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. 1996 Oct 1;93(20):10638–10641. doi: 10.1073/pnas.93.20.10638

YY1 and c-Myc associate in vivo in a manner that depends on c-Myc levels.

A Shrivastava 1, J Yu 1, S Artandi 1, K Calame 1
PMCID: PMC38206  PMID: 8855231

Abstract

The c-Myc oncoprotein has previously been shown to associate with transcription regulator YY1 and to inhibit its activity. We show herein that endogenous c-Myc and YY1 associate in vivo and that changes in c-Myc levels, which accompany mitogenic stimulation or differentiation of cultured cells, affect the ratio of free to c-Myc-associated YY1. We have also investigated the mechanism by which association with c-Myc inhibits YY1's ability to regulate transcription. c-Myc does not block binding of YY1 to DNA. However, protein association studies suggest that c-Myc interferes with the ability of YY1 to contact basal transcription proteins TATA-binding protein and TFIIB.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Atchison M. L., Meyuhas O., Perry R. P. Localization of transcriptional regulatory elements and nuclear factor binding sites in mouse ribosomal protein gene rpL32. Mol Cell Biol. 1989 May;9(5):2067–2074. doi: 10.1128/mcb.9.5.2067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Austin R. J., Biggin M. D. A domain of the even-skipped protein represses transcription by preventing TFIID binding to a promoter: repression by cooperative blocking. Mol Cell Biol. 1995 Sep;15(9):4683–4693. doi: 10.1128/mcb.15.9.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barton C. H., Mann D. A., Walsh F. S. Characterization of the human N-CAM promoter. Biochem J. 1990 May 15;268(1):161–168. doi: 10.1042/bj2680161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bauknecht T., Angel P., Royer H. D., zur Hausen H. Identification of a negative regulatory domain in the human papillomavirus type 18 promoter: interaction with the transcriptional repressor YY1. EMBO J. 1992 Dec;11(12):4607–4617. doi: 10.1002/j.1460-2075.1992.tb05563.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bello-Fernandez C., Packham G., Cleveland J. L. The ornithine decarboxylase gene is a transcriptional target of c-Myc. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7804–7808. doi: 10.1073/pnas.90.16.7804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Benvenisty N., Leder A., Kuo A., Leder P. An embryonically expressed gene is a target for c-Myc regulation via the c-Myc-binding sequence. Genes Dev. 1992 Dec;6(12B):2513–2523. doi: 10.1101/gad.6.12b.2513. [DOI] [PubMed] [Google Scholar]
  7. Bird R. C., Kung T. Y., Wu G., Young-White R. R. Variations in c-fos mRNA expression during serum induction and the synchronous cell cycle. Biochem Cell Biol. 1990 May;68(5):858–862. doi: 10.1139/o90-127. [DOI] [PubMed] [Google Scholar]
  8. Chen S., Mills L., Perry P., Riddle S., Wobig R., Lown R., Millette R. L. Transactivation of the major capsid protein gene of herpes simplex virus type 1 requires a cellular transcription factor. J Virol. 1992 Jul;66(7):4304–4314. doi: 10.1128/jvi.66.7.4304-4314.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Christy R. J., Kaestner K. H., Geiman D. E., Lane M. D. CCAAT/enhancer binding protein gene promoter: binding of nuclear factors during differentiation of 3T3-L1 preadipocytes. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2593–2597. doi: 10.1073/pnas.88.6.2593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chung S., Perry R. P. The importance of downstream delta-factor binding elements for the activity of the rpL32 promoter. Nucleic Acids Res. 1993 Jul 11;21(14):3301–3308. doi: 10.1093/nar/21.14.3301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cole M. D. The myc oncogene: its role in transformation and differentiation. Annu Rev Genet. 1986;20:361–384. doi: 10.1146/annurev.ge.20.120186.002045. [DOI] [PubMed] [Google Scholar]
  12. Cory S. Activation of cellular oncogenes in hemopoietic cells by chromosome translocation. Adv Cancer Res. 1986;47:189–234. doi: 10.1016/s0065-230x(08)60200-6. [DOI] [PubMed] [Google Scholar]
  13. Evan G. I., Littlewood T. D. The role of c-myc in cell growth. Curr Opin Genet Dev. 1993 Feb;3(1):44–49. doi: 10.1016/s0959-437x(05)80339-9. [DOI] [PubMed] [Google Scholar]
  14. Farnham P. J., Means A. L. Sequences downstream of the transcription initiation site modulate the activity of the murine dihydrofolate reductase promoter. Mol Cell Biol. 1990 Apr;10(4):1390–1398. doi: 10.1128/mcb.10.4.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Flanagan J. R., Becker K. G., Ennist D. L., Gleason S. L., Driggers P. H., Levi B. Z., Appella E., Ozato K. Cloning of a negative transcription factor that binds to the upstream conserved region of Moloney murine leukemia virus. Mol Cell Biol. 1992 Jan;12(1):38–44. doi: 10.1128/mcb.12.1.38. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gaubatz S., Meichle A., Eilers M. An E-box element localized in the first intron mediates regulation of the prothymosin alpha gene by c-myc. Mol Cell Biol. 1994 Jun;14(6):3853–3862. doi: 10.1128/mcb.14.6.3853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Greenberg M. E., Ziff E. B. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. doi: 10.1038/311433a0. [DOI] [PubMed] [Google Scholar]
  18. Grignani F., Lombardi L., Inghirami G., Sternas L., Cechova K., Dalla-Favera R. Negative autoregulation of c-myc gene expression is inactivated in transformed cells. EMBO J. 1990 Dec;9(12):3913–3922. doi: 10.1002/j.1460-2075.1990.tb07612.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gu W., Bhatia K., Magrath I. T., Dang C. V., Dalla-Favera R. Binding and suppression of the Myc transcriptional activation domain by p107. Science. 1994 Apr 8;264(5156):251–254. doi: 10.1126/science.8146655. [DOI] [PubMed] [Google Scholar]
  20. Guo B., Odgren P. R., van Wijnen A. J., Last T. J., Nickerson J., Penman S., Lian J. B., Stein J. L., Stein G. S. The nuclear matrix protein NMP-1 is the transcription factor YY1. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10526–10530. doi: 10.1073/pnas.92.23.10526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hariharan N., Kelley D. E., Perry R. P. Delta, a transcription factor that binds to downstream elements in several polymerase II promoters, is a functionally versatile zinc finger protein. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9799–9803. doi: 10.1073/pnas.88.21.9799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hateboer G., Timmers H. T., Rustgi A. K., Billaud M., van 't Veer L. J., Bernards R. TATA-binding protein and the retinoblastoma gene product bind to overlapping epitopes on c-Myc and adenovirus E1A protein. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8489–8493. doi: 10.1073/pnas.90.18.8489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hsiao K. M., McMahon S. L., Farnham P. J. Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter. Genes Dev. 1994 Jul 1;8(13):1526–1537. doi: 10.1101/gad.8.13.1526. [DOI] [PubMed] [Google Scholar]
  24. Inghirami G., Grignani F., Sternas L., Lombardi L., Knowles D. M., Dalla-Favera R. Down-regulation of LFA-1 adhesion receptors by C-myc oncogene in human B lymphoblastoid cells. Science. 1990 Nov 2;250(4981):682–686. doi: 10.1126/science.2237417. [DOI] [PubMed] [Google Scholar]
  25. Inouye C. J., Seto E. Relief of YY1-induced transcriptional repression by protein-protein interaction with the nucleolar phosphoprotein B23. J Biol Chem. 1994 Mar 4;269(9):6506–6510. [PubMed] [Google Scholar]
  26. Kelly K., Siebenlist U. The regulation and expression of c-myc in normal and malignant cells. Annu Rev Immunol. 1986;4:317–338. doi: 10.1146/annurev.iy.04.040186.001533. [DOI] [PubMed] [Google Scholar]
  27. Koller B. H., Orr H. T. Cloning and complete sequence of an HLA-A2 gene: analysis of two HLA-A alleles at the nucleotide level. J Immunol. 1985 Apr;134(4):2727–2733. [PubMed] [Google Scholar]
  28. Lachman H. M., Skoultchi A. I. Expression of c-myc changes during differentiation of mouse erythroleukaemia cells. Nature. 1984 Aug 16;310(5978):592–594. doi: 10.1038/310592a0. [DOI] [PubMed] [Google Scholar]
  29. Lee J. S., Galvin K. M., See R. H., 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. doi: 10.1101/gad.9.10.1188. [DOI] [PubMed] [Google Scholar]
  30. Lee J. S., Galvin K. M., 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. doi: 10.1073/pnas.90.13.6145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lee T. C., Shi Y., Schwartz R. J. 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. doi: 10.1073/pnas.89.20.9814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Li L. H., Nerlov C., Prendergast G., MacGregor D., Ziff E. B. c-Myc represses transcription in vivo by a novel mechanism dependent on the initiator element and Myc box II. EMBO J. 1994 Sep 1;13(17):4070–4079. doi: 10.1002/j.1460-2075.1994.tb06724.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Lüscher B., Eisenman R. N. New light on Myc and Myb. Part I. Myc. Genes Dev. 1990 Dec;4(12A):2025–2035. doi: 10.1101/gad.4.12a.2025. [DOI] [PubMed] [Google Scholar]
  34. Maheswaran S., Lee H., Sonenshein G. E. Intracellular association of the protein product of the c-myc oncogene with the TATA-binding protein. Mol Cell Biol. 1994 Feb;14(2):1147–1152. doi: 10.1128/mcb.14.2.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Mai S., Jalava A. c-Myc binds to 5' flanking sequence motifs of the dihydrofolate reductase gene in cellular extracts: role in proliferation. Nucleic Acids Res. 1994 Jun 25;22(12):2264–2273. doi: 10.1093/nar/22.12.2264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Marcu K. B., Bossone S. A., Patel A. J. myc function and regulation. Annu Rev Biochem. 1992;61:809–860. doi: 10.1146/annurev.bi.61.070192.004113. [DOI] [PubMed] [Google Scholar]
  37. Marcu K. B. Regulation of expression of the c-myc proto-oncogene. Bioessays. 1987 Jan;6(1):28–32. doi: 10.1002/bies.950060108. [DOI] [PubMed] [Google Scholar]
  38. Meier V. S., Groner B. The nuclear factor YY1 participates in repression of the beta-casein gene promoter in mammary epithelial cells and is counteracted by mammary gland factor during lactogenic hormone induction. Mol Cell Biol. 1994 Jan;14(1):128–137. doi: 10.1128/mcb.14.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Meyuhas O., Klein A. The mouse ribosomal protein L7 gene. Its primary structure and functional analysis of the promoter region. J Biol Chem. 1990 Jul 15;265(20):11465–11473. [PubMed] [Google Scholar]
  40. Natesan S., Gilman M. Z. DNA bending and orientation-dependent function of YY1 in the c-fos promoter. Genes Dev. 1993 Dec;7(12B):2497–2509. doi: 10.1101/gad.7.12b.2497. [DOI] [PubMed] [Google Scholar]
  41. Park K., Atchison M. L. Isolation of a candidate repressor/activator, NF-E1 (YY-1, delta), that binds to the immunoglobulin kappa 3' enhancer and the immunoglobulin heavy-chain mu E1 site. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9804–9808. doi: 10.1073/pnas.88.21.9804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Pear W. S., Nolan G. P., Scott M. L., Baltimore D. Production of high-titer helper-free retroviruses by transient transfection. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8392–8396. doi: 10.1073/pnas.90.18.8392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Peters B., Merezhinskaya N., Diffley J. F., Noguchi C. T. Protein-DNA interactions in the epsilon-globin gene silencer. J Biol Chem. 1993 Feb 15;268(5):3430–3437. [PubMed] [Google Scholar]
  44. Philipp A., Schneider A., Väsrik I., Finke K., Xiong Y., Beach D., Alitalo K., Eilers M. Repression of cyclin D1: a novel function of MYC. Mol Cell Biol. 1994 Jun;14(6):4032–4043. doi: 10.1128/mcb.14.6.4032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Reisman D., Elkind N. B., Roy B., Beamon J., Rotter V. c-Myc trans-activates the p53 promoter through a required downstream CACGTG motif. Cell Growth Differ. 1993 Feb;4(2):57–65. [PubMed] [Google Scholar]
  46. Riggs K. J., Merrell K. T., Wilson G., Calame K. Common factor 1 is a transcriptional activator which binds in the c-myc promoter, the skeletal alpha-actin promoter, and the immunoglobulin heavy-chain enhancer. Mol Cell Biol. 1991 Mar;11(3):1765–1769. doi: 10.1128/mcb.11.3.1765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Riggs K. J., Saleque S., Wong K. K., Merrell K. T., Lee J. S., Shi Y., Calame K. Yin-yang 1 activates the c-myc promoter. Mol Cell Biol. 1993 Dec;13(12):7487–7495. doi: 10.1128/mcb.13.12.7487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Roy A. L., Carruthers C., Gutjahr T., Roeder R. G. Direct role for Myc in transcription initiation mediated by interactions with TFII-I. Nature. 1993 Sep 23;365(6444):359–361. doi: 10.1038/365359a0. [DOI] [PubMed] [Google Scholar]
  49. Rustgi A. K., Dyson N., Bernards R. Amino-terminal domains of c-myc and N-myc proteins mediate binding to the retinoblastoma gene product. Nature. 1991 Aug 8;352(6335):541–544. doi: 10.1038/352541a0. [DOI] [PubMed] [Google Scholar]
  50. Seto E., Lewis B., Shenk T. Interaction between transcription factors Sp1 and YY1. Nature. 1993 Sep 30;365(6445):462–464. doi: 10.1038/365462a0. [DOI] [PubMed] [Google Scholar]
  51. Shi Y., Seto E., Chang L. S., Shenk T. Transcriptional repression by YY1, a human GLI-Krüppel-related protein, and relief of repression by adenovirus E1A protein. Cell. 1991 Oct 18;67(2):377–388. doi: 10.1016/0092-8674(91)90189-6. [DOI] [PubMed] [Google Scholar]
  52. 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. doi: 10.1093/nar/22.24.5151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Shrivastava A., Saleque S., Kalpana G. V., Artandi S., Goff S. P., Calame K. Inhibition of transcriptional regulator Yin-Yang-1 by association with c-Myc. Science. 1993 Dec 17;262(5141):1889–1892. doi: 10.1126/science.8266081. [DOI] [PubMed] [Google Scholar]
  54. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  55. Tanaka M., Herr W. Differential transcriptional activation by Oct-1 and Oct-2: interdependent activation domains induce Oct-2 phosphorylation. Cell. 1990 Feb 9;60(3):375–386. doi: 10.1016/0092-8674(90)90589-7. [DOI] [PubMed] [Google Scholar]
  56. Tibensky D., Delovitch T. L. Promoter region of HLA-C genes: regulatory elements common to and different from those of HLA-A and HLA-B genes. Immunogenetics. 1990;32(3):210–213. doi: 10.1007/BF02114976. [DOI] [PubMed] [Google Scholar]
  57. Um M., Li C., Manley J. L. The transcriptional repressor even-skipped interacts directly with TATA-binding protein. Mol Cell Biol. 1995 Sep;15(9):5007–5016. doi: 10.1128/mcb.15.9.5007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. 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. doi: 10.1016/0092-8674(94)90387-5. [DOI] [PubMed] [Google Scholar]
  59. Vincent C. K., Gualberto A., Patel C. V., Walsh K. Different regulatory sequences control creatine kinase-M gene expression in directly injected skeletal and cardiac muscle. Mol Cell Biol. 1993 Feb;13(2):1264–1272. doi: 10.1128/mcb.13.2.1264. [DOI] [PMC free article] [PubMed] [Google Scholar]

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