Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1998 Jul 1;26(13):3247–3254. doi: 10.1093/nar/26.13.3247

Genetic characterisation of hda1+, a putative fission yeast histone deacetylase gene.

T G Olsson 1, K Ekwall 1, R C Allshire 1, P Sunnerhagen 1, J F Partridge 1, W A Richardson 1
PMCID: PMC147680  PMID: 9628926

Abstract

hda1+ (histone deacetylase 1) is a fission yeast gene which is highly similar in sequence to known histone deacetylase genes in humans and budding yeast. We have investigated if this putative histone deacetylase contributes to transcriptional silencing in the fission yeast Schizosaccharomyces pombe. A precise deletion allele of the hda1+ open reading frame was created. Cells lacking the hda1+ gene are viable. However, genetic analysis reveals that cells without hda1 + display enhanced gene repression/silencing of marker genes, residing adjacent to telomeres, close to the silent mating-type loci and within centromere I. This phenotype is very similar to that recently reported for rpd3 mutants both in Drosophila and budding yeast. No defects in chromosome segregation or changes in telomere length were detected. Cells lacking the hda1+ gene display reduced sporulation. Growth of hda1 cells is partially inhibited by low concentrations of Trichostatin A (TSA), a known inhibitor of histone deacetylase enzymes. TSA treatment is also able to overcome the enhanced silencing found in heterochromatic regions of hda1 cells. These results indicate a genetic redundancy with respect to deacetylase genes and partially overlapping functions of these in fission yeast. The significance of these results is discussed in the light of recent discoveries from other eukaryotes.

Full Text

The Full Text of this article is available as a PDF (539.5 KB).

Selected References

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

  1. ALLFREY V. G., FAULKNER R., MIRSKY A. E. ACETYLATION AND METHYLATION OF HISTONES AND THEIR POSSIBLE ROLE IN THE REGULATION OF RNA SYNTHESIS. Proc Natl Acad Sci U S A. 1964 May;51:786–794. doi: 10.1073/pnas.51.5.786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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. 1995 Jan 15;9(2):218–233. doi: 10.1101/gad.9.2.218. [DOI] [PubMed] [Google Scholar]
  3. Belyaev N., Keohane A. M., Turner B. M. Differential underacetylation of histones H2A, H3 and H4 on the inactive X chromosome in human female cells. Hum Genet. 1996 May;97(5):573–578. doi: 10.1007/BF02281863. [DOI] [PubMed] [Google Scholar]
  4. Brownell J. E., Allis C. D. Special HATs for special occasions: linking histone acetylation to chromatin assembly and gene activation. Curr Opin Genet Dev. 1996 Apr;6(2):176–184. doi: 10.1016/s0959-437x(96)80048-7. [DOI] [PubMed] [Google Scholar]
  5. Carmen A. A., Rundlett S. E., Grunstein M. HDA1 and HDA3 are components of a yeast histone deacetylase (HDA) complex. J Biol Chem. 1996 Jun 28;271(26):15837–15844. doi: 10.1074/jbc.271.26.15837. [DOI] [PubMed] [Google Scholar]
  6. Cooper J. P., Nimmo E. R., Allshire R. C., Cech T. R. Regulation of telomere length and function by a Myb-domain protein in fission yeast. Nature. 1997 Feb 20;385(6618):744–747. doi: 10.1038/385744a0. [DOI] [PubMed] [Google Scholar]
  7. De Rubertis F., Kadosh D., Henchoz S., Pauli D., Reuter G., Struhl K., Spierer P. The histone deacetylase RPD3 counteracts genomic silencing in Drosophila and yeast. Nature. 1996 Dec 12;384(6609):589–591. doi: 10.1038/384589a0. [DOI] [PubMed] [Google Scholar]
  8. Ekwall K., Nimmo E. R., Javerzat J. P., Borgstrøm B., Egel R., Cranston G., Allshire R. 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. 1996 Nov;109(Pt 11):2637–2648. doi: 10.1242/jcs.109.11.2637. [DOI] [PubMed] [Google Scholar]
  9. Ekwall K., Olsson T., Turner B. M., Cranston G., Allshire R. C. Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres. Cell. 1997 Dec 26;91(7):1021–1032. doi: 10.1016/s0092-8674(00)80492-4. [DOI] [PubMed] [Google Scholar]
  10. Ekwall K., Ruusala T. Mutations in rik1, clr2, clr3 and clr4 genes asymmetrically derepress the silent mating-type loci in fission yeast. Genetics. 1994 Jan;136(1):53–64. doi: 10.1093/genetics/136.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Enomoto S., Berman J. Chromatin assembly factor I contributes to the maintenance, but not the re-establishment, of silencing at the yeast silent mating loci. Genes Dev. 1998 Jan 15;12(2):219–232. doi: 10.1101/gad.12.2.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Grunstein M. Histone acetylation in chromatin structure and transcription. Nature. 1997 Sep 25;389(6649):349–352. doi: 10.1038/38664. [DOI] [PubMed] [Google Scholar]
  13. Hoffman C. S., Winston F. A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli. Gene. 1987;57(2-3):267–272. doi: 10.1016/0378-1119(87)90131-4. [DOI] [PubMed] [Google Scholar]
  14. Jeppesen P., Turner B. M. The inactive X chromosome in female mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic marker for gene expression. Cell. 1993 Jul 30;74(2):281–289. doi: 10.1016/0092-8674(93)90419-q. [DOI] [PubMed] [Google Scholar]
  15. Kanter-Smoler G., Dahlkvist A., Sunnerhagen P. Improved method for rapid transformation of intact Schizosaccharomyces pombe cells. Biotechniques. 1994 May;16(5):798–800. [PubMed] [Google Scholar]
  16. Khochbin S., Wolffe A. P. The origin and utility of histone deacetylases. FEBS Lett. 1997 Dec 15;419(2-3):157–160. doi: 10.1016/s0014-5793(97)01423-3. [DOI] [PubMed] [Google Scholar]
  17. Ladomery M., Lyons S., Sommerville J. Xenopus HDm, a maternally expressed histone deacetylase, belongs to an ancient family of acetyl-metabolizing enzymes. Gene. 1997 Oct 1;198(1-2):275–280. doi: 10.1016/s0378-1119(97)00325-9. [DOI] [PubMed] [Google Scholar]
  18. Leipe D. D., Landsman D. Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are members of an ancient protein superfamily. Nucleic Acids Res. 1997 Sep 15;25(18):3693–3697. doi: 10.1093/nar/25.18.3693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Monson E. K., de Bruin D., Zakian V. A. The yeast Cac1 protein is required for the stable inheritance of transcriptionally repressed chromatin at telomeres. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13081–13086. doi: 10.1073/pnas.94.24.13081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Moreno S., Klar A., Nurse P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 1991;194:795–823. doi: 10.1016/0076-6879(91)94059-l. [DOI] [PubMed] [Google Scholar]
  21. Nimmo E. R., Cranston G., Allshire R. C. Telomere-associated chromosome breakage in fission yeast results in variegated expression of adjacent genes. EMBO J. 1994 Aug 15;13(16):3801–3811. doi: 10.1002/j.1460-2075.1994.tb06691.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rundlett S. E., Carmen A. A., Kobayashi R., Bavykin S., Turner B. M., Grunstein M. HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14503–14508. doi: 10.1073/pnas.93.25.14503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Taunton J., Hassig C. A., Schreiber S. L. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science. 1996 Apr 19;272(5260):408–411. doi: 10.1126/science.272.5260.408. [DOI] [PubMed] [Google Scholar]
  24. Tazi J., Bird A. Alternative chromatin structure at CpG islands. Cell. 1990 Mar 23;60(6):909–920. doi: 10.1016/0092-8674(90)90339-g. [DOI] [PubMed] [Google Scholar]
  25. Thon G., Cohen A., Klar A. J. Three additional linkage groups that repress transcription and meiotic recombination in the mating-type region of Schizosaccharomyces pombe. Genetics. 1994 Sep;138(1):29–38. doi: 10.1093/genetics/138.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Thon G., Klar A. J. Directionality of fission yeast mating-type interconversion is controlled by the location of the donor loci. Genetics. 1993 Aug;134(4):1045–1054. doi: 10.1093/genetics/134.4.1045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Thon G., Klar A. J. The clr1 locus regulates the expression of the cryptic mating-type loci of fission yeast. Genetics. 1992 Jun;131(2):287–296. doi: 10.1093/genetics/131.2.287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Vannier D., Balderes D., Shore D. Evidence that the transcriptional regulators SIN3 and RPD3, and a novel gene (SDS3) with similar functions, are involved in transcriptional silencing in S. cerevisiae. Genetics. 1996 Dec;144(4):1343–1353. doi: 10.1093/genetics/144.4.1343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Verreault A., Kaufman P. D., Kobayashi R., Stillman B. Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4. Cell. 1996 Oct 4;87(1):95–104. doi: 10.1016/s0092-8674(00)81326-4. [DOI] [PubMed] [Google Scholar]
  30. Vidal M., Gaber R. F. RPD3 encodes a second factor required to achieve maximum positive and negative transcriptional states in Saccharomyces cerevisiae. Mol Cell Biol. 1991 Dec;11(12):6317–6327. doi: 10.1128/mcb.11.12.6317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wach A., Brachat A., Pöhlmann R., Philippsen P. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast. 1994 Dec;10(13):1793–1808. doi: 10.1002/yea.320101310. [DOI] [PubMed] [Google Scholar]
  32. Yoshida M., Kijima M., Akita M., Beppu T. Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem. 1990 Oct 5;265(28):17174–17179. [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES