Synergistic repression of anaerobic genes by Mot3 and Rox1 in Saccharomyces cerevisiae

Sertil, O.

doi:10.1093/nar/gkg792

Cited by 88Fungal and yeast genetics researchBacterial Genetics and BiotechnologyGenomics and Chromatin Dynamics

Synergistic repression of anaerobic genes by Mot3 and Rox1 in Saccharomyces cerevisiae

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Sertil, O.·2003·Nucleic Acids Research

DOI 10.1093/nar/gkg792PMC PMC219473

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Abstract

Two groups of anaerobic genes (genes induced in anaerobic cells and repressed in aerobic cells) are negatively regulated by heme, a metabolite present only in aerobic cells. Members of both groups, the hypoxic genes and the DAN/TIR/ERG genes, are jointly repressed under aerobic conditions by two factors. One is Rox1, an HMG protein, and the second, originally designated Rox7, is shown here to be Mot3, a global C2H2 zinc finger regulator. Repression of anaerobic genes results from co-induction of Mot3 and Rox1 in aerobic cells. Repressor synthesis is triggered by heme, which de-represses a mechanism controlling expression of both MOT3 and ROX1 in anaerobic cells; it includes Hap1, Tup1, Ssn6 and a fourth unidentified factor. The constitutive expression of various anaerobic genes in aerobic rox1Delta or mot3Delta cells directly implies that neither factor can repress by itself at endogenous levels and that stringent aerobic repression results from the concerted action of both. Mot3 and Rox1 are not essential components of a single complex, since each can repress independently in the absence of the other, when artificially induced at high levels. Moreover, the two repression mechanisms appear to be distinct: as shown here repression of ANB1 by Rox1 alone requires Tup1-Ssn6, whereas repression by Mot3 does not. Though artificially high levels of either factor can repress well, the absolute efficiency observed in normal cells when both are present-at much lower levels-demonstrates a novel inhibitory synergy. Evidently, expression levels for the two mutually dependent repressors are calibrated to permit a range of variation in basal aerobic expression at different promoters with differing operator site combinations.

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Mot3 represses the expression of hypoxic, DAN/TIR/PAU and ERG genes including ERG2, ERG6 and ERG9.
“In addition, to limit Ecm22 function [75], the transcriptional factor Mot3 also represses the expression of hypoxic, DAN/TIR/PAU and ERG genes including ERG2, ERG6 and ERG9 (Figure 3A) [86,89,90,91,92,93].”
From Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae (2020) · cites this paper as [89]
Rox1 and Mot3 regulatory factors act synergistically to achieve stringent repression of target genes.
“Rox1 and Mot3 regulatory factors act synergistically to achieve stringent repression of target genes [89,90].”
From Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae (2020) · cites this paper as [89]

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New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites
Gietz, R. D., & Sugino, A. (1988) · Gene · doi:10.1016/0378-1119(88)90185-0 · Cited by 2,901 · see citing works
Construction of a set of convenient saccharomyces cerevisiae strains that are isogenic to S288C
Winston, F., Dollard, C. A., & Ricupero‐Hovasse, S. L. (1995) · Yeast · doi:10.1002/yea.320110107 · Cited by 949 · see citing works
Ssn6-Tup1 is a general repressor of transcription in yeast
Keleher, C. A., Redd, M. J., Schultz, J., Carlson, M., & Johnson, A. D. (1992) · Cell · doi:10.1016/0092-8674(92)90146-4 · Cited by 666 · see citing works
Regulation of gene expression by oxygen in Saccharomyces cerevisiae
Zitomer, R. S., & Lowry, C. V. (1992) · Microbiological Reviews · doi:10.1128/mr.56.1.1-11.1992 · Cited by 413 · see citing works
Functional dissection of the yeast Cyc8–Tupl transcriptional co-repressor complex
Tzamarias, D., & Struhl, K. (1994) · Nature · doi:10.1038/369758a0 · Cited by 337 · see citing works
Upc2p and Ecm22p, Dual Regulators of Sterol Biosynthesis in Saccharomyces cerevisiae
Vik, Å., & Rine, J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.19.6395-6405.2001 · Cited by 277 · see citing works
Identification of three mannoproteins in the cell wall of Saccharomyces cerevisiae
van der Vaart, J. M., P., L. H., Chapman, J. W., Klis, F. M., & Verrips, C. T. (1995) · Journal of Bacteriology · doi:10.1128/jb.177.11.3104-3110.1995 · Cited by 240 · see citing works
Reciprocal Regulation of Anaerobic and Aerobic Cell Wall Mannoprotein Gene Expression in Saccharomyces cerevisiae
Abramova, N., Sertil, O., Mehta, S., & Lowry, C. V. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.9.2881-2887.2001 · Cited by 157 · see citing works
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The Rox1 repressor of the Saccharomyces cerevisiae hypoxic genes is a specific DNA-binding protein with a high-mobility-group motif.
Balasubramanian, B., Lowry, C. V., & Zitomer, R. S. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.10.6071 · Cited by 140 · see citing works
Regulation of gene expression by oxygen in Saccharomyces cerevisiae.
Zitomer, R. S., & Lowry, C. V. (1992) · Microbiological Reviews · doi:10.1128/mmbr.56.1.1-11.1992 · Cited by 129 · see citing works
Regulatory Mechanisms Controlling Expression of the DAN/TIR Mannoprotein Genes During Anaerobic Remodeling of the Cell Wall in Saccharomyces cerevisiae
Abramova, N. E., Cohen, B. D., Sertil, O., Kapoor, R., Davies, K. J. A., & Lowry, C. V. (2001) · Genetics · doi:10.1093/genetics/157.3.1169 · Cited by 128 · see citing works
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Cti6, a PHD Domain Protein, Bridges the Cyc8-Tup1 Corepressor and the SAGA Coactivator to Overcome Repression at GAL1
Papamichos‐Chronakis, M., Petrakis, T., Ktistaki, E., Topalidou, I., & Tzamarias, D. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00545-2 · Cited by 126 · see citing works
A Mutation in a Purported Regulatory Gene Affects Control of Sterol Uptake in Saccharomyces cerevisiae
Crowley, J. H., Leak, F. W., Shianna, K. V., Tove, S., & Parks, L. W. (1998) · Journal of Bacteriology · doi:10.1128/jb.180.16.4177-4183.1998 · Cited by 123 · see citing works
ROX1 encodes a heme-induced repression factor regulating ANB1 and CYC7 of Saccharomyces cerevisiae.
Lowry, C. V., & Zitomer, R. S. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.11.4651 · Cited by 116 · see citing works
A Complex Composed of Tup1 and Ssn6 Represses Transcription in Vitro
Redd, M. J., Arnaud, M. B., & Johnson, A. D. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.17.11193 · Cited by 102 · see citing works
HAP1 and ROX1 Form a Regulatory Pathway in the Repression of HEM13 Transcription in Saccharomyces cerevisiae
Keng, T. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.6.2616-2623.1992 · Cited by 101 · see citing works
Multiple elements and auto-repression regulate Rox1, a repressor of hypoxic genes in Saccharomyces cerevisiae.
Deckert, J., Perini, R. F., Balasubramanian, B., & Zitomer, R. S. (1995) · Genetics · doi:10.1093/genetics/139.3.1149 · Cited by 101 · see citing works
Modulator sequences mediate oxygen regulation of CYC1 and a neighboring gene in yeast.
Lowry, C. V., Weiss, J. L., Walthall, D. A., et al. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.1.151 · Cited by 95 · see citing works
Induction and repression of DAN1 and the family of anaerobic mannoprotein genes in Saccharomyces cerevisiae occurs through a complex array of regulatory sites
Cohen, B. D. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.3.799 · Cited by 88 · see citing works
HAP1 and ROX1 form a regulatory pathway in the repression of HEM13 transcription in Saccharomyces cerevisiae.
Keng, T. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.6.2616 · Cited by 83 · see citing works
Mot3 is a transcriptional repressor of ergosterol biosynthetic genes and is required for normal vacuolar function in Saccharomyces cerevisiae
Hongay, C., Jia, N., Bard, M., & Winston, F. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf415 · Cited by 72 · see citing works
A hypoxic consensus operator and a constitutive activation region regulate the ANB1 gene of Saccharomyces cerevisiae.
Lowry, C. V., Cerdán, M. E., & Zitomer, R. S. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.11.5921 · Cited by 67 · see citing works
Elements Involved in Oxygen Regulation of the Saccharomyces Cerevisiae CYC7 Gene
Zitomer, R. S., Sellers, J. W., McCarter, D. W., et al. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.6.2212-2220.1987 · Cited by 66 · see citing works
A yeast protein with homology to the β-subunit of G proteins is involved in control of heme-regulated and catabolite-repressed genes
Zhang, M., Rosenblum, L. S., Lowry, C. V., et al. (1991) · Gene · doi:10.1016/0378-1119(91)90047-f · Cited by 65 · see citing works
Mot3, a Zn Finger Transcription Factor That Modulates Gene Expression and Attenuates Mating Pheromone Signaling in Saccharomyces cerevisiae
Grishin, A., Rothenberg, M. E., Downs, M. A., & Blumer, K. (1998) · Genetics · doi:10.1093/genetics/149.2.879 · Cited by 57 · see citing works
Roles of Transcription Factor Mot3 and Chromatin in Repression of the Hypoxic Gene ANB1 in Yeast
Kastaniotis, A. J., Mennella, T. A., Konrad, C., et al. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.19.7088-7098.2000 · Cited by 55 · see citing works
Regulation by low temperatures and anaerobiosis of a yeast gene specifying a putative GPI‐anchored plasma membrane
Donzeau, M., Bourdineaud, J., & Lauquin, G. J. ‐. (1996) · Molecular Microbiology · doi:10.1111/j.1365-2958.1996.tb02631.x · Cited by 52 · see citing works
The DAN1 gene of S. cerevisiae is regulated in parallel with the hypoxic genes, but by a different mechanism
Sertil, O., Cohen, B. D., Davies, K. J. A., & Lowry, C. V. (1997) · Gene · doi:10.1016/s0378-1119(97)00028-0 · Cited by 50 · see citing works
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The Rox1 Repressor of the Saccharomyces cerevisiae Hypoxic Genes is a Specific DNA-Binding Protein with a High-Mobility-Group Motif
Balasubramanian, B., Lowry, C. V., & Zitomer, R. S. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.10.6071-6078.1993 · Cited by 48 · see citing works
Elements involved in oxygen regulation of the Saccharomyces cerevisiae CYC7 gene.
Zitomer, R. S., Sellers, J. W., McCarter, D. W., et al. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.6.2212 · Cited by 46 · see citing works
Mutational Analysis of the Tup1 General Repressor of Yeast
Carrico, P. M., & Zitomer, R. S. (1998) · Genetics · doi:10.1093/genetics/148.2.637 · Cited by 42 · see citing works
Identification and Analysis of Mot3, a Zinc Finger Protein That Binds to the Retrotransposon Ty Long Terminal Repeat (δ) in Saccharomyces cerevisiae
Madison, J. M., Dudley, A. M., & Winston, F. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.4.1879 · Cited by 29 · see citing works
ROX1 Encodes a Heme-Induced Repression Factor Regulating ANB1 and CYC7 of Saccharomyces cerevisiae
Lowry, C. V., & Zitomer, R. S. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.11.4651-4658.1988 · Cited by 27 · see citing works

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Luo, Z., & van Vuuren, H. J. J. (2009) · Microbiology · doi:10.1099/mic.0.030726-0 · Cited by 54 · see citing works
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Authors: Sertil, O.
Affiliations: Albany Medical College (US)
Corresponding author: Sertil, O.
Venue: Nucleic Acids Research
Publisher: Oxford University Press (OUP)
Published: 2003-10-15
Volume: 31
Issue: 20
Pages: 5831-5837
ISSN: 0305-1048 (ISSN-L)
1362-4962
DOI: 10.1093/nar/gkg792
PMC: PMC219473
OpenAlex: W2023135280
Cited by: 88
References: 33
Citations by year: 2026: 2 · 2025: 2 · 2024: 4 · 2022: 6 · 2021: 2 · 2020: 6 · 2019: 3 · 2018: 1 · 2017: 4 · 2015: 2 · 2014: 2 · 2013: 7 · 2012: 4
FWCI: 1.84
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Nucleic Acids Research (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: roX1, heme regulation, C2H2 zinc finger transcription factor, high mobility group proteins, HAP1, transcriptional synergy, Saccharomyces cerevisiae
MeSH terms: Aerobiosis, Anaerobiosis, DNA-Binding Proteins, Dose-Response Relationship, Drug, Glycoproteins, Heme, Mutation, Nuclear Proteins, Oxygen, Repressor Proteins, RNA, Fungal, Saccharomyces cerevisiae, Transcription Factors, Gene Expression Regulation, Fungal, Saccharomyces cerevisiae Proteins

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Synergistic repression of anaerobic genes by Mot3 and Rox1 in Saccharomyces cerevisiae

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