A Few Glances at the Function of Chromatin and Nuclear Higher-Order Structure in Transcription Regulation

  • Jovan Mirkovitch
Part of the NATO ASI Series book series (volume 105)

Abstract

Gene therapy necessitates the accurate expression of a transferred gene; that is the gene has to be expressed at precise levels in the right cell at the appropriate time. Much before “Gene Therapists” started to show up in laboratories throughout the world, cells had devised a large number of mechanisms to reach that goal, that is to tightly regulate the expression of about 100,000 genes. The most common mechanism utilized by cells for controlling gene expression occurs at the transcriptional level. In this case, deciding if a gene will be transcribed or not, and adjusting the level of transcription initiation and elongation, determine the amounts of gene products. Although the cell has found it advantageous to control the expression of many genes at many other downstream steps, control at the transcriptional level prevents the synthesis of useless molecules and the utilization of further control levels.

Keyword

gene therapy nucleus chromatin transcription insulator chromatin domain nucleosome chromatin remodeling histone acetylation 

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References

  1. 1.
    Bonifer, C., M. C. Huber, U. Jagle, N. Faust, and A. E. Sippel. 1996. Prerequisites for tissue specific and position independent expression of a gene locus in transgenic mice. Journal of Molecular Medicine 74:663–71.PubMedCrossRefGoogle Scholar
  2. 2.
    Cairns, B. R., Y. Lorch, Y. Li, M. C. Zhang, L. Lacomis, H. Erdjumentbromage, P. Tempst, J. Du, B. Laurent, and R. D. Kornberg. 1996. RSC, an essential, abundant chromatin-remodeling complex. Cell 87:1249–1260.PubMedCrossRefGoogle Scholar
  3. 3.
    Chavez, S., and M. Beato. 1997. Nucleosome-mediated synergism between transcription factors on the mouse mammary tumor virus promoter. Proceedings of the National Academy of Sciences of the United States of America 94:2885–90.PubMedCrossRefGoogle Scholar
  4. 4.
    Englander, E. W., and B. H. Howard. 1996. A naturally occurring T14A11 tract blocks nucleosome formation over the human neurofibromatosis type 1 (NFl)-Alu element The journal of Biological Chemistry 271:5819–5823.PubMedCrossRefGoogle Scholar
  5. 5.
    Felsenfeld, G. 1996. Chromatin unfolds. Cell 86:13–19.PubMedCrossRefGoogle Scholar
  6. 6.
    Felsenfeld, G., J. Boyes, J. Chung, D. Clark, and Y. Studitsky. 1996. Chromatin structure and gene expression. Proceedings of the National Academy of Sciences of the United States of America (USA) 93:9384938–8.Google Scholar
  7. 7.
    Festenstein, R., M. Tolaini, P. Corbella, C. Mamalaki, J. Parrington, M. Fox, A. Miliou, M. Jones, and D. Kioussis. 1996. Locus control region function and heterochromatin-induced position effect variegation. Science 271:1123–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Gaudreau, L., A. Schmid, D. Blaschke, M. Ptashne, and W. Horz. 1997. RNA polymerase II holoenzyme recruitment is sufficient to remodel chromatin at the yeast PHO5 promoter. Cell 89:55–62.PubMedCrossRefGoogle Scholar
  9. 9.
    Gerasimova, T. I., and Y. G. Corces. 1996. Boundary and insulator elements in chromosomes. Current Opinion in Genetics & Development 6:185–92.CrossRefGoogle Scholar
  10. 10.
    Gross, D. S., and W. T. Garrard. 1988. Nuclease hypersensitive sites in chromatin. Annual Review of Biochemistry 57:159–197.PubMedCrossRefGoogle Scholar
  11. 11.
    Jenuwein, T., W. C. Forrester, H. L. Fernandez, G. Laible, M. Dull, and R. Grosschedl. 1997. Extension of chromatin accessibility by nuclear matrix attachment regions. Nature 385:269–72.PubMedCrossRefGoogle Scholar
  12. 12.
    Kingston, R. E., C. A. Bunker, and A. N. Imbalzano. 1996. Repression and activation by multiprotein complexes that alter chromatin structure. Genes & Development 10:905–920.CrossRefGoogle Scholar
  13. 13.
    Lu, Q., L. L. Wallrath, and S. C. Elgin. 1995. The role of a positioned nucleosome at the Drosophila melanogaster hsp26 promoter. EMBO Journal 14:4738–46.PubMedGoogle Scholar
  14. 14.
    Milot, E., P. Fraser, and F. Grosveld. 1996. Position effects and genetic disease. Trends in Genetics 12:123–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Mizzen, C. A., X. J. Yang, T. Kokubo, J. E. Brownell, A. J. Bannister, T. Owenhughes, J. Workman, L. Wang, S. L. Berger, T. Kouzarides, Y. Nakatani, and C. D. Allis. 1996. The TAF(II)250 subunit of TKIID has histone acetyltransferase activity. Cell 87:1261–1270.PubMedCrossRefGoogle Scholar
  16. 16.
    Ogryzko, V. V., R. L. Schiltz, V. Russanova, B. H. Howard, and Y. Nakatani. 1996. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 87:953–959.PubMedCrossRefGoogle Scholar
  17. 17.
    Owen-Highes, T. A., and J. L. Workman. 1994. Experimental analysis of chromatin function in transcription control. Critical Reviews in Eukaryotic Gene Expression 4:403–441.Google Scholar
  18. 18.
    Paranjape, S. M., R. T. Kamakaka, and J. T. Kadonaga. 1994. Role of chromatin structure in the regulation of transcription by RNA polymerase II. Annual Review of Biochemistry 63:265–97.PubMedCrossRefGoogle Scholar
  19. 19.
    Pazin, M. J., and J. T. Kadonaga. 1997. SWI2/SNF2 and related proteins: ATP-driven motors that disrupt protein-DNA interactions?. [Review] [20 refs]. Cell 88:737–40.PubMedCrossRefGoogle Scholar
  20. 20.
    Pazin, M. J., and J. T. Kadonaga. 1997. What’s up and down with histone deacetylation and transcription? Cell 89:325–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Pruss, D., B. Bartholomew, J. Persinger, J. Hayes, G. Arents, E. N. Moudrianakis, and A. P. Wolffe. 1996. An asymmetric model for the nucleosome: a binding site for linker histones inside the DNA gyres. Science 274:614–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Quivy, J. P., and P. B. Becker. 1996. The architecture of the heat-inducible Drosophila hsp27 promoter in nuclei. Journal of Molecular Biology 256:249–63.PubMedCrossRefGoogle Scholar
  23. 23.
    Roth, S. Y., and C. D. Allis. 1996. The subunit-exchange model of histone acetylation. Trends in Cell Biology 6:371–375.PubMedCrossRefGoogle Scholar
  24. 24.
    Saitoh, Y., and U. K. Laemmli. 1994. Metaphase chromosome structure: bands arise from a differential folding path of the highly AT-rich scaffold. Cell 76:609–22.PubMedCrossRefGoogle Scholar
  25. 25.
    Schild, C., F. X. Claret, W. Wahli, and A. P. Wolffe. 1993. A nucleosome-dependent static loop potentiates estrogen-regulated transcription from the Xenopus vitellogenin B1 promoter in vitro. EMBO Journal 12:423–33.PubMedGoogle Scholar
  26. 26.
    Sippel, A. E., H. Saueressig, M. C. Huber, H. C. Hoefer, A. Stief, U. Borgmeyer, and C. Bonifer. 1996. Identification of cis-acting elements as DNase I hypersensitive sites in lysozyme gene chromatin. Methods in Enzymology 274:233–46.PubMedCrossRefGoogle Scholar
  27. 27.
    Svaren, J., and W. Horz. 1997. Transcription factors vs nucleosomes: regulation of the PHO5 promoter in yeast. Trends in Biochemical Sciences 22:93–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Thomas, G. H., and S. C. Elgin. 1988. Protein/DNA architecture of the DNase I hypersensitive region of the Drosophila hsp26 promoter. EMBO Journal 7:2191–2201.PubMedGoogle Scholar
  29. 29.
    Tsukiyama, T., and C. Wu. 1995. Purification and properties of an ATP-dependent nucleosome remodeling factor. Cell 83:1011–20.PubMedCrossRefGoogle Scholar
  30. 30.
    van Holde, K., and J. Zlatanova. 1996. What determines the folding of the chromatin fiber? Proceedings of the National Academy of Sciences of the United States of America 93:10548–55.PubMedCrossRefGoogle Scholar
  31. 31.
    Vargaweisz, P. D., M. Wilm, E. Bonte, K. Dumas, M. Mann, and P. B. Becker. 1997. Chromatin-remodelling factor CHRAC contains the ATPases ISWI and topoisomerase EL Nature 388:598–602.CrossRefGoogle Scholar
  32. 32.
    Wade, P. A., D. Pruss, and A. P. Wolffe. 1997. Histone acetylation: chromatin in action. Trends in Biochemical Sciences 22:128–32.PubMedCrossRefGoogle Scholar
  33. 33.
    Wallace, M. R., L. B. Andersen, A. M. Saulino, P. E. Gregory, T. W. Glover, and F. S. Collins. 1991. A de novo Alu insertion results in neurofibromatosis type 1. Nature 353:864–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Wang, B. C., J. Rose, G. Arents, and E. N. Moudrianakis. 1994. The octameric histone core of the nucleosome. Structural issues resolved. Journal of Molecular Biology 236:179–88.PubMedCrossRefGoogle Scholar
  35. 35.
    Weintraub, H., and M. Groudine. 1976. Chromosomal subunits in active genes have an altered conformation. Science 193:848–56.PubMedCrossRefGoogle Scholar
  36. 36.
    Wolffe, A. P. 1996. Histone deacetylase: a regulator of transcription. Science 272:371–2.PubMedCrossRefGoogle Scholar
  37. 37.
    Wolffe, A. P., and D. Pruss. 1996. Targeting chromatin disruption: Transcription regulators that acetylate histones. Cell 84:817–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Zhao, K., E. Kas, E. Gonzalez, and U. K. Laemmli. 1993. SAR- dependent mobilization of histone H1 by HMG-I/Y in vitro: HMG-I/Y is enriched in H1-depleted chromatin. EMBO Journal 12:3237–47.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Jovan Mirkovitch
    • 1
  1. 1.Swiss Institute for Experimental Cancer Research (ISREC)EpalingesSwitzerland

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