Abstract
Abstract The Sin3-Rpd3 histone deacetylase complex, conserved between human and yeast, represses transcription when targeted by promoter-specific transcription factors. SIN3 and RPD3 also affect transcriptional silencing at the HM mating loci and at telomeres in yeast. Interestingly, however, deletion of the SIN3 and RPD3 genes enhances silencing, implying that the Sin3-Rpd3 complex functions to counteract, rather than to establish or maintain, silencing. Here we demonstrate that Sin3, Rpd3, and Sap30, a novel component of the Sin3-Rpd3 complex, affect silencing not only at the HMR and telomeric loci, but also at the rDNA locus. The effects on silencing at all three loci are dependent upon the histone deacetylase activity of Rpd3. Enhanced silencing associated with sin3Δ, rpd3Δ, and sap30Δ is differentially dependent upon Sir2 and Sir4 at the telomeric and rDNA loci and is also dependent upon the ubiquitin-conjugating enzyme Rad6 (Ubc2). We also show that the Cac3 subunit of the CAF-I chromatin assembly factor and Sin3-Rpd3 exert antagonistic effects on silencing. Strikingly, deletion of GCN5, which encodes a histone acetyltransferase, enhances silencing in a manner similar to deletion of RPD3. A model that integrates the effects of rpd3Δ, gcn5Δ, and cac3Δ on silencing is proposed.
References
78
Referenced
88
10.1073/pnas.82.23.8048
/ Proc. Natl. Acad. Sci. USA / Deposition-related histone acetylation in micronuclei of conjugating Tetrahymena by Allis (1985)10.1101/gad.8.10.1133
/ Genes Dev. / Overcoming telomeric silencing: a trans-activator competes to establish gene expression in a cell cycle-dependent way by Aparicio (1994)10.1016/0092-8674(91)90049-5
/ Cell / Modifiers of position effect are shared between telomeric and silent mating-type loci in S. cerevisiae by Aparicio (1991)10.1007/BF00330984
/ Mol. Gen. Genet. / A positive selection for mutants lacking orotidine-5′-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance by Boeke (1984)10.1101/gad.7.4.592
/ Genes Dev. / Transcriptional silencing in yeast is associated with reduced nucleosome acetylation by Braunstein (1993)10.1128/MCB.16.8.4349
/ Mol. Cell. Biol. / Efficient transcriptional silencing in Saccharomyces cerevisiae requires a heterochromatin histone acetylation pattern by Braunstein (1996)10.1101/gad.11.2.255
/ Genes Dev. / Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast by Bryk (1997)10.1016/S0021-9258(18)54049-7
/ J. Biol. Chem. / Nucleosome structural changes during derepression of silent mating-type loci in yeast by Chen-Cleland (1993)10.1038/384589a0
/ Nature / The histone deacetylase RPD3 counteracts genomic silencing in Drosophila and yeast by De Rubertis (1996)10.1101/gad.12.2.219
/ Genes Dev. / Chromatin assembly factor I contributes to the maintenance, but not the re-establishment, of silencing at the yeast silent mating loci by Enomoto (1998)10.1101/gad.11.3.358
/ Genes Dev. / RLF2, a subunit of yeast chromatin assembly factor-I, is required for telomeric chromatin function in vivo by Enomoto (1997)10.1093/emboj/16.21.6495
/ EMBO J. / Direct evidence for SIR2 modulation of chromatin structure in yeast rDNA by Fritze (1997)10.1016/0378-1119(88)90185-0
/ Gene / New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites by Gietz (1988)10.1073/pnas.89.9.4062
/ Proc. Natl. Acad. Sci. USA / Telomere-proximal DNA in Saccharomyces cerevisiae is refractory to methyltransferase activity in vivo by Gottschling (1992)10.1016/0092-8674(90)90141-Z
/ Cell / Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription by Gottschling (1990)10.1016/S0092-8674(00)81160-5
/ Cell / Yeast heterochromatin: regulation of its assembly and inheritance by histones by Grunstein (1998)10.1016/S0021-9258(18)45791-2
/ J. Biol. Chem. / Ubi-quitin-mediated degradation of histone H3 does not require the substrate-binding ubiquitin protein ligase, E3, or attachment of polyubiquitin chains by Haas (1990)10.1016/0092-8674(95)90512-X
/ Cell / Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast by Hecht (1995)10.1128/MCB.16.10.5717
/ Mol. Cell. Biol. / The dose of a putative ubiquitin-specific protease affects position-effect variegation in Drosophila melanogaster by Henchoz (1996)10.1016/S0168-9525(97)01219-5
/ Trends Genet. / Exploring and explaining epi-genetic effects by Henikoff (1997)10.1128/MCB.17.11.6693
/ Mol. Cell. Biol. / The ubiquitin-conjugating enzyme Rad6 (Ubc2) is required for silencing in Saccharomyces cerevisiae by Huang (1997){'key': '2022010313563340700_R22', 'first-page': '688', 'article-title': 'Cloning and characterization of four SIR genes of Saccharomyces cerevisiae', 'volume': '6', 'author': 'Ivy', 'year': '1986', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Cloning and characterization of four SIR genes of Saccharomyces cerevisiae by Ivy (1986)10.1016/S0168-9525(97)01180-3
/ Trends Genet. / DNA methylation and imprinting: why bother? by Jaenisch (1997)10.1016/S0092-8674(00)80217-2
/ Cell / Repression by Ume6 involves recruitment of a complex containing Sin3 corepressor and Rpd3 histone deacetylase to target promoters by Kadosh (1997)10.1101/gad.12.6.797
/ Genes Dev. / Histone deacetylase activity of Rpd3 is important for transcriptional repression in vivo by Kadosh (1998)10.1093/genetics/130.2.285
/ Genetics / Elimination of the yeast RAD6 ubiquitin conjugase enhances base-pair transitions and G·C→T·A transversions as well as transposition of the Ty element: implications for the control of spontaneous mutation by Kang (1992)10.1128/MCB.17.8.4852
/ Mol. Cell. Biol. / A large protein complex containing the yeast Sin3p and Rpd3 transcriptional regulators by Kasten (1997)10.1101/gad.11.3.345
/ Genes Dev. / Ultraviolet radiation sensitivity and reduction of telomeric silencing in Saccharomyces cerevisiae cells lacking chromatin assembly factor-I by Kaufman (1997)10.1128/MCB.18.8.4793
/ Mol. Cell. Biol. / Hir proteins are required for position-dependent gene silencing in Saccharomyces cerevisiae in the absence of chromatin assembly factor I by Kaufman (1998)10.1016/0092-8674(88)90006-2
/ Cell / Extremely conserved histone H4 N terminus is dispensable for growth but essential for repressing the silent mating loci in yeast by Kayne (1988)10.1038/383269a0
/ Nature / Transcription-linked acetylation by Gcn5p of histones H3 and H4 at specific lysines by Kuo (1996)10.1101/gad.12.5.627
/ Genes Dev. / Histone acetyltransferase activity of yeast Gcn5p is required for the activation of target genes in vivo by Kuo (1998)10.1101/gad.7.7a.1146
/ Genes Dev. / RAP1 and telomere structure regulate telomere position effects in Saccharomyces cerevisiae by Kyrion (1993)10.1093/genetics/133.3.499
/ Genetics / A ubiquitin-conjugating enzyme, RAD6, affects the distribution of Ty1 retrotransposon integration positions by Liebman (1993)10.1073/pnas.95.12.6693
/ Proc. Natl. Acad. Sci. USA / Deposition-related sites K5/K12 in histone H4 are not required for nucleosome deposition in yeast by Ma (1998){'key': '2022010313563340700_R36', 'first-page': '4441', 'article-title': 'Functional domains of SIR4, a gene required for position effect regulation in Saccharomyces cerevisiae', 'volume': '7', 'author': 'Marshall', 'year': '1987', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Functional domains of SIR4, a gene required for position effect regulation in Saccharomyces cerevisiae by Marshall (1987)10.1073/pnas.95.1.132
/ Proc. Natl. Acad. Sci. USA / Drosophila NURF-55, a WD repeat protein involved in histone metabolism by Martinez-Balbas (1998)10.1126/science.2106160
/ Science / Genetic analysis of histone H4: essential role of lysines subject to reversible acetylation by Megee (1990)10.1016/S0092-8674(00)80139-7
/ Cell / A deubiquitinating enzyme interacts with SIR4 and regulates silencing in S. cerevisiae by Moazed (1996)10.1073/pnas.94.24.13081
/ Proc. Natl. Acad. Sci. USA / The yeast Cac1 protein is required for the stable inheritance of transcriptionally repressed chromatin at telomeres by Monson (1997)10.1016/S0092-8674(00)81155-1
/ Cell / RNA and the epigenetic regulation of X chromosome inactivation by Panning (1998){'key': '2022010313563340700_R42', 'first-page': '4932', 'article-title': 'Point mutations in the yeast histone H4 gene prevent silencing of the silent mating type locus HML', 'volume': '10', 'author': 'Park', 'year': '1990', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Point mutations in the yeast histone H4 gene prevent silencing of the silent mating type locus HML by Park (1990)10.1016/S0092-8674(00)81325-2
/ Cell / The major cytoplasmic histone acetyltransferase in yeast: links to chromatin replication and histone metabolism by Parthun (1996)10.1128/MCB.17.8.4830
/ Mol. Cell. Biol. / Characterization of the Wtm proteins, a novel family of Saccharomyces cerevisiae transcriptional modulators with roles in meiotic regulation and silencing by Pemberton (1997)10.1128/MCB.18.2.1049
/ Mol. Cell. Biol. / Mutations in chromatin components suppress a defect of Gcn5 protein in Saccharomyces cerevisiae by Perez-Martin (1998){'key': '2022010313563340700_R46', 'first-page': '1017', 'article-title': 'Mutations in RAD6, a yeast gene encoding a ubiquitin-conjugating enzyme, stimulate retrotransposition', 'volume': '10', 'author': 'Picologlou', 'year': '1990', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Mutations in RAD6, a yeast gene encoding a ubiquitin-conjugating enzyme, stimulate retrotransposition by Picologlou (1990)10.1146/annurev.ge.27.120193.000341
/ Annu. Rev. Genet. / DNA repair genes and proteins of Saccharomyces cerevisiae by Prakash (1993)10.1128/MCB.18.8.4783
/ Mol. Cell. Biol. / Yeast Ty1 retrotransposition is stimulated by a synergistic interaction between mutations in chromatin assembly factor I and histone regulatory proteins by Qian (1998)10.1101/gad.7.7a.1133
/ Genes Dev. / Silent domains are assembled continuously from the telomere and are defined by promoter distance and strength, and by SIR3 dosage by Renauld (1993)10.1093/genetics/116.1.9
/ Genetics / Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae by Rine (1987)10.1016/S0092-8674(00)80154-3
/ Cell / Inactivation of the HR6B ubiquitin-conjugating DNA repair enzyme in mice causes male sterility associated with chromatin modification by Roest (1996)10.1016/0076-6879(91)94022-5
/ Methods Enzymol. / Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast by Rothstein (1991)10.1073/pnas.93.25.14503
/ Proc. Natl. Acad. Sci. USA / HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription by Rundlett (1996)10.1038/33952
/ Nature / Transcriptional repression by UME6 involves deacetylation of lysine 5 of histone H4 by RPD3 by Rundlett (1998)10.1016/0076-6879(91)94004-V
/ Methods Enzymol. / Getting started with yeast by Sherman (1991)10.1016/S0168-9525(97)01198-0
/ Trends Genet. / An uncertain silence by Sherman (1997)10.1093/genetics/122.1.19
/ Genetics / A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae by Sikorski (1989)10.1093/genetics/150.2.613
/ Genetics / Identification of high-copy disruptors of telomeric silencing in Saccharomyces cerevisiae by Singer (1998)10.1101/gad.6.2.186
/ Genes Dev. / Active genes in budding yeast display enhanced in vivo accessibility to foreign DNA methylases: a novel in vivo probe for chromatin structure of yeast by Singh (1992)10.1128/MCB.18.9.5511
/ Mol. Cell. Biol. / A novel function of the DNA repair gene rhp6 in mating-type silencing by chromatin remodeling in fission yeast by Singh (1998)10.1101/gad.11.2.241
/ Genes Dev. / An unusual form of transcriptional silencing in yeast ribosomal DNA by Smith (1997)10.1002/j.1460-2075.1991.tb08031.x
/ EMBO J. / Stepwise assembly of chromatin during DNA replication in vitro by Smith (1991)10.1093/genetics/149.3.1205
/ Genetics / Distribution of a limited Sir2 protein pool regulates the strength of yeast rDNA silencing and is modulated by Sir4p by Smith (1998)10.1128/MCB.19.4.3184
/ Mol. Cell. Biol. / A genetic selection for ribosomal DNA silencing defects identifies multiple DNA replication and chromatin-modulating factors by Smith (1999)10.1016/S0021-9258(17)32348-7
/ J. Biol. Chem. / Non-random acetylation of histone H4 by a cytoplasmic histone acetyltransferase as determined by novel methodology by Sobel (1994)10.1073/pnas.92.4.1237
/ Proc. Natl. Acad. Sci. USA / Conservation of deposition-related acetylation sites in newly synthesized histones H3 and H4 by Sobel (1995)10.1101/gad.2.11.1476
/ Genes Dev. / The RAD6 protein of Saccharomyces cerevisiae polyubiquitinates histones, and its acidic domain mediates this activity by Sung (1988)10.1073/pnas.88.17.7749
/ Proc. Natl. Acad. Sci. USA / Separation of transcriptional activation and silencing functions of the RAP1-encoded repressor/activator protein 1: isolation of viable mutants affecting both silencing and telomere length by Sussel (1991)10.1126/science.272.5260.408
/ Science / A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p by Taunton (1996)10.1038/369245a0
/ Nature / Histone H3 amino terminus is required for telomeric and silent mating locus repression in yeast by Thompson (1994)10.1016/0092-8674(92)90417-B
/ Cell / Histone H4 isoforms acetylated at specific lysine residues define individual chromosomes and chromatin domains in Drosophila polytene nuclei by Turner (1992)10.1093/genetics/144.4.1343
/ Genetics / Evidence that the transcriptional regulators SIN3 and RPD3, and a novel gene (SDS3) with similar functions, are involved in transcriptional silencing in S. cerevisiae by Vannier (1996)10.1016/S0092-8674(00)81326-4
/ Cell / Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4 by Verreault (1996)10.1016/S0092-8674(00)81159-9
/ Cell / Beyond the nucleosome: epigenetic aspects of position-effect variegation in Drosophila by Wakimoto (1998)10.1101/gad.12.5.640
/ Genes Dev. / Critical residues for histone acetylation by Gcn5, functioning in Ada and SAGA complexes, are also required for transcriptional function in vivo by Wang (1998)10.1016/S0092-8674(00)80216-0
/ Cell / Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex by Zhang (1997)10.1016/S1097-2765(00)80102-1
/ Mol. Cell / SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex by Zhang (1998)10.1128/MCB.15.3.1698
/ Mol. Cell. Biol. / HPR1 encodes a global positive regulator of transcription in Saccharomyces cerevisiae by Zhu (1995)
Dates
Type | When |
---|---|
Created | 4 years, 4 months ago (April 27, 2021, 10:54 p.m.) |
Deposited | 3 years, 7 months ago (Jan. 3, 2022, 12:38 p.m.) |
Indexed | 1 month, 4 weeks ago (July 2, 2025, 3:11 p.m.) |
Issued | 26 years, 1 month ago (July 1, 1999) |
Published | 26 years, 1 month ago (July 1, 1999) |
Published Online | 26 years, 1 month ago (July 1, 1999) |
Published Print | 26 years, 1 month ago (July 1, 1999) |
@article{Sun_1999, title={A General Requirement for the Sin3-Rpd3 Histone Deacetylase Complex in Regulating Silencing in Saccharomyces cerevisiae}, volume={152}, ISSN={1943-2631}, url={http://dx.doi.org/10.1093/genetics/152.3.921}, DOI={10.1093/genetics/152.3.921}, number={3}, journal={Genetics}, publisher={Oxford University Press (OUP)}, author={Sun, Zu-Wen and Hampsey, Michael}, year={1999}, month=jul, pages={921–932} }