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PMID: 10982821 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Type B histone acetyltransferase Hat1p participates in telomeric silencing.

Molecular and cellular biology ·Vol. 20 ·No. 19 ·2000-10-00 ·Pages 7051-8

Kelly TJ, Qin S, Gottschling DE, Parthun MR

Abstract

Hat1p and Hat2p are the two subunits of a type B histone acetyltransferase from Saccharomyces cerevisiae that acetylates free histone H4 on lysine 12 in vitro. However, the role for these gene products in chromatin function has been unclear, as deletions of the HAT1 and/or HAT2 gene displayed no obvious phenotype. We have now identified a role for Hat1p and Hat2p in telomeric silencing. Telomeric silencing is the transcriptional repression of telomere-proximal genes and is mediated by a special chromatin structure. While there was no change in the level of silencing on a telomeric gene when the HAT1 or HAT2 gene was deleted, a significant silencing defect was observed when hat1Delta or hat2Delta was combined with mutations of the histone H3 NH(2)-terminal tail. Specifically, when at least two lysine residues were changed to arginine in the histone H3 tail, a hat1Delta-dependent telomeric silencing defect was observed. The most dramatic effects were seen when one of the two changes was in lysine 14. In further analysis, we found that a single lysine out of the five in the histone H3 tail was sufficient to mediate silencing. However, K14 was the best at preserving silencing, followed by K23 and then K27; K9 and K18 alone were insufficient. Mutational analysis of the histone H4 tail indicated that the role of Hat1p in telomeric silencing was mediated solely through lysine 12. Thus, in contrast to other histone acetyltransferases, Hat1p activity was required for transcriptional repression rather than gene activation.

MeSH Terms
Acetylation Acetyltransferases/genetics,physiology Amino Acid Substitution Chromatin/metabolism Fungal Proteins/genetics,physiology Gene Deletion Gene Expression Regulation, Fungal Gene Silencing Heterochromatin/metabolism Histone Acetyltransferases Histones/metabolism Mutation, Missense Protein Processing, Post-Translational Saccharomyces cerevisiae/enzymology,genetics Saccharomyces cerevisiae Proteins Telomere/metabolism Transcription, Genetic Transcriptional Activation
Chemicals
Chromatin Fungal Proteins Heterochromatin Histones Saccharomyces cerevisiae Proteins Acetyltransferases Histone Acetyltransferases histone acetyltransferase type B complex
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kelly T J
The Department of Molecular and Cellular Biochemistry, Cellular and Developmental Biology Program, The Ohio State University, Columbus, Ohio 43210, USA.
Qin S
Gottschling D E
Parthun M R
References (71)
71 references, click to expand
  1. Purification and properties of the Xenopus Hat1 acetyltransferase: association with the 14-3-3 proteins in the oocyte nucleus.
    Biochemistry. 1999 Oct 5;38(40):13085-93 PMID: 10529179
  2. ACETYLATION AND METHYLATION OF HISTONES AND THEIR POSSIBLE ROLE IN THE REGULATION OF RNA SYNTHESIS.
    Proc Natl Acad Sci U S A. 1964 May;51:786-94 PMID: 14172992
  3. Histone H3 N-terminal mutations allow hyperactivation of the yeast GAL1 gene in vivo.
    EMBO J. 1992 Sep;11(9):3297-306 PMID: 1505519
  4. Transcriptional silencing in yeast is associated with reduced nucleosome acetylation.
    Genes Dev. 1993 Apr;7(4):592-604 PMID: 8458576
  5. Silent domains are assembled continuously from the telomere and are defined by promoter distance and strength, and by SIR3 dosage.
    Genes Dev. 1993 Jul;7(7A):1133-45 PMID: 8319906
  6. A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae.
    Nucleic Acids Res. 1993 Jul 11;21(14):3329-30 PMID: 8341614
  7. A retinoblastoma-binding protein related to a negative regulator of Ras in yeast.
    Nature. 1993 Aug 12;364(6438):648-52 PMID: 8350924
  8. Transcription-linked acetylation by Gcn5p of histones H3 and H4 at specific lysines.
    Nature. 1996 Sep 19;383(6597):269-72 PMID: 8805705
  9. The major cytoplasmic histone acetyltransferase in yeast: links to chromatin replication and histone metabolism.
    Cell. 1996 Oct 4;87(1):85-94 PMID: 8858151
  10. Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4.
    Cell. 1996 Oct 4;87(1):95-104 PMID: 8858152
  11. The transcriptional coactivators p300 and CBP are histone acetyltransferases.
    Cell. 1996 Nov 29;87(5):953-9 PMID: 8945521
  12. The TAF(II)250 subunit of TFIID has histone acetyltransferase activity.
    Cell. 1996 Dec 27;87(7):1261-70 PMID: 8980232
  13. Histones in transit: cytosolic histone complexes and diacetylation of H4 during nucleosome assembly in human cells.
    Biochemistry. 1997 Jan 21;36(3):469-80 PMID: 9012662
  14. Ultraviolet radiation sensitivity and reduction of telomeric silencing in Saccharomyces cerevisiae cells lacking chromatin assembly factor-I.
    Genes Dev. 1997 Feb 1;11(3):345-57 PMID: 9030687
  15. RLF2, a subunit of yeast chromatin assembly factor-I, is required for telomeric chromatin function in vivo.
    Genes Dev. 1997 Feb 1;11(3):358-70 PMID: 9030688
  16. Histone deacetylase activity is required for full transcriptional repression by mSin3A.
    Cell. 1997 May 2;89(3):341-7 PMID: 9150133
  17. Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex.
    Cell. 1997 May 2;89(3):357-64 PMID: 9150135
  18. GCN5-related histone N-acetyltransferases belong to a diverse superfamily that includes the yeast SPT10 protein.
    Trends Biochem Sci. 1997 May;22(5):154-5 PMID: 9175471
  19. Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300.
    Cell. 1997 Aug 8;90(3):569-80 PMID: 9267036
  20. Two new S-phase-specific genes from Saccharomyces cerevisiae.
    Yeast. 1997 Sep 15;13(11):1029-42 PMID: 9290207
  21. Steroid receptor coactivator-1 is a histone acetyltransferase.
    Nature. 1997 Sep 11;389(6647):194-8 PMID: 9296499
  22. Crystal structure of the nucleosome core particle at 2.8 A resolution.
    Nature. 1997 Sep 18;389(6648):251-60 PMID: 9305837
  23. Novel substrate specificity of the histone acetyltransferase activity of HIV-1-Tat interactive protein Tip60.
    J Biol Chem. 1997 Dec 5;272(49):30595-8 PMID: 9388189
  24. 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):13081-6 PMID: 9371803
  25. Drosophila NURF-55, a WD repeat protein involved in histone metabolism.
    Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):132-7 PMID: 9419341
  26. Histone H3 amino terminus is required for telomeric and silent mating locus repression in yeast.
    Nature. 1994 May 19;369(6477):245-7 PMID: 8183346
  27. RAP1: a protean regulator in yeast.
    Trends Genet. 1994 Nov;10(11):408-12 PMID: 7809947
  28. Conservation of deposition-related acetylation sites in newly synthesized histones H3 and H4.
    Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1237-41 PMID: 7862667
  29. 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):583-92 PMID: 7867066
  30. The p150 and p60 subunits of chromatin assembly factor I: a molecular link between newly synthesized histones and DNA replication.
    Cell. 1995 Jun 30;81(7):1105-14 PMID: 7600578
  31. Identification of a gene encoding a yeast histone H4 acetyltransferase.
    J Biol Chem. 1995 Oct 20;270(42):24674-7 PMID: 7559580
  32. Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast.
    J Biol Chem. 1995 Oct 27;270(43):25507-13 PMID: 7503932
  33. The RCAF complex mediates chromatin assembly during DNA replication and repair.
    Nature. 1999 Dec 2;402(6761):555-60 PMID: 10591219
  34. Processing of newly synthesized histone molecules.
    Science. 1975 Oct 10;190(4210):117-28 PMID: 1166303
  35. Nonrandom utilization of acetylation sites in histones isolated from Tetrahymena. Evidence for functionally distinct H4 acetylation sites.
    J Biol Chem. 1986 Jan 25;261(3):1071-6 PMID: 3080415
  36. Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae.
    Genetics. 1987 May;116(1):9-22 PMID: 3297920
  37. 5-Fluoroorotic acid as a selective agent in yeast molecular genetics.
    Methods Enzymol. 1987;154:164-75 PMID: 3323810
  38. Purification and characterization of CAF-I, a human cell factor required for chromatin assembly during DNA replication in vitro.
    Cell. 1989 Jul 14;58(1):15-25 PMID: 2546672
  39. A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae.
    Nucleic Acids Res. 1990 May 25;18(10):3091-2 PMID: 2190191
  40. Genetic evidence for an interaction between SIR3 and histone H4 in the repression of the silent mating loci in Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1990 Aug;87(16):6286-90 PMID: 2201024
  41. Point mutations in the yeast histone H4 gene prevent silencing of the silent mating type locus HML.
    Mol Cell Biol. 1990 Sep;10(9):4932-4 PMID: 2117703
  42. Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription.
    Cell. 1990 Nov 16;63(4):751-62 PMID: 2225075
  43. The YDp plasmids: a uniform set of vectors bearing versatile gene disruption cassettes for Saccharomyces cerevisiae.
    Yeast. 1991 Jul;7(5):475-7 PMID: 1897313
  44. Modifiers of position effect are shared between telomeric and silent mating-type loci in S. cerevisiae.
    Cell. 1991 Sep 20;66(6):1279-87 PMID: 1913809
  45. Histone H4 isoforms acetylated at specific lysine residues define individual chromosomes and chromatin domains in Drosophila polytene nuclei.
    Cell. 1992 Apr 17;69(2):375-84 PMID: 1568251
  46. Loss of transcriptional silencing causes sterility in old mother cells of S. cerevisiae.
    Cell. 1996 Feb 23;84(4):633-42 PMID: 8598049
  47. Yeast histone H3 and H4 amino termini are important for nucleosome assembly in vivo and in vitro: redundant and position-independent functions in assembly but not in gene regulation.
    Genes Dev. 1996 Mar 15;10(6):686-99 PMID: 8598296
  48. Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation.
    Cell. 1996 Mar 22;84(6):843-51 PMID: 8601308
  49. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p.
    Science. 1996 Apr 19;272(5260):408-11 PMID: 8602529
  50. Silencing and heritable domains of gene expression.
    Annu Rev Cell Dev Biol. 1995;11:519-48 PMID: 8689568
  51. Special HATs for special occasions: linking histone acetylation to chromatin assembly and gene activation.
    Curr Opin Genet Dev. 1996 Apr;6(2):176-84 PMID: 8722174
  52. A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A.
    Nature. 1996 Jul 25;382(6589):319-24 PMID: 8684459
  53. Efficient transcriptional silencing in Saccharomyces cerevisiae requires a heterochromatin histone acetylation pattern.
    Mol Cell Biol. 1996 Aug;16(8):4349-56 PMID: 8754835
  54. Yeast SAS silencing genes and human genes associated with AML and HIV-1 Tat interactions are homologous with acetyltransferases.
    Nat Genet. 1996 Sep;14(1):42-9 PMID: 8782818
  55. Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1 acetyltransferase.
    Curr Biol. 1998 Jan 15;8(2):96-108 PMID: 9427644
  56. 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):219-32 PMID: 9436982
  57. Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications.
    Yeast. 1998 Jan 30;14(2):115-32 PMID: 9483801
  58. ESA1 is a histone acetyltransferase that is essential for growth in yeast.
    Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3561-5 PMID: 9520405
  59. HAT1 and HAT2 proteins are components of a yeast nuclear histone acetyltransferase enzyme specific for free histone H4.
    J Biol Chem. 1998 May 15;273(20):12599-605 PMID: 9575221
  60. Yeast heterochromatin: regulation of its assembly and inheritance by histones.
    Cell. 1998 May 1;93(3):325-8 PMID: 9590166
  61. Deposition-related sites K5/K12 in histone H4 are not required for nucleosome deposition in yeast.
    Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6693-8 PMID: 9618474
  62. Hir proteins are required for position-dependent gene silencing in Saccharomyces cerevisiae in the absence of chromatin assembly factor I.
    Mol Cell Biol. 1998 Aug;18(8):4793-806 PMID: 9671489
  63. Identification of high-copy disruptors of telomeric silencing in Saccharomyces cerevisiae.
    Genetics. 1998 Oct;150(2):613-32 PMID: 9755194
  64. Gcn5p, a transcription-related histone acetyltransferase, acetylates nucleosomes and folded nucleosomal arrays in the absence of other protein subunits.
    J Biol Chem. 1998 Dec 4;273(49):32388-92 PMID: 9829967
  65. Expanded lysine acetylation specificity of Gcn5 in native complexes.
    J Biol Chem. 1999 Feb 26;274(9):5895-900 PMID: 10026213
  66. Esa1p is an essential histone acetyltransferase required for cell cycle progression.
    Mol Cell Biol. 1999 Apr;19(4):2515-26 PMID: 10082517
  67. Chromatin assembly: biochemical identities and genetic redundancy.
    Curr Opin Genet Dev. 1999 Apr;9(2):185-90 PMID: 10322140
  68. A general requirement for the Sin3-Rpd3 histone deacetylase complex in regulating silencing in Saccharomyces cerevisiae.
    Genetics. 1999 Jul;152(3):921-32 PMID: 10388812
  69. Histone acetyltransferase complexes.
    Semin Cell Dev Biol. 1999 Apr;10(2):169-77 PMID: 10441070
  70. Histone deacetylases: complex transducers of nuclear signals.
    Semin Cell Dev Biol. 1999 Apr;10(2):179-88 PMID: 10441071
  71. A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme.
    Mol Cell. 1999 Jul;4(1):123-8 PMID: 10445034
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.19.7051-7058.2000
Published
2000-10-00
Pages
7051-8
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC86239
Subset
IM
Grants
NIGMS NIH HHS · R01 GM043893 · United States
NIGMS NIH HHS · GM43893 · United States
External Links
PubMed source DOI: 10.1128/MCB.20.19.7051-7058.2000 PMC Full Text View journal details
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