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. 1982 Mar;79(6):1795–1799. doi: 10.1073/pnas.79.6.1795

Organization of human histone genes.

F Sierra, A Lichtler, F Marashi, R Rickles, T Van Dyke, S Clark, J Wells, G Stein, J Stein
PMCID: PMC346067  PMID: 6281786

Abstract

We describe the isolation and initial characterization of seven independent lambda Charon 4A recombinant phages which contain human histone genomic sequences (designated lambda HHG). Restriction maps of these clones and localization of the genes coding for histones H2A, H2B, H3, and H4 are presented. The presence of histone encoding regions in the lambda HHG clones was demonstrated by several independent criteria including hybridization with specific DNA probes, hybrid selection/in vitro translation, and hybridization of lambda HHG DNAs to reserve Southern blots containing cytoplasmic RNAs from G1-, S-, and arabinofuranosylcytosine (cytosine arabinoside)-treated S-phase cells. In addition, the lambda HHG DNAs were shown to protect in vivo labeled H4 mRNAs from S1 nuclease digestion. Based on the analysis of the lambda HHG clones, human histone genes appear to be clustered in the genome. However, gene clusters do not seem to be present in identical tandem repeats. The lambda HHG clones described in this report fall into at least three distinct types of arrangement. One of these arrangements contains two coding regions for each of the histones H3 and H4. The arrangement of histone genes in the human genome, therefore, appears to be different from that in the sea urchin and Drosophila genomes in which each of the five histone-encoding regions (H1, H2A, H2B, H3, and H4) is present only once in each tandemly repeated cluster. At least one clone, lambda HHG 41, contains, in addition to the histone genes, a region that hybridizes with a cytoplasmic RNA approximately 330 nucleotides in length. This RNA is not similar in size to known histone-encoding RNAs and is present in the cytoplasm of HeLa cells predominantly in the G1 phase of the cell cycle.

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Selected References

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

  1. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  2. Berk A. J., Sharp P. A. Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids. Cell. 1977 Nov;12(3):721–732. doi: 10.1016/0092-8674(77)90272-0. [DOI] [PubMed] [Google Scholar]
  3. Blattner F. R., Williams B. G., Blechl A. E., Denniston-Thompson K., Faber H. E., Furlong L., Grunwald D. J., Kiefer D. O., Moore D. D., Schumm J. W. Charon phages: safer derivatives of bacteriophage lambda for DNA cloning. Science. 1977 Apr 8;196(4286):161–169. doi: 10.1126/science.847462. [DOI] [PubMed] [Google Scholar]
  4. Borun T. W., Gabrielli F., Ajiro K., Zweidler A., Baglioni C. Further evidence of transcriptional and translational control of histone messenger RNA during the HeLa S3 cycle. Cell. 1975 Jan;4(1):59–67. doi: 10.1016/0092-8674(75)90134-8. [DOI] [PubMed] [Google Scholar]
  5. Borun T. W., Scharff M. D., Robbins E. Rapidly labeled, polyribosome-associated RNA having the properties of histone messenger. Proc Natl Acad Sci U S A. 1967 Nov;58(5):1977–1983. doi: 10.1073/pnas.58.5.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chandler M. E., Kedes L. H., Cohn R. H., Yunis J. J. Genes coding for histone proteins in man are located on the distal end of the long arm of chromosome 7. Science. 1979 Aug 31;205(4409):908–910. doi: 10.1126/science.472711. [DOI] [PubMed] [Google Scholar]
  7. Clewell D. B., Helinski D. R. Properties of a supercoiled deoxyribonucleic acid-protein relaxation complex and strand specificity of the relaxation event. Biochemistry. 1970 Oct 27;9(22):4428–4440. doi: 10.1021/bi00824a026. [DOI] [PubMed] [Google Scholar]
  8. Detke S., Lichtler A., Phillips I., Stein J., Stein G. Reassessment of histone gene expression during cell cycle in human cells by using homologous H4 histone cDNA. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4995–4999. doi: 10.1073/pnas.76.10.4995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Detke S., Stein J. L., Stein G. S. Synthesis of histone messenger RNAs by RNA polymerase II in nuclei from S phase HeLa S3 cells. Nucleic Acids Res. 1978 May;5(5):1515–1528. doi: 10.1093/nar/5.5.1515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Engel J. D., Dodgson J. B. Histone genes are clustered but not tandemly repeated in the chicken genome. Proc Natl Acad Sci U S A. 1981 May;78(5):2856–2860. doi: 10.1073/pnas.78.5.2856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gallwitz D., Breindl M. Synthesis of histones in a rabbit reticulocyte cell-free system directed by a polyribosomal RNA fraction from synchronized HeLa cells. Biochem Biophys Res Commun. 1972 Jun 9;47(5):1106–1111. doi: 10.1016/0006-291x(72)90948-5. [DOI] [PubMed] [Google Scholar]
  12. Gallwitz D., Mueller G. C. Histone synthesis in vitro on HeLa cell microsomes. The nature of the coupling to deoxyribonucleic acid synthesis. J Biol Chem. 1969 Nov 10;244(21):5947–5952. [PubMed] [Google Scholar]
  13. Harvey R. P., Wells J. R. Isolation of a genomal clone containing chicken histone genes. Nucleic Acids Res. 1979 Dec 11;7(7):1787–1798. doi: 10.1093/nar/7.7.1787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Hereford L., Fahrner K., Woolford J., Jr, Rosbash M., Kaback D. B. Isolation of yeast histone genes H2A and H2B. Cell. 1979 Dec;18(4):1261–1271. doi: 10.1016/0092-8674(79)90237-x. [DOI] [PubMed] [Google Scholar]
  16. Jacobs-Lorena M., Baglioni C., Borun T. W. Translation of messenger RNA for histones from HeLa cells by a cell-free extract from mouse ascites tumor. Proc Natl Acad Sci U S A. 1972 Aug;69(8):2095–2099. doi: 10.1073/pnas.69.8.2095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jansing R. L., Stein J. L., Stein G. S. Activation of histone gene transcription by nonhistone chromosomal proteins in WI-38 human diploid fibroblasts. Proc Natl Acad Sci U S A. 1977 Jan;74(1):173–177. doi: 10.1073/pnas.74.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kedes L. H. Histone genes and histone messengers. Annu Rev Biochem. 1979;48:837–870. doi: 10.1146/annurev.bi.48.070179.004201. [DOI] [PubMed] [Google Scholar]
  19. Lawn R. M., Fritsch E. F., Parker R. C., Blake G., Maniatis T. The isolation and characterization of linked delta- and beta-globin genes from a cloned library of human DNA. Cell. 1978 Dec;15(4):1157–1174. doi: 10.1016/0092-8674(78)90043-0. [DOI] [PubMed] [Google Scholar]
  20. Lichtler A. C., Detke S., Phillips I. R., Stein G. S., Stein J. L. Multiple forms of H4 histone mRNA in human cells. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1942–1946. doi: 10.1073/pnas.77.4.1942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Maniatis T., Jeffrey A., Kleid D. G. Nucleotide sequence of the rightward operator of phage lambda. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1184–1188. doi: 10.1073/pnas.72.3.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mans R. J., Huff N. J. Utilization of ribonucleic acid and deoxyoligomer primers for polyadenylic acid synthesis by adenosine triphosphate: polynucleotidylexotransferase from maize. J Biol Chem. 1975 May 25;250(10):3672–3678. [PubMed] [Google Scholar]
  23. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. McMaster G. K., Beard P., Engers H. D., Hirt B. Characterization of an immunosuppressive parvovirus related to the minute virus of mice. J Virol. 1981 Apr;38(1):317–326. doi: 10.1128/jvi.38.1.317-326.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McMaster G. K., Samulski R. J., Stein J. L., Stein G. S. Rapid purification of covalently closed circular DNAs of bacterial plasmids and animal tumor viruses. Anal Biochem. 1980 Nov 15;109(1):47–54. doi: 10.1016/0003-2697(80)90008-1. [DOI] [PubMed] [Google Scholar]
  26. Overton G. C., Weinberg E. S. Length and sequence heterogeneity of the histone gene repeat unit of the sea urchin, S. purpuratus. Cell. 1978 Jun;14(2):247–257. doi: 10.1016/0092-8674(78)90111-3. [DOI] [PubMed] [Google Scholar]
  27. Panyim S., Chalkley R. High resolution acrylamide gel electrophoresis of histones. Arch Biochem Biophys. 1969 Mar;130(1):337–346. doi: 10.1016/0003-9861(69)90042-3. [DOI] [PubMed] [Google Scholar]
  28. Rickles R., Marashi F., Sierra F., Clark S., Wells J., Stein J., Stein G. Analysis of histone gene expression during the cell cycle in HeLa cells by using cloned human histone genes. Proc Natl Acad Sci U S A. 1982 Feb;79(3):749–753. doi: 10.1073/pnas.79.3.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Seiler-Tuyns A., Birnstiel M. L. Structure and expression in L-cells of a cloned H4 histone gene of the mouse. J Mol Biol. 1981 Oct 5;151(4):607–625. doi: 10.1016/0022-2836(81)90426-5. [DOI] [PubMed] [Google Scholar]
  31. Sittman D. B., Chiu I. M., Pan C. J., Cohn R. H., Kedes L. H., Marzluff W. F. Isolation of two clusters of mouse histone genes. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4078–4082. doi: 10.1073/pnas.78.7.4078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  33. Spalding J., Kajiwara K., Mueller G. C. The metabolism of basic proteins in HeLa cell nuclei. Proc Natl Acad Sci U S A. 1966 Nov;56(5):1535–1542. doi: 10.1073/pnas.56.5.1535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stein G. S., Borun T. W. The synthesis of acidic chromosomal proteins during the cell cycle of HeLa S-3 cells. I. The accelerated accumulation of acidic residual nuclear protein before the initiation of DNA replication. J Cell Biol. 1972 Feb;52(2):292–307. doi: 10.1083/jcb.52.2.292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Stein G. S., Stein J. L., Park W. D., Detke S., Lichtler A. C., Shephard E. A., Jansing R. L., Phillips I. R. Regulation of histone gene expression in HeLa S3 cells. Cold Spring Harb Symp Quant Biol. 1978;42(Pt 2):1107–1120. doi: 10.1101/sqb.1978.042.01.112. [DOI] [PubMed] [Google Scholar]
  36. Stein G., Park W., Thrall C., Mans R., Stein J. Regulation of cell cycle stage-specific transcription of histone genes from chromatin by non-histone chromosomal proteins. Nature. 1975 Oct 30;257(5529):764–767. doi: 10.1038/257764a0. [DOI] [PubMed] [Google Scholar]
  37. Stein J. L., Thrall C. L., Park W. D., Mans R. J., Stein G. S. Hybridization analysis of histone messenger RNA: association with polyribosomes during the cell cycle. Science. 1975 Aug 15;189(4202):557–558. doi: 10.1126/science.1145212. [DOI] [PubMed] [Google Scholar]
  38. Ullrich A., Shine J., Chirgwin J., Pictet R., Tischer E., Rutter W. J., Goodman H. M. Rat insulin genes: construction of plasmids containing the coding sequences. Science. 1977 Jun 17;196(4296):1313–1319. doi: 10.1126/science.325648. [DOI] [PubMed] [Google Scholar]
  39. Wilson M. C., Melli M. Determination of the number of histone genes in human DNA. J Mol Biol. 1977 Mar 5;110(3):511–535. doi: 10.1016/s0022-2836(77)80110-1. [DOI] [PubMed] [Google Scholar]

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