Multiple single-stranded cis elements are associated with activated chromatin of the human c-myc gene in vivo (original) (raw)

Abstract

Transcription activation and repression of eukaryotic genes are associated with conformational and topological changes of the DNA and chromatin, altering the spectrum of proteins associated with an active gene. Segments of the human c-myc gene possessing non-B structure in vivo located with enzymatic and chemical probes. Sites hypertensive to cleavage with single-strand-specific S1 nuclease or the single-strand-selective agent potassium permanganate included the major promoters P1 and P2 as well as the far upstream sequence element (FUSE) and CT elements, which bind, respectively, the single-strand-specific factors FUSE-binding protein and heterogeneous nuclear ribonucleoprotein K in vitro. Active and inactive c-myc genes yielded different patterns of S1 nuclease and permanganate sensitivity, indicating alternative chromatin configurations of active and silent genes. The melting of specific cis elements of active c-myc genes in vivo suggested that transcriptionally associated torsional strain might assist strand separation and facilitate factor binding. Therefore, the interaction of FUSE-binding protein and heterogeneous nuclear ribonucleoprotein K with supercoiled DNA was studied. Remarkably, both proteins recognize their respective elements torsionally strained but not as liner duplexes. Single-strand- or supercoil-dependent gene regulatory proteins may directly link alterations in DNA conformation and topology with changes in gene expression.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. Aller P., Rius C., Mata F., Zorrilla A., Cabañas C., Bellón T., Bernabeu C. Camptothecin induces differentiation and stimulates the expression of differentiation-related genes in U-937 human promonocytic leukemia cells. Cancer Res. 1992 Mar 1;52(5):1245–1251. [PubMed] [Google Scholar]
  2. Avigan M. I., Strober B., Levens D. A far upstream element stimulates c-myc expression in undifferentiated leukemia cells. J Biol Chem. 1990 Oct 25;265(30):18538–18545. [PubMed] [Google Scholar]
  3. Battey J., Moulding C., Taub R., Murphy W., Stewart T., Potter H., Lenoir G., Leder P. The human c-myc oncogene: structural consequences of translocation into the IgH locus in Burkitt lymphoma. Cell. 1983 Oct;34(3):779–787. doi: 10.1016/0092-8674(83)90534-2. [DOI] [PubMed] [Google Scholar]
  4. Bazar L., Meighen D., Harris V., Duncan R., Levens D., Avigan M. Targeted melting and binding of a DNA regulatory element by a transactivator of c-myc. J Biol Chem. 1995 Apr 7;270(14):8241–8248. doi: 10.1074/jbc.270.14.8241. [DOI] [PubMed] [Google Scholar]
  5. Bentley D. L., Groudine M. A block to elongation is largely responsible for decreased transcription of c-myc in differentiated HL60 cells. Nature. 1986 Jun 12;321(6071):702–706. doi: 10.1038/321702a0. [DOI] [PubMed] [Google Scholar]
  6. Bentley D. L., Groudine M. Novel promoter upstream of the human c-myc gene and regulation of c-myc expression in B-cell lymphomas. Mol Cell Biol. 1986 Oct;6(10):3481–3489. doi: 10.1128/mcb.6.10.3481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Berg J. M. Sp1 and the subfamily of zinc finger proteins with guanine-rich binding sites. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11109–11110. doi: 10.1073/pnas.89.23.11109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bergemann A. D., Johnson E. M. The HeLa Pur factor binds single-stranded DNA at a specific element conserved in gene flanking regions and origins of DNA replication. Mol Cell Biol. 1992 Mar;12(3):1257–1265. doi: 10.1128/mcb.12.3.1257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bergemann A. D., Ma Z. W., Johnson E. M. Sequence of cDNA comprising the human pur gene and sequence-specific single-stranded-DNA-binding properties of the encoded protein. Mol Cell Biol. 1992 Dec;12(12):5673–5682. doi: 10.1128/mcb.12.12.5673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Borowiec J. A., Zhang L., Sasse-Dwight S., Gralla J. D. DNA supercoiling promotes formation of a bent repression loop in lac DNA. J Mol Biol. 1987 Jul 5;196(1):101–111. doi: 10.1016/0022-2836(87)90513-4. [DOI] [PubMed] [Google Scholar]
  11. Bossone S. A., Asselin C., Patel A. J., Marcu K. B. MAZ, a zinc finger protein, binds to c-MYC and C2 gene sequences regulating transcriptional initiation and termination. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7452–7456. doi: 10.1073/pnas.89.16.7452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dayn A., Malkhosyan S., Mirkin S. M. Transcriptionally driven cruciform formation in vivo. Nucleic Acids Res. 1992 Nov 25;20(22):5991–5997. doi: 10.1093/nar/20.22.5991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. DesJardins E., Hay N. Repeated CT elements bound by zinc finger proteins control the absolute and relative activities of the two principal human c-myc promoters. Mol Cell Biol. 1993 Sep;13(9):5710–5724. doi: 10.1128/mcb.13.9.5710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dony C., Kessel M., Gruss P. Post-transcriptional control of myc and p53 expression during differentiation of the embryonal carcinoma cell line F9. Nature. 1985 Oct 17;317(6038):636–639. doi: 10.1038/317636a0. [DOI] [PubMed] [Google Scholar]
  15. Dunaway M., Ostrander E. A. Local domains of supercoiling activate a eukaryotic promoter in vivo. Nature. 1993 Feb 25;361(6414):746–748. doi: 10.1038/361746a0. [DOI] [PubMed] [Google Scholar]
  16. Duncan R., Bazar L., Michelotti G., Tomonaga T., Krutzsch H., Avigan M., Levens D. A sequence-specific, single-strand binding protein activates the far upstream element of c-myc and defines a new DNA-binding motif. Genes Dev. 1994 Feb 15;8(4):465–480. doi: 10.1101/gad.8.4.465. [DOI] [PubMed] [Google Scholar]
  17. Duncan R., Collins I., Tomonaga T., Zhang T., Levens D. A unique transactivation sequence motif is found in the carboxyl-terminal domain of the single-strand-binding protein FBP. Mol Cell Biol. 1996 May;16(5):2274–2282. doi: 10.1128/mcb.16.5.2274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Duyao M. P., Buckler A. J., Sonenshein G. E. Interaction of an NF-kappa B-like factor with a site upstream of the c-myc promoter. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4727–4731. doi: 10.1073/pnas.87.12.4727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Dyson P. J., Littlewood T. D., Forster A., Rabbitts T. H. Chromatin structure of transcriptionally active and inactive human c-myc alleles. EMBO J. 1985 Nov;4(11):2885–2891. doi: 10.1002/j.1460-2075.1985.tb04018.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Dyson P. J., Rabbitts T. H. Chromatin structure around the c-myc gene in Burkitt lymphomas with upstream and downstream translocation points. Proc Natl Acad Sci U S A. 1985 Apr;82(7):1984–1988. doi: 10.1073/pnas.82.7.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Eick D., Bornkamm G. W. Transcriptional arrest within the first exon is a fast control mechanism in c-myc gene expression. Nucleic Acids Res. 1986 Nov 11;14(21):8331–8346. doi: 10.1093/nar/14.21.8331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Freeman L. A., Garrard W. T. DNA supercoiling in chromatin structure and gene expression. Crit Rev Eukaryot Gene Expr. 1992;2(2):165–209. [PubMed] [Google Scholar]
  23. Fukuchi K., Tomoyasu S., Watanabe K., Suzuki H., Kaetsu T., Takagi Y., Tsuruoka N., Gomi K. Increased expression of the proto-oncogene, c-myc, in human neuroblastoma cells by reversible inhibition of cell growth. Anticancer Res. 1991 Nov-Dec;11(6):1967–1973. [PubMed] [Google Scholar]
  24. Garrity P. A., Wold B. J. Effects of different DNA polymerases in ligation-mediated PCR: enhanced genomic sequencing and in vivo footprinting. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1021–1025. doi: 10.1073/pnas.89.3.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Gazin C., Dupont de Dinechin S., Hampe A., Masson J. M., Martin P., Stehelin D., Galibert F. Nucleotide sequence of the human c-myc locus: provocative open reading frame within the first exon. EMBO J. 1984 Feb;3(2):383–387. doi: 10.1002/j.1460-2075.1984.tb01816.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Giardina C., Lis J. T. Dynamic protein-DNA architecture of a yeast heat shock promoter. Mol Cell Biol. 1995 May;15(5):2737–2744. doi: 10.1128/mcb.15.5.2737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Giardina C., Pérez-Riba M., Lis J. T. Promoter melting and TFIID complexes on Drosophila genes in vivo. Genes Dev. 1992 Nov;6(11):2190–2200. doi: 10.1101/gad.6.11.2190. [DOI] [PubMed] [Google Scholar]
  28. Grosso L. E., Pitot H. C. Transcriptional regulation of c-myc during chemically induced differentiation of HL-60 cultures. Cancer Res. 1985 Feb;45(2):847–850. [PubMed] [Google Scholar]
  29. Hiebert S. W., Lipp M., Nevins J. R. E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor. Proc Natl Acad Sci U S A. 1989 May;86(10):3594–3598. doi: 10.1073/pnas.86.10.3594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Hochschild A., Ptashne M. Cooperative binding of lambda repressors to sites separated by integral turns of the DNA helix. Cell. 1986 Mar 14;44(5):681–687. doi: 10.1016/0092-8674(86)90833-0. [DOI] [PubMed] [Google Scholar]
  31. Kahn J. D., Yun E., Crothers D. M. Detection of localized DNA flexibility. Nature. 1994 Mar 10;368(6467):163–166. doi: 10.1038/368163a0. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Kohl N. E., Kanda N., Schreck R. R., Bruns G., Latt S. A., Gilbert F., Alt F. W. Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell. 1983 Dec;35(2 Pt 1):359–367. doi: 10.1016/0092-8674(83)90169-1. [DOI] [PubMed] [Google Scholar]
  34. Krumm A., Hickey L. B., Groudine M. Promoter-proximal pausing of RNA polymerase II defines a general rate-limiting step after transcription initiation. Genes Dev. 1995 Mar 1;9(5):559–572. doi: 10.1101/gad.9.5.559. [DOI] [PubMed] [Google Scholar]
  35. Krumm A., Meulia T., Brunvand M., Groudine M. The block to transcriptional elongation within the human c-myc gene is determined in the promoter-proximal region. Genes Dev. 1992 Nov;6(11):2201–2213. doi: 10.1101/gad.6.11.2201. [DOI] [PubMed] [Google Scholar]
  36. Larsen A., Weintraub H. An altered DNA conformation detected by S1 nuclease occurs at specific regions in active chick globin chromatin. Cell. 1982 Jun;29(2):609–622. doi: 10.1016/0092-8674(82)90177-5. [DOI] [PubMed] [Google Scholar]
  37. Liu L. F., Wang J. C. Supercoiling of the DNA template during transcription. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7024–7027. doi: 10.1073/pnas.84.20.7024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. Michelotti E. F., Tomonaga T., Krutzsch H., Levens D. Cellular nucleic acid binding protein regulates the CT element of the human c-myc protooncogene. J Biol Chem. 1995 Apr 21;270(16):9494–9499. doi: 10.1074/jbc.270.16.9494. [DOI] [PubMed] [Google Scholar]
  40. Negishi Y., Nishita Y., Saëgusa Y., Kakizaki I., Galli I., Kihara F., Tamai K., Miyajima N., Iguchi-Ariga S. M., Ariga H. Identification and cDNA cloning of single-stranded DNA binding proteins that interact with the region upstream of the human c-myc gene. Oncogene. 1994 Apr;9(4):1133–1143. [PubMed] [Google Scholar]
  41. Nielsen P. E. Chemical and photochemical probing of DNA complexes. J Mol Recognit. 1990 Feb;3(1):1–25. doi: 10.1002/jmr.300030102. [DOI] [PubMed] [Google Scholar]
  42. Ramsperger U., Stahl H. Unwinding of chromatin by the SV40 large T antigen DNA helicase. EMBO J. 1995 Jul 3;14(13):3215–3225. doi: 10.1002/j.1460-2075.1995.tb07324.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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]
  44. Riou J. F., Lefevre D., Riou G. Stimulation of the topoisomerase II induced DNA cleavage sites in the c-myc protooncogene by antitumor drugs is associated with gene expression. Biochemistry. 1989 Nov 14;28(23):9104–9110. doi: 10.1021/bi00449a022. [DOI] [PubMed] [Google Scholar]
  45. Rubin C. M., Schmid C. W. Pyrimidine-specific chemical reactions useful for DNA sequencing. Nucleic Acids Res. 1980 Oct 24;8(20):4613–4619. doi: 10.1093/nar/8.20.4613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sasse-Dwight S., Gralla J. D. Footprinting protein-DNA complexes in vivo. Methods Enzymol. 1991;208:146–168. doi: 10.1016/0076-6879(91)08012-7. [DOI] [PubMed] [Google Scholar]
  47. Sasse-Dwight S., Gralla J. D. Probing co-operative DNA-binding in vivo. The lac O1:O3 interaction. J Mol Biol. 1988 Jul 5;202(1):107–119. doi: 10.1016/0022-2836(88)90523-2. [DOI] [PubMed] [Google Scholar]
  48. Schubach W., Groudine M. Alteration of c-myc chromatin structure by avian leukosis virus integration. Nature. 1984 Feb 23;307(5953):702–708. doi: 10.1038/307702a0. [DOI] [PubMed] [Google Scholar]
  49. Shi Y., Glynn J. M., Guilbert L. J., Cotter T. G., Bissonnette R. P., Green D. R. Role for c-myc in activation-induced apoptotic cell death in T cell hybridomas. Science. 1992 Jul 10;257(5067):212–214. doi: 10.1126/science.1378649. [DOI] [PubMed] [Google Scholar]
  50. Siebenlist U., Bressler P., Kelly K. Two distinct mechanisms of transcriptional control operate on c-myc during differentiation of HL60 cells. Mol Cell Biol. 1988 Feb;8(2):867–874. doi: 10.1128/mcb.8.2.867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Siebenlist U., Hennighausen L., Battey J., Leder P. Chromatin structure and protein binding in the putative regulatory region of the c-myc gene in Burkitt lymphoma. Cell. 1984 Jun;37(2):381–391. doi: 10.1016/0092-8674(84)90368-4. [DOI] [PubMed] [Google Scholar]
  52. Skerka C., Zipfel P. F., Siebenlist U. Two regulatory domains are required for downregulation of c-myc transcription in differentiating U937 cells. Oncogene. 1993 Aug;8(8):2135–2143. [PubMed] [Google Scholar]
  53. Spencer C. A., Groudine M. Control of c-myc regulation in normal and neoplastic cells. Adv Cancer Res. 1991;56:1–48. doi: 10.1016/s0065-230x(08)60476-5. [DOI] [PubMed] [Google Scholar]
  54. Spencer C. A., LeStrange R. C., Novak U., Hayward W. S., Groudine M. The block to transcription elongation is promoter dependent in normal and Burkitt's lymphoma c-myc alleles. Genes Dev. 1990 Jan;4(1):75–88. doi: 10.1101/gad.4.1.75. [DOI] [PubMed] [Google Scholar]
  55. Strobl L. J., Eick D. Hold back of RNA polymerase II at the transcription start site mediates down-regulation of c-myc in vivo. EMBO J. 1992 Sep;11(9):3307–3314. doi: 10.1002/j.1460-2075.1992.tb05409.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Strobl L. J., Kohlhuber F., Mautner J., Polack A., Eick D. Absence of a paused transcription complex from the c-myc P2 promoter of the translocation chromosome in Burkitt's lymphoma cells: implication for the c-myc P1/P2 promoter shift. Oncogene. 1993 Jun;8(6):1437–1447. [PubMed] [Google Scholar]
  57. Takai T., Nishita Y., Iguchi-Ariga S. M., Ariga H. Molecular cloning of MSSP-2, a c-myc gene single-strand binding protein: characterization of binding specificity and DNA replication activity. Nucleic Acids Res. 1994 Dec 25;22(25):5576–5581. doi: 10.1093/nar/22.25.5576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Takimoto M., Quinn J. P., Farina A. R., Staudt L. M., Levens D. fos/jun and octamer-binding protein interact with a common site in a negative element of the human c-myc gene. J Biol Chem. 1989 May 25;264(15):8992–8999. [PubMed] [Google Scholar]
  59. Takimoto M., Tomonaga T., Matunis M., Avigan M., Krutzsch H., Dreyfuss G., Levens D. Specific binding of heterogeneous ribonucleoprotein particle protein K to the human c-myc promoter, in vitro. J Biol Chem. 1993 Aug 25;268(24):18249–18258. [PubMed] [Google Scholar]
  60. Tomonaga T., Levens D. Heterogeneous nuclear ribonucleoprotein K is a DNA-binding transactivator. J Biol Chem. 1995 Mar 3;270(9):4875–4881. doi: 10.1074/jbc.270.9.4875. [DOI] [PubMed] [Google Scholar]
  61. Vassilev L., Johnson E. M. An initiation zone of chromosomal DNA replication located upstream of the c-myc gene in proliferating HeLa cells. Mol Cell Biol. 1990 Sep;10(9):4899–4904. doi: 10.1128/mcb.10.9.4899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Walters M. C., Fiering S., Eidemiller J., Magis W., Groudine M., Martin D. I. Enhancers increase the probability but not the level of gene expression. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7125–7129. doi: 10.1073/pnas.92.15.7125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Watanabe T., Sariban E., Mitchell T., Kufe D. Human c-myc and N-ras expression during induction of HL-60 cellular differentiation. Biochem Biophys Res Commun. 1985 Feb 15;126(3):999–1005. doi: 10.1016/0006-291x(85)90284-0. [DOI] [PubMed] [Google Scholar]
  64. Wittig B., Wölfl S., Dorbic T., Vahrson W., Rich A. Transcription of human c-myc in permeabilized nuclei is associated with formation of Z-DNA in three discrete regions of the gene. EMBO J. 1992 Dec;11(12):4653–4663. doi: 10.1002/j.1460-2075.1992.tb05567.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Wolf D. A., Strobl L. J., Pullner A., Eick D. Variable pause positions of RNA polymerase II lie proximal to the c-myc promoter irrespective of transcriptional activity. Nucleic Acids Res. 1995 Sep 11;23(17):3373–3379. doi: 10.1093/nar/23.17.3373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Wu C. The 5' ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature. 1980 Aug 28;286(5776):854–860. doi: 10.1038/286854a0. [DOI] [PubMed] [Google Scholar]
  67. Zhang X. Y., Jabrane-Ferrat N., Asiedu C. K., Samac S., Peterlin B. M., Ehrlich M. The major histocompatibility complex class II promoter-binding protein RFX (NF-X) is a methylated DNA-binding protein. Mol Cell Biol. 1993 Nov;13(11):6810–6818. doi: 10.1128/mcb.13.11.6810. [DOI] [PMC free article] [PubMed] [Google Scholar]