Skip to main content
Log in

Is human histone gene expression autogenously regulated?

  • Current Thinking
  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Summary

It has been well documented that core and H1 histone mRNAs accumulate in a manner which closely parallels the initiation of DNA synthesis and histone protein synthesis, suggesting that the onset of histone gene expression early during S phase is at least in part transcriptionally mediated. In fact, it appears that throughout S phase the synthesis of histone proteins is modulated by the availability of histone mRNAs. On the other hand, the stability of histone mRNAs and the destabilization of histone mRNAs when DNA replication is completed or inhibited are highly selective, tightly coupled and largely post-transcriptionally controlled. We present a model to account for histone mRNA turnover whereby the natural or inhibitor-induced termination of DNA replication results in an immediate loss of high affinity binding sites for newly synthesized histone proteins which in turn brings about a transient accumulation of unbound histones. These unbound histones could modify the histone translation complex, via interactions with polysomal histone mRNAs, in such a manner as to render histone mRNAs accessible to cellular ribonucleases. This type of mechanism would be operative solely at the post-transcriptional level and would be compatible with the rapid, RNA synthesis-independent destabilization of histone mRNAs which occurs following inhibition of DNA replication, as well as with the requirement for protein synthesis for histone mRNA destabilization to be initiated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Isenberg I: Histories. Ann Rev Biochem 48: 159–191, 1979.

    Google Scholar 

  2. McGhee JD, Felsenfeld G: Nucleosome structure. Ann Rev Biochem 49: 1115–1156, 1980.

    Google Scholar 

  3. Felsenfeld G, McGhee J: Methylation and gene control. Nature 296: 602–603, 1982.

    Google Scholar 

  4. Weisbrod S: Active chromatin. Nature 297: 289–295, 1982.

    Google Scholar 

  5. Elgin SCR, Weintraub H: Chromosomal proteins and chromatin structure. Ann Rev Biochem 44: 725–774, 1975.

    Google Scholar 

  6. Kornberg RD: Structure of chromatin. Ann Rev Biochem 46: 931, 1977.

    Google Scholar 

  7. Heintz N, Zernik M, Roeder RG: The structure of the human histone genes: clustered but not tandemly repeated. Cell 24: 661–668, 1981.

    Google Scholar 

  8. Sierra F, Lichtler A, Marashi F, Rickles R, Van Dyke T, Clark S, Wells J, Stein G, Stein J: Organization of human histone genes. Proc Natl Acad Sci USA 79: 1795–1799, 1982.

    Google Scholar 

  9. Stein GS, Sierra F, Stein JL, Plumb M, Marashi F, Carrozi N, Prokopp K, Baumbach L: Organization and expression of human histone genes. In Stein GS, Stein JL, Marzluff WF (eds), Histone Genes. John Wiley and Sons, New York, 1984, pp 397–455.

    Google Scholar 

  10. Sierra F, Stein G, Stein J: Structure and in vitro transcription of a human H4 histone gene. Nucl Acids Res 11: 7069–7086, 1983.

    Google Scholar 

  11. Zhong R, Roeder RG, Heintz N: The primary structure and expression of four cloned human histone genes. Nucl Acids Res 11: 7409–7425, 1983.

    Google Scholar 

  12. Carozzi N, Marashi F, Plumb M, Zimmerman S, Zimmerman A, Wells JRE, Stein G, Stein J: Clustering of human H1 and core histone genes. Science 224: 1115–1117, 1984.

    Google Scholar 

  13. Rickles R, Marashi F, Sierra F, Wells J, Stein J, Stein G: Analysis of histone gene expression during the cell cycle in HeLa cells using cloned human histone genes. Proc Natl Acad Sci USA 79: 749–753, 1982.

    Google Scholar 

  14. Lichtler AC, Sierra F, Clark S, Wells JRE, Stein GS, Stein JL: The multiple H4 histone mRNAs of HeLa cells are encoded in different genes. Nature 298: 195–198, 1982.

    Google Scholar 

  15. Heintz N, Sive HL, Roeder RG: Regulation of human histone gene expression: kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle. Mol Cell Biol 3: 539–550, 1983.

    Google Scholar 

  16. Plumb MA, Stein G, Stein J: Coordinate regulation of multiple histone mRNAs during the cell cycle in HeLa cells. Nucl Acids Res 11 (8): 2391–2410, 1983.

    Google Scholar 

  17. Plumb M, Stein J, Stein G: Coordinate expression of H1 and core human histone genes. Proc Natl Acad Sci USA 81: 434–438, 1984.

    Google Scholar 

  18. Green L, Stein G, Stein J: Histone gene expression in human diploid fibroblasts: analysis of histone mRNA levels using cloned human histone genes. Mol Cell Biochem 60: 123–130, 1984.

    Google Scholar 

  19. Marashi F, Green L, Briggs R, Hnilica L, Stein JL, Stein GS: Variations in the organization and expression of human histone genes in normal diploid and tumor cell lines. Anticancer Res 4: 69–74, 1984.

    Google Scholar 

  20. Sittman DB, Chin I-M, Pan C-J, Cohn RH, Kedes LH, Marzluff MF: Isolation of two clusters of mouse histone genes. Proc Natl Acad Sci USA 78: 4078–4082, 1981.

    Google Scholar 

  21. Sittman DB, Graves RA, Marzluff WF: Histone mRNA concentrations are regulated at the level of transcription and mRNA degradation. Proc Natl Acad Sci USA 80: 1849–1853, 1983.

    Google Scholar 

  22. DeLisle AJ, Graves RA, Marzluff WF, Johnson LF: Regulation of histone mRNA production and stability in serum-stimulated mouse 3T6 fibroblasts. Mol Cell Biol 3: 1920–1929, 1983.

    Google Scholar 

  23. Alterman R-BM, Ganguly S, Schulze DH, Marzluff WF, Schildkraut CL, Skoultchi AI: Cell cylce regulation of mouse H3 histone mRNA metabolism. Mol Cell Biol 4: 123–132, 1984.

    Google Scholar 

  24. Zweidler A: Core histone variants of the mouse: primary structure and differential expression. In Stein GS, Stein JL, Marzluff WF (eds), Histone Genes. John Wiley and Sons, New York, 1984, pp 339–371.

    Google Scholar 

  25. Seiler-Tuyns A, Birnstiel ML: Structure and expression in L-cells of a cloned H4 histone gene of the mouse. J Mol Biol 151: 607–625, 1981.

    Google Scholar 

  26. Prescott DM: The synthesis of total macronuclear protein, histone and DNA during the cell cycle in Euplotes erystomus. J Cell Biol 31: 1–9, 1966.

    Google Scholar 

  27. Bloch DP, Macquigg RA, Brack SD, Wu J-R: The synthesis of deoxyribonucleic acid and histone in the onion root meristem. J Cell Biol 33: 451–466, 1967.

    Google Scholar 

  28. Allfrey V, Littau VC, Mirsky AE: On the role of histones in regulating ribonucleic acid synthesis in the cell nucleus. Proc Natl Acad Sci USA 49: 414–421, 1963.

    Google Scholar 

  29. Huang RCC, Bonner J: Histone, a suppressor of chromosomal RNA synthesis. Proc Natl Acad Sci USA 48: 1216–1222, 1962.

    Google Scholar 

  30. Alfret M: Quantitative cytochemical studies on patterns of nuclear growth. In Fine Structure of Cells. Interscience, New York, 1955, pp 137–163.

    Google Scholar 

  31. Robbins E, Borun TW: The cytoplasmic synthesis of histories in HeLa cells and its temporal relationship to DNA replication. Proc Natl Acad Sci USA 57: 409–416, 1967.

    Google Scholar 

  32. Spaulding J, Kajiwara K, Mueller GC: The metabolism of basic proteins in HeLa cell nuclei. Proc Natl Acad Sci USA 56: 1535–1542, 1966.

    Google Scholar 

  33. Stein GS, Borun TW: The synthesis of acidic chromosomal proteins during the cell cycle of HeLa S3 cells. I. The accelerated accumulation of acidic residual nuclear protein before the initiation of DNA replication. J Cell Biol 52: 292, 1972.

    Google Scholar 

  34. Jacobs-Lorena M, Baglioni C, Borun TW: The translation of messenger for histones from HeLa cells by a cell-free extract from mouse ascites tumor. Proc Natl Acad Sci USA 69: 2095–2099, 1972.

    Google Scholar 

  35. Stein GS, Park WD, Thrall CL, Mans RJ, Stein JL: Regulation of histone gene transcription during the cell cycle by nonhistone chromosomal proteins. Nature 257: 764–767, 1975.

    Google Scholar 

  36. Jansing RL, Stein JL, Stein GS: Activation of histone gene transcription in nonhistone chromosomal proteins in WI-38 human diploid fibroblasts. Proc Natl Acad Sci USA 74: 173–177, 1977.

    Google Scholar 

  37. Detke S, Lichtler A, Phillips I, Stein J, Stein G: Reassessment of histone gene expression during the cell cycle in human cells by using homologous H4 histone cDNA. Proc Natl Acad Sci USA 76: 4995–4999, 1979.

    Google Scholar 

  38. Park WD, Stein JL, Stein GS: Activation of in vitro histone gene transcription from HeLa S3 chromatin by S phase nonhistone chromosomal proteins. Biochemistry 15: 3296–3300, 1976.

    Google Scholar 

  39. Parker I, Fitschen W: Histone mRNA metabolism during the mouse fibroblast cell cycle. Cell Diff 9: 23–30, 1980.

    Google Scholar 

  40. Plumb M, Stein J, Stein G: Influence of DNA synthesis inhibition on the coordinate expression of core human histone genes during S phase. Nucl Acids Res 11: 7927–7945, 1983.

    Google Scholar 

  41. Baumbach I., Marashi F, Plumb M, Stein G, Stein J: Inhibition of DNA replication coordinately reduces cellular levels of core and H1 histone mRNAs: requirement for protein synthesis. Biochemistry 23: 1618–1625, 1984.

    Google Scholar 

  42. Stimac E, Groppi VE, Coffino P: Increased histone mRNA levels during inhibition of protein synthesis. Biochem Biophys Res Commun 114(1): 131–137, 1983.

    Google Scholar 

  43. Hirschhorn R, Marashi F, Baserga R, Stein J, Stein G: Expression of histone genes in a G1-specific temperature sensitive mutant of the cell cycle. Biochemistry 23: 3731–3739, 1984.

    Google Scholar 

  44. Flint SJ, Plumb MA, Stein GS, Stein JL: Influence of adenovirus on expression of human histone genes. Mol Cell Biol 4: 1363–1371, 1981.

    Google Scholar 

  45. Butler WB, Mueller GC: Biochim Biophys Acta 294: 481–486, 1973.

    Google Scholar 

  46. Helms S, Baumbach L, Stein G, Stein J: Requirement of protein synthesis for the coupling of histone mRNA levels and DNA replication. FEBS Lett 168 (1): 65–69, 1984.

    Google Scholar 

  47. Osley MA, Hereford L: Identification of a sequence responsible for periodic synthesis of yeast histone 2A mRNA. Proc Natl Acad Sci USA 79: 7689–7693, 1982.

    Google Scholar 

  48. Iqbal A, Plumb MA, Stein JL, Stein GS, Schildkraut CL: Coordinate replication of members of the multigene family of core and H1 human histonegenes. Proc Natl Acad Sci USA (in press).

  49. Wu RS, Bonner WM: Separation of basal histone synthesis from S phase histone synthesis in dividing cells. Cell 27: 321–330, 1981.

    Google Scholar 

  50. Chiu I-M, Marzluff WF: Uncoordinate synthesis of histone H1 in cells arrested in the G1 phase. Biochim Biophys Acta 699: 173–182, 1981.

    Google Scholar 

  51. Groppi VE Jr, Coffino P: G1 and S phase mammalian cells synthesize histones at equivalent rates. Cell 21: 195–204, 1980.

    Google Scholar 

  52. Lennox RW, Cohen LH: The H1 subtypes of mammals: metabolic characteristics and tissue distribution. In Stein GS, Stein JL, Marzluff WF (eds), Historic Genes. John Wiley and Sons, New York, 1984, pp 373–395.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stein, G.S., Stein, J.L. Is human histone gene expression autogenously regulated?. Mol Cell Biochem 64, 105–110 (1984). https://doi.org/10.1007/BF00224767

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00224767

Keywords

Navigation