Suppression of gene expression by homologous transgenes (original) (raw)

Abstract

When a wild-type strain of_Neurospora crassa_ is transformed with different portions of the carotenogenic albino 1 or albino 3 genes, up to 30–35% of the transformants show an albino phenotype. The albino transformants presented a variety of phenotypes ranging from white or yellow to dark yellow colour. The ectopically integrated sequences provoke a severe impairment of the expression of the endogenous_al-1_ or_al-3_ genes. This phenomenon, that has been termed quelling, is found to be spontaneously and progressively reversible. In fact, all of the albino transformants have an unstable phenotype and revert progressively to wild type or intermediate phenotypes over a prolonged culturing time. The phenotypic reversion is characterised by a progressive release of the transcriptional inhibition and seems to correlate with the reduction of the number of the ectopic integrated sequences. However, there is no strict correlation between the copy number of the ectopic sequences and the intensity of quelling, as indicated by the existence of albino transformants containing only 1–2 ectopic sequences. The nature of the molecular events determining the onset of quelling is unclear, in any event, these are likely to involve some kind of interaction between the resident genes and ectopically integrated exogenous sequences. Recent evidences on a possible mechanism are presented.

Access this article

Log in via an institution

Subscribe and save

• Starting from 10 chapters or articles per month
• Access and download chapters and articles from more than 300k books and 2,500 journals
• Cancel anytime View plans

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

• Barry C, Faugeron G & Rossignol J (1993) Methylation induced premeiotically in_Ascobolus_: Coextension with DNA repeat lengths and effect on transcript elongation. Proc. Natl. Acad. Sci. USA 90: 4557–4561
  PubMed Google Scholar
• Bird AP (1986) CpG rich islands and the function of DNA methylation. Nature 321: 209–213
  PubMed Google Scholar
• Brussian JA, Karlin-Neumann GA, Lu Huang & Tobin EM (1993) An Arabidopsis mutant with a reduced level of cab140 RNA is a result of cosuppression. Plant Cell 5: 667–677
  Article PubMed Google Scholar
• Bull JH & Wootton JC (1984) Heavily methylated amplified DNA in transformants of_Neurospora crassa_. Nature 310: 701–704
  PubMed Google Scholar
• Carattoli A, Romano N, Ballario P, Morelli G & Macino G (1991) The_Neurospora crassa_ carotenoid biosynthetic gene (albino-3) reveals highly conserved regions among prenyltransferases. J. Biol. Chem. 266: 5854–5859
  PubMed Google Scholar
• Cedar H (1988) DNA methylation and gene activity. Cell 53: 3–4
  Article PubMed Google Scholar
• de Carvalho F, Gheyesen G, Kushnir S, van Montagu M, Inze D & Castresana C (1992) Suppression of β-1–3 glucanase transgene expression in homozygous plants. EMBO J. 11: 2595–2602
  PubMed Google Scholar
• Doerfler W (1983) DNA methylation and gene activity. Ann. Rev. Biochem. 52: 93–124
  PubMed Google Scholar
• Ebbole D & Sachs MS (1990) A rapid and simple method for isolation of_Neurospora crassa_ homokaryons using microconidia. Neurospora Newslett. 37: 17–18
  Google Scholar
• Elkind Y, Edwards R, Mavandad M, Hedrick SA, Ribak O, Dixon RA & Lamb CJ (1990) Abnormal plant development and down regulation of phenylpropanoid biosynthesis in trnsgenic tobacco containing a heterologous phenylalanine ammonia lyase gene. Proc. Natl. Acad. Sci. USA 87: 9057–9061
  PubMed Google Scholar
• Faugeron G, Rhounim L & Rossignol JL (1990) How does the cell count the number of ectopic copies of a gene in the premeiotic inactivation process acting in_Ascobolus immersus?_ Genetics 124: 585–591
  PubMed Google Scholar
• Goring D, Thomson L, & Rothstein SJ (1991) Transformation of a partial nopaline synthase gene into tobacco suppresses the expression of a resident wild-type gene. Proc. Natl. Acad. Sci. USA 88: 1770–1774
  PubMed Google Scholar
• Goyon C & Faugeron G (1989) Targeted transformation of_Ascobolus immersus_ and_de novo_ methylation of the resulted duplicated sequences. Mol. Cell. Biol. 9: 2818–2827
  PubMed Google Scholar
• Hart CM, Fischer B, Neuhaus JM & Meins F (1992) Regulated inactivation of homologous gene expression in transgenic Nicotiana sylvestris plants containing a defense-releted tobacco chitinase gene. Mol Gen. Genet. 235: 179–188
  PubMed Google Scholar
• Jones PA (1985) Altering gene expression with 5-azacytidine. Cell 40: 485–486
  Article PubMed Google Scholar
• Matzke MA, Primig M, Trnovsky J & Matzke AJM (1989) Reversible methylation and inactivation of marker genes in sequentially transformed tobacco plants EMBO J. 8: 643–648
  Google Scholar
• Mittelsten Scheid O, Paszkowski J & Potrykus I (1991) Reversible inactivation of a transgene in_Arabidopsis thaliana_. Mol. Gen. Genet. 228: 104–112
  PubMed Google Scholar
• Mol J, van Blockland RV & Kooter J (1991) More about cosuppression. Trends Biotech. 9: 182–183
  Google Scholar
• Napoli C, Lemieux C & Jorgensen R (1990) Introduction of a chimeric chalcone synthase gene into Petunia results in reversible co-suppression of homologous genes in trans. Plant Cell 2: 279–289
  Article PubMed Google Scholar
• Nelson M & McClelland M (1989) Effect of site specific methylation or DNA modification methyltransferases and restriction endonucleases. Nucleic Acid Res. 17, supplement: r389–415
  Google Scholar
• Nelson MA, Morelli G, Carattoli A, Romano N & Macino G (1989) Molecular cloning of a_Neurospora crassa_ carotenoid biosynthtic gene (albino-3) regulated by blue light and the products of white collar genes. Mol. Cell. Biol. 9: 1271–1276
  PubMed Google Scholar
• Pandit NN & Russo VEA (1992) Reversible inactivation of a foreign gene, hph, during the asexual cycle in_Neurospora crassa_ transformants. Mol. Gen. Genet. 234: 412–422
  PubMed Google Scholar
• Razin A & Riggs AD (1980) DNA methylation and gene function. Science 210: 604–610
  PubMed Google Scholar
• Romano N & Macino G (1992) Quelling: Transient inactivation of gene expression in_Neurospora crassa_ by transformation with homologous sequences. Mol. Microbiol. 6: 3343–3353
  PubMed Google Scholar
• Schmidhauser TJ, Lauter FR, Russo VEA & Yanofsky C (1990) Cloning, sequence and photoregulation of al-1, a carotenoid biosynthetic gene of_Neurospora crassa_. Mol. Cell. Biol. 10: 5064–5070
  PubMed Google Scholar
• Selker EV (1990) Premeiotic instability of repeated sequences in_Neurospora crassa_, Ann. Rev. Genet. 24: 579–613
  PubMed Google Scholar
• Selker EV, Cambareri EB, Jensen BC & Haach KK (1987) Rearrangement of duplicated DNA in specialized cells of Neurospora. Cell 51: 741–752
  PubMed Google Scholar
• Smith CJS, Watson CF, Bird CR, Ray J, Schuch W & Grierson D (1990) Expression of a truncated tomato polygalacturonase gene inhibits expression of the endogenous gene in transgenic plants. Mol. Gen. Genet. 224: 477–481
  PubMed Google Scholar
• van der Krol AR, Mur LA, Beld M, Mol JNM & Stuitje AR (1990) Flavonoid genes in petunia: Addition of a limited number of gene copies may lead to a suppression of gene expression. Plant Cell 2: 291–299
  Article PubMed Google Scholar

Download references

Author information

Authors and Affiliations

1. Dipartimento Biopatologia Umana, Sezione di Biologia Cellulare, Università di Roma ‘La Sapienza’, Policlinico Umberto I, I-00161, Rome, Italy
   Carlo Cogoni, Nicoletta Romano & Giuseppe Macino

Authors

1. Carlo Cogoni
2. Nicoletta Romano
3. Giuseppe Macino

Rights and permissions

About this article

Cite this article

Cogoni, C., Romano, N. & Macino, G. Suppression of gene expression by homologous transgenes.Antonie van Leeuwenhoek 65, 205–209 (1994). https://doi.org/10.1007/BF00871948

Download citation

• Issue date: September 1994
• DOI: https://doi.org/10.1007/BF00871948

Key words