, C., Asfaw, Y. G., & Steinbach, W. J. (2014) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit530 · Cited by 62 · see citing works
Integrative Responses to High pH Stress in S. cerevisiae
Ariño, J. (2010) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2010.0044 · Cited by 62 · see citing works
“…signals from calcineurin activation (via Crz1) at CDRE elements located at positions (cid:2) 813/ (cid:2) 821 and (cid:2) 727/ (cid:2) 719 (Mendizabal et al., 2001), from the Snf1 pathway, via both Mig1/Mig2 and Nrg1, and also receives input from the Rim101pathway (via Nrg1) (Platara et…”
Direct Regulation of Genes Involved in Glucose Utilization by the Calcium/Calcineurin Pathway
Ruiz, A., Serrano, R., & Ariño, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708683200 · Cited by 60 · see citing works
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Martínez-Montañés, F., Pascual‐Ahuir, A., & Proft, M. (2010) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2010.0046 · Cited by 60 · see citing works
Self-citationTian, Y., Elbing, K., & Hohmann, S. (2008) · Microbiology · doi:10.1099/mic.0.2008/020149-0 · Cited by 53 · see citing works
“, 2001), the calcineurin pathway (Hirata et al., 1995; Mendizabal et al., 2001; Mendoza et al., 1994, 1996), the TOR pathway (Crespo et al.”
BackgroundInfluentialCanadell, D., García‐Martínez, J., Alepuz, P. M., Pérez-Ortín, J. E., & Ariño, J. (2015) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2015.04.001 · Cited by 49 · see citing works
Jung, K.-W., Strain, A. K., Nielsen, K., Jung, K.-H., & Bahn, Y. (2012) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2012.02.001 · Cited by 48 · see citing works
“The calcium/ calcineurin signaling pathway controls ENA1 expression through the Crz1 transcription factor (Mendizabal et al., 2001).”
BackgroundFox, D. S., Cox, G. M., & Heitman, J. (2003) · Eukaryotic Cell · doi:10.1128/ec.2.5.1025-1035.2003 · Cited by 47 · see citing works
Ruiz, A., González, A., García‐Salcedo, R., Ramos, J., & Ariño, J. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05370.x · Cited by 45 · see citing works
“…the calcineurin pathway, which results in binding of the positive transcription factor Crz1p/Tcn1p to a specific calcineurin response element (CDRE) in the ENA1 promoter, thus enhancing expression of the gene (Matheos et al., 1997; Stathopoulos and Cyert, 1997; Mendizabal et al., 1998; 2001).”
BackgroundPinchai, N., Juvvadi, P. R., Fortwendel, J. R., Perfect, B. Z., Rogg, L. E., Asfaw, Y. G., & Steinbach, W. J. (2010) · Eukaryotic Cell · doi:10.1128/ec.00378-09 · Cited by 43 · see citing works
Petrezsélyová, S., López‐Malo, M., Canadell, D., Roque, A., Serra‐Cardona, A., Marqués, M. C., Vilaprinyó, E., Alves, R., Yenush, L., & Ariño, J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158424 · Cited by 35 · see citing works
“It has been shown that mutation of the downstream ENA1 CDRE element was able to largely abolish the transcriptional response to calcium and high pH stress, and there is evidence that short regions containing the ENA1–712/-733 region are able to drive transcription in response to calcium [23], high pH [10], or as a res…”
BackgroundResultInfluentialPanadero, J., Hernandez-Lopez, M., Prieto, J. A., & Rández‐Gil, F. (2007) · Applied and Environmental Microbiology · doi:10.1128/aem.02651-06 · Cited by 34 · see citing works
“promoters of most salt-responsive genes (22, 42, 48).”
BackgroundGenome-wide recruitment profiling of transcription factor Crz1 in response to high pH stress
Roque, A., Petrezsélyová, S., Serra‐Cardona, A., & Ariño, J. (2016) · BMC Genomics · doi:10.1186/s12864-016-3006-6 · Cited by 34 · see citing works
“We found that 43 out of the 100 promoters showing recruitment of Crz1 where induced by calcium and that in 14 cases (PHO89, ENA1, CRH1, YHR097C, YPS1, YLR257W, TMA10, DIA1, CHS1, YNL208W, YOL014W, LCL1, SUR1, FLC1) dependence on calcineurin was proposed.”
InfluentialEspeso, E. A. (2016) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-25304-6_7 · Cited by 33 · see citing works
Tate, J. J., & Cooper, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609550200 · Cited by 32 · see citing works
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“…regulation of NKA by CaN is also supported by extensive data on the yeast analog of NKA, ENA1, in which stress-induced expression of ENA1 is mediated by CaN through activation of the transcription factor Crz1 (Mendoza et al., 1994; Mendizabal et al., 2001; Ruiz et al., 2003; Ruiz and Ariño, 2007).”
BackgroundGene-by-environment interactions influence the fitness cost of gene copy-number variation in yeast
Robinson, D., Vanacloig-Pedros, E., Cai, R., Place, M., Hose, J., & Gasch, A. P. (2023) · G3 Genes Genomes Genetics · doi:10.1093/g3journal/jkad159 · Cited by 26 · see citing works
“Interestingly, several other genes uniquely beneficial to one or more wild strains transcriptionally up-regulate ENA1 , including CK2 whose OE benefited all strains and CRZ1 that was highly beneficial to BC187 (Tenney and Glover 1999; Mendizabal et al .”
BackgroundDissection of the Candida albicans class I chitin synthase promoters
Lenardon, M. D., Lesiak, I., Munro, C. A., & Gow, N. A. R. (2009) · Molecular Genetics and Genomics · doi:10.1007/s00438-009-0423-0 · Cited by 26 · see citing works
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BackgroundRegulation of Trk‐dependent potassium transport by the calcineurin pathway involves the Hal5 kinase
Casado, C., Yenush, L., Melero, C., Ruiz, M. D. C., Serrano, R., Pérez‐Valle, J., Ariño, J., & Ramos, J. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.04.042 · Cited by 26 · see citing works
Self-citationTolerance to alkaline ambient pH in Aspergillus nidulans depends on the activity of ENA proteins
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Tian, Y., García‐Salcedo, R., Ramos, J., & Hohmann, S. (2006) · Eukaryotic Cell · doi:10.1128/ec.00215-06 · Cited by 23 · see citing works
“The calcineurin protein phosphatase, consisting of the Cmp1 and Cmp2 catalytic subunits and the Cnb1 regulatory subunit, controls expression of ENA1 via the Crz1 transcription factor (18, 25 , 26, 42).”
BackgroundIon homeostasis in Saccharomyces cerevisiae under NaCl stress
Wadskog, I., & Adler, L. (2007) · Springer eBooks · doi:10.1007/3-540-45611-2_5 · Cited by 21 · see citing works
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“It has been proposed that Mg2+ starvation causes an increase in cytoplasmic free calcium leading to calcium signaling (Mendizabal et al., 2001; Hu et al., 2007; Wiesenberger et al., 2007).”
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“This region contains the ENA1 downstream CDRE, which is known to bind Crz1 with high affinity and constitutes the main determinant of the induction response to calcium and alkaline pH [13,42,43].”
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“cerevisiae, calcineurin activity is activated by specific environmental conditions, such as high pH, high levels of Ca and Na, and elevated temperature (Cyert 2001; Mendizabal et al. 2001; Yoshimoto et al. 2002; Serrano et al. 2002).”
BackgroundNitrogen-dependent calcineurin activation in the yeast Hansenula polymorpha
Rodríguez, C., Galindo, L. R., & Siverio, J. M. (2013) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2013.01.007 · Cited by 4 · see citing works
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“Crzl/Hal8 is a positive regulator of ENA1 expression and its promoter element in Figure 4) has recently been identified ( Mendizabal et al., 2001 ).”
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- Authors
- Mendizabal, I., Pascual-Ahuir, A., Serrano, R., & de Larrinoa, I.
- Affiliations
- University of the Basque Country (ES)
- Instituto de Biología Molecular y Celular de Plantas (ES)
- ORCID
- Mendizabal, I.
- Venue
- Molecular Genetics and Genomics
- Published
- 2001-07
- Volume
- 265
- Issue
- 5
- Pages
- 801-811
- ISSN
- 1617-4615 (ISSN-L)
- 1617-4623
- OpenAlex
- W2075097894
- Cited by
- 57
- References
- 0
- Citations by year
- 2024: 1 · 2023: 2 · 2020: 2 · 2019: 2 · 2018: 1 · 2016: 3 · 2015: 4 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Genetics and Genomics (publishedVersion)
- PubMed (publishedVersion)
- 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 › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- calcineurin, promoter regulation, upstream activating sequence, calcium signaling, osmotic stress, transcriptional induction, upstream element, transcription factor binding affinity, Saccharomyces cerevisiae
- MeSH terms
- Adenosine Triphosphatases, Sodium-Potassium-Exchanging ATPase, Base Sequence, DNA-Binding Proteins, Molecular Sequence Data, Promoter Regions, Genetic, Saccharomyces cerevisiae, Transcription Factors, Transcriptional Activation, Trans-Activators, Gene Expression Regulation, Fungal, Calcineurin, Cation Transport Proteins, Saccharomyces cerevisiae Proteins
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