Skip to main content
Genetics logoLink to Genetics
. 2003 Nov;165(3):1045–1058. doi: 10.1093/genetics/165.3.1045

Cellular differentiation in response to nutrient availability: The repressor of meiosis, Rme1p, positively regulates invasive growth in Saccharomyces cerevisiae.

Dewald van Dyk 1, Guy Hansson 1, Isak S Pretorius 1, Florian F Bauer 1
PMCID: PMC1462853  PMID: 14668363

Abstract

In the yeast Saccharomyces cerevisiae, the transition from a nutrient-rich to a nutrient-limited growth medium typically leads to the implementation of a cellular adaptation program that results in invasive growth and/or the formation of pseudohyphae. Complete depletion of essential nutrients, on the other hand, leads either to entry into a nonbudding, metabolically quiescent state referred to as G0 in haploid strains or to meiosis and sporulation in diploids. Entry into meiosis is repressed by the transcriptional regulator Rme1p, a zinc-finger-containing DNA-binding protein. In this article, we show that Rme1p positively regulates invasive growth and starch metabolism in both haploid and diploid strains by directly modifying the transcription of the FLO11 (also known as MUC1) and STA2 genes, which encode a cell wall-associated protein essential for invasive growth and a starch-degrading glucoamylase, respectively. Genetic evidence suggests that Rme1p functions independently of identified signaling modules that regulate invasive growth and of other transcription factors that regulate FLO11 and that the activation of FLO11 is dependent on the presence of a promoter sequence that shows significant homology to identified Rme1p response elements (RREs). The data suggest that Rme1p functions as a central switch between different cellular differentiation pathways.

Full Text

The Full Text of this article is available as a PDF (300.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berben G., Dumont J., Gilliquet V., Bolle P. A., Hilger F. The YDp plasmids: a uniform set of vectors bearing versatile gene disruption cassettes for Saccharomyces cerevisiae. Yeast. 1991 Jul;7(5):475–477. doi: 10.1002/yea.320070506. [DOI] [PubMed] [Google Scholar]
  2. Blumental-Perry Anna, Li Weishi, Simchen Giora, Mitchell Aaron P. Repression and activation domains of RME1p structurally overlap, but differ in genetic requirements. Mol Biol Cell. 2002 May;13(5):1709–1721. doi: 10.1091/mbc.01-09-0468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Botstein D., Falco S. C., Stewart S. E., Brennan M., Scherer S., Stinchcomb D. T., Struhl K., Davis R. W. Sterile host yeasts (SHY): a eukaryotic system of biological containment for recombinant DNA experiments. Gene. 1979 Dec;8(1):17–24. doi: 10.1016/0378-1119(79)90004-0. [DOI] [PubMed] [Google Scholar]
  4. Brachmann C. B., Davies A., Cost G. J., Caputo E., Li J., Hieter P., Boeke J. D. Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications. Yeast. 1998 Jan 30;14(2):115–132. doi: 10.1002/(SICI)1097-0061(19980130)14:2<115::AID-YEA204>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  5. Conlan R. S., Tzamarias D. Sfl1 functions via the co-repressor Ssn6-Tup1 and the cAMP-dependent protein kinase Tpk2. J Mol Biol. 2001 Jun 22;309(5):1007–1015. doi: 10.1006/jmbi.2001.4742. [DOI] [PubMed] [Google Scholar]
  6. Covitz P. A., Mitchell A. P. Repression by the yeast meiotic inhibitor RME1. Genes Dev. 1993 Aug;7(8):1598–1608. doi: 10.1101/gad.7.8.1598. [DOI] [PubMed] [Google Scholar]
  7. Covitz P. A., Song W., Mitchell A. P. Requirement for RGR1 and SIN4 in RME1-dependent repression in Saccharomyces cerevisiae. Genetics. 1994 Nov;138(3):577–586. doi: 10.1093/genetics/138.3.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cross F. R. Starting the cell cycle: what's the point? Curr Opin Cell Biol. 1995 Dec;7(6):790–797. doi: 10.1016/0955-0674(95)80062-x. [DOI] [PubMed] [Google Scholar]
  9. Frenz L. M., Johnson A. L., Johnston L. H. Rme1, which controls CLN2 expression in Saccharomyces cerevisiae, is a nuclear protein that is cell cycle regulated. Mol Genet Genomics. 2001 Nov;266(3):374–384. doi: 10.1007/s004380100515. [DOI] [PubMed] [Google Scholar]
  10. Gagiano M., Van Dyk D., Bauer F. F., Lambrechts M. G., Pretorius I. S. Divergent regulation of the evolutionarily closely related promoters of the Saccharomyces cerevisiae STA2 and MUC1 genes. J Bacteriol. 1999 Oct;181(20):6497–6508. doi: 10.1128/jb.181.20.6497-6508.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gagiano M., van Dyk D., Bauer F. F., Lambrechts M. G., Pretorius I. S. Msn1p/Mss10p, Mss11p and Muc1p/Flo11p are part of a signal transduction pathway downstream of Mep2p regulating invasive growth and pseudohyphal differentiation in Saccharomyces cerevisiae. Mol Microbiol. 1999 Jan;31(1):103–116. doi: 10.1046/j.1365-2958.1999.01151.x. [DOI] [PubMed] [Google Scholar]
  12. Gagiano Marco, Bauer Florian F., Pretorius Isak S. The sensing of nutritional status and the relationship to filamentous growth in Saccharomyces cerevisiae. FEMS Yeast Res. 2002 Dec;2(4):433–470. doi: 10.1111/j.1567-1364.2002.tb00114.x. [DOI] [PubMed] [Google Scholar]
  13. Gagiano Marco, Bester Michael, van Dyk Dewald, Franken Jaco, Bauer Florian F., Pretorius Isak S. Mss11p is a transcription factor regulating pseudohyphal differentiation, invasive growth and starch metabolism in Saccharomyces cerevisiae in response to nutrient availability. Mol Microbiol. 2003 Jan;47(1):119–134. doi: 10.1046/j.1365-2958.2003.03247.x. [DOI] [PubMed] [Google Scholar]
  14. Gancedo J. M. Control of pseudohyphae formation in Saccharomyces cerevisiae. FEMS Microbiol Rev. 2001 Jan;25(1):107–123. doi: 10.1111/j.1574-6976.2001.tb00573.x. [DOI] [PubMed] [Google Scholar]
  15. Gasch A. P., Spellman P. T., Kao C. M., Carmel-Harel O., Eisen M. B., Storz G., Botstein D., Brown P. O. Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell. 2000 Dec;11(12):4241–4257. doi: 10.1091/mbc.11.12.4241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gietz R. D., Sugino A. New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites. Gene. 1988 Dec 30;74(2):527–534. doi: 10.1016/0378-1119(88)90185-0. [DOI] [PubMed] [Google Scholar]
  17. Gimeno C. J., Ljungdahl P. O., Styles C. A., Fink G. R. Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS. Cell. 1992 Mar 20;68(6):1077–1090. doi: 10.1016/0092-8674(92)90079-r. [DOI] [PubMed] [Google Scholar]
  18. Jones J. S., Prakash L. Yeast Saccharomyces cerevisiae selectable markers in pUC18 polylinkers. Yeast. 1990 Sep-Oct;6(5):363–366. doi: 10.1002/yea.320060502. [DOI] [PubMed] [Google Scholar]
  19. Kassir Y., Granot D., Simchen G. IME1, a positive regulator gene of meiosis in S. cerevisiae. Cell. 1988 Mar 25;52(6):853–862. doi: 10.1016/0092-8674(88)90427-8. [DOI] [PubMed] [Google Scholar]
  20. Kron S. J., Gow N. A. Budding yeast morphogenesis: signalling, cytoskeleton and cell cycle. Curr Opin Cell Biol. 1995 Dec;7(6):845–855. doi: 10.1016/0955-0674(95)80069-7. [DOI] [PubMed] [Google Scholar]
  21. Kuchin Sergei, Vyas Valmik K., Carlson Marian. Snf1 protein kinase and the repressors Nrg1 and Nrg2 regulate FLO11, haploid invasive growth, and diploid pseudohyphal differentiation. Mol Cell Biol. 2002 Jun;22(12):3994–4000. doi: 10.1128/MCB.22.12.3994-4000.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Köhler Tim, Wesche Stefanie, Taheri Naimeh, Braus Gerhard H., Mösch Hans-Ulrich. Dual role of the Saccharomyces cerevisiae TEA/ATTS family transcription factor Tec1p in regulation of gene expression and cellular development. Eukaryot Cell. 2002 Oct;1(5):673–686. doi: 10.1128/EC.1.5.673-686.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lambrechts M. G., Bauer F. F., Marmur J., Pretorius I. S. Muc1, a mucin-like protein that is regulated by Mss10, is critical for pseudohyphal differentiation in yeast. Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8419–8424. doi: 10.1073/pnas.93.16.8419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lo W. S., Dranginis A. M. The cell surface flocculin Flo11 is required for pseudohyphae formation and invasion by Saccharomyces cerevisiae. Mol Biol Cell. 1998 Jan;9(1):161–171. doi: 10.1091/mbc.9.1.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Loeb J. D., Kerentseva T. A., Pan T., Sepulveda-Becerra M., Liu H. Saccharomyces cerevisiae G1 cyclins are differentially involved in invasive and pseudohyphal growth independent of the filamentation mitogen-activated protein kinase pathway. Genetics. 1999 Dec;153(4):1535–1546. doi: 10.1093/genetics/153.4.1535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Madhani H. D., Fink G. R. The control of filamentous differentiation and virulence in fungi. Trends Cell Biol. 1998 Sep;8(9):348–353. doi: 10.1016/s0962-8924(98)01298-7. [DOI] [PubMed] [Google Scholar]
  27. Madhani H. D., Styles C. A., Fink G. R. MAP kinases with distinct inhibitory functions impart signaling specificity during yeast differentiation. Cell. 1997 Nov 28;91(5):673–684. doi: 10.1016/s0092-8674(00)80454-7. [DOI] [PubMed] [Google Scholar]
  28. Mizuno T., Nakazawa N., Remgsamrarn P., Kunoh T., Oshima Y., Harashima S. The Tup1-Ssn6 general repressor is involved in repression of IME1 encoding a transcriptional activator of meiosis in Saccharomyces cerevisiae. Curr Genet. 1998 Apr;33(4):239–247. doi: 10.1007/s002940050332. [DOI] [PubMed] [Google Scholar]
  29. Mösch H. U., Roberts R. L., Fink G. R. Ras2 signals via the Cdc42/Ste20/mitogen-activated protein kinase module to induce filamentous growth in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5352–5356. doi: 10.1073/pnas.93.11.5352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Oehlen L. J., Cross F. R. Potential regulation of Ste20 function by the Cln1-Cdc28 and Cln2-Cdc28 cyclin-dependent protein kinases. J Biol Chem. 1998 Sep 25;273(39):25089–25097. doi: 10.1074/jbc.273.39.25089. [DOI] [PubMed] [Google Scholar]
  31. Pan X., Heitman J. Cyclic AMP-dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Mol Cell Biol. 1999 Jul;19(7):4874–4887. doi: 10.1128/mcb.19.7.4874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pan X., Heitman J. Sok2 regulates yeast pseudohyphal differentiation via a transcription factor cascade that regulates cell-cell adhesion. Mol Cell Biol. 2000 Nov;20(22):8364–8372. doi: 10.1128/mcb.20.22.8364-8372.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Radcliffe P. A., Binley K. M., Trevethick J., Hall M., Sudbery P. E. Filamentous growth of the budding yeast Saccharomyces cerevisiae induced by overexpression of the WHi2 gene. Microbiology. 1997 Jun;143(Pt 6):1867–1876. doi: 10.1099/00221287-143-6-1867. [DOI] [PubMed] [Google Scholar]
  34. Robertson L. S., Fink G. R. The three yeast A kinases have specific signaling functions in pseudohyphal growth. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13783–13787. doi: 10.1073/pnas.95.23.13783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rupp S., Summers E., Lo H. J., Madhani H., Fink G. MAP kinase and cAMP filamentation signaling pathways converge on the unusually large promoter of the yeast FLO11 gene. EMBO J. 1999 Mar 1;18(5):1257–1269. doi: 10.1093/emboj/18.5.1257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Shenhar G., Kassir Y. A positive regulator of mitosis, Sok2, functions as a negative regulator of meiosis in Saccharomyces cerevisiae. Mol Cell Biol. 2001 Mar;21(5):1603–1612. doi: 10.1128/MCB.21.5.1603-1612.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Shimizu M., Li W., Shindo H., Mitchell A. P. Transcriptional repression at a distance through exclusion of activator binding in vivo. Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):790–795. doi: 10.1073/pnas.94.3.790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Shimizu M., Murase A., Hara M., Shindo H., Mitchell A. P. A C-terminal segment with properties of alpha-helix is essential for DNA binding and in vivo function of zinc finger protein Rme1p. J Biol Chem. 2001 Jul 20;276(40):37680–37685. doi: 10.1074/jbc.M105342200. [DOI] [PubMed] [Google Scholar]
  39. Toone W. M., Johnson A. L., Banks G. R., Toyn J. H., Stuart D., Wittenberg C., Johnston L. H. Rme1, a negative regulator of meiosis, is also a positive activator of G1 cyclin gene expression. EMBO J. 1995 Dec 1;14(23):5824–5832. doi: 10.1002/j.1460-2075.1995.tb00270.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Vershon A. K., Pierce M. Transcriptional regulation of meiosis in yeast. Curr Opin Cell Biol. 2000 Jun;12(3):334–339. doi: 10.1016/s0955-0674(00)00104-6. [DOI] [PubMed] [Google Scholar]
  41. Ward M. P., Gimeno C. J., Fink G. R., Garrett S. SOK2 may regulate cyclic AMP-dependent protein kinase-stimulated growth and pseudohyphal development by repressing transcription. Mol Cell Biol. 1995 Dec;15(12):6854–6863. doi: 10.1128/mcb.15.12.6854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Webber A. L., Lambrechts M. G., Pretorius I. S. MSS11, a novel yeast gene involved in the regulation of starch metabolism. Curr Genet. 1997 Oct;32(4):260–266. doi: 10.1007/s002940050275. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES