Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Sep;82(17):5622–5626. doi: 10.1073/pnas.82.17.5622

Regulated expression of mammalian histone H4 genes in vivo requires a trans-acting transcription factor.

O Capasso, N Heintz
PMCID: PMC390603  PMID: 3862085

Abstract

Mouse L cells containing integrated copies of a human histone H4 gene have been obtained by cotransfection with the herpesvirus thymidine kinase gene. Nuclease S1 assays of RNA from several independent cell lines show that the expression of the introduced H4 gene is regulated during the cell cycle. One of these cell lines (line 6-8) contains more than 60 human H4 gene copies per haploid genome and does not express the endogenous mouse histone H4 mRNA. In contrast, the expression of the mouse H2a and H3 mRNAs in this cell line is not perturbed. In cell revertants that have lost the majority of the human H4 gene copies, the expression of the mouse H4 mRNA is restored, demonstrating that the mouse genes remain functional although not expressed. The rate of transcription of the histone H4 genes in clone 6-8 is at least 10-fold greater than that of the parental cell line and it is regulated during traversal of the cell cycle. These results show that the expression of mammalian histone H4 genes involves both a trans-acting transcriptional regulatory factor and an H4-specific activity. We propose that cell cycle regulation of histone gene expression may be effected through subtype-specific transcriptional regulatory proteins.

Full text

PDF
5622

Images in this article

5623Image
on p.5623
5623Image
on p.5623
5624Image
on p.5624
5624Image
on p.5624
5624Image
on p.5624
5624Image
on p.5624
5624Image
on p.5624
5624Image
on p.5624
5625Image
on p.5625
5625Image
on p.5625
5625Image
on p.5625
5625Image
on p.5625

Selected References

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

  1. Babich A., Feldman L. T., Nevins J. R., Darnell J. E., Jr, Weinberger C. Effect of adenovirus on metabolism of specific host mRNAs: transport control and specific translational discrimination. Mol Cell Biol. 1983 Jul;3(7):1212–1221. doi: 10.1128/mcb.3.7.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bayer B. M., Kruth H. S., Vaughan M., Beaven M. A. Arrest of cultured cells in the G1 phase of the cell cycle by indomethacin. J Pharmacol Exp Ther. 1979 Jul;210(1):106–111. [PubMed] [Google Scholar]
  3. Clayton D. F., Darnell J. E., Jr Changes in liver-specific compared to common gene transcription during primary culture of mouse hepatocytes. Mol Cell Biol. 1983 Sep;3(9):1552–1561. doi: 10.1128/mcb.3.9.1552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clerc R. G., Bucher P., Strub K., Birnstiel M. L. Transcription of a cloned Xenopus laevis H4 histone gene in the homologous frog oocyte system depends on an evolutionary conserved sequence motif in the -50 region. Nucleic Acids Res. 1983 Dec 20;11(24):8641–8657. doi: 10.1093/nar/11.24.8641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  6. Hanly S. M., Bleecker G. C., Heintz N. Identification of promoter elements necessary for transcriptional regulation of a human histone H4 gene in vitro. Mol Cell Biol. 1985 Feb;5(2):380–389. doi: 10.1128/mcb.5.2.380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Heintz N., Roeder R. G. Transcription of human histone genes in extracts from synchronized HeLa cells. Proc Natl Acad Sci U S A. 1984 May;81(9):2713–2717. doi: 10.1073/pnas.81.9.2713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Heintz N., Sive H. L., Roeder R. G. 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. 1983 Apr;3(4):539–550. doi: 10.1128/mcb.3.4.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Heintz N., Zernik M., Roeder R. G. The structure of the human histone genes: clustered but not tandemly repeated. Cell. 1981 Jun;24(3):661–668. doi: 10.1016/0092-8674(81)90092-1. [DOI] [PubMed] [Google Scholar]
  10. Hereford L. M., Osley M. A., Ludwig T. R., 2nd, McLaughlin C. S. Cell-cycle regulation of yeast histone mRNA. Cell. 1981 May;24(2):367–375. doi: 10.1016/0092-8674(81)90326-3. [DOI] [PubMed] [Google Scholar]
  11. Kao H. T., Nevins J. R. Transcriptional activation and subsequent control of the human heat shock gene during adenovirus infection. Mol Cell Biol. 1983 Nov;3(11):2058–2065. doi: 10.1128/mcb.3.11.2058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Littlefield J. W. The use of drug-resistant markers to study the hybridization of mouse fibroblasts. Exp Cell Res. 1966 Jan;41(1):190–196. doi: 10.1016/0014-4827(66)90558-1. [DOI] [PubMed] [Google Scholar]
  13. Maxson R., Cohn R., Kedes L., Mohun T. Expression and organization of histone genes. Annu Rev Genet. 1983;17:239–277. doi: 10.1146/annurev.ge.17.120183.001323. [DOI] [PubMed] [Google Scholar]
  14. Nilsen T., Baglioni C. Unusual base-pairing of newly synthesized DNA in HeLa cells. J Mol Biol. 1979 Sep 25;133(3):319–338. doi: 10.1016/0022-2836(79)90396-6. [DOI] [PubMed] [Google Scholar]
  15. Osley M. A., Hereford L. M. Yeast histone genes show dosage compensation. Cell. 1981 May;24(2):377–384. doi: 10.1016/0092-8674(81)90327-5. [DOI] [PubMed] [Google Scholar]
  16. Osley M. A., Hereford L. Identification of a sequence responsible for periodic synthesis of yeast histone 2A mRNA. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7689–7693. doi: 10.1073/pnas.79.24.7689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pedrali-Noy G., Spadari S., Miller-Faurès A., Miller A. O., Kruppa J., Koch G. Synchronization of HeLa cell cultures by inhibition of DNA polymerase alpha with aphidicolin. Nucleic Acids Res. 1980 Jan 25;8(2):377–387. doi: 10.1093/nar/8.2.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Robbins E., Borun T. W. The cytoplasmic synthesis of histones in hela cells and its temporal relationship to DNA replication. Proc Natl Acad Sci U S A. 1967 Feb;57(2):409–416. doi: 10.1073/pnas.57.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Roginski R. S., Skoultchi A. I., Henthorn P., Smithies O., Hsiung N., Kucherlapati R. Coordinate modulation of transfected HSV thymidine kinase and human globin genes. Cell. 1983 Nov;35(1):149–155. doi: 10.1016/0092-8674(83)90217-9. [DOI] [PubMed] [Google Scholar]
  20. Seiler-Tuyns A., Pantazis P., Bonner W., Hamer D., Kumar A. A mouse histone H4 gene carried by an SV40 vector is accurately expressed in infected monkey cells. DNA. 1984 Jun;3(3):215–222. doi: 10.1089/dna.1.1984.3.215. [DOI] [PubMed] [Google Scholar]
  21. Sittman D. B., Graves R. A., Marzluff W. F. Histone mRNA concentrations are regulated at the level of transcription and mRNA degradation. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1849–1853. doi: 10.1073/pnas.80.7.1849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sive H. L., Heintz N., Roeder R. G. Regulation of human histone gene expression during the HeLa cell cycle requires protein synthesis. Mol Cell Biol. 1984 Dec;4(12):2723–2734. doi: 10.1128/mcb.4.12.2723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wigler M., Sweet R., Sim G. K., Wold B., Pellicer A., Lacy E., Maniatis T., Silverstein S., Axel R. Transformation of mammalian cells with genes from procaryotes and eucaryotes. Cell. 1979 Apr;16(4):777–785. doi: 10.1016/0092-8674(79)90093-x. [DOI] [PubMed] [Google Scholar]
  24. Zhong R., Roeder R. G., Heintz N. The primary structure and expression of four cloned human histone genes. Nucleic Acids Res. 1983 Nov 11;11(21):7409–7425. doi: 10.1093/nar/11.21.7409. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES