Neurochemical Research

, Volume 17, Issue 11, pp 1049–1055 | Cite as

The dynamic properties of neuronal chromatin are modulated by triiodothyronine

  • Alessandro Cestelli
  • Roberto Gristina
  • Daniele Castiglia
  • Carlo Di Liegro
  • Giovanni Savettieri
  • Guiseppe Salemi
  • Italia Di Liegro
Original Articles

Abstract

The effect of triiodothyronine (T3) on the rate of synthesis of nuclear proteins was studied during terminal differentiation of rat cortical neurons cultured in a serum-free medium. To this aim total and acid soluble nuclear proteins were analyzed by different electrophoretic techniques. Our results show that: 1) during maturation in vitro, neuronal nuclei undergo a dramatic change in the rate at which different classes of histones and high mobility group (HMG) proteins are synthesized; the synthetic activity, measured as incorporation of radioactive precursors into nuclear proteins, slows indeed down with age: especially evident is the decrease in core histones synthesis; at day 15, on the other hand, HMG 14 and 17 and ubiquitinated H2A (A24) are synthesized at a high rate, especially in T3-treated neurons; 2) neurons treated with T3 show, at any age tested, a higher level of lysine incorporation into nuclear proteins; 3) even if during the first days of culture neurons synthesize core histones more actively in the presence of T3, there is no accumulation of these proteins at later stages, as compared with untreated cells. Possible implications of these data and relationship with the chromatin rearrangement which accompanies neuronal terminal differentiation are discussed.

Key Words

CNS development chromatin triiodothyronine neurons 

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References

  1. 1.
    Allan, J., Rau, D.C., Harborne, N., and Gould, H. 1984. Higher order structure in a short repeat length chromatin. J. Cell Biol. 98:1320–1327.Google Scholar
  2. 2.
    Banchev, T., Srebreva, J., Zlatanova, J., and Tsanev, R. 1988. Immunofluorescent localization of histone H1° in the nuclei of proliferating and differentiating Friend cells. Exp. Cell Res. 177:1–8.Google Scholar
  3. 3.
    Bohm, L., and Crane-Robinson, C. 1984. Proteases as structural probes for chromatin: the domain structure of histones. Biosci. Rep. 4:365–386.Google Scholar
  4. 4.
    Brown, I. R. 1978. Postnatal appearance of a short DNA repeat length in neurons of the cerebral cortex. Biochem. Biophys. Res. Commun. 84:285–292.Google Scholar
  5. 5.
    Cestelli, A., Castiglia, D., Di Liegro, C., and Di Liegro, I. 1992. Quanlitative differences in nuclear proteins correlate with neuronal terminal differentiation. Cell Mol. Neurobiol. 12:33–43.Google Scholar
  6. 6.
    Cestelli, A., Di Liegro, I., Castiglia, D., Gristina, R., Ferraro, D., Salemi, G., and Savettieri, G. 1987. Triiodothyronine-induced shortening of chromatin repeat length in neurons cultured in a chemically defined medium. J. Neurochem. 48:1053–1059.Google Scholar
  7. 7.
    Cestelli, A., Savettieri, G., Ferraro, D., and Vitale, F. 1985. Formulation of a novel synthetic medium for selectively culturing rat CNS neurons. Dev. Brain Res. 22:219–227.Google Scholar
  8. 8.
    Di Liegro, I., and Cestelli, A. 1990. The relative proportion of H1° and A24 is reversed in oligodendrocytes during rat brain development. Cell Mol. Neurobiol. 10:267–274.Google Scholar
  9. 9.
    Di Liegro, I., Cestelli, A., Barbieri, G., and Giallongo, A. 1991. Developmental changes of neuron-specific enolase mRNA in primary cultures of rat neurons. Cell. Mol. Neurobiol. 11:289–294.Google Scholar
  10. 10.
    Di Liegro, I., Savettieri, G. and Cestelli, A. 1987. Cellular mechanism of action of thyroid hormones. Differentiation 35:165–175.Google Scholar
  11. 11.
    Evans, R. M. 1988. The steroid and thyroid hormone receptor superfamily. Science 240:889–895.Google Scholar
  12. 12.
    Fais, D., Prusov, A. N., and Poliakov, V. Yu. 1989. The anchorosome, a special chromatin granule for the anchorage of the interphase chromosome to the nuclear envelope. Cell Biol. Internatl. Rep. 13:747–758.Google Scholar
  13. 13.
    Finley, D., and Varshavsky, A. 1985. The ubiquitin system-functions and mechanisms. Trends Biochem. Sci. 10:343–347.Google Scholar
  14. 14.
    Gonzales, P. J., and Palacian, E. 1990. Structural and transcriptional properties of different nucleosomal particles containing high mobility group proteins 14 and 17 (HMG 14/17). J. Biol. Chem. 265:8225–8229.Google Scholar
  15. 15.
    Green, S., and Chambon, P. 1986. A superfamily of potentially oncogenetic hormone receptors. Nature 324:615–617.Google Scholar
  16. 16.
    Greenberg, D. M., and Rothstein, M. 1957. Methods for chemical synthesis, isolation, and degradation of labeled compounds as applied in metabolic studies of aminoacids and proteins. Methods Enzymol. 4:652–731.Google Scholar
  17. 17.
    Greenwood, P. D., and Brown, I. R. 1982. Developmental changes in DNase I digestability and RNA template activity of neuronal nuclei relative to the postnatal appearance of a short DNA repeat length. Neurochem. Res. 7:965–975.Google Scholar
  18. 18.
    Greenwood, P. D., Silver, J. C., and Brown, I. R. 1981. Analysis of histones associated with neuronal and glial nuclei exhibiting divergent DNA repeat length. J. Neurochem. 37:498–505.Google Scholar
  19. 19.
    Hoppner, W., Susmuth, W., O'Brien, C., Seitz, H. J., Luda, D., and Harneit, A. 1985. Cooperative effect of thyroid and glucocorticoid hormones on the induction of hepatic phosphoenolpyruvate carboxykinase in vivo and in cultured hepatocytes. Eur. J. Biochem. 159:399–405.Google Scholar
  20. 20.
    Isenberg, I. 1979. Histones. Ann. Rev. Biochem. 48:159–191.Google Scholar
  21. 21.
    Ivanov, T. R., and Brown, I. R. 1989. Genes expressed in cortical neurons. Chromatin conformation and DNase I hypersensitive sites. Neurochem. Res. 14:129–137.Google Scholar
  22. 22.
    Jaeger, A. W., and Kuenzle, C. C. 1982. The chromatin repeat length of brain cortex and cerebellar neurons changes concomitant with terminal differentiation. EMBO J. 1:811–816.Google Scholar
  23. 23.
    Kinlaw, W. B., Schwartz, H. L., Towle, H. C., and Oppenheimer, J. H. 1986. Opposing effects of glucagon and triiodothyronine on the hepatic levels of messenger ribonucleic acids S14 and the dependence of such effects on circadian factors. J. Clin. Invest. 78:1091–1096.Google Scholar
  24. 24.
    Laemmli, U. K. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685.Google Scholar
  25. 25.
    Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.Google Scholar
  26. 26.
    Magnuson, M. A., Dozin, B., and Nikodem, V. M. 1985. Regulation of specific rat liver messenger ribonucleic acids by triiodothyronine. J. Biol. Chem. 260:5906–5912.Google Scholar
  27. 27.
    Mariash, C. N., Seeling, S., Schwartz, H. L., and Oppenheimer, J. H. 1986. Rapid synergistic interaction between thyroid hormone and carbohydrate on mRNA S14 induction. J. Biol. Chem. 261:9583–9586.Google Scholar
  28. 28.
    Nunez, E. A. 1989. The erb-A family receptors for thyroid hormones, steroids, vitamin D and retinoic acid: characteristics and modulation. Curr. Op. Cell Biol. 1:177–185.Google Scholar
  29. 29.
    O'Malley, B. 1990. The Steroid Receptor Superfamily: More excitement predicted for the future. Mol. Endocrinol. 4:363–369.Google Scholar
  30. 30.
    Pearson, E. C., Bates, D. L., Prospero, T. D., and Thomas, J. O. 1984. Neuronal nuclei and glial nuclei from mammalian cerebral cortex. Nucleosomal repeat lengths, DNA contents and H1 contents. Eur. J. Biochem. 144:353–360.Google Scholar
  31. 31.
    Pina, B., and Suau, P. 1985. Core histone variants and ubiquitinated histones 2A and 2B of rat cerebral cortex neurons. Biochem. Biophys. Res. Commun. 133:505–510.Google Scholar
  32. 32.
    Savettieri, G., Di Liegro, I., and Cestelli, A. 1989. Action of thyroid hormones on developing CNS at the molecular level. In: Biological Aspects of Neuron Activity. Bonavita, V., and Piccoli, F., eds. Fidia Biomedical Information.Google Scholar
  33. 33.
    Thomas, J. O., and Thompson, R. J. 1977. Variation in chromatin structure in two cell types from the same tissue: a short DNA repeat length in cerebral cortex neurons. Cell 10:633–640.Google Scholar
  34. 34.
    Weisbrod, S., and Weintraub, H. 1979. Isolation of a subclass of nuclear proteins responsible for conferring a DNase I-sensitive structure on globin chromatin. Proc. Natl. Acad. Sci. USA 76:630–634.Google Scholar

Copyright information

© Plenum Publishing Corporation 1992

Authors and Affiliations

  • Alessandro Cestelli
    • 1
  • Roberto Gristina
    • 1
  • Daniele Castiglia
    • 1
  • Carlo Di Liegro
    • 1
  • Giovanni Savettieri
    • 2
  • Guiseppe Salemi
    • 2
  • Italia Di Liegro
    • 1
  1. 1.Dipartimento di Biologia Cellulare e dello Sviluppo “Alberto Monroy”PalermoItaly
  2. 2.Clinica NeurologicaUniversità degli StudiPalermoItaly

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