Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1996 Jun 3;15(11):2791–2801.

Nitrogen metabolite signalling involves the C-terminus and the GATA domain of the Aspergillus transcription factor AREA and the 3' untranslated region of its mRNA.

A Platt 1, T Langdon 1, H N Arst Jr 1, D Kirk 1, D Tollervey 1, J M Sanchez 1, M X Caddick 1
PMCID: PMC450215  PMID: 8654376

Abstract

AREA is a GATA transcription factor which mediates nitrogen metabolite repression in Aspergillus nidulans in response to intracellular glutamine levels. We have identified and localized three elements important to modulation of AREA function: a region of 13 residues within the DNA-binding GATA domain which forms a putative extended loop structure, the 12 C-terminal residues, and sequences within a 218 nucleotide region of the 3' UTR. The 12 C-terminal residues are also required for transcriptional activation at a subset of loci under areA control. Specific deletions within the 3' UTR and the C-terminus cause similar levels of derepression and the mutations are additive, implicating two principal signal transduction pathways. The contribution of the 3' UTR to AREA modulation is effected at the level of transcript stability such that the areA mRNA is at least five times more stable under nitrogen-derepressing conditions than it is under repressing growth conditions.

Full text

PDF
2791

Images in this article

2794Image
on p.2794
2797Image
on p.2797

Selected References

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

  1. Arceci R. J., King A. A., Simon M. C., Orkin S. H., Wilson D. B. Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart. Mol Cell Biol. 1993 Apr;13(4):2235–2246. doi: 10.1128/mcb.13.4.2235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arst H. N., Jr A near terminal pericentric inversion leads to nitrogen metabolite derepression in Aspergillus nidulans. Mol Gen Genet. 1982;188(3):490–493. doi: 10.1007/BF00330054. [DOI] [PubMed] [Google Scholar]
  3. Arst H. N., Jr, Cove D. J. Nitrogen metabolite repression in Aspergillus nidulans. Mol Gen Genet. 1973 Nov 2;126(2):111–141. doi: 10.1007/BF00330988. [DOI] [PubMed] [Google Scholar]
  4. Arst H. N., Jr, Kudla B., Martinez-Rossi N., Caddick M. X., Sibley S., Davies R. W. Aspergillus and mouse share a new class of 'zinc finger' protein. Trends Genet. 1989 Sep;5(9):291–291. doi: 10.1016/0168-9525(89)90105-4. [DOI] [PubMed] [Google Scholar]
  5. Arst H. N., Jr, Scazzocchio C. Initiator constitutive mutation with an 'up-promoter' effect in Aspergillus nidulans. Nature. 1975 Mar 6;254(5495):31–34. doi: 10.1038/254031a0. [DOI] [PubMed] [Google Scholar]
  6. Caddick M. X., Arst H. N., Jr Nitrogen regulation in Aspergillus: are two fingers better than one? Gene. 1990 Oct 30;95(1):123–127. doi: 10.1016/0378-1119(90)90422-n. [DOI] [PubMed] [Google Scholar]
  7. Caddick M. X. Nitrogen metabolite repression. Prog Ind Microbiol. 1994;29:323–353. [PubMed] [Google Scholar]
  8. Cannons A. C., Pendleton L. C. Possible role for mRNA stability in the ammonium-controlled regulation of nitrate reductase expression. Biochem J. 1994 Feb 1;297(Pt 3):561–565. doi: 10.1042/bj2970561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Crawford N. M., Arst H. N., Jr The molecular genetics of nitrate assimilation in fungi and plants. Annu Rev Genet. 1993;27:115–146. doi: 10.1146/annurev.ge.27.120193.000555. [DOI] [PubMed] [Google Scholar]
  10. Crossley M., Merika M., Orkin S. H. Self-association of the erythroid transcription factor GATA-1 mediated by its zinc finger domains. Mol Cell Biol. 1995 May;15(5):2448–2456. doi: 10.1128/mcb.15.5.2448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cunningham T. S., Cooper T. G. Expression of the DAL80 gene, whose product is homologous to the GATA factors and is a negative regulator of multiple nitrogen catabolic genes in Saccharomyces cerevisiae, is sensitive to nitrogen catabolite repression. Mol Cell Biol. 1991 Dec;11(12):6205–6215. doi: 10.1128/mcb.11.12.6205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cybis J., Weglenski P. Arginase induction in Aspergillus nidulans. The appearance and decay of the coding capacity of messenger. Eur J Biochem. 1972 Oct;30(2):262–268. doi: 10.1111/j.1432-1033.1972.tb02094.x. [DOI] [PubMed] [Google Scholar]
  13. Darlington A. J., Scazzocchio C. Use of analogues and the substrate-sensitivity of mutants in analysis of purine uptake and breakdown in Aspergillus nidulans. J Bacteriol. 1967 Mar;93(3):937–940. doi: 10.1128/jb.93.3.937-940.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Decker C. J., Parker R. Mechanisms of mRNA degradation in eukaryotes. Trends Biochem Sci. 1994 Aug;19(8):336–340. doi: 10.1016/0968-0004(94)90073-6. [DOI] [PubMed] [Google Scholar]
  15. Diallinas G., Scazzocchio C. A gene coding for the uric acid-xanthine permease of Aspergillus nidulans: inactivational cloning, characterization, and sequence of a cis-acting mutation. Genetics. 1989 Jun;122(2):341–350. doi: 10.1093/genetics/122.2.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Drevet J. R., Skeiky Y. A., Iatrou K. GATA-type zinc finger motif-containing sequences and chorion gene transcription factors of the silkworm Bombyx mori. J Biol Chem. 1994 Apr 8;269(14):10660–10667. [PubMed] [Google Scholar]
  17. Evans T., Felsenfeld G. The erythroid-specific transcription factor Eryf1: a new finger protein. Cell. 1989 Sep 8;58(5):877–885. doi: 10.1016/0092-8674(89)90940-9. [DOI] [PubMed] [Google Scholar]
  18. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  19. Fidel S., Doonan J. H., Morris N. R. Aspergillus nidulans contains a single actin gene which has unique intron locations and encodes a gamma-actin. Gene. 1988 Oct 30;70(2):283–293. doi: 10.1016/0378-1119(88)90200-4. [DOI] [PubMed] [Google Scholar]
  20. Fu Y. H., Marzluf G. A. nit-2, the major nitrogen regulatory gene of Neurospora crassa, encodes a protein with a putative zinc finger DNA-binding domain. Mol Cell Biol. 1990 Mar;10(3):1056–1065. doi: 10.1128/mcb.10.3.1056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Haas H., Bauer B., Redl B., Stöffler G., Marzluf G. A. Molecular cloning and analysis of nre, the major nitrogen regulatory gene of Penicillium chrysogenum. Curr Genet. 1995 Jan;27(2):150–158. doi: 10.1007/BF00313429. [DOI] [PubMed] [Google Scholar]
  22. Hynes M. J., Pateman J. A. The genetic analysis of regulation of amidase synthesis in Aspergillus nidulans. I. Mutants able to utilize acrylamide. Mol Gen Genet. 1970;108(2):97–106. doi: 10.1007/BF02430516. [DOI] [PubMed] [Google Scholar]
  23. Hynes M. J. Studies on the role of the areA gene in the regulation of nitrogen catabolism in Aspergillus nidulans. Aust J Biol Sci. 1975 Jun;28(3):301–313. doi: 10.1071/bi9750301. [DOI] [PubMed] [Google Scholar]
  24. Joulin V., Bories D., Eléouet J. F., Labastie M. C., Chrétien S., Mattéi M. G., Roméo P. H. A T-cell specific TCR delta DNA binding protein is a member of the human GATA family. EMBO J. 1991 Jul;10(7):1809–1816. doi: 10.1002/j.1460-2075.1991.tb07706.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Katz M. E., Hynes M. J. Characterization of the amdR-controlled lamA and lamB genes of Aspergillus nidulans. Genetics. 1989 Jun;122(2):331–339. doi: 10.1093/genetics/122.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kelley C., Blumberg H., Zon L. I., Evans T. GATA-4 is a novel transcription factor expressed in endocardium of the developing heart. Development. 1993 Jul;118(3):817–827. doi: 10.1242/dev.118.3.817. [DOI] [PubMed] [Google Scholar]
  27. Kudla B., Caddick M. X., Langdon T., Martinez-Rossi N. M., Bennett C. F., Sibley S., Davies R. W., Arst H. N., Jr The regulatory gene areA mediating nitrogen metabolite repression in Aspergillus nidulans. Mutations affecting specificity of gene activation alter a loop residue of a putative zinc finger. EMBO J. 1990 May;9(5):1355–1364. doi: 10.1002/j.1460-2075.1990.tb08250.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Langdon T., Sheerins A., Ravagnani A., Gielkens M., Caddick M. X., Arst H. N., Jr Mutational analysis reveals dispensability of the N-terminal region of the Aspergillus transcription factor mediating nitrogen metabolite repression. Mol Microbiol. 1995 Sep;17(5):877–888. doi: 10.1111/j.1365-2958.1995.mmi_17050877.x. [DOI] [PubMed] [Google Scholar]
  29. Laverriere A. C., MacNeill C., Mueller C., Poelmann R. E., Burch J. B., Evans T. GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut. J Biol Chem. 1994 Sep 16;269(37):23177–23184. [PubMed] [Google Scholar]
  30. Lee W. M., Lin C., Curran T. Activation of the transforming potential of the human fos proto-oncogene requires message stabilization and results in increased amounts of partially modified fos protein. Mol Cell Biol. 1988 Dec;8(12):5521–5527. doi: 10.1128/mcb.8.12.5521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Leuther K. K., Salmeron J. M., Johnston S. A. Genetic evidence that an activation domain of GAL4 does not require acidity and may form a beta sheet. Cell. 1993 Feb 26;72(4):575–585. doi: 10.1016/0092-8674(93)90076-3. [DOI] [PubMed] [Google Scholar]
  32. Magasanik B. Regulation of transcription of the glnALG operon of Escherichia coli by protein phosphorylation. Biochimie. 1989 Sep-Oct;71(9-10):1005–1012. doi: 10.1016/0300-9084(89)90104-1. [DOI] [PubMed] [Google Scholar]
  33. Martin D. I., Orkin S. H. Transcriptional activation and DNA binding by the erythroid factor GF-1/NF-E1/Eryf 1. Genes Dev. 1990 Nov;4(11):1886–1898. doi: 10.1101/gad.4.11.1886. [DOI] [PubMed] [Google Scholar]
  34. Meijlink F., Curran T., Miller A. D., Verma I. M. Removal of a 67-base-pair sequence in the noncoding region of protooncogene fos converts it to a transforming gene. Proc Natl Acad Sci U S A. 1985 Aug;82(15):4987–4991. doi: 10.1073/pnas.82.15.4987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Merika M., Orkin S. H. DNA-binding specificity of GATA family transcription factors. Mol Cell Biol. 1993 Jul;13(7):3999–4010. doi: 10.1128/mcb.13.7.3999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Merika M., Orkin S. H. Functional synergy and physical interactions of the erythroid transcription factor GATA-1 with the Krüppel family proteins Sp1 and EKLF. Mol Cell Biol. 1995 May;15(5):2437–2447. doi: 10.1128/mcb.15.5.2437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Minehart P. L., Magasanik B. Sequence and expression of GLN3, a positive nitrogen regulatory gene of Saccharomyces cerevisiae encoding a protein with a putative zinc finger DNA-binding domain. Mol Cell Biol. 1991 Dec;11(12):6216–6228. doi: 10.1128/mcb.11.12.6216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Muhlrad D., Parker R. Premature translational termination triggers mRNA decapping. Nature. 1994 Aug 18;370(6490):578–581. doi: 10.1038/370578a0. [DOI] [PubMed] [Google Scholar]
  39. Omichinski J. G., Clore G. M., Schaad O., Felsenfeld G., Trainor C., Appella E., Stahl S. J., Gronenborn A. M. NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1. Science. 1993 Jul 23;261(5120):438–446. doi: 10.1126/science.8332909. [DOI] [PubMed] [Google Scholar]
  40. PONTECORVO G., ROPER J. A., HEMMONS L. M., MACDONALD K. D., BUFTON A. W. J. The genetics of Aspergillus nidulans. Adv Genet. 1953;5:141–238. doi: 10.1016/s0065-2660(08)60408-3. [DOI] [PubMed] [Google Scholar]
  41. Pateman J. A., Dunn E., Mackay E. M. Urea and thiourea transport in Aspergillus nidulans. Biochem Genet. 1982 Aug;20(7-8):777–790. doi: 10.1007/BF00483973. [DOI] [PubMed] [Google Scholar]
  42. Peters D. G., Caddick M. X. Direct analysis of native and chimeric GATA specific DNA binding proteins from Aspergillus nidulans. Nucleic Acids Res. 1994 Dec 11;22(24):5164–5172. doi: 10.1093/nar/22.24.5164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Platt A., Ravagnani A., Arst H., Jr, Kirk D., Langdon T., Caddick M. X. Mutational analysis of the C-terminal region of AREA, the transcription factor mediating nitrogen metabolite repression in Aspergillus nidulans. Mol Gen Genet. 1996 Jan 15;250(1):106–114. doi: 10.1007/BF02191830. [DOI] [PubMed] [Google Scholar]
  44. Rand K. N., Arst H. N., Jr A mutation in Aspergillus nidulans which affects the regulation of nitrite reductase and is tightly linked to its structural gene. Mol Gen Genet. 1977 Sep 21;155(1):67–75. doi: 10.1007/BF00268562. [DOI] [PubMed] [Google Scholar]
  45. Rand K. N., Arst H. N., Jr Mutations in nirA gene of Aspergillus nidulans and nitrogen metabolism. Nature. 1978 Apr 20;272(5655):732–734. doi: 10.1038/272732a0. [DOI] [PubMed] [Google Scholar]
  46. Shaffer P. M., Arst H. N., Jr, Estberg L., Fernando L., Ly T., Sitter M. An asparaginase of Aspergillus nidulans is subject to oxygen repression in addition to nitrogen metabolite repression. Mol Gen Genet. 1988 May;212(2):337–341. doi: 10.1007/BF00334704. [DOI] [PubMed] [Google Scholar]
  47. Shaffer P. M., Arst H. N., Jr Regulation of pyrimidine salvage in Aspergillus nidulans: a role for the major regulatory gene are A mediating nitrogen metabolite repression. Mol Gen Genet. 1984;198(2):139–145. doi: 10.1007/BF00328713. [DOI] [PubMed] [Google Scholar]
  48. Stanbrough M., Rowen D. W., Magasanik B. Role of the GATA factors Gln3p and Nil1p of Saccharomyces cerevisiae in the expression of nitrogen-regulated genes. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9450–9454. doi: 10.1073/pnas.92.21.9450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Stankovich M., Platt A., Caddick M. X., Langdon T., Shaffer P. M., Arst H. N., Jr C-terminal truncation of the transcriptional activator encoded by areA in Aspergillus nidulans results in both loss-of-function and gain-of-function phenotypes. Mol Microbiol. 1993 Jan;7(1):81–87. doi: 10.1111/j.1365-2958.1993.tb01099.x. [DOI] [PubMed] [Google Scholar]
  50. Tilburn J., Sarkar S., Widdick D. A., Espeso E. A., Orejas M., Mungroo J., Peñalva M. A., Arst H. N., Jr The Aspergillus PacC zinc finger transcription factor mediates regulation of both acid- and alkaline-expressed genes by ambient pH. EMBO J. 1995 Feb 15;14(4):779–790. doi: 10.1002/j.1460-2075.1995.tb07056.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Tsai S. F., Martin D. I., Zon L. I., D'Andrea A. D., Wong G. G., Orkin S. H. Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature. 1989 Jun 8;339(6224):446–451. doi: 10.1038/339446a0. [DOI] [PubMed] [Google Scholar]
  52. Voisard C., Wang J., McEvoy J. L., Xu P., Leong S. A. urbs1, a gene regulating siderophore biosynthesis in Ustilago maydis, encodes a protein similar to the erythroid transcription factor GATA-1. Mol Cell Biol. 1993 Nov;13(11):7091–7100. doi: 10.1128/mcb.13.11.7091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Wiame J. M., Grenson M., Arst H. N., Jr Nitrogen catabolite repression in yeasts and filamentous fungi. Adv Microb Physiol. 1985;26:1–88. doi: 10.1016/s0065-2911(08)60394-x. [DOI] [PubMed] [Google Scholar]
  54. Xiao X., Fu Y. H., Marzluf G. A. The negative-acting NMR regulatory protein of Neurospora crassa binds to and inhibits the DNA-binding activity of the positive-acting nitrogen regulatory protein NIT2. Biochemistry. 1995 Jul 11;34(27):8861–8868. doi: 10.1021/bi00027a038. [DOI] [PubMed] [Google Scholar]
  55. Yamamoto M., Ko L. J., Leonard M. W., Beug H., Orkin S. H., Engel J. D. Activity and tissue-specific expression of the transcription factor NF-E1 multigene family. Genes Dev. 1990 Oct;4(10):1650–1662. doi: 10.1101/gad.4.10.1650. [DOI] [PubMed] [Google Scholar]
  56. Yang H. Y., Evans T. Distinct roles for the two cGATA-1 finger domains. Mol Cell Biol. 1992 Oct;12(10):4562–4570. doi: 10.1128/mcb.12.10.4562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Yang H. Y., Evans T. Homotypic interactions of chicken GATA-1 can mediate transcriptional activation. Mol Cell Biol. 1995 Mar;15(3):1353–1363. doi: 10.1128/mcb.15.3.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Yang Z., Gu L., Romeo P. H., Bories D., Motohashi H., Yamamoto M., Engel J. D. Human GATA-3 trans-activation, DNA-binding, and nuclear localization activities are organized into distinct structural domains. Mol Cell Biol. 1994 Mar;14(3):2201–2212. doi: 10.1128/mcb.14.3.2201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Young J. L., Jarai G., Fu Y. H., Marzluf G. A. Nucleotide sequence and analysis of NMR, a negative-acting regulatory gene in the nitrogen circuit of Neurospora crassa. Mol Gen Genet. 1990 Jun;222(1):120–128. doi: 10.1007/BF00283032. [DOI] [PubMed] [Google Scholar]
  60. Young J. L., Marzluf G. A. Molecular comparison of the negative-acting nitrogen control gene, nmr, in Neurospora crassa and other Neurospora and fungal species. Biochem Genet. 1991 Oct;29(9-10):447–459. [PubMed] [Google Scholar]
  61. Zon L. I., Tsai S. F., Burgess S., Matsudaira P., Bruns G. A., Orkin S. H. The major human erythroid DNA-binding protein (GF-1): primary sequence and localization of the gene to the X chromosome. Proc Natl Acad Sci U S A. 1990 Jan;87(2):668–672. doi: 10.1073/pnas.87.2.668. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES