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. 2002 Oct;162(2):973–976. doi: 10.1093/genetics/162.2.973

SIR2-induced inviability is suppressed by histone H4 overexpression.

Mirela Matecic 1, Shelagh Stuart 1, Scott G Holmes 1
PMCID: PMC1462276  PMID: 12399404

Abstract

We have identified histone H4 as a high-expression suppressor of Sir2-induced inviability in yeast cells. Overexpression of histone H3 does not suppress Sir2-induced lethality, nor does overexpression of histone H4 alleles associated with silencing defects. These results suggest a direct and specific interaction between Sir2 and H4 in the silencing mechanism.

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Selected References

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  1. 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. 1993 Apr;7(4):592–604. doi: 10.1101/gad.7.4.592. [DOI] [PubMed] [Google Scholar]
  2. Braunstein M., Sobel R. E., Allis C. D., Turner B. M., Broach J. R. Efficient transcriptional silencing in Saccharomyces cerevisiae requires a heterochromatin histone acetylation pattern. Mol Cell Biol. 1996 Aug;16(8):4349–4356. doi: 10.1128/mcb.16.8.4349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Costanzo M. C., Crawford M. E., Hirschman J. E., Kranz J. E., Olsen P., Robertson L. S., Skrzypek M. S., Braun B. R., Hopkins K. L., Kondu P. YPD, PombePD and WormPD: model organism volumes of the BioKnowledge library, an integrated resource for protein information. Nucleic Acids Res. 2001 Jan 1;29(1):75–79. doi: 10.1093/nar/29.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. D'Amours D., Desnoyers S., D'Silva I., Poirier G. G. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J. 1999 Sep 1;342(Pt 2):249–268. [PMC free article] [PubMed] [Google Scholar]
  5. Fedor-Chaiken M., Deschenes R. J., Broach J. R. SRV2, a gene required for RAS activation of adenylate cyclase in yeast. Cell. 1990 Apr 20;61(2):329–340. doi: 10.1016/0092-8674(90)90813-t. [DOI] [PubMed] [Google Scholar]
  6. Gartenberg M. R. The Sir proteins of Saccharomyces cerevisiae: mediators of transcriptional silencing and much more. Curr Opin Microbiol. 2000 Apr;3(2):132–137. doi: 10.1016/s1369-5274(00)00064-3. [DOI] [PubMed] [Google Scholar]
  7. Ghidelli S., Donze D., Dhillon N., Kamakaka R. T. Sir2p exists in two nucleosome-binding complexes with distinct deacetylase activities. EMBO J. 2001 Aug 15;20(16):4522–4535. doi: 10.1093/emboj/20.16.4522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goodwin P. M., Lewis P. J., Davies M. I., Skidmore C. J., Shall S. The effect of gamma radiation and neocarzinostatin on NAD and ATP levels in mouse leukaemia cells. Biochim Biophys Acta. 1978 Nov 1;543(4):576–582. doi: 10.1016/0304-4165(78)90312-4. [DOI] [PubMed] [Google Scholar]
  9. Hecht A., Laroche T., Strahl-Bolsinger S., Gasser S. M., Grunstein M. Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast. Cell. 1995 Feb 24;80(4):583–592. doi: 10.1016/0092-8674(95)90512-x. [DOI] [PubMed] [Google Scholar]
  10. Holmes S. G., Rose A. B., Steuerle K., Saez E., Sayegh S., Lee Y. M., Broach J. R. Hyperactivation of the silencing proteins, Sir2p and Sir3p, causes chromosome loss. Genetics. 1997 Mar;145(3):605–614. doi: 10.1093/genetics/145.3.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Imai S., Armstrong C. M., Kaeberlein M., Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000 Feb 17;403(6771):795–800. doi: 10.1038/35001622. [DOI] [PubMed] [Google Scholar]
  12. Landry J., Sutton A., Tafrov S. T., Heller R. C., Stebbins J., Pillus L., Sternglanz R. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc Natl Acad Sci U S A. 2000 May 23;97(11):5807–5811. doi: 10.1073/pnas.110148297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Liu H., Krizek J., Bretscher A. Construction of a GAL1-regulated yeast cDNA expression library and its application to the identification of genes whose overexpression causes lethality in yeast. Genetics. 1992 Nov;132(3):665–673. doi: 10.1093/genetics/132.3.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Megee P. C., Morgan B. A., Mittman B. A., Smith M. M. Genetic analysis of histone H4: essential role of lysines subject to reversible acetylation. Science. 1990 Feb 16;247(4944):841–845. doi: 10.1126/science.2106160. [DOI] [PubMed] [Google Scholar]
  15. Moazed D. Enzymatic activities of Sir2 and chromatin silencing. Curr Opin Cell Biol. 2001 Apr;13(2):232–238. doi: 10.1016/s0955-0674(00)00202-7. [DOI] [PubMed] [Google Scholar]
  16. Park E. C., Szostak J. W. Point mutations in the yeast histone H4 gene prevent silencing of the silent mating type locus HML. Mol Cell Biol. 1990 Sep;10(9):4932–4934. doi: 10.1128/mcb.10.9.4932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shore D. The Sir2 protein family: A novel deacetylase for gene silencing and more. Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14030–14032. doi: 10.1073/pnas.011506198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Smith J. S., Brachmann C. B., Celic I., Kenna M. A., Muhammad S., Starai V. J., Avalos J. L., Escalante-Semerena J. C., Grubmeyer C., Wolberger C. A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6658–6663. doi: 10.1073/pnas.97.12.6658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tanny J. C., Dowd G. J., Huang J., Hilz H., Moazed D. An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing. Cell. 1999 Dec 23;99(7):735–745. doi: 10.1016/s0092-8674(00)81671-2. [DOI] [PubMed] [Google Scholar]
  20. Thompson J. S., Ling X., Grunstein M. Histone H3 amino terminus is required for telomeric and silent mating locus repression in yeast. Nature. 1994 May 19;369(6477):245–247. doi: 10.1038/369245a0. [DOI] [PubMed] [Google Scholar]
  21. Wyrick J. J., Holstege F. C., Jennings E. G., Causton H. C., Shore D., Grunstein M., Lander E. S., Young R. A. Chromosomal landscape of nucleosome-dependent gene expression and silencing in yeast. Nature. 1999 Nov 25;402(6760):418–421. doi: 10.1038/46567. [DOI] [PubMed] [Google Scholar]

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