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Abstract 


The Saccharomyces cerevisiae SWI/SNF complex is a 2-MDa multimeric assembly that facilitates transcriptional enhancement by antagonizing chromatin-mediated transcriptional repression. We show here that mutations in ADA2, ADA3, and GCN5, which are believed to encode subunits of a nuclear histone acetyltransferase complex, cause phenotypes strikingly similar to that of swi/snf mutants. ADA2, ADA3, and GCN5 are required for full expression of all SWI/SNF-dependent genes tested, including HO, SUC2, INO1, and Ty elements. Furthermore, mutations in the SIN1 gene, which encodes a nonhistone chromatin component, or mutations in histone H3 or H4 partially alleviate the transcriptional defects caused by ada/gcn5 or swi/snf mutations. We also find that ada2 swi1, ada3 swi1, and gcn5 swi1 double mutants are inviable and that mutations in SIN1 allow viability of these double mutants. We have partially purified three chromatographically distinct GCN5-dependent acetyltransferase activities, and we show that these enzymes can acetylate both histones and Sin1p. We propose a model in which the ADA/GCN5 and SWI/SNF complexes facilitate activator function by acting in concert to disrupt or modify chromatin structure.

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Mol Cell Biol. 1997 Nov; 17(11): 6212–6222.
PMCID: PMC232472
PMID: 9343382

Role for ADA/GCN5 products in antagonizing chromatin-mediated transcriptional repression.

Abstract

The Saccharomyces cerevisiae SWI/SNF complex is a 2-MDa multimeric assembly that facilitates transcriptional enhancement by antagonizing chromatin-mediated transcriptional repression. We show here that mutations in ADA2, ADA3, and GCN5, which are believed to encode subunits of a nuclear histone acetyltransferase complex, cause phenotypes strikingly similar to that of swi/snf mutants. ADA2, ADA3, and GCN5 are required for full expression of all SWI/SNF-dependent genes tested, including HO, SUC2, INO1, and Ty elements. Furthermore, mutations in the SIN1 gene, which encodes a nonhistone chromatin component, or mutations in histone H3 or H4 partially alleviate the transcriptional defects caused by ada/gcn5 or swi/snf mutations. We also find that ada2 swi1, ada3 swi1, and gcn5 swi1 double mutants are inviable and that mutations in SIN1 allow viability of these double mutants. We have partially purified three chromatographically distinct GCN5-dependent acetyltransferase activities, and we show that these enzymes can acetylate both histones and Sin1p. We propose a model in which the ADA/GCN5 and SWI/SNF complexes facilitate activator function by acting in concert to disrupt or modify chromatin structure.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Allan J, Harborne N, Rau DC, Gould H. Participation of core histone "tails" in the stabilization of the chromatin solenoid. J Cell Biol. 1982 May;93(2):285–297. [Europe PMC free article] [Abstract] [Google Scholar]
  • Andrews BJ, Herskowitz I. Identification of a DNA binding factor involved in cell-cycle control of the yeast HO gene. Cell. 1989 Apr 7;57(1):21–29. [Abstract] [Google Scholar]
  • Ausio J, Dong F, van Holde KE. Use of selectively trypsinized nucleosome core particles to analyze the role of the histone "tails" in the stabilization of the nucleosome. J Mol Biol. 1989 Apr 5;206(3):451–463. [Abstract] [Google Scholar]
  • Barlev NA, Candau R, Wang L, Darpino P, Silverman N, Berger SL. Characterization of physical interactions of the putative transcriptional adaptor, ADA2, with acidic activation domains and TATA-binding protein. J Biol Chem. 1995 Aug 18;270(33):19337–19344. [Abstract] [Google Scholar]
  • Berger SL, Piña B, Silverman N, Marcus GA, Agapite J, Regier JL, Triezenberg SJ, Guarente L. Genetic isolation of ADA2: a potential transcriptional adaptor required for function of certain acidic activation domains. Cell. 1992 Jul 24;70(2):251–265. [Abstract] [Google Scholar]
  • Berger SL, Cress WD, Cress A, Triezenberg SJ, Guarente L. Selective inhibition of activated but not basal transcription by the acidic activation domain of VP16: evidence for transcriptional adaptors. Cell. 1990 Jun 29;61(7):1199–1208. [Abstract] [Google Scholar]
  • Brandl CJ, Furlanetto AM, Martens JA, Hamilton KS. Characterization of NGG1, a novel yeast gene required for glucose repression of GAL4p-regulated transcription. EMBO J. 1993 Dec 15;12(13):5255–5265. [Europe PMC free article] [Abstract] [Google Scholar]
  • Breeden L, Nasmyth K. Cell cycle control of the yeast HO gene: cis- and trans-acting regulators. Cell. 1987 Feb 13;48(3):389–397. [Abstract] [Google Scholar]
  • Brownell JE, Allis CD. An activity gel assay detects a single, catalytically active histone acetyltransferase subunit in Tetrahymena macronuclei. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6364–6368. [Europe PMC free article] [Abstract] [Google Scholar]
  • Brownell JE, Zhou J, Ranalli T, Kobayashi R, Edmondson DG, Roth SY, Allis CD. Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell. 1996 Mar 22;84(6):843–851. [Abstract] [Google Scholar]
  • Cairns BR, Levinson RS, Yamamoto KR, Kornberg RD. Essential role of Swp73p in the function of yeast Swi/Snf complex. Genes Dev. 1996 Sep 1;10(17):2131–2144. [Abstract] [Google Scholar]
  • Cairns BR, Kim YJ, Sayre MH, Laurent BC, Kornberg RD. A multisubunit complex containing the SWI1/ADR6, SWI2/SNF2, SWI3, SNF5, and SNF6 gene products isolated from yeast. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1950–1954. [Europe PMC free article] [Abstract] [Google Scholar]
  • Celenza JL, Carlson M. Cloning and genetic mapping of SNF1, a gene required for expression of glucose-repressible genes in Saccharomyces cerevisiae. Mol Cell Biol. 1984 Jan;4(1):49–53. [Europe PMC free article] [Abstract] [Google Scholar]
  • Chiang YC, Komarnitsky P, Chase D, Denis CL. ADR1 activation domains contact the histone acetyltransferase GCN5 and the core transcriptional factor TFIIB. J Biol Chem. 1996 Dec 13;271(50):32359–32365. [Abstract] [Google Scholar]
  • Côté J, Quinn J, Workman JL, Peterson CL. Stimulation of GAL4 derivative binding to nucleosomal DNA by the yeast SWI/SNF complex. Science. 1994 Jul 1;265(5168):53–60. [Abstract] [Google Scholar]
  • Dallas PB, Yaciuk P, Moran E. Characterization of monoclonal antibodies raised against p300: both p300 and CBP are present in intracellular TBP complexes. J Virol. 1997 Feb;71(2):1726–1731. [Europe PMC free article] [Abstract] [Google Scholar]
  • Edmondson DG, Smith MM, Roth SY. Repression domain of the yeast global repressor Tup1 interacts directly with histones H3 and H4. Genes Dev. 1996 May 15;10(10):1247–1259. [Abstract] [Google Scholar]
  • Fletcher TM, Hansen JC. The nucleosomal array: structure/function relationships. Crit Rev Eukaryot Gene Expr. 1996;6(2-3):149–188. [Abstract] [Google Scholar]
  • Garcia-Ramirez M, Dong F, Ausio J. Role of the histone "tails" in the folding of oligonucleosomes depleted of histone H1. J Biol Chem. 1992 Sep 25;267(27):19587–19595. [Abstract] [Google Scholar]
  • Gietz RD, Schiestl RH. Applications of high efficiency lithium acetate transformation of intact yeast cells using single-stranded nucleic acids as carrier. Yeast. 1991 Apr;7(3):253–263. [Abstract] [Google Scholar]
  • Georgakopoulos T, Thireos G. Two distinct yeast transcriptional activators require the function of the GCN5 protein to promote normal levels of transcription. EMBO J. 1992 Nov;11(11):4145–4152. [Europe PMC free article] [Abstract] [Google Scholar]
  • Grunstein M. Histone function in transcription. Annu Rev Cell Biol. 1990;6:643–678. [Abstract] [Google Scholar]
  • Guide to yeast genetics and molecular biology. Methods Enzymol. 1991;194:1–863. [Abstract] [Google Scholar]
  • Han M, Kim UJ, Kayne P, Grunstein M. Depletion of histone H4 and nucleosomes activates the PHO5 gene in Saccharomyces cerevisiae. EMBO J. 1988 Jul;7(7):2221–2228. [Europe PMC free article] [Abstract] [Google Scholar]
  • Hansen JC, Ausio J, Stanik VH, van Holde KE. Homogeneous reconstituted oligonucleosomes, evidence for salt-dependent folding in the absence of histone H1. Biochemistry. 1989 Nov 14;28(23):9129–9136. [Abstract] [Google Scholar]
  • Happel AM, Swanson MS, Winston F. The SNF2, SNF5 and SNF6 genes are required for Ty transcription in Saccharomyces cerevisiae. Genetics. 1991 May;128(1):69–77. [Europe PMC free article] [Abstract] [Google Scholar]
  • Hecht A, Laroche T, Strahl-Bolsinger S, Gasser SM, 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. [Abstract] [Google Scholar]
  • Henriksson A, Almlöf T, Ford J, McEwan IJ, Gustafsson JA, Wright AP. Role of the Ada adaptor complex in gene activation by the glucocorticoid receptor. Mol Cell Biol. 1997 Jun;17(6):3065–3073. [Europe PMC free article] [Abstract] [Google Scholar]
  • Hirschhorn JN, Brown SA, Clark CD, Winston F. Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure. Genes Dev. 1992 Dec;6(12A):2288–2298. [Abstract] [Google Scholar]
  • Horiuchi J, Silverman N, Marcus GA, Guarente L. ADA3, a putative transcriptional adaptor, consists of two separable domains and interacts with ADA2 and GCN5 in a trimeric complex. Mol Cell Biol. 1995 Mar;15(3):1203–1209. [Europe PMC free article] [Abstract] [Google Scholar]
  • Imbalzano AN, Kwon H, Green MR, Kingston RE. Facilitated binding of TATA-binding protein to nucleosomal DNA. Nature. 1994 Aug 11;370(6489):481–485. [Abstract] [Google Scholar]
  • Jiang YW, Stillman DJ. Regulation of HIS4 expression by the Saccharomyces cerevisiae SIN4 transcriptional regulator. Genetics. 1995 May;140(1):103–114. [Europe PMC free article] [Abstract] [Google Scholar]
  • Kemphues KJ, Raff EC, Kaufman TC. Genetic analysis of B2t, the structural gene for a testis-specific beta-tubulin subunit in Drosophila melanogaster. Genetics. 1983 Oct;105(2):345–356. [Europe PMC free article] [Abstract] [Google Scholar]
  • Kemphues KJ, Kaufman TC, Raff RA, Raff EC. The testis-specific beta-tubulin subunit in Drosophila melanogaster has multiple functions in spermatogenesis. Cell. 1982 Dec;31(3 Pt 2):655–670. [Abstract] [Google Scholar]
  • Kruger W, Peterson CL, Sil A, Coburn C, Arents G, Moudrianakis EN, Herskowitz I. Amino acid substitutions in the structured domains of histones H3 and H4 partially relieve the requirement of the yeast SWI/SNF complex for transcription. Genes Dev. 1995 Nov 15;9(22):2770–2779. [Abstract] [Google Scholar]
  • Kruger W, Herskowitz I. A negative regulator of HO transcription, SIN1 (SPT2), is a nonspecific DNA-binding protein related to HMG1. Mol Cell Biol. 1991 Aug;11(8):4135–4146. [Europe PMC free article] [Abstract] [Google Scholar]
  • Kuo MH, Brownell JE, Sobel RE, Ranalli TA, Cook RG, Edmondson DG, Roth SY, Allis CD. Transcription-linked acetylation by Gcn5p of histones H3 and H4 at specific lysines. Nature. 1996 Sep 19;383(6597):269–272. [Abstract] [Google Scholar]
  • Kwon H, Imbalzano AN, Khavari PA, Kingston RE, Green MR. Nucleosome disruption and enhancement of activator binding by a human SW1/SNF complex. Nature. 1994 Aug 11;370(6489):477–481. [Abstract] [Google Scholar]
  • Marcus GA, Silverman N, Berger SL, Horiuchi J, Guarente L. Functional similarity and physical association between GCN5 and ADA2: putative transcriptional adaptors. EMBO J. 1994 Oct 17;13(20):4807–4815. [Europe PMC free article] [Abstract] [Google Scholar]
  • Melcher K, Johnston SA. GAL4 interacts with TATA-binding protein and coactivators. Mol Cell Biol. 1995 May;15(5):2839–2848. [Europe PMC free article] [Abstract] [Google Scholar]
  • Miller ME, Cairns BR, Levinson RS, Yamamoto KR, Engel DA, Smith MM. Adenovirus E1A specifically blocks SWI/SNF-dependent transcriptional activation. Mol Cell Biol. 1996 Oct;16(10):5737–5743. [Europe PMC free article] [Abstract] [Google Scholar]
  • Muchardt C, Reyes JC, Bourachot B, Leguoy E, Yaniv M. The hbrm and BRG-1 proteins, components of the human SNF/SWI complex, are phosphorylated and excluded from the condensed chromosomes during mitosis. EMBO J. 1996 Jul 1;15(13):3394–3402. [Europe PMC free article] [Abstract] [Google Scholar]
  • Neigeborn L, Carlson M. Genes affecting the regulation of SUC2 gene expression by glucose repression in Saccharomyces cerevisiae. Genetics. 1984 Dec;108(4):845–858. [Europe PMC free article] [Abstract] [Google Scholar]
  • Paranjape SM, Kamakaka RT, Kadonaga JT. Role of chromatin structure in the regulation of transcription by RNA polymerase II. Annu Rev Biochem. 1994;63:265–297. [Abstract] [Google Scholar]
  • Peterson CL, Herskowitz I. Characterization of the yeast SWI1, SWI2, and SWI3 genes, which encode a global activator of transcription. Cell. 1992 Feb 7;68(3):573–583. [Abstract] [Google Scholar]
  • Peterson CL, Dingwall A, Scott MP. Five SWI/SNF gene products are components of a large multisubunit complex required for transcriptional enhancement. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2905–2908. [Europe PMC free article] [Abstract] [Google Scholar]
  • Peterson CL, Kruger W, Herskowitz I. A functional interaction between the C-terminal domain of RNA polymerase II and the negative regulator SIN1. Cell. 1991 Mar 22;64(6):1135–1143. [Abstract] [Google Scholar]
  • Peterson CL, Tamkun JW. The SWI-SNF complex: a chromatin remodeling machine? Trends Biochem Sci. 1995 Apr;20(4):143–146. [Abstract] [Google Scholar]
  • Pham TA, Hwung YP, McDonnell DP, O'Malley BW. Transactivation functions facilitate the disruption of chromatin structure by estrogen receptor derivatives in vivo. J Biol Chem. 1991 Sep 25;266(27):18179–18187. [Abstract] [Google Scholar]
  • Piña B, Berger S, Marcus GA, Silverman N, Agapite J, Guarente L. ADA3: a gene, identified by resistance to GAL4-VP16, with properties similar to and different from those of ADA2. Mol Cell Biol. 1993 Oct;13(10):5981–5989. [Europe PMC free article] [Abstract] [Google Scholar]
  • Prelich G, Winston F. Mutations that suppress the deletion of an upstream activating sequence in yeast: involvement of a protein kinase and histone H3 in repressing transcription in vivo. Genetics. 1993 Nov;135(3):665–676. [Europe PMC free article] [Abstract] [Google Scholar]
  • Quinn J, Fyrberg AM, Ganster RW, Schmidt MC, Peterson CL. DNA-binding properties of the yeast SWI/SNF complex. Nature. 1996 Feb 29;379(6568):844–847. [Abstract] [Google Scholar]
  • Rose MD, Novick P, Thomas JH, Botstein D, Fink GR. A Saccharomyces cerevisiae genomic plasmid bank based on a centromere-containing shuttle vector. Gene. 1987;60(2-3):237–243. [Abstract] [Google Scholar]
  • Rundlett SE, Carmen AA, Kobayashi R, Bavykin S, Turner BM, 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Saleh A, Lang V, Cook R, Brandl CJ. Identification of native complexes containing the yeast coactivator/repressor proteins NGG1/ADA3 and ADA2. J Biol Chem. 1997 Feb 28;272(9):5571–5578. [Abstract] [Google Scholar]
  • Silverman N, Agapite J, Guarente L. Yeast ADA2 protein binds to the VP16 protein activation domain and activates transcription. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11665–11668. [Europe PMC free article] [Abstract] [Google Scholar]
  • Steinberg RA, Agard DA. Turnover of regulatory subunit of cyclic AMP-dependent protein kinase in S49 mouse lymphoma cells. Regulation by catalytic subunit and analogs of cyclic AMP. J Biol Chem. 1981 Nov 10;256(21):10731–10734. [Abstract] [Google Scholar]
  • Stern M, Jensen R, Herskowitz I. Five SWI genes are required for expression of the HO gene in yeast. J Mol Biol. 1984 Oct 5;178(4):853–868. [Abstract] [Google Scholar]
  • Sterner R, Vidali G, Heinrikson RL, Allfrey VG. Postsynthetic modification of high mobility group proteins. Evidence that high mobility group proteins are acetylated. J Biol Chem. 1978 Nov 10;253(21):7601–7604. [Abstract] [Google Scholar]
  • Stillman DJ, Dorland S, Yu Y. Epistasis analysis of suppressor mutations that allow HO expression in the absence of the yeast SW15 transcriptional activator. Genetics. 1994 Mar;136(3):781–788. [Europe PMC free article] [Abstract] [Google Scholar]
  • Treich I, Cairns BR, de los Santos T, Brewster E, Carlson M. SNF11, a new component of the yeast SNF-SWI complex that interacts with a conserved region of SNF2. Mol Cell Biol. 1995 Aug;15(8):4240–4248. [Europe PMC free article] [Abstract] [Google Scholar]
  • Wolffe AP, Pruss D. Targeting chromatin disruption: Transcription regulators that acetylate histones. Cell. 1996 Mar 22;84(6):817–819. [Abstract] [Google Scholar]
  • Wong LC, Sharpe DJ, Wong SS. High-mobility group and other nonhistone substrates for nuclear histone N-acetyltransferase. Biochem Genet. 1991 Oct;29(9-10):461–475. [Abstract] [Google Scholar]
  • Workman JL, Taylor IC, Kingston RE. Activation domains of stably bound GAL4 derivatives alleviate repression of promoters by nucleosomes. Cell. 1991 Feb 8;64(3):533–544. [Abstract] [Google Scholar]
  • Yang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y. A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature. 1996 Jul 25;382(6589):319–324. [Abstract] [Google Scholar]
  • Yoshinaga SK, Peterson CL, Herskowitz I, Yamamoto KR. Roles of SWI1, SWI2, and SWI3 proteins for transcriptional enhancement by steroid receptors. Science. 1992 Dec 4;258(5088):1598–1604. [Abstract] [Google Scholar]

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