Abstract
Several mouse and human genes encoding the DNA-binding homeobox domain are implicated here in haematopoiesis, a differentiation process maintained throughout life. Four homeobox cDNA clones were isolated from bone marrow and spleen of adult mice and two from the human leukaemia cell line K562. They derive from the Hox 1.1, Hox 2.3, Hox 6.1 genes and two previously undescribed genes, one of a type (paired) not found before in vertebrates. A survey of 36 cell lines of the lymphoid, myeloid and erythroid lineages revealed that certain homeobox transcripts were almost ubiquitous, while others were restricted to certain lineages or even particular cell lines. The expression pattern altered in a myeloid and an erythroid line induced to terminal differentiation, and in novel lines that had switched from a lymphoid to a myeloid phenotype. Altogether, the haemopoietic compartment may contain up to 20 homeobox transcripts. In one myeloid leukaemia, DNA rearrangement has perturbed expression. These findings suggest that homeobox genes may influence developmental decisions within the haemopoietic system.
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- Acampora D., Pannese M., D'Esposito M., Simeone A., Boncinelli E. Human homoeobox-containing genes in development. Hum Reprod. 1987 Jul;2(5):407–414. doi: 10.1093/oxfordjournals.humrep.a136559. [DOI] [PubMed] [Google Scholar]
- Adams J. M., Harris A. W., Pinkert C. A., Corcoran L. M., Alexander W. S., Cory S., Palmiter R. D., Brinster R. L. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature. 1985 Dec 12;318(6046):533–538. doi: 10.1038/318533a0. [DOI] [PubMed] [Google Scholar]
- Baron A., Featherstone M. S., Hill R. E., Hall A., Galliot B., Duboule D. Hox-1.6: a mouse homeo-box-containing gene member of the Hox-1 complex. EMBO J. 1987 Oct;6(10):2977–2986. doi: 10.1002/j.1460-2075.1987.tb02603.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bopp D., Burri M., Baumgartner S., Frigerio G., Noll M. Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila. Cell. 1986 Dec 26;47(6):1033–1040. doi: 10.1016/0092-8674(86)90818-4. [DOI] [PubMed] [Google Scholar]
- Boyd A. W., Schrader J. W. Derivation of macrophage-like lines from the pre-B lymphoma ABLS 8.1 using 5-azacytidine. Nature. 1982 Jun 24;297(5868):691–693. doi: 10.1038/297691a0. [DOI] [PubMed] [Google Scholar]
- Claverie J. M., Sauvaget I. A new protein sequence data bank. Nature. 1985 Nov 7;318(6041):19–19. doi: 10.1038/318019a0. [DOI] [PubMed] [Google Scholar]
- Colberg-Poley A. M., Voss S. D., Chowdhury K., Gruss P. Structural analysis of murine genes containing homoeo box sequences and their expression in embryonal carcinoma cells. 1985 Apr 25-May 1Nature. 314(6013):713–718. doi: 10.1038/314713a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Collins S. J., Ruscetti F. W., Gallagher R. E., Gallo R. C. Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proc Natl Acad Sci U S A. 1978 May;75(5):2458–2462. doi: 10.1073/pnas.75.5.2458. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cooper P. C., Metcalf D., Burgess A. W. Biochemical and functional characterization of mature progeny purified from a myelomonocytic leukemia cell line. Leuk Res. 1982;6(3):313–327. doi: 10.1016/0145-2126(82)90093-5. [DOI] [PubMed] [Google Scholar]
- Davis R. L., Weintraub H., Lassar A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987 Dec 24;51(6):987–1000. doi: 10.1016/0092-8674(87)90585-x. [DOI] [PubMed] [Google Scholar]
- Dexter T. M., Allen T. D., Scott D., Teich N. M. Isolation and characterisation of a bipotential haematopoietic cell line. Nature. 1979 Feb 8;277(5696):471–474. doi: 10.1038/277471a0. [DOI] [PubMed] [Google Scholar]
- Dexter T. M., Garland J., Scott D., Scolnick E., Metcalf D. Growth of factor-dependent hemopoietic precursor cell lines. J Exp Med. 1980 Oct 1;152(4):1036–1047. doi: 10.1084/jem.152.4.1036. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dexter T. M., Spooncer E. Growth and differentiation in the hemopoietic system. Annu Rev Cell Biol. 1987;3:423–441. doi: 10.1146/annurev.cb.03.110187.002231. [DOI] [PubMed] [Google Scholar]
- Dube S. K., Pragnell I. B., Kluge N., Gaedicke G., Steinheider G., Ostertag W. Induction of endogenous and of spleen focus-forming viruses during dimethylsulfoxide-induced differentiation of mouse erythroleukemia cells transformed by spleen focus-forming virus. Proc Natl Acad Sci U S A. 1975 May;72(5):1863–1867. doi: 10.1073/pnas.72.5.1863. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duboule D., Baron A., Mähl P., Galliot B. A new homeo-box is present in overlapping cosmid clones which define the mouse Hox-1 locus. EMBO J. 1986 Aug;5(8):1973–1980. doi: 10.1002/j.1460-2075.1986.tb04452.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Fraser J. K., Berridge M. V. Induction of B-lymphocyte antigens on the chronic myeloid leukemic cell line K562 using sodium butyrate. Exp Hematol. 1987 May;15(4):406–413. [PubMed] [Google Scholar]
- Frigerio G., Burri M., Bopp D., Baumgartner S., Noll M. Structure of the segmentation gene paired and the Drosophila PRD gene set as part of a gene network. Cell. 1986 Dec 5;47(5):735–746. doi: 10.1016/0092-8674(86)90516-7. [DOI] [PubMed] [Google Scholar]
- 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]
- Greenberger J. S., Sakakeeny M. A., Humphries R. K., Eaves C. J., Eckner R. J. Demonstration of permanent factor-dependent multipotential (erythroid/neutrophil/basophil) hematopoietic progenitor cell lines. Proc Natl Acad Sci U S A. 1983 May;80(10):2931–2935. doi: 10.1073/pnas.80.10.2931. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hart C. P., Awgulewitsch A., Fainsod A., McGinnis W., Ruddle F. H. Homeo box gene complex on mouse chromosome 11: molecular cloning, expression in embryogenesis, and homology to a human homeo box locus. Cell. 1985 Nov;43(1):9–18. doi: 10.1016/0092-8674(85)90007-8. [DOI] [PubMed] [Google Scholar]
- 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]
- Hozumi M. Established leukemia cell lines: their role in the understanding and control of leukemia proliferation. Crit Rev Oncol Hematol. 1985;3(3):235–277. doi: 10.1016/s1040-8428(85)80028-7. [DOI] [PubMed] [Google Scholar]
- KLEIN E., KLEIN G. ANTIGENIC PROPERTIES OF LYMPHOMAS INDUCED BY THE MOLONEY AGENT. J Natl Cancer Inst. 1964 Mar;32:547–568. [PubMed] [Google Scholar]
- Kemp D. J., Harris A. W., Cory S., Adams J. M. Expression of the immunoglobulin C mu gene in mouse T and B lymphoid and myeloid cell lines. Proc Natl Acad Sci U S A. 1980 May;77(5):2876–2880. doi: 10.1073/pnas.77.5.2876. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kessel M., Schulze F., Fibi M., Gruss P. Primary structure and nuclear localization of a murine homeodomain protein. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5306–5310. doi: 10.1073/pnas.84.15.5306. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Laskov R., Scharff M. D. Synthesis, assembly, and secretion of gamma globulin by mouse myeloma cells. I. Adaptation of the Merwin plasma cell tumor-11 to culture, cloning, and characterization of gamma globulin subunits. J Exp Med. 1970 Mar 1;131(3):515–541. doi: 10.1084/jem.131.3.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li C. L., Johnson G. R. Stimulation of multipotential, erythroid and other murine haematopoietic progenitor cells by adherent cell lines in the absence of detectable multi-CSF (IL-3). Nature. 1985 Aug 15;316(6029):633–636. doi: 10.1038/316633a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Lozzio C. B., Lozzio B. B. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975 Mar;45(3):321–334. [PubMed] [Google Scholar]
- Macdonald P. M., Ingham P., Struhl G. Isolation, structure, and expression of even-skipped: a second pair-rule gene of Drosophila containing a homeo box. Cell. 1986 Dec 5;47(5):721–734. doi: 10.1016/0092-8674(86)90515-5. [DOI] [PubMed] [Google Scholar]
- Martin G. R. Nomenclature for homoeobox-containing genes. Nature. 1987 Jan 1;325(6099):21–22. doi: 10.1038/325021b0. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Rabin M., Ferguson-Smith A., Hart C. P., Ruddle F. H. Cognate homeo-box loci mapped on homologous human and mouse chromosomes. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9104–9108. doi: 10.1073/pnas.83.23.9104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ralph P., Ho M. K., Litcofsky P. B., Springer T. A. Expression and induction in vitro of macrophage differentiation antigens on murine cell lines. J Immunol. 1983 Jan;130(1):108–114. [PubMed] [Google Scholar]
- 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]
- Sebastio G., D'Esposito M., Montanucci M., Simeone A., Auricchio S., Boncinelli E. Modulated expression of human homeobox genes in differentiating intestinal cells. Biochem Biophys Res Commun. 1987 Jul 31;146(2):751–756. doi: 10.1016/0006-291x(87)90593-6. [DOI] [PubMed] [Google Scholar]
- Sharpe P. T., Miller J. R., Evans E. P., Burtenshaw M. D., Gaunt S. J. Isolation and expression of a new mouse homeobox gene. Development. 1988 Feb;102(2):397–407. doi: 10.1242/dev.102.2.397. [DOI] [PubMed] [Google Scholar]
- Shtivelman E., Lifshitz B., Gale R. P., Canaani E. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature. 1985 Jun 13;315(6020):550–554. doi: 10.1038/315550a0. [DOI] [PubMed] [Google Scholar]
- Siden E. J., Baltimore D., Clark D., Rosenberg N. E. Immunoglobulin synthesis by lymphoid cells transformed in vitro by Abelson murine leukemia virus. Cell. 1979 Feb;16(2):389–396. doi: 10.1016/0092-8674(79)90014-x. [DOI] [PubMed] [Google Scholar]
- Simeone A., Mavilio F., Acampora D., Giampaolo A., Faiella A., Zappavigna V., D'Esposito M., Pannese M., Russo G., Boncinelli E. Two human homeobox genes, c1 and c8: structure analysis and expression in embryonic development. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4914–4918. doi: 10.1073/pnas.84.14.4914. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Snow M. H. New data from mammalian homoeobox-containing genes. Nature. 1986 Dec 18;324(6098):618–619. doi: 10.1038/324618a0. [DOI] [PubMed] [Google Scholar]
- Tetteroo P. A., Massaro F., Mulder A., Schreuder-van Gelder R., von dem Borne A. E. Megakaryoblastic differentiation of proerythroblastic K562 cell-line cells. Leuk Res. 1984;8(2):197–206. doi: 10.1016/0145-2126(84)90143-7. [DOI] [PubMed] [Google Scholar]
- Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]