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The chromo and SET domains of the Clr4 protein are essential for silencing in fission yeast

Nature Genetics volume 19, pages 192–195 (1998)Cite this article

Abstract

Heritable inactivation of specific regions of the genome is a widespread, possibly universal phenomenon for gene regulation in eukaryotes. Self-perpetuating, clonally inherited chromatin structure has been proposed as the explanation for such phenomena as position-effect variegation1,2 (PEV) and control of segment determination and differentiation in flies3, X-chromosome inactivation and parental imprinting in mammals4,5, gene silencing by paramutation in maize6 and silencing of the mating-type loci in yeasts7,8. We have now found that the clr4 gene, which is essential for silencing of centromeres9 and the mating-type loci in Schizosaccharomyces pombe8,10, encodes a protein with high homology to the product of Su(var)3-9, a gene affecting PEV in Drosophila1. Like Su(var)3-9p, Clr4p contains SET and chromo domains, motifs found in proteins that modulate chromatin structure. Site-directed mutations in the conserved residues of the chromo domain confirm that it is required for proper silencing and directional switching of the mating type, like SET domain. Surprisingly, RNA differential display experiments demonstrated that clr4+ can mediate transcriptional activation of certain other loci. These results show that clr4 plays a critical role in silencing at mating-type loci and centromeres through the organization of repressive chromatin structure and demonstrate a new, activator function for Clr4p.

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Figure 1: Sequence and domain homology of Clr4p.
Figure 2: Sporulation phenotypes of clr4 mutants.
Figure 3: Northern-blot analysis showing that regulation of cdl genes depends on clr4 function.

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References

  1. Tschiersch, B. et al. The protein encoded by the Drosophila position-effect variegation suppressor gene Su(var)3-9 combines domains of antagonistic regulators of homeotic gene complexes. EMBO J. 13, 3822–3831 (1994).

    Article  CAS  Google Scholar 

  2. Csink, A.K. Henikoff, S. Genetic modification of heterochromatic association and nuclear organization in Drosophila. Nature 381, 529–531 ( 1996).

    Article  CAS  Google Scholar 

  3. Chan, C.S., Rastelli, L. Pirrotta, V. A Polycomb response element in the Ubx gene that determines an epigenetically inherited state of repression. EMBO J. 13, 2553–2564 (1994).

    Article  CAS  Google Scholar 

  4. Lyon, M.F. et al. Lack of inactivation of a mouse X-linked gene physically separated from the inactivation centre. J. Embryol. Exp. Morphol. 97, 75–85 (1986).

    CAS  PubMed  Google Scholar 

  5. Ainscough, J.F. Koide, T. Tada, M. Barton, S. Surani, M.A. Imprinting of Igf2 and H19 from a 130 kb YAC transgene . Development 124, 3621–3632 (1997).

    CAS  PubMed  Google Scholar 

  6. Hollick, J.B. Patterson, G.I. Coe, E.H., Jr. Cone, K.C. Chandler, V. Allelic interactions heritably alter the activity of a metastable maize pl allele. Genetics 141, 709–719 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Braunstein, M. Rose, A.B. Holmes, S.G. Allis, C.D. Broach, J.R. Transcriptional silencing in yeast is associated with reduced nucleosome acetylation. Genes Dev. 7, 592–604 (1993).

    Article  CAS  Google Scholar 

  8. Klar, A.J.S. Ivanova, A.V. Dalgaard, J.C. Bonaduce M.J. Grewal, S.I.S. Multiple epigenetic events regulate mating-type switching of fission yeast. In: Epigenetics, (eds Chadwick, D.J. and Casdew, G.) 87–103 (Wiley & Sons, Chichester, 1998).

    Google Scholar 

  9. Allshire, R.C. Transcriptional silencing in the fission yeast: a manifestation of higher order chromatin structure and function. in: Epigenetic mechanisms of gene expression, (eds Russo, V.E.A., Martienssen, R.A. & Riggs, A.D.) 443–466 (Cold Spring Harbor Laboratory Press, New York, 1996).

    Google Scholar 

  10. Grewal, S.I. Klar, A.J.S. A recombinationally repressed region between mat2 and mat3 loci shares homology to centromeric repeats and regulates directionality of mating-type switching in fission yeast. Genetics 146, 1221–1238 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Hoheisel J.D. et al. High resolution cosmid and P1 maps spanning the 14 Mb genome of the fission yeast S. pombe. Cell 73, 103–120 (1993).

    Article  Google Scholar 

  12. Dingwall, C., Laskey R.A. Nuclear targeting sequences--a consensus ? Trends Biochem. Sci. 16, 478–481 (1991).

    Article  CAS  Google Scholar 

  13. Singh, P.B. Molecular mechanisms of cellular determination: their relation to chromatin structure and parental imprinting. J. Cell Sci. 107, 2653–2668 (1994).

    CAS  PubMed  Google Scholar 

  14. Platero, J.S. Hartnett, T. Eissenberg, J.C. Functional analysis of the chromo domain of HP1. EMBO J. 14, 3977–3986 (1995).

    Article  CAS  Google Scholar 

  15. Messmer, S. Franke, A. Paro, R. Analysis of the functional role of the Polycomb chromo domain in Drosophila melanogaster. Genes Dev. 6, 1241–1254 (1992).

    Article  CAS  Google Scholar 

  16. Ball, L.J. et al. Structure of the chromatin binding (chromo) domain from mouse modifier protein 1. EMBO J. 16, 2473–2481 (1997).

    Article  CAS  Google Scholar 

  17. Thon, G. Cohen A. Klar, A.J.S. Three additional linkage groups that repress transcription and meiotic recombination in the mating-type region of Schizosaccharomyces pombe. Genetics 138, 29–38 ( 1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Thon, G. Klar, A.J.S. Directionality of fission yeast mating-type interconversion is controlled by the location of the donor loci. Genetics 134, 1045–1054 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Engelke, U., Grabowski, L., Gutz, H., Heim, L. Schmidt, H. Molecular characterization of h- mutants of Schizosaccharomyces pombe. Curr. Genet. 12, 532–542 (1987).

    Article  Google Scholar 

  20. Hardy, C.F., Balderes, D., Shore, D. Dissection of a carboxy-terminal region of the yeast regulatory protein RAP1 with effects on both transcriptional activation and silencing. Mol. Cell. Biol. 12, 1209–1217 (1992).

    Article  CAS  Google Scholar 

  21. Liang, P. Pardee A.B. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 257, 967–971 (1992).

    Article  CAS  Google Scholar 

  22. Allshire, R.C., Nimmo, E.R., Ekwall, K., Javerzat, J.P. Cranston, G. Mutations derepressing silent centromeric domains in fission yeast disrupt chromosome segregation. Genes Dev. 9, 218–233 (1995).

    Article  CAS  Google Scholar 

  23. Sawin, K.E. Nurse, P. Identification of fission yeast nuclear markers using random polypeptide fusions with fluorecsent protein. Proc. Natl. Acad. Sci. USA 94, 15146–15151 (1996).

    Article  Google Scholar 

  24. Bryk, M. et al. Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast. Genes Dev. 11, 255–269 ( 1997).

    Article  CAS  Google Scholar 

  25. Ekwall, K. et al. Mutations in the fission yeast silencing factors clr4+ and rik1+ disrupt the localisation of the chromo domain protein Swi6p and impair centromere function . J. Cell Sci. 109, 2637–2648 (1996).

    CAS  PubMed  Google Scholar 

  26. Jiang, Y.W. Stillman, D.J. Involvement of the SIN4 global transcriptional regulator in the chromatin structure of Saccharomyces cerevisiae. Mol. Cell. Biol. 12, 4503–4514 (1992).

    Article  CAS  Google Scholar 

  27. Nislow, C., Ray, E. Pillus, L. SET1, A yeast member of the trithorax family, functions in transcriptional silencing and diverse cellular processes. Mol. Biol. Cell. 8 2421–2436 (1997).

    Article  CAS  Google Scholar 

  28. Moreno, S., Klar, A.J.S. Nurse, P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 194, 795–823 (1991).

    Article  CAS  Google Scholar 

  29. Ho, S.N., Hunt, H.D., Horton, R.M., Pullen, J.K. Pease, L.R. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 77, 51–59 (1989).

    Article  CAS  Google Scholar 

  30. Altshul, S.F., Miller, W., Myers, E.W. Lipman, D.J. 1990 Basic local alignment search tool. J. Mol. Biol. 215, 404–410 (1990).

    Google Scholar 

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Acknowledgements

We thank members of the Gene Regulation and Chromosome Biology Laboratory for helpful discussions, especially J. Sabl for helpful comments on the manuscript, D. Beach and P. Young for the S. pombe library and A. Arthur for editing the manuscript. This work was sponsored by the National Cancer Institute, DHHS, under contract with ABL.

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  1. NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Gene Regulation and Chromosome Biology Laboratory, Frederick, 21702-1201, Maryland, USA

    Alla V. Ivanova, Michael J. Bonaduce, Sergey V. Ivanov & Amar J. S. Klar

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  1. Alla V. Ivanova
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  2. Michael J. Bonaduce
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  4. Amar J. S. Klar
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Correspondence to Amar J. S. Klar.

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Ivanova, A., Bonaduce, M., Ivanov, S. et al. The chromo and SET domains of the Clr4 protein are essential for silencing in fission yeast. Nat Genet 19, 192–195 (1998). https://doi.org/10.1038/566

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