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Mol Cell Biol. Jul 1997; 17(7): 3723–3732.
PMCID: PMC232224

Multiple mechanisms of transcriptional repression by YY1.

Abstract

The four C-terminal GLI-Krüppel type zinc fingers of YY1 have been identified as a transcriptional repression domain. Previous reports have proposed DNA-bending and activator-quenching mechanisms for this zinc finger-mediated repression. In addition, previous work indicated that p300 and CBP might be involved in YY1-mediated repression. We have analyzed these possible models for the zinc finger-mediated repression. The role of each zinc finger in the repression and DNA-binding functions was determined by using a structure-and-function approach. We show that zinc finger 2 of YY1 plays a central role in both DNA binding and transcriptional repression. However, a survey of a panel of YY1 mutants indicates that these two functions can be separated, which argues against the DNA-bending model for repression. We show that the physical interaction between YY1 and p300, a coactivator for CREB, is not sufficient for repression of CREB-mediated transcription. Our studies indicate that YY1 functions as an activator-specific repressor. Repression of CTF-1-directed transcription may be accomplished through direct physical interaction between YY1 and this activator. In contrast, physical interaction is not necessary for YY1 to repress Sp1- and CREB-mediated transcription. Rather, the repression likely reflects an ability of YY1 to interfere with communication between these activators and their targets within the general transcription machinery. Taken together, our results suggest that YY1 employs multiple mechanisms to achieve activator-specific repression.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • 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]
  • Bauknecht T, Jundt F, Herr I, Oehler T, Delius H, Shi Y, Angel P, Zur Hausen H. A switch region determines the cell type-specific positive or negative action of YY1 on the activity of the human papillomavirus type 18 promoter. J Virol. 1995 Jan;69(1):1–12. [PMC free article] [PubMed]
  • Bauknecht T, See RH, Shi Y. A novel C/EBP beta-YY1 complex controls the cell-type-specific activity of the human papillomavirus type 18 upstream regulatory region. J Virol. 1996 Nov;70(11):7695–7705. [PMC free article] [PubMed]
  • Bushmeyer S, Park K, Atchison ML. Characterization of functional domains within the multifunctional transcription factor, YY1. J Biol Chem. 1995 Dec 15;270(50):30213–30220. [PubMed]
  • Chiang CM, Roeder RG. Cloning of an intrinsic human TFIID subunit that interacts with multiple transcriptional activators. Science. 1995 Jan 27;267(5197):531–536. [PubMed]
  • Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature. 1993 Oct 28;365(6449):855–859. [PubMed]
  • Courey AJ, Tjian R. Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif. Cell. 1988 Dec 2;55(5):887–898. [PubMed]
  • Cowell IG. Repression versus activation in the control of gene transcription. Trends Biochem Sci. 1994 Jan;19(1):38–42. [PubMed]
  • Dai P, Akimaru H, Tanaka Y, Hou DX, Yasukawa T, Kanei-Ishii C, Takahashi T, Ishii S. CBP as a transcriptional coactivator of c-Myb. Genes Dev. 1996 Mar 1;10(5):528–540. [PubMed]
  • Dignam JD, Lebovitz RM, Roeder RG. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. [PMC free article] [PubMed]
  • Eckner R, Ewen ME, Newsome D, Gerdes M, DeCaprio JA, Lawrence JB, Livingston DM. Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dev. 1994 Apr 15;8(8):869–884. [PubMed]
  • Gilks CB, Bear SE, Grimes HL, Tsichlis PN. Progression of interleukin-2 (IL-2)-dependent rat T cell lymphoma lines to IL-2-independent growth following activation of a gene (Gfi-1) encoding a novel zinc finger protein. Mol Cell Biol. 1993 Mar;13(3):1759–1768. [PMC free article] [PubMed]
  • Harlow E, Whyte P, Franza BR, Jr, Schley C. Association of adenovirus early-region 1A proteins with cellular polypeptides. Mol Cell Biol. 1986 May;6(5):1579–1589. [PMC free article] [PubMed]
  • Houbaviy HB, Usheva A, Shenk T, Burley SK. Cocrystal structure of YY1 bound to the adeno-associated virus P5 initiator. Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13577–13582. [PMC free article] [PubMed]
  • Hyde-DeRuyscher RP, Jennings E, Shenk T. DNA binding sites for the transcriptional activator/repressor YY1. Nucleic Acids Res. 1995 Nov 11;23(21):4457–4465. [PMC free article] [PubMed]
  • Johnson AD. The price of repression. Cell. 1995 Jun 2;81(5):655–658. [PubMed]
  • Kaelin WG, Jr, Krek W, Sellers WR, DeCaprio JA, Ajchenbaum F, Fuchs CS, Chittenden T, Li Y, Farnham PJ, Blanar MA, et al. Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties. Cell. 1992 Jul 24;70(2):351–364. [PubMed]
  • Klug A, Schwabe JW. Protein motifs 5. Zinc fingers. FASEB J. 1995 May;9(8):597–604. [PubMed]
  • Kwok RP, Lundblad JR, Chrivia JC, Richards JP, Bächinger HP, Brennan RG, Roberts SG, Green MR, Goodman RH. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature. 1994 Jul 21;370(6486):223–226. [PubMed]
  • Lee JS, Galvin KM, See RH, Eckner R, Livingston D, Moran E, Shi Y. Relief of YY1 transcriptional repression by adenovirus E1A is mediated by E1A-associated protein p300. Genes Dev. 1995 May 15;9(10):1188–1198. [PubMed]
  • Lee JS, Galvin KM, Shi Y. Evidence for physical interaction between the zinc-finger transcription factors YY1 and Sp1. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6145–6149. [PMC free article] [PubMed]
  • Lee JS, See RH, Galvin KM, Wang J, Shi Y. Functional interactions between YY1 and adenovirus E1A. Nucleic Acids Res. 1995 Mar 25;23(6):925–931. [PMC free article] [PubMed]
  • Lee JS, Zhang X, Shi Y. Differential interactions of the CREB/ATF family of transcription factors with p300 and adenovirus E1A. J Biol Chem. 1996 Jul 26;271(30):17666–17674. [PubMed]
  • Lee TC, Shi Y, Schwartz RJ. Displacement of BrdUrd-induced YY1 by serum response factor activates skeletal alpha-actin transcription in embryonic myoblasts. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9814–9818. [PMC free article] [PubMed]
  • Lee TC, Zhang Y, Schwartz RJ. Bifunctional transcriptional properties of YY1 in regulating muscle actin and c-myc gene expression during myogenesis. Oncogene. 1994 Apr;9(4):1047–1052. [PubMed]
  • Levine M, Manley JL. Transcriptional repression of eukaryotic promoters. Cell. 1989 Nov 3;59(3):405–408. [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]
  • Lu SY, Rodriguez M, Liao WS. YY1 represses rat serum amyloid A1 gene transcription and is antagonized by NF-kappa B during acute-phase response. Mol Cell Biol. 1994 Sep;14(9):6253–6263. [PMC free article] [PubMed]
  • Luckow B, Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. [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]
  • Mermod N, O'Neill EA, Kelly TJ, Tjian R. The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain. Cell. 1989 Aug 25;58(4):741–753. [PubMed]
  • Natesan S, Gilman MZ. DNA bending and orientation-dependent function of YY1 in the c-fos promoter. Genes Dev. 1993 Dec;7(12B):2497–2509. [PubMed]
  • O'Connor MJ, Tan SH, Tan CH, Bernard HU. YY1 represses human papillomavirus type 16 transcription by quenching AP-1 activity. J Virol. 1996 Oct;70(10):6529–6539. [PMC free article] [PubMed]
  • Oelgeschläger M, Janknecht R, Krieg J, Schreek S, Lüscher B. Interaction of the co-activator CBP with Myb proteins: effects on Myb-specific transactivation and on the cooperativity with NF-M. EMBO J. 1996 Jun 3;15(11):2771–2780. [PMC free article] [PubMed]
  • Pavletich NP, Pabo CO. Crystal structure of a five-finger GLI-DNA complex: new perspectives on zinc fingers. Science. 1993 Sep 24;261(5129):1701–1707. [PubMed]
  • Pavletich NP, Pabo CO. Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A. Science. 1991 May 10;252(5007):809–817. [PubMed]
  • Riggs KJ, Saleque S, Wong KK, Merrell KT, Lee JS, Shi Y, Calame K. Yin-yang 1 activates the c-myc promoter. Mol Cell Biol. 1993 Dec;13(12):7487–7495. [PMC free article] [PubMed]
  • Sadowski I, Ptashne M. A vector for expressing GAL4(1-147) fusions in mammalian cells. Nucleic Acids Res. 1989 Sep 25;17(18):7539–7539. [PMC free article] [PubMed]
  • Seto E, Lewis B, Shenk T. Interaction between transcription factors Sp1 and YY1. Nature. 1993 Sep 30;365(6445):462–464. [PubMed]
  • Seto E, Shi Y, Shenk T. YY1 is an initiator sequence-binding protein that directs and activates transcription in vitro. Nature. 1991 Nov 21;354(6350):241–245. [PubMed]
  • Sheng M, Thompson MA, Greenberg ME. CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. Science. 1991 Jun 7;252(5011):1427–1430. [PubMed]
  • Shrivastava A, Calame K. An analysis of genes regulated by the multi-functional transcriptional regulator Yin Yang-1. Nucleic Acids Res. 1994 Dec 11;22(24):5151–5155. [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]
  • Usheva A, Shenk T. TATA-binding protein-independent initiation: YY1, TFIIB, and RNA polymerase II direct basal transcription on supercoiled template DNA. Cell. 1994 Mar 25;76(6):1115–1121. [PubMed]
  • Usheva A, Shenk T. YY1 transcriptional initiator: protein interactions and association with a DNA site containing unpaired strands. Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13571–13576. [PMC free article] [PubMed]
  • Wang HG, Rikitake Y, Carter MC, Yaciuk P, Abraham SE, Zerler B, Moran E. Identification of specific adenovirus E1A N-terminal residues critical to the binding of cellular proteins and to the control of cell growth. J Virol. 1993 Jan;67(1):476–488. [PMC free article] [PubMed]
  • Yang WM, Inouye C, Zeng Y, Bearss D, Seto E. Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12845–12850. [PMC free article] [PubMed]
  • Yee SP, Branton PE. Detection of cellular proteins associated with human adenovirus type 5 early region 1A polypeptides. Virology. 1985 Nov;147(1):142–153. [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]

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