Abstract
We discuss three major processes that silence genes in filamentous fungi. Repeat-induced point mutation (RIP) causes permanent silencing of repeated genes inNeurospora crassa by peppering them with G:C to A:T mutations during the premeiotic stage of the sexual cycle. A related process, methylation induced premeiotically (MIP), operates during the sexual cycle inAscobolus immersus andCoprinus cinereus to reversibly silence repeated sequences by methylating them. Both processes appear to use a homologous pairing mechanism to sense the presence of duplications. Both MIP and RIP result in dense methylation of cytosines located in nonsymmetrical sequences. This methylation is either always (for MIP) or sometimes (for RIP) maintained during vegetative growth by a novel, epigenetic maintenance mechanism that is not well understood. The third silencing process, quelling inN. crassa, appears to involve post-transcriptional or cotranscriptional disruption of gene expression by transcripts produced from certain transgene loci. This form of silencing seems similar to silencing processes described in many plant species. Each of these genesilencing processes involves silencing of repeated sequences. Thus each is potentially useful for preventing proliferation of selfish DNA elements and for maintaining genome integrity by suppressing chromosomal rearrangements.
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References
Barry C., Faugeron G. and Rossignol J.-L. 1993 Methylation induced premeiotically inAscobolus: Coextension with DNA repeat lengths and effect on transcript elongation.Proc. Natl. Acad. Sci. USA 90: 4557–4561
Bestor T. 1987 Supercoiling-dependent sequence specificity of mammalian DNA methyltransferase.Nucl. Acids Res. 15: 3835–3843
Bestor T. H. and Ingram V. M. 1983 Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA.Proc. Natl. Acad. Sci. USA 80: 5559–5563
Bowring F. J. and Catcheside D. E. A. 1993 The effect ofrec-2 on repeat-induced point-mutation (RIP) and recombination events that excise DNA sequence duplications at thehis-3 locus inNeurospora crassa.Curr. Genet. 23: 496–500
Cambareri E. B., Jensen B. C., Schabtach E. and Selker E. U. 1989 Repeat-induced G-C to A-T mutations inNeurospora.Science 244: 1571–1575
Cambareri E. B., Singer M. J. and Selker E. U. 1991 Recurrence of repeat-induced point mutation (RIP) inNeurospora crassa.Genetics 127: 699–710
Cogoni C., Irelan J. T., Schumacher M., Schmidhauser T. J., Selker E. U. and Macino G. 1996 Transgene silencing of theal-1 gene in vegetative cells ofNeurospora is mediated by a cytoplasmic effector and does not depend on DNA:DNA interactions or DNA methylation.EMBO J. 15: 3153–3163
Colot V., Goyon C., Faugeron G. and Rossignol, J.-L. 1995 Methylation of repeated DNA sequences and genome stability inAscobolus immersus.Can. J. Bot. 73: s221-s225
Colot V., Maloisel L. and Rossignol J.-L. 1996 lnterchromosomal transfer of epigenetic states inAscobolus: transfer of DNA methylation is mechanistically related to homologous recombination.Cell 86: 855–864
Faugeron G., Rhounim L. and Rossignol J.-L. 1990 How does the cell count the number of ectopic copies of a gene in the premeiotic inactivation process acting inAscobolus immersus? Genetics 124: 585–591
Fincham J. R. S., Connerton I. F., Notarianni E. and Harrington K. 1989 Premeiotic disruption of duplicated and triplicated copies of theNeurospora crassa am (glutamate dehydrogenase) gene,Curr.Genet. 15: 327–334
Foss H. M. and Selker E. U. 1991 Efficient DNA pairing in aNeurospora mutant defective in chromosome pairing.Mol. Gen. Genet. 231: 49–52
Foss, E. J., Garrett P. W., Kinsey J. A. and Selker E. U. 1991 Specificity of repeat induced point mutation (RIP) inNeurospora: Sensitivity of non-Neurospora sequences, a natural diverged tandem duplication, and unique DNA adjacent to a duplicated region.Genetics 127: 711–717.
Foss H. M., Roberts C. J., Claeys K. M. and Selker E. U. 1993 Abnormal chromosome behavior inNeurospora mutants defective in DNA methylation.Science 262: 1737–1741
Freedman T. and Pukkila P. J. 1993De novo methylation of repeated sequences inCoprinus cinereus.Genetics 135: 357–366
Goyon C. and Faugeron G. 1989 Targeted transformation ofAscobolus immersus andde new methylation of the resulting duplicated DNA sequences.Mol. Cell. Biol. 9: 2818–2827
Goyon C., Nogueira T. I. V. and Faugeron G. 1994 Perpetuation of cytosine methylation inAscobolus immersus implies a novel type of maintenance methylase.J. Mol. Biol. 240: 42–51
Goyon C., Barry C., Grégoire A., Faugeron G. and Rossignol J.-L. 1996a Methylation of DNA repeats of decreasing sizes inAscobolus immersus.Mol. Cell. Biol. 16: 3054–3065
Goyon C., Rossignol J.-L. and Faugeron G. 1996b Native DNA repeats and methylation inAscobolus. Nucl. Acids Res. (in press)
Grayburn W. S. and Selker E. U. 1989 A natural case of RIP: Degeneration of DNA sequence in an ancestral tandem duplication.Mol. Cell. Biol. 9: 4416–4421
Gruenbaum Y., Cedar H. and Razin A. 1982 Substrate and sequence specificity of a eukaryotic DNA methylase.Nature 295: 620–622
Holliday R. and Pugh J. E. 1975 DNA modification mechanisms and gene activity during development.Science 187: 226–232
Irelan J. T., Hagemann A. T. and Selker E. U. 1994 High fequency repeat-induced point mutation (RIP) is not associated with efficient recombination inNeurospora.Genetics 138: 1093–1103
Kinsey J. A. and Helber J. 1989 Isolation of a transposable element fromNeurospora crassa.Proc. Natl. Acad. Sci. USA 86: 1929–1933
Kinsey J. A., Garrett-Engele P. W., Cambareri E. B. and Selker E. U. 1994 TheNeurospora transposonTad is sensitive to repeat-induced point mutation (RIP).Genetics 138: 657–664
Krumlauf R. and Marzluf G. A. 1979 Characterization of the sequence complexity and organization of theNeurospora crassa genome.Biochemistry 18: 3705–3713
Matzke M. A. and Matzke A. J. 1995 Homology-dependent gene silencing in transgenic plants: what does it really tell us?Trends Genet. 11: 1–3
Orbach M. J., Vollrath D., Davis R. W. and Yanofsky C. 1988 An electrophoretic karyotypeof Neurospora crassa.Mol. Cell. Biol. 8: 1469–1473
Pandit N. N. and Russo V. E. A. 1992 Reversible inactivation of a foreign gene,hph, during the asexual cycle inNeurospora crassa transformants.Mol. Gen. Genet. 234: 412–422
Raju N. B. and Perkins D. D. 1978 Barren perithecia inNeurospora crassa.Can. J. Genet. Cytol. 20: 41–59
Rhounim L., Rossignol J.-L. and Faugeron G. 1992 Epimutation of repeated genes inAscobolus immersus.EMBO J. 11: 4451–4457
Riggs A. D. 1975 X-inactivation, differentiation and DNA methylation.Cytogenet. Cell Genet. 14: 9–25
Roberts C. J. and Selker E. U. 1995 Mutations affecting the biosynthesis of S-adenosylmethionine cause reduction of DNA methylation inNeurospora crassa.Nucl. Acids Res. 23: 4818–4826
Romano N. and Macino G. 1992 Quelling: transient inactivation of gene expression inNeurospora crassa by transformation with homologous sequences.Mol. Microbiol. 6: 3343–3353
Rossignol J.-L. and Faugeron G. 1994 Gene inactivation triggered by recognition between DNA repeats.Experientia 50: 307–317
Schechtman, M. G. 1990 Characterization of telomere DNA fromNeurospora crassa.Gene 88: 159–165
Selker E.U. 1990 Premeiotic instability of repeated sequences inNeurospora crassa.Annu. Rev. Genet. 24: 579–613
Selker E. U. and Garrett P. W. 1988 DNA sequence duplications trigger gene inactivation inNeurospora crassa.Proc. Natl. Acad. Sci. USA 85: 6870–6874
Selker E. U., Cambareri E. B., Jensen B. C. and Haack K. R. 1987a Rearrangement of duplicated DNA in specialized cells ofNeurospora.Cell 51: 741–752
Selker E. U., Jensen B. C. and Richardson G. A. 1987b A portable signal causing faithful DNA methylationde novo in Neurospora crassa.Science 238: 48–53
Selker E. U., Fritz D. Y. and Singer M. J. 1993 Dense non-symmetrical DNA methylation resulting from repeat-induced point mutation (RIP) inNeurospora.Science 262: 1724–1728
Shen J. C., Rideout W. M. III and Jones P. A. 1992 High frequency mutagenesis by a DNA methyltrans-ferase.Cell 71: 1073–1080
Singer M. J., Kuzminova E. A., Tharp A., Margolin B. S. and Selker E. U. 1995a Different frequencies of RIP among early vs. late ascospores ofNeurospora crassa.Fungal Genet. Newsl. 42: 74–75
Singer M. J., Marcotte B. A. and Selker E. U. 1995b DNA methylation associated with repeat-induced point mutation inNeurospora crassa.Mol. Cell. Biol. 15: 5586–5597
Smith S. S., Kan J. L. C., Baker D. J., Kaplan B. E. and Dembek P. 1991 Recognition of unusual DNA structures by human DNA (cytosine-5) methyltransferase.J. Mol. Biol. 217: 39–51
Yebra M. J. and Bhagwat A. S. 1995 A cytosine methyltransferase converts 5-methylcytosine in DNA to thymine.Biochemistry 34: 14752–14757
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Irelan, J.T., Selker, E.U. Gene silencing in filamentous fungi: RIP, MIP and quelling. J. Genet. 75, 313–324 (1996). https://doi.org/10.1007/BF02966311
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DOI: https://doi.org/10.1007/BF02966311