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Gene Review

ROX1  -  Rox1p

Saccharomyces cerevisiae S288c

Synonyms: Heme-dependent repression factor, Hypoxic function repressor, Repressor ROX1, YP9499.20, YPR065W
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Disease relevance of ROX1


High impact information on ROX1

  • DNA-binding repressor proteins mediate regulation of yeast genes by cell type (Mcm1/alpha 2 and a1/alpha 2), glucose (Mig1) and oxygen (Rox1) (refs 1-4 respectively) [3].
  • Expression of GPD2 is also unaffected by ROX1 and ROX3, encoding putative regulators of hypoxic and stress-controlled gene expression [4].
  • A number of trans-acting mutations affecting a gene designated ROX1 caused constitutive expression of both the fused and wild-type genes, indicating that the ROX1 gene product operates through the ANB1 modulator sequence at the level of transcription [5].
  • Rfg1, a protein related to the Saccharomyces cerevisiae hypoxic regulator Rox1, controls filamentous growth and virulence in Candida albicans [6].
  • Repression of two other hypoxic genes in which Mot3 sites were associated with Rox1 sites was reduced in the deletion strain, but other hypoxic genes were unaffected [7].

Biological context of ROX1

  • Finally, ROX1 was mapped to yeast chromosome XVI, near the ARO7-OSM2 locus [1].
  • Oxygen levels are sensed by changes in heme biosynthesis, which controls the transcription of the ROX1 gene, encoding a protein that binds to the regulatory region of each hypoxic gene to repress transcription [8].
  • Under aerobic conditions oxygen control of gene expression is exerted through the activator Hap1 and the repressor Rox1 [9].
  • One is Rox1, an HMG protein, and the second, originally designated Rox7, is shown here to be Mot3, a global C2H2 zinc finger regulator [10].
  • The results of the deletion analysis show that the negative control of the AAC3 gene by oxygen and ROX1 factor is mediated by an upstream repression sequence consisting of a T-rich segment adjacent to the consensus elements that are present in the 5' flanking regions of several other yeast genes [11].

Associations of ROX1 with chemical compounds

  • Evidence that ROX1 binds to DNA or is part of a DNA-binding complex is described [12].
  • Repression of ERG11 expression was dependent upon the ROX1 repressor and additional repressor(s) designated as Old (overexpression of lanosterol demethylase) [13].
  • We report that ROX1 deletion resulted in 2.5- to 16-fold-lower susceptibilities to azoles and terbinafine [14].
  • Rox1 mediated repression. Oxygen dependent repression in yeast [15].
  • We report here cross-regulation between Rox1 and Mot3 and Rfx1 in the regulation of the RNR genes encoding ribonucleotide diphosphate reductase [16].

Physical interactions of ROX1

  • This hypothesis was confirmed by using a set of fusions between sequences encoding the GAL4 DNA-binding domain and portions of ROX1 [17].
  • To determine the DNA sequence requirements for repression, we carried out a mutational analysis of the consensus Rox1-binding site and an analysis of the arrangement of the Rox1 sites into operators in the hypoxic ANB1 gene [18].
  • Under hypoxic conditions, heme levels fall, and a heme-deficient Hap1 complex represses ROX1 expression [19].
  • Chromatin immunoprecipitation assays indicated that Rox1 stabilized Mot3 binding to DNA [20].
  • The hypoxic genes of Saccharomyces cerevisiae are transcriptionally repressed during aerobic growth through recruitment of the Ssn6/Tup1 general repression complex by the DNA binding protein Rox1 [20].

Regulatory relationships of ROX1

  • In the absence of heme, Cyp1p activated HEM13 and strongly repressed ROX1, allowing de-repression of HEM13 [21].
  • In Saccharomyces cerevisiae the anaerobic (oxygen-repressed) ANB1 gene and a group of aerobic (oxygen-induced) genes are coordinately regulated by the ROX1 gene [22].
  • Finally, FET4 expression is regulated in response to oxygen by the Rox1 repressor [23].
  • The ROX1 locus of S. cerevisiae is known to regulate CYC1, COXVb, and ANB1 genes at the transcriptional level; the ROX1 locus thus regulates all known anaerobically expressed genes that are involved in different cellular functions such as respiration and protein synthesis [24].
  • The heme-Hap1 complex activates transcription of the ROX1 gene that encodes a repressor of one set of hypoxic genes [19].

Other interactions of ROX1

  • The regulatory region of one well-studied hypoxic gene, ANB1, is comprised of two operators, OpA and OpB, each of which has two strong Rox1 binding sites, yet OpA represses transcription almost 10 times more effectively than OpB [7].
  • With regard to the effect brought about by the deletion of rox1 and srb10, correspondence cluster analysis revealed that the transcriptome profile in aerobic conditions is very similar in the wild-type and both deletion strains [25].
  • The repression of hypoxic genes under normoxic conditions results from Hap1-mediated activation of ROX1 transcription [9].
  • Repression of anaerobic genes results from co-induction of Mot3 and Rox1 in aerobic cells [10].
  • Furthermore, oxygen repression of the hypoxic HEM13 gene was not affected by the deletion nor was this putative ROX1 gene regulated positively by oxygen as is the case for the S. cerevisiae gene [26].

Analytical, diagnostic and therapeutic context of ROX1


  1. 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. Mol. Cell. Biol. (1993) [Pubmed]
  2. Transcript analysis of 203 novel genes from Saccharomyces cerevisiae in hap1 and rox1 mutant backgrounds. Lombardía, L.J., Cadahía-Rodríguez, J.L., Freire-Picos, M.A., González-Siso, M.I., Rodríguez-Torres, A.M., Cerdán, M.E. Genome (2000) [Pubmed]
  3. Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex. Tzamarias, D., Struhl, K. Nature (1994) [Pubmed]
  4. The two isoenzymes for yeast NAD+-dependent glycerol 3-phosphate dehydrogenase encoded by GPD1 and GPD2 have distinct roles in osmoadaptation and redox regulation. Ansell, R., Granath, K., Hohmann, S., Thevelein, J.M., Adler, L. EMBO J. (1997) [Pubmed]
  5. Oxygen regulation of anaerobic and aerobic genes mediated by a common factor in yeast. Lowry, C.V., Zitomer, R.S. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  6. Rfg1, a protein related to the Saccharomyces cerevisiae hypoxic regulator Rox1, controls filamentous growth and virulence in Candida albicans. Kadosh, D., Johnson, A.D. Mol. Cell. Biol. (2001) [Pubmed]
  7. Roles of transcription factor Mot3 and chromatin in repression of the hypoxic gene ANB1 in yeast. Kastaniotis, A.J., Mennella, T.A., Konrad, C., Torres, A.M., Zitomer, R.S. Mol. Cell. Biol. (2000) [Pubmed]
  8. Approaches to the study of Rox1 repression of the hypoxic genes in the yeast Saccharomyces cerevisiae. Zitomer, R.S., Limbach, M.P., Rodriguez-Torres, A.M., Balasubramanian, B., Deckert, J., Snow, P.M. Methods (1997) [Pubmed]
  9. A microarray-assisted screen for potential Hap1 and Rox1 target genes in Saccharomyces cerevisiae. Ter Linde, J.J., Steensma, H.Y. Yeast (2002) [Pubmed]
  10. Synergistic repression of anaerobic genes by Mot3 and Rox1 in Saccharomyces cerevisiae. Sertil, O., Kapoor, R., Cohen, B.D., Abramova, N., Lowry, C.V. Nucleic Acids Res. (2003) [Pubmed]
  11. Transcriptional control of AAC3 gene encoding mitochondrial ADP/ATP translocator in Saccharomyces cerevisiae by oxygen, heme and ROX1 factor. Sabová, L., Zeman, I., Supek, F., Kolarov, J. Eur. J. Biochem. (1993) [Pubmed]
  12. Regulation of gene expression by oxygen in Saccharomyces cerevisiae. Zitomer, R.S., Lowry, C.V. Microbiol. Rev. (1992) [Pubmed]
  13. Multiple regulatory elements control expression of the gene encoding the Saccharomyces cerevisiae cytochrome P450, lanosterol 14 alpha-demethylase (ERG11). Turi, T.G., Loper, J.C. J. Biol. Chem. (1992) [Pubmed]
  14. ROX1 and ERG regulation in Saccharomyces cerevisiae: implications for antifungal susceptibility. Henry, K.W., Nickels, J.T., Edlind, T.D. Eukaryotic Cell (2002) [Pubmed]
  15. Rox1 mediated repression. Oxygen dependent repression in yeast. Kastaniotis, A.J., Zitomer, R.S. Adv. Exp. Med. Biol. (2000) [Pubmed]
  16. Synergy among differentially regulated repressors of the ribonucleotide diphosphate reductase genes of Saccharomyces cerevisiae. Klinkenberg, L.G., Webb, T., Zitomer, R.S. Eukaryotic Cell (2006) [Pubmed]
  17. Mutational analysis of Rox1, a DNA-bending repressor of hypoxic genes in Saccharomyces cerevisiae. Deckert, J., Rodriguez Torres, A.M., Simon, J.T., Zitomer, R.S. Mol. Cell. Biol. (1995) [Pubmed]
  18. The anatomy of a hypoxic operator in Saccharomyces cerevisiae. Deckert, J., Torres, A.M., Hwang, S.M., Kastaniotis, A.J., Zitomer, R.S. Genetics (1998) [Pubmed]
  19. Regulation of hypoxic gene expression in yeast. Zitomer, R.S., Carrico, P., Deckert, J. Kidney Int. (1997) [Pubmed]
  20. Combinatorial repression of the hypoxic genes of Saccharomyces cerevisiae by DNA binding proteins Rox1 and Mot3. Klinkenberg, L.G., Mennella, T.A., Luetkenhaus, K., Zitomer, R.S. Eukaryotic Cell (2005) [Pubmed]
  21. Positive and negative elements involved in the differential regulation by heme and oxygen of the HEM13 gene (coproporphyrinogen oxidase) in Saccharomyces cerevisiae. Amillet, J.M., Buisson, N., Labbe-Bois, R. Curr. Genet. (1995) [Pubmed]
  22. Negative regulation of the Saccharomyces cerevisiae ANB1 gene by heme, as mediated by the ROX1 gene product. Lowry, C.V., Lieber, R.H. Mol. Cell. Biol. (1986) [Pubmed]
  23. Combinatorial control of yeast FET4 gene expression by iron, zinc, and oxygen. Waters, B.M., Eide, D.J. J. Biol. Chem. (2002) [Pubmed]
  24. The ANB1 locus of Saccharomyces cerevisiae encodes the protein synthesis initiation factor eIF-4D. Mehta, K.D., Leung, D., Lefebvre, L., Smith, M. J. Biol. Chem. (1990) [Pubmed]
  25. The yeast transcriptome in aerobic and hypoxic conditions: effects of hap1, rox1, rox3 and srb10 deletions. Becerra, M., Lombardía-Ferreira, L.J., Hauser, N.C., Hoheisel, J.D., Tizon, B., Cerdán, M.E. Mol. Microbiol. (2002) [Pubmed]
  26. The DNA binding protein Rfg1 is a repressor of filamentation in Candida albicans. Khalaf, R.A., Zitomer, R.S. Genetics (2001) [Pubmed]
  27. REO1 and ROX1 are alleles of the same gene which encodes a transcriptional repressor of hypoxic genes in Saccharomyces cerevisiae. Kwast, K.E., Burke, P.V., Brown, K., Poyton, R.O. Curr. Genet. (1997) [Pubmed]
  28. Genomic analyses of anaerobically induced genes in Saccharomyces cerevisiae: functional roles of Rox1 and other factors in mediating the anoxic response. Kwast, K.E., Lai, L.C., Menda, N., James, D.T., Aref, S., Burke, P.V. J. Bacteriol. (2002) [Pubmed]
  29. Characterization of the DNA binding and bending HMG domain of the yeast hypoxic repressor Rox1. Deckert, J., Khalaf, R.A., Hwang, S.M., Zitomer, R.S. Nucleic Acids Res. (1999) [Pubmed]
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