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. 1988 Dec 20;7(13):4283–4290. doi: 10.1002/j.1460-2075.1988.tb03326.x

DNA rearrangement of a homeobox gene in myeloid leukaemic cells.

C Blatt 1, D Aberdam 1, R Schwartz 1, L Sachs 1
PMCID: PMC455142  PMID: 2907477

Abstract

A homeobox gene rearrangement has been detected in WEHI-3B mouse myeloid leukaemic cells. The rearranged gene was identified as Hox-2.4 which is a member of the Hox-2 gene cluster on mouse chromosome 11. Both the normal and the rearranged genes were cloned and analysed, and the rearranged genomic Hox-2.4 gene was sequenced. The results indicate that the rearrangement is due to insertion of an intracisternal A particle 5' upstream to Hox-2.4 and that this resulted in constitutive expression of the homeobox gene. It is suggested that constitutive expression of the homeobox gene may interrupt the normal development program in these leukaemic cells.

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Selected References

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

  1. Akam M. E. The location of Ultrabithorax transcripts in Drosophila tissue sections. EMBO J. 1983;2(11):2075–2084. doi: 10.1002/j.1460-2075.1983.tb01703.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  3. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Awgulewitsch A., Utset M. F., Hart C. P., McGinnis W., Ruddle F. H. Spatial restriction in expression of a mouse homoeo box locus within the central nervous system. 1986 Mar 27-Apr 2Nature. 320(6060):328–335. doi: 10.1038/320328a0. [DOI] [PubMed] [Google Scholar]
  5. Bacheler L., Fan H. Isolation of recombinant DNA clones carrying complete integrated proviruses of Moloney murine leukemia virus. J Virol. 1981 Jan;37(1):181–190. doi: 10.1128/jvi.37.1.181-190.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Beachy P. A., Helfand S. L., Hogness D. S. Segmental distribution of bithorax complex proteins during Drosophila development. Nature. 1985 Feb 14;313(6003):545–551. doi: 10.1038/313545a0. [DOI] [PubMed] [Google Scholar]
  7. Boles T. C., Hogan M. E. DNA structure equilibria in the human c-myc gene. Biochemistry. 1987 Jan 27;26(2):367–376. doi: 10.1021/bi00376a006. [DOI] [PubMed] [Google Scholar]
  8. Breier G., Bućan M., Francke U., Colberg-Poley A. M., Gruss P. Sequential expression of murine homeo box genes during F9 EC cell differentiation. EMBO J. 1986 Sep;5(9):2209–2215. doi: 10.1002/j.1460-2075.1986.tb04486.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Breier G., Dressler G. R., Gruss P. Primary structure and developmental expression pattern of Hox 3.1, a member of the murine Hox 3 homeobox gene cluster. EMBO J. 1988 May;7(5):1329–1336. doi: 10.1002/j.1460-2075.1988.tb02948.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Burgess A. W., Metcalf D. Characterization of a serum factor stimulating the differentiation of myelomonocytic leukemic cells. Int J Cancer. 1980 Nov 15;26(5):647–654. doi: 10.1002/ijc.2910260517. [DOI] [PubMed] [Google Scholar]
  11. Canaani E., Dreazen O., Klar A., Rechavi G., Ram D., Cohen J. B., Givol D. Activation of the c-mos oncogene in a mouse plasmacytoma by insertion of an endogenous intracisternal A-particle genome. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7118–7122. doi: 10.1073/pnas.80.23.7118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chan H. W., Bryan T., Moore J. L., Staal S. P., Rowe W. P., Martin M. A. Identification of ecotropic proviral sequences in inbred mouse strains with a cloned subgenomic DNA fragment. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5779–5783. doi: 10.1073/pnas.77.10.5779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Colberg-Poley A. M., Voss S. D., Chowdhury K., Stewart C. L., Wagner E. F., Gruss P. Clustered homeo boxes are differentially expressed during murine development. Cell. 1985 Nov;43(1):39–45. doi: 10.1016/0092-8674(85)90010-8. [DOI] [PubMed] [Google Scholar]
  14. Desplan C., Theis J., O'Farrell P. H. The Drosophila developmental gene, engrailed, encodes a sequence-specific DNA binding activity. Nature. 1985 Dec 19;318(6047):630–635. doi: 10.1038/318630a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fainsod A., Bogarad L. D., Ruusala T., Lubin M., Crothers D. M., Ruddle F. H. The homeo domain of a murine protein binds 5' to its own homeo box. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9532–9536. doi: 10.1073/pnas.83.24.9532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fibi M., Zink B., Kessel M., Colberg-Poley A. M., Labeit S., Lehrach H., Gruss P. Coding sequence and expression of the homeobox gene Hox 1.3. Development. 1988 Feb;102(2):349–359. doi: 10.1242/dev.102.2.349. [DOI] [PubMed] [Google Scholar]
  17. Frischauf A. M., Lehrach H., Poustka A., Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. doi: 10.1016/s0022-2836(83)80190-9. [DOI] [PubMed] [Google Scholar]
  18. Gaunt S. J., Miller J. R., Powell D. J., Duboule D. Homoeobox gene expression in mouse embryos varies with position by the primitive streak stage. Nature. 1986 Dec 18;324(6098):662–664. doi: 10.1038/324662a0. [DOI] [PubMed] [Google Scholar]
  19. Gehring W. J. Homeo boxes in the study of development. Science. 1987 Jun 5;236(4806):1245–1252. doi: 10.1126/science.2884726. [DOI] [PubMed] [Google Scholar]
  20. Hart C. P., Fainsod A., Ruddle F. H. Sequence analysis of the murine Hox-2.2, -2.3, and -2.4 homeo boxes: evolutionary and structural comparisons. Genomics. 1987 Oct;1(2):182–195. doi: 10.1016/0888-7543(87)90011-5. [DOI] [PubMed] [Google Scholar]
  21. Hauser C. A., Joyner A. L., Klein R. D., Learned T. K., Martin G. R., Tjian R. Expression of homologous homeo-box-containing genes in differentiated human teratocarcinoma cells and mouse embryos. Cell. 1985 Nov;43(1):19–28. doi: 10.1016/0092-8674(85)90008-x. [DOI] [PubMed] [Google Scholar]
  22. Hawley R. G., Shulman M. J., Hozumi N. Transposition of two different intracisternal A particle elements into an immunoglobulin kappa-chain gene. Mol Cell Biol. 1984 Dec;4(12):2565–2572. doi: 10.1128/mcb.4.12.2565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hoey T., Levine M. Divergent homeo box proteins recognize similar DNA sequences in Drosophila. Nature. 1988 Apr 28;332(6167):858–861. doi: 10.1038/332858a0. [DOI] [PubMed] [Google Scholar]
  24. Jackson I. J., Schofield P., Hogan B. A mouse homoeo box gene is expressed during embryogenesis and in adult kidney. Nature. 1985 Oct 24;317(6039):745–748. doi: 10.1038/317745a0. [DOI] [PubMed] [Google Scholar]
  25. Krumlauf R., Holland P. W., McVey J. H., Hogan B. L. Developmental and spatial patterns of expression of the mouse homeobox gene, Hox 2.1. Development. 1987 Apr;99(4):603–617. doi: 10.1242/dev.99.4.603. [DOI] [PubMed] [Google Scholar]
  26. Kuff E. L., Feenstra A., Lueders K., Smith L., Hawley R., Hozumi N., Shulman M. Intracisternal A-particle genes as movable elements in the mouse genome. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1992–1996. doi: 10.1073/pnas.80.7.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Laughon A., Scott M. P. Sequence of a Drosophila segmentation gene: protein structure homology with DNA-binding proteins. Nature. 1984 Jul 5;310(5972):25–31. doi: 10.1038/310025a0. [DOI] [PubMed] [Google Scholar]
  28. Le Mouellic H., Condamine H., Brûlet P. Pattern of transcription of the homeo gene Hox-3.1 in the mouse embryo. Genes Dev. 1988 Jan;2(1):125–135. doi: 10.1101/gad.2.1.125. [DOI] [PubMed] [Google Scholar]
  29. Lee J. C., Hapel A. J., Ihle J. N. Constitutive production of a unique lymphokine (IL 3) by the WEHI-3 cell line. J Immunol. 1982 Jun;128(6):2393–2398. [PubMed] [Google Scholar]
  30. Levine M., Rubin G. M., Tjian R. Human DNA sequences homologous to a protein coding region conserved between homeotic genes of Drosophila. Cell. 1984 Oct;38(3):667–673. doi: 10.1016/0092-8674(84)90261-7. [DOI] [PubMed] [Google Scholar]
  31. Lonai P., Arman E., Czosnek H., Ruddle F. H., Blatt C. New murine homeoboxes: structure, chromosomal assignment, and differential expression in adult erythropoiesis. DNA. 1987 Oct;6(5):409–418. doi: 10.1089/dna.1987.6.409. [DOI] [PubMed] [Google Scholar]
  32. Lotem J., Sachs L. Genetic dissection of the control of normal differentiation in myeloid leukemic cells. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5554–5558. doi: 10.1073/pnas.74.12.5554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Lueders K. K., Kuff E. L. Intracisternal A-particle genes: identification in the genome of Mus musculus and comparison of multiple isolates from a mouse gene library. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3571–3575. doi: 10.1073/pnas.77.6.3571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Mavilio F., Simeone A., Giampaolo A., Faiella A., Zappavigna V., Acampora D., Poiana G., Russo G., Peschle C., Boncinelli E. Differential and stage-related expression in embryonic tissues of a new human homoeobox gene. Nature. 1986 Dec 18;324(6098):664–668. doi: 10.1038/324664a0. [DOI] [PubMed] [Google Scholar]
  35. McGinnis W., Garber R. L., Wirz J., Kuroiwa A., Gehring W. J. A homologous protein-coding sequence in Drosophila homeotic genes and its conservation in other metazoans. Cell. 1984 Jun;37(2):403–408. doi: 10.1016/0092-8674(84)90370-2. [DOI] [PubMed] [Google Scholar]
  36. McKeon C., Schmidt A., de Crombrugghe B. A sequence conserved in both the chicken and mouse alpha 2(I) collagen promoter contains sites sensitive to S1 nuclease. J Biol Chem. 1984 May 25;259(10):6636–6640. [PubMed] [Google Scholar]
  37. Meijlink F., de Laaf R., Verrijzer P., Destrée O., Kroezen V., Hilkens J., Deschamps J. A mouse homeobox containing gene on chromosome 11: sequence and tissue-specific expression. Nucleic Acids Res. 1987 Sep 11;15(17):6773–6786. doi: 10.1093/nar/15.17.6773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Mirkin S. M., Lyamichev V. I., Drushlyak K. N., Dobrynin V. N., Filippov S. A., Frank-Kamenetskii M. D. DNA H form requires a homopurine-homopyrimidine mirror repeat. Nature. 1987 Dec 3;330(6147):495–497. doi: 10.1038/330495a0. [DOI] [PubMed] [Google Scholar]
  39. Nudel U., Katcoff D., Zakut R., Shani M., Carmon Y., Finer M., Czosnek H., Ginsburg I., Yaffe D. Isolation and characterization of rat skeletal muscle and cytoplasmic actin genes. Proc Natl Acad Sci U S A. 1982 May;79(9):2763–2767. doi: 10.1073/pnas.79.9.2763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Odenwald W. F., Taylor C. F., Palmer-Hill F. J., Friedrich V., Jr, Tani M., Lazzarini R. A. Expression of a homeo domain protein in noncontact-inhibited cultured cells and postmitotic neurons. Genes Dev. 1987 Jul;1(5):482–496. doi: 10.1101/gad.1.5.482. [DOI] [PubMed] [Google Scholar]
  41. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  42. Rubin M. R., Toth L. E., Patel M. D., D'Eustachio P., Nguyen-Huu M. C. A mouse homeo box gene is expressed in spermatocytes and embryos. Science. 1986 Aug 8;233(4764):663–667. doi: 10.1126/science.3726554. [DOI] [PubMed] [Google Scholar]
  43. Ryder K., Silver S., DeLucia A. L., Fanning E., Tegtmeyer P. An altered DNA conformation in origin region I is a determinant for the binding of SV40 large T antigen. Cell. 1986 Mar 14;44(5):719–725. doi: 10.1016/0092-8674(86)90838-x. [DOI] [PubMed] [Google Scholar]
  44. Sachs L. Constitutive uncoupling of pathways of gene expression that control growth and differentiation in myeloid leukemia: a model for the origin and progression of malignancy. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6152–6156. doi: 10.1073/pnas.77.10.6152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Sachs L. The molecular control of blood cell development. Science. 1987 Dec 4;238(4832):1374–1379. doi: 10.1126/science.3317831. [DOI] [PubMed] [Google Scholar]
  46. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Scheidereit C., Geisse S., Westphal H. M., Beato M. The glucocorticoid receptor binds to defined nucleotide sequences near the promoter of mouse mammary tumour virus. Nature. 1983 Aug 25;304(5928):749–752. doi: 10.1038/304749a0. [DOI] [PubMed] [Google Scholar]
  48. Scott M. P., Carroll S. B. The segmentation and homeotic gene network in early Drosophila development. Cell. 1987 Dec 4;51(5):689–698. doi: 10.1016/0092-8674(87)90092-4. [DOI] [PubMed] [Google Scholar]
  49. Shapiro M. B., Senapathy P. RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res. 1987 Sep 11;15(17):7155–7174. doi: 10.1093/nar/15.17.7155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Shen-Ong G. L., Keath E. J., Piccoli S. P., Cole M. D. Novel myc oncogene RNA from abortive immunoglobulin-gene recombination in mouse plasmacytomas. Cell. 1982 Dec;31(2 Pt 1):443–452. doi: 10.1016/0092-8674(82)90137-4. [DOI] [PubMed] [Google Scholar]
  51. Shepherd J. C., McGinnis W., Carrasco A. E., De Robertis E. M., Gehring W. J. Fly and frog homoeo domains show homologies with yeast mating type regulatory proteins. Nature. 1984 Jul 5;310(5972):70–71. doi: 10.1038/310070a0. [DOI] [PubMed] [Google Scholar]
  52. 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]
  53. Wong P. M., Chung S. W., Nienhuis A. W. Retroviral transfer and expression of the interleukin-3 gene in hemopoietic cells. Genes Dev. 1987 Jun;1(4):358–365. doi: 10.1101/gad.1.4.358. [DOI] [PubMed] [Google Scholar]
  54. Ymer S., Tucker W. Q., Campbell H. D., Young I. G. Nucleotide sequence of the intracisternal A-particle genome inserted 5' to the interleukin-3 gene of the leukemia cell line WEHI-3B. Nucleic Acids Res. 1986 Jul 25;14(14):5901–5918. doi: 10.1093/nar/14.14.5901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Ymer S., Tucker W. Q., Sanderson C. J., Hapel A. J., Campbell H. D., Young I. G. Constitutive synthesis of interleukin-3 by leukaemia cell line WEHI-3B is due to retroviral insertion near the gene. Nature. 1985 Sep 19;317(6034):255–258. doi: 10.1038/317255a0. [DOI] [PubMed] [Google Scholar]

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