The Nuclear Matrix: an Organizing Structure for the Interphase Nucleus and Chromosome

  • Kenneth J. Pienta
  • Donald S. Coffey
Part of the NATO ASI Series book series (NSSA, volume 98)


The interphase nucleus is characterized by a nuclear matrix structure that forms a residual scaffolding network composed of only 10% of the total nuclear proteins. The nuclear matrix contains residual elements of the pore-complex lamina, the nucleolus, and an intranuclear fibrous network. The matrix provides the basic shape and structure of the nucleus. In the interphase nucleus this nuclear matrix has been reported to be a central element in the organization of DNA loop domains and contains fixed sites for DNA replication and transcription. In this study, we have analyzed the role of the nuclear matrix and the DNA loop domains in the organization and structure of the number four human chromosome. A scale model is proposed and constructed that closely approximates the observed structural dimensions of this chromosome. The model is composed of equivalent 30 nm diameter filaments formed from solenoid with 6 nucleosomes per turn. This 30 nm solenoid filament is organized into loops of DNA each containing approximately 60,000 base pairs; each loop is anchored at its base to the nuclear matrix structure. A radial loop chromosome model containing 18 of these loops per turn forms a new unit of chromosome structure termed the miniband. Each miniband contains approximately one million base pairs of DNA and this is equivalent to a centimorgan in DNA content. Approximately 106 of these minibands are stacked longitudinally along a central axis to form the final chromatid. The role of the nuclear matrix in this organization is presented. The accuracy of the proposed model is tested by comparing its features with the known properties of the number four human chromosome.


Metaphase Chromosome Nuclear Matrix Interphase Nucleus Loop Domain Nuclear Protein Matrix 


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  1. 1.
    R. Berezney and D. S. Coffey, Identification of a nuclear protein matrix, Biochem. Biophys. Res. Commun. 60:1410–1417 (1974).PubMedCrossRefGoogle Scholar
  2. 2.
    R. Berezney and D. S. Coffey, The nuclear protein matrix, isolation, structure and function, Advances in Enzyme Regulation 14:63–100 (1976).PubMedCrossRefGoogle Scholar
  3. 3a.
    R. Berezney and D. S. Coffey, Nuclear matrix: isolation and characterization of a framework structure from rat liver nuclei, J. Cell Biol. 73:616–637 (1977).PubMedCrossRefGoogle Scholar
  4. 3b.
    R. Berezney and D. S. Coffey, Nuclear protein matrix: association with newly synthesized DNA, Science 189:291–293 (1975).PubMedCrossRefGoogle Scholar
  5. 4.
    D. E. Comings and T. A. Okada, Nuclear proteins. III. The fibrillar nature of the nuclear matrix, Exp. Cell Res. 103:341–360 (1976).PubMedCrossRefGoogle Scholar
  6. 5.
    F. Wunderlich and G. Herlan, A reversible contractile nuclear matrix, its isolation, structure and composition, J. Cell Biol. 73:271–278 (1977).PubMedCrossRefGoogle Scholar
  7. 6.
    L. D. Hodge, P. Mancini, F. M. Davis, and P. Heywood, Nuclear matrix of HeLa S3 cells, J. Cell Biol. 72:192–208 (1977).CrossRefGoogle Scholar
  8. 7.
    P. A. Fisher, M. Berrios, and G. Blobel. Isolation and characterization of a proteinaceous subnuclear fraction composed of nuclear matrix, peripheral lamina, and nuclear pore complexes from embryos of Drosophila melanogaster, J. Cell Biol. 92:674–686 (1982).PubMedCrossRefGoogle Scholar
  9. 8.
    J. H. Shaper, D. M. Pardoll, S. H. Kaufmann, E. R. Barrack, B. Vogelstein, and D. S. Coffey, The relationship of the nuclear matrix to cellular structure and function, Adv. Enz. Reg. 17:213–248 (1979).CrossRefGoogle Scholar
  10. 9.
    E. R. Barrack, and D. S. Coffey, Biological properties of the nuclear matrix: steriod hormone binding, Recent Prog. Horm. Res. 38:133–195 (1982).PubMedGoogle Scholar
  11. 10.
    E. R. Barrack and D. S. Coffey, Hormone receptors and the nuclear matrix, in: “Gene Regulation by Steroid Hormones II,” A. K. Roy and J. H. Clark, eds., Springer-Verlag, New York (1983).Google Scholar
  12. 11.
    V. M. Dvorkin and B. D. Vanyushin, Replication and kinetics of the reassociation of DNA of the nuclear matrix of the regenerating rat liver, Biochem. (USSR) 43:1297–1301 (1978).Google Scholar
  13. 12.
    P. Dijkwel, L. Mullenders, and F. Wanka, Eucaryotic chromosome replication, in: “Annual Review of Genetics,” 9, E. Roman, ed., Annual Reviews, Inc., Palo Alto (1979).Google Scholar
  14. 13.
    D. M. Pardoll, B. Vogelstein, and D. S. Coffey, A fixed site of DNA replication in eucaryotic cells, Cell 19:527–536 (1980).PubMedCrossRefGoogle Scholar
  15. 14.
    B. Vogelstein, D. M. Pardoll, and D. S. Coffey, Supercoiled loops and eucaryotic DNA replication, Cell 22:79–85 (1980).PubMedCrossRefGoogle Scholar
  16. 15.
    S. J. McCready, J. Godwin, D. W. Mason, I. A. Brazell, and P. R. Cook, DNA is replicated at the nuclear cage, J. Cell Sci. 46: 365–386 (1980).PubMedGoogle Scholar
  17. 16.
    R. Berezney and L. A. Buchholtz, Dynamic association of replicating DNA fragments with the nuclear matrix of regenerating liver, Exp. Cell Res. 132:1–13 (1981).PubMedCrossRefGoogle Scholar
  18. 17.
    H. C. Smith and R. Berezney, DNA polymerase is tightly bound to the nuclear matrix of actively replicating liver, Biochem. Biophys. Res. Commun. 97:1541–1547 (1980).PubMedCrossRefGoogle Scholar
  19. 18.
    B. D. Nelkin, D. M. Pardoll, and B. Vogelstein, Localization of SV40 genes within supercoiled loop domains, Nucleic Acids Res. 8:5623–5633 (1980).PubMedCrossRefGoogle Scholar
  20. 19.
    S. I. Robinson, B. D. Nelkin, and B. Vogelstein, The ovalbumin gene is associated with the nuclear matrix of chicken oviduct cells, Cell 28:99–106 (1982).PubMedCrossRefGoogle Scholar
  21. 20.
    T. E. Miller, C. Huang, and A. O. Pogo, Rat liver nuclear skeleton and ribonucleoprotein complexes containing hnRNA, J. Cell Biol. 76:675–691 (1978).PubMedCrossRefGoogle Scholar
  22. 21.
    R. Herman, L. Weymouth, and S. Penman, Heterogeneous nuclear RNA-protein fibers in chromatin-depleted nuclei, J. Cell Biol. 78:663 674 (1978).Google Scholar
  23. 22.
    B. H. Long, C.-Y. Huang, and A. O. Pogo, Isolation and characterization of the nuclear matrix in Friend erythroleukemia cells: chromatin and hnRNA interactions with the nuclear matrix, Cell 18:1079–1090 (1979).PubMedCrossRefGoogle Scholar
  24. 23.
    C. A. G. van Eekelen and W. J. van Venrooij, hnRNA and its attachment to a nuclear protein matrix, J. Cell Biol. 88:554–563 (1981).PubMedCrossRefGoogle Scholar
  25. 24.
    D. A. Jackson, S. J. McCready, and P. R. Cook, RNA is synthesized at the nuclear cage, Nature 292:552–555 (1981).PubMedCrossRefGoogle Scholar
  26. 25.
    E. C. M. Mariman, C. A. G. van Eekelen, R. J. Reinders, A. J. M. Berns, and W. J. van Venrooij, Adenoviral heterogeneous nuclear RNA is associated with the host nuclear matrix during splicing, J. Mol. Biol. 154:102–119 (1982).CrossRefGoogle Scholar
  27. 26a.
    E. R. Barrack, E. F. Hawkins, S. L. Allen, L. L. Hicks, and D. S. Coffey, Concepts related to salt resistant estradiol receptors in rat uterine nuclei: nuclear matrix, Biochem. Biophys. Res. Commun. 79:829–836 (1977).PubMedCrossRefGoogle Scholar
  28. 26b.
    E. R. Barrack and D. S. Coffey, The specific binding of estrogens and androgens to the nuclear matrix of sex hormone responsive tissues, J. Biol. Chem. 255:7265–7275 (1980).PubMedGoogle Scholar
  29. 27.
    E. R. Barrack, The nuclear matrix of the prostate contains acceptor sites for androgen receptors, Endocrinology 113:430–432 (1983).PubMedCrossRefGoogle Scholar
  30. 28.
    P. R. Cook, I. A. Brazell, and E. Jost, Characterization of nuclear structures containing superhelical DNA, J. Cell Sci. 22:303–324 (1976).PubMedGoogle Scholar
  31. 29.
    C. Benyajati and A. Worcel, Isolation, characterization and structure of the folded interphase genome of Drosophila melanogaster, Cell 9:393–407 (1976).PubMedCrossRefGoogle Scholar
  32. 30.
    J. R. Paulson and U. K. Laemmli, The structure of histone-depleted metaphase chromosomes, Cell 12:817–828 (1977).PubMedCrossRefGoogle Scholar
  33. 31.
    J. A. Huberman and A. D. Riggs, On the mechanism of DNA replication in mammalian chromosomes, J. Mol. Biol. 32:327–341 (1968).PubMedCrossRefGoogle Scholar
  34. 32.
    J. T. Finch and A. Klug, Solenoid model for superstructure in chromatin, Proc. Natl. Acad, Sci. USA 73:1897–1901 (1976).CrossRefGoogle Scholar
  35. 33.
    C. Nicolini, Chromatin structure: From nuclei to genes (Review), Anticancer Research 3:63–86 (1983).PubMedGoogle Scholar
  36. 34.
    B. Cavazza, V. Trefiletti, F. Piolo, E. Ricci, and E. Patrone, Higher-order structure of chromatin from calf thymus, J. Cell Sci. 62:81–102 (1983).PubMedGoogle Scholar
  37. 35.
    A. L. Olins and D. E. Olins, Stereo electron microscopy of the 23 nm chromatin fibers in isolated nuclei, J. Cell Biol. 81:260–265 (1979).PubMedCrossRefGoogle Scholar
  38. 36.
    F. Kendall, F. Beltsame, S. Zictz, A. Belmont, and C. Nicolini, The quinternary chromatin-DNA structure. Three-dimensional reconstruction and functional significance, Cell Biophys. 2:373–404 (1980).PubMedGoogle Scholar
  39. 37.
    F. Thoma, I. M. Koller, and A. Klug, Involvement of histone H1 in the organization of the nucleosome and of the salt-dependent superstructures of chromatin, J. Cell Biol. 83:403–427 (1979).PubMedCrossRefGoogle Scholar
  40. 38.
    G. P. Georgiev, S. A. Nedspasov, and V. U. Bakayev, Supranucleosomal levels of chromatin organization, in: “The Cell Nucleus,” 6, H. Busch, ed., Academic Press, New York (1978).Google Scholar
  41. 39.
    U. K. Laemmli, Levels of organization of the DNA in eukaryotic chromosomes, Pharmacol. Revs. 30:469–476 (1979).Google Scholar
  42. 40.
    W. C. Earnshaw and U. K. Laemmli, Architecture of metaphase chromosomes and chromosome scaffolds, J. Cell Biol. 96:84–93 (1983).PubMedCrossRefGoogle Scholar
  43. 41.
    A. Leth Bak, J. Zeuthen, and F. H. C. Crick, Higher-order structure of human mitotic chromosomes, Proc. Natl. Acad. Sci. USA 74:1595–1599 (1977).CrossRefGoogle Scholar
  44. 42.
    J. Sedat and L. Manuelidis, A direct approach to the structure of eukaryotic chromosomes, CSHSQB XII:331–350 (1977).Google Scholar
  45. 43.
    K. W. Adolph and L. R. Kreisman, Surface structure and isolated metaphase chromosomes, Exp. Cell Res. 147:155–166 (1983).PubMedCrossRefGoogle Scholar
  46. 44.
    M. P. F. Marsden and U. K. Laemmli, Metaphase chromosome structure: evidence for a radial loop model, Cell 17:849–858 (1979).PubMedCrossRefGoogle Scholar
  47. 45.
    E. J. Dupraw, “DNA and Chromosomes,” Holt, Rinehart, Winston, New York (1970).Google Scholar
  48. 46.
    R. Hancock and T. Boulikas, Functional organization in the nucleus, Int. Rev. Cytol. 79:165–214 (1982).PubMedCrossRefGoogle Scholar
  49. 47.
    T. Igo-Kemenes, W. Horz, and M. G. Zachau, Chromatin, Ann. Rev. Biochem. 51:89–121 (1982).PubMedCrossRefGoogle Scholar
  50. 48.
    K. R. Utsumi, Studies on the structure of chromosomes. II. Chromosome fibers as revealed by scanning electron microscopy, Cell Structure and Function 6:395–401 (1981).CrossRefGoogle Scholar
  51. 49.
    K. W. Adolph, Isolation and structural organization of human mitotic chromosomes, Chromosoma 76:23–33 (1980).PubMedCrossRefGoogle Scholar
  52. 50.
    U. K. Laemmli, J. Cell Sci., Suppl. 1 (1984).Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Kenneth J. Pienta
    • 1
  • Donald S. Coffey
    • 1
  1. 1.Departments of Urology, Oncology and PharmacologyJohns Hopkins University School of MedicineBaltimoreUSA

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