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Mol Cell Biol. Oct 1996; 16(10): 5737–5743.
PMCID: PMC231574

Adenovirus E1A specifically blocks SWI/SNF-dependent transcriptional activation.


Expression of the adenovirus E1A243 oncoprotein in Saccharomyces cerevisiae produces a slow-growth phenotype with accumulation of cells in the G1 phase of the cell cycle. This effect is due to the N-terminal and CR1 domains of E1A243, which in rodent cells are involved in triggering cellular transformation and also in binding to the cellular transcriptional coactivator p300. A genetic screen was undertaken to identify genes required for the function of E1A243 in S. cerevisiae. This screen identified SNF12, a gene encoding the 73-kDa subunit of the SWI/SNF transcriptional regulatory complex. Mutation of genes encoding known members of the SWI/SNF complex also led to loss of E1A function, suggesting that the SWI/SNF complex is a target of E1A243. Moreover, expression of E1A in wild-type cells specifically blocked transcriptional activation of the INO1 and SUC2 genes, whose activation pathways are distinct but have a common requirement for the SWI/SNF complex. These data demonstrate a specific functional interaction between E1A and the SWI/SNF complex and suggest that a similar interaction takes place in rodent and human cells.

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Selected References

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  • Arany Z, Newsome D, Oldread E, Livingston DM, Eckner R. A family of transcriptional adaptor proteins targeted by the E1A oncoprotein. Nature. 1995 Mar 2;374(6517):81–84. [PubMed]
  • Arany Z, Sellers WR, Livingston DM, Eckner R. E1A-associated p300 and CREB-associated CBP belong to a conserved family of coactivators. Cell. 1994 Jun 17;77(6):799–800. [PubMed]
  • Bartlett R, Nurse P. Yeast as a model system for understanding the control of DNA replication in Eukaryotes. Bioessays. 1990 Oct;12(10):457–463. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Carlson M, Laurent BC. The SNF/SWI family of global transcriptional activators. Curr Opin Cell Biol. 1994 Jun;6(3):396–402. [PubMed]
  • 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. [PubMed]
  • Coulombe B, Killeen M, Liljelund P, Honda B, Xiao H, Ingles CJ, Greenblatt J. Identification of three mammalian proteins that bind to the yeast TATA box protein TFIID. Gene Expr. 1992;2(2):99–110. [PubMed]
  • Dingwall C, Kandels-Lewis S, Séraphin B. A family of Ran binding proteins that includes nucleoporins. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7525–7529. [PMC free article] [PubMed]
  • Dunaief JL, Strober BE, Guha S, Khavari PA, Alin K, Luban J, Begemann M, Crabtree GR, Goff SP. The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest. Cell. 1994 Oct 7;79(1):119–130. [PubMed]
  • Dyson N, Harlow E. Adenovirus E1A targets key regulators of cell proliferation. Cancer Surv. 1992;12:161–195. [PubMed]
  • Egan C, Jelsma TN, Howe JA, Bayley ST, Ferguson B, Branton PE. Mapping of cellular protein-binding sites on the products of early-region 1A of human adenovirus type 5. Mol Cell Biol. 1988 Sep;8(9):3955–3959. [PMC free article] [PubMed]
  • Engel DA, Hardy S, Shenk T. cAMP acts in synergy with E1A protein to activate transcription of the adenovirus early genes E4 and E1A. Genes Dev. 1988 Dec;2(12A):1517–1528. [PubMed]
  • Engel DA, Muller U, Gedrich RW, Eubanks JS, Shenk T. Induction of c-fos mRNA and AP-1 DNA-binding activity by cAMP in cooperation with either the adenovirus 243- or the adenovirus 289-amino acid E1A protein. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3957–3961. [PMC free article] [PubMed]
  • Estruch F, Carlson M. SNF6 encodes a nuclear protein that is required for expression of many genes in Saccharomyces cerevisiae. Mol Cell Biol. 1990 Jun;10(6):2544–2553. [PMC free article] [PubMed]
  • Gedrich RW, Bayley ST, Engel DA. Induction of AP-1 DNA-binding activity and c-fos mRNA by the adenovirus 243R E1A protein and cyclic AMP requires domains necessary for transformation. J Virol. 1992 Oct;66(10):5849–5859. [PMC free article] [PubMed]
  • Gietz D, St Jean A, Woods RA, Schiestl RH. Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Res. 1992 Mar 25;20(6):1425–1425. [PMC free article] [PubMed]
  • Harlow E, Franza BR, Jr, Schley C. Monoclonal antibodies specific for adenovirus early region 1A proteins: extensive heterogeneity in early region 1A products. J Virol. 1985 Sep;55(3):533–546. [PMC free article] [PubMed]
  • Hatakeyama M, Brill JA, Fink GR, Weinberg RA. Collaboration of G1 cyclins in the functional inactivation of the retinoblastoma protein. Genes Dev. 1994 Aug 1;8(15):1759–1771. [PubMed]
  • Hirsch JP, Henry SA. Expression of the Saccharomyces cerevisiae inositol-1-phosphate synthase (INO1) gene is regulated by factors that affect phospholipid synthesis. Mol Cell Biol. 1986 Oct;6(10):3320–3328. [PMC free article] [PubMed]
  • 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. [PubMed]
  • 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. [PubMed]
  • Janaswami PM, Kalvakolanu DV, Zhang Y, Sen GC. Transcriptional repression of interleukin-6 gene by adenoviral E1A proteins. J Biol Chem. 1992 Dec 5;267(34):24886–24891. [PubMed]
  • Kalvakolanu DV, Liu J, Hanson RW, Harter ML, Sen GC. Adenovirus E1A represses the cyclic AMP-induced transcription of the gene for phosphoenolpyruvate carboxykinase (GTP) in hepatoma cells. J Biol Chem. 1992 Feb 5;267(4):2530–2536. [PubMed]
  • Keleher CA, Redd MJ, Schultz J, Carlson M, Johnson AD. Ssn6-Tup1 is a general repressor of transcription in yeast. Cell. 1992 Feb 21;68(4):709–719. [PubMed]
  • Kelleher RJ, 3rd, Flanagan PM, Chasman DI, Ponticelli AS, Struhl K, Kornberg RD. Yeast and human TFIIDs are interchangeable for the response to acidic transcriptional activators in vitro. Genes Dev. 1992 Feb;6(2):296–303. [PubMed]
  • Kornuc M, Altman R, Harrich D, Garcia J, Chao J, Kayne P, Gaynor R. Adenovirus transcriptional regulatory regions are conserved in mammalian cells and Saccharomyces cerevisiae. Mol Cell Biol. 1988 Sep;8(9):3717–3725. [PMC free article] [PubMed]
  • Kraus VB, Inostroza JA, Yeung K, Reinberg D, Nevins JR. Interaction of the Dr1 inhibitory factor with the TATA binding protein is disrupted by adenovirus E1A. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6279–6282. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Laurent BC, Carlson M. Yeast SNF2/SWI2, SNF5, and SNF6 proteins function coordinately with the gene-specific transcriptional activators GAL4 and Bicoid. Genes Dev. 1992 Sep;6(9):1707–1715. [PubMed]
  • Laurent BC, Treich I, Carlson M. Role of yeast SNF and SWI proteins in transcriptional activation. Cold Spring Harb Symp Quant Biol. 1993;58:257–263. [PubMed]
  • Laurent BC, Treitel MA, Carlson M. The SNF5 protein of Saccharomyces cerevisiae is a glutamine- and proline-rich transcriptional activator that affects expression of a broad spectrum of genes. Mol Cell Biol. 1990 Nov;10(11):5616–5625. [PMC free article] [PubMed]
  • Lawrence CW. Classical mutagenesis techniques. Methods Enzymol. 1991;194:273–281. [PubMed]
  • Lefebvre L, Smith M. Mutational and functional analysis of dominant SPT2 (SIN1) suppressor alleles in Saccharomyces cerevisiae. Mol Cell Biol. 1993 Sep;13(9):5393–5407. [PMC free article] [PubMed]
  • Lewis BA, Tullis G, Seto E, Horikoshi N, Weinmann R, Shenk T. Adenovirus E1A proteins interact with the cellular YY1 transcription factor. J Virol. 1995 Mar;69(3):1628–1636. [PMC free article] [PubMed]
  • Lundblad JR, Kwok RP, Laurance ME, Harter ML, Goodman RH. Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. Nature. 1995 Mar 2;374(6517):85–88. [PubMed]
  • Malhotra P, Manohar CF, Swaminathan S, Toyama R, Dhar R, Reichel R, Thimmapaya B. E2F site activates transcription in fission yeast Schizosaccharomyces pombe and binds to a 30-kDa transcription factor. J Biol Chem. 1993 Sep 25;268(27):20392–20401. [PubMed]
  • Miller ME, Engel DA, Smith MM. Cyclic AMP signaling is required for function of the N-terminal and CR1 domains of adenovirus E1A in Saccharomyces cerevisiae. Oncogene. 1995 Oct 19;11(8):1623–1630. [PubMed]
  • Muchardt C, Sardet C, Bourachot B, Onufryk C, Yaniv M. A human protein with homology to Saccharomyces cerevisiae SNF5 interacts with the potential helicase hbrm. Nucleic Acids Res. 1995 Apr 11;23(7):1127–1132. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • 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. [PubMed]
  • Peterson CL, Tamkun JW. The SWI-SNF complex: a chromatin remodeling machine? Trends Biochem Sci. 1995 Apr;20(4):143–146. [PubMed]
  • Powers S. Genetic analysis of ras homologs in yeasts. Semin Cancer Biol. 1992 Aug;3(4):209–218. [PubMed]
  • Shortle D, Novick P, Botstein D. Construction and genetic characterization of temperature-sensitive mutant alleles of the yeast actin gene. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4889–4893. [PMC free article] [PubMed]
  • Shrivastava A, Saleque S, Kalpana GV, Artandi S, Goff SP, Calame K. Inhibition of transcriptional regulator Yin-Yang-1 by association with c-Myc. Science. 1993 Dec 17;262(5141):1889–1892. [PubMed]
  • Sikorski RS, Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. [PMC free article] [PubMed]
  • Strober BE, Dunaief JL, Guha, Goff SP. Functional interactions between the hBRM/hBRG1 transcriptional activators and the pRB family of proteins. Mol Cell Biol. 1996 Apr;16(4):1576–1583. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Vincent AC, Struhl K. ACR1, a yeast ATF/CREB repressor. Mol Cell Biol. 1992 Dec;12(12):5394–5405. [PMC free article] [PubMed]
  • Wada T, Nogi Y, Handa H, Fukasawa T. Strain-specific lethal effect of the adenovirus E1a protein on Saccharomyces cerevisiae. Biochem Biophys Res Commun. 1990 Jul 31;170(2):470–476. [PubMed]
  • Whyte P, Williamson NM, Harlow E. Cellular targets for transformation by the adenovirus E1A proteins. Cell. 1989 Jan 13;56(1):67–75. [PubMed]
  • Wills C, Martin T, Melham T. Effect on gluconeogenesis of mutants blocking two mitochondrial transport systems in the yeast Saccharomyces cerevisiae. Arch Biochem Biophys. 1986 Apr;246(1):306–320. [PubMed]
  • Winston F, Carlson M. Yeast SNF/SWI transcriptional activators and the SPT/SIN chromatin connection. Trends Genet. 1992 Nov;8(11):387–391. [PubMed]
  • Wolffe AP. Transcriptional activation. Switched-on chromatin. Curr Biol. 1994 Jun 1;4(6):525–528. [PubMed]
  • 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. [PubMed]
  • Zhou Q, Gedrich RW, Engel DA. Transcriptional repression of the c-fos gene by YY1 is mediated by a direct interaction with ATF/CREB. J Virol. 1995 Jul;69(7):4323–4330. [PMC free article] [PubMed]
  • Zieler HA, Walberg M, Berg P. Suppression of mutations in two Saccharomyces cerevisiae genes by the adenovirus E1A protein. Mol Cell Biol. 1995 Jun;15(6):3227–3237. [PMC free article] [PubMed]

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