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
. 1992 Apr 15;89(8):3424–3428. doi: 10.1073/pnas.89.8.3424

Immunoglobulin heavy-chain and CD3 delta-chain gene enhancers are DNase I-hypersensitive in hemopoietic progenitor cells.

A M Ford 1, C A Bennett 1, L E Healy 1, E Navarro 1, E Spooncer 1, M F Greaves 1
PMCID: PMC48880  PMID: 1533043

Abstract

Multipotential interleukin 3-dependent non-immortalized murine hemopoietic progenitor cells have DNase I-hypersensitive sites in the immunoglobulin heavy-chain and CD3 delta enhancers and transcribe germ-line T-cell antigen receptor gamma-chain (TCR gamma), but not IgM or TCR beta, genes. Induction of myeloid differentiation in these cells clones down expression and/or transcriptional accessibility of the immunoglobulin heavy-chain and TCR gamma genes. The CD3 delta enhancer region remains DNase I-hypersensitive but closes down in B cells. In embryonic stem cells and pan-mesodermal cells, these genes or enhancer regions are neither expressed nor DNase I-hypersensitive. These data suggest that lineage potential may be programmed, at least in part, by alterations in the accessibility or conformation of regulatory regions of genes and that some promiscuity of gene expression and/or accessibility can precede lineage commitment and maturation in progenitor cells induced to self-renew by interleukin 3.

Full text

PDF
3425

Images in this article

3425Image
on p.3425
3426Image
on p.3426
3427Image
on p.3427

Selected References

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

  1. Alt F. W., Blackwell T. K., DePinho R. A., Reth M. G., Yancopoulos G. D. Regulation of genome rearrangement events during lymphocyte differentiation. Immunol Rev. 1986 Feb;89:5–30. doi: 10.1111/j.1600-065x.1986.tb01470.x. [DOI] [PubMed] [Google Scholar]
  2. Alt F. W., Yancopoulos G. D., Blackwell T. K., Wood C., Thomas E., Boss M., Coffman R., Rosenberg N., Tonegawa S., Baltimore D. Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J. 1984 Jun;3(6):1209–1219. doi: 10.1002/j.1460-2075.1984.tb01955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Alt F., Rosenberg N., Lewis S., Thomas E., Baltimore D. Organization and reorganization of immunoglobulin genes in A-MULV-transformed cells: rearrangement of heavy but not light chain genes. Cell. 1981 Dec;27(2 Pt 1):381–390. doi: 10.1016/0092-8674(81)90421-9. [DOI] [PubMed] [Google Scholar]
  4. Blackman M. A., Koshland M. E. Specific 5' and 3' regions of the mu-chain gene are undermethylated at distinct stages of B-cell differentiation. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3809–3813. doi: 10.1073/pnas.82.11.3809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bothwell A. L., Paskind M., Reth M., Imanishi-Kari T., Rajewsky K., Baltimore D. Heavy chain variable region contribution to the NPb family of antibodies: somatic mutation evident in a gamma 2a variable region. Cell. 1981 Jun;24(3):625–637. doi: 10.1016/0092-8674(81)90089-1. [DOI] [PubMed] [Google Scholar]
  6. Burgess A. W., Camakaris J., Metcalf D. Purification and properties of colony-stimulating factor from mouse lung-conditioned medium. J Biol Chem. 1977 Mar 25;252(6):1998–2003. [PubMed] [Google Scholar]
  7. Caplan A. I., Ordahl C. P. Irreversible gene repression model for control of development. Science. 1978 Jul 14;201(4351):120–130. doi: 10.1126/science.351805. [DOI] [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. Clevers H., Alarcon B., Wileman T., Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol. 1988;6:629–662. doi: 10.1146/annurev.iy.06.040188.003213. [DOI] [PubMed] [Google Scholar]
  10. Coffman R. L., Weissman I. L. B220: a B cell-specific member of th T200 glycoprotein family. Nature. 1981 Feb 19;289(5799):681–683. doi: 10.1038/289681a0. [DOI] [PubMed] [Google Scholar]
  11. Cowan N. J., Secher D. S., Milstein C. Intracellular immunoglobulin chain synthesis in non-secreting variants of a mouse myeloma: detection of inactive light-chain messenger RNA. J Mol Biol. 1974 Dec 25;90(4):691–701. doi: 10.1016/0022-2836(74)90533-6. [DOI] [PubMed] [Google Scholar]
  12. Davidson W. F., Pierce J. H., Rudikoff S., Morse H. C., 3rd Relationships between B cell and myeloid differentiation. Studies with a B lymphocyte progenitor line, HAFTL-1. J Exp Med. 1988 Jul 1;168(1):389–407. doi: 10.1084/jem.168.1.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Dexter T. M. Stromal cell associated haemopoiesis. J Cell Physiol Suppl. 1982;1:87–94. doi: 10.1002/jcp.1041130414. [DOI] [PubMed] [Google Scholar]
  15. Emorine L., Kuehl M., Weir L., Leder P., Max E. E. A conserved sequence in the immunoglobulin J kappa-C kappa intron: possible enhancer element. Nature. 1983 Aug 4;304(5925):447–449. doi: 10.1038/304447a0. [DOI] [PubMed] [Google Scholar]
  16. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  17. Ford A. M., Watt S. M., Furley A. J., Molgaard H. V., Greaves M. F. Cell lineage specificity of chromatin configuration around the immunoglobulin heavy chain enhancer. EMBO J. 1988 Aug;7(8):2393–2399. doi: 10.1002/j.1460-2075.1988.tb03084.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Furley A. J., Mizutani S., Weilbaecher K., Dhaliwal H. S., Ford A. M., Chan L. C., Molgaard H. V., Toyonaga B., Mak T., van den Elsen P. Developmentally regulated rearrangement and expression of genes encoding the T cell receptor-T3 complex. Cell. 1986 Jul 4;46(1):75–87. doi: 10.1016/0092-8674(86)90861-5. [DOI] [PubMed] [Google Scholar]
  19. Furley A. J., Reeves B. R., Mizutani S., Altass L. J., Watt S. M., Jacob M. C., van den Elsen P., Terhorst C., Greaves M. F. Divergent molecular phenotypes of KG1 and KG1a myeloid cell lines. Blood. 1986 Nov;68(5):1101–1107. [PubMed] [Google Scholar]
  20. Georgopoulos K., van den Elsen P., Bier E., Maxam A., Terhorst C. A T cell-specific enhancer is located in a DNase I-hypersensitive area at the 3' end of the CD3-delta gene. EMBO J. 1988 Aug;7(8):2401–2407. doi: 10.1002/j.1460-2075.1988.tb03085.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gordon M. Y. Hemopoietic growth factors and receptors: bound and free. Cancer Cells. 1991 Apr;3(4):127–133. [PubMed] [Google Scholar]
  22. Greaves M. F., Brown G. Purification of human T and B lymphocytes. J Immunol. 1974 Jan;112(1):420–423. [PubMed] [Google Scholar]
  23. Heyworth C. M., Dexter T. M., Kan O., Whetton A. D. The role of hemopoietic growth factors in self-renewal and differentiation of IL-3-dependent multipotential stem cells. Growth Factors. 1990;2(2-3):197–211. doi: 10.3109/08977199009071506. [DOI] [PubMed] [Google Scholar]
  24. Hoatlin M. E., Kozak S. L., Lilly F., Chakraborti A., Kozak C. A., Kabat D. Activation of erythropoietin receptors by Friend viral gp55 and by erythropoietin and down-modulation by the murine Fv-2r resistance gene. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9985–9989. doi: 10.1073/pnas.87.24.9985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Holmes K. L., Pierce J. H., Davidson W. F., Morse H. C., 3rd Murine hematopoietic cells with pre-B or pre-B/myeloid characteristics are generated by in vitro transformation with retroviruses containing fes, ras, abl, and src oncogenes. J Exp Med. 1986 Aug 1;164(2):443–457. doi: 10.1084/jem.164.2.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kranz D. M., Saito H., Heller M., Takagaki Y., Haas W., Eisen H. N., Tonegawa S. Limited diversity of the rearranged T-cell gamma gene. 1985 Feb 28-Mar 6Nature. 313(6005):752–755. doi: 10.1038/313752a0. [DOI] [PubMed] [Google Scholar]
  27. Palacios R., Karasuyama H., Rolink A. Ly1+ PRO-B lymphocyte clones. Phenotype, growth requirements and differentiation in vitro and in vivo. EMBO J. 1987 Dec 1;6(12):3687–3693. doi: 10.1002/j.1460-2075.1987.tb02702.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pevny L., Simon M. C., Robertson E., Klein W. H., Tsai S. F., D'Agati V., Orkin S. H., Costantini F. Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature. 1991 Jan 17;349(6306):257–260. doi: 10.1038/349257a0. [DOI] [PubMed] [Google Scholar]
  29. Reznikoff C. A., Brankow D. W., Heidelberger C. Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Res. 1973 Dec;33(12):3231–3238. [PubMed] [Google Scholar]
  30. Robertson E., Bradley A., Kuehn M., Evans M. Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector. Nature. 1986 Oct 2;323(6087):445–448. doi: 10.1038/323445a0. [DOI] [PubMed] [Google Scholar]
  31. Samelson L. E., Lindsten T., Fowlkes B. J., van den Elsen P., Terhorst C., Davis M. M., Germain R. N., Schwartz R. H. Expression of genes of the T-cell antigen receptor complex in precursor thymocytes. 1985 Jun 27-Jul 3Nature. 315(6022):765–768. doi: 10.1038/315765a0. [DOI] [PubMed] [Google Scholar]
  32. Siebenlist U., Hennighausen L., Battey J., Leder P. Chromatin structure and protein binding in the putative regulatory region of the c-myc gene in Burkitt lymphoma. Cell. 1984 Jun;37(2):381–391. doi: 10.1016/0092-8674(84)90368-4. [DOI] [PubMed] [Google Scholar]
  33. Spooncer E., Boettiger D., Dexter T. M. Continuous in vitro generation of multipotential stem cell clones from src-infected cultures. Nature. 1984 Jul 19;310(5974):228–230. doi: 10.1038/310228a0. [DOI] [PubMed] [Google Scholar]
  34. Spooncer E., Heyworth C. M., Dunn A., Dexter T. M. Self-renewal and differentiation of interleukin-3-dependent multipotent stem cells are modulated by stromal cells and serum factors. Differentiation. 1986;31(2):111–118. doi: 10.1111/j.1432-0436.1986.tb00391.x. [DOI] [PubMed] [Google Scholar]
  35. Storb U., Arp B., Wilson R. The switch region associated with immunoglobulin C mu genes is DNase I hypersensitive in T lymphocytes. Nature. 1981 Nov 5;294(5836):90–92. doi: 10.1038/294090a0. [DOI] [PubMed] [Google Scholar]
  36. Su L. K., Kadesch T. The immunoglobulin heavy-chain enhancer functions as the promoter for I mu sterile transcription. Mol Cell Biol. 1990 Jun;10(6):2619–2624. doi: 10.1128/mcb.10.6.2619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Warner N. L., Moore M. A., Metcalf D. A transplantable myelomonocytic leukemia in BALB-c mice: cytology, karyotype, and muramidase content. J Natl Cancer Inst. 1969 Oct;43(4):963–982. [PubMed] [Google Scholar]
  38. Watt S. M., Burgess A. W., Metcalf D. Isolation and surface labeling of murine polymorphonuclear neutrophils. J Cell Physiol. 1979 Jul;100(1):1–21. doi: 10.1002/jcp.1041000102. [DOI] [PubMed] [Google Scholar]
  39. Willison K. R., Dudley K., Potter J. Molecular cloning and sequence analysis of a haploid expressed gene encoding t complex polypeptide 1. Cell. 1986 Mar 14;44(5):727–738. doi: 10.1016/0092-8674(86)90839-1. [DOI] [PubMed] [Google Scholar]
  40. Wotton D., Flanagan B. F., Owen M. J. Chromatin configuration of the human CD2 gene locus during T-cell development. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4195–4199. doi: 10.1073/pnas.86.11.4195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wyke J. A., Stoker A. W., Searle S., Spooncer E., Simmons P., Dexter T. M. Perturbed hemopoiesis and the generation of multipotential stem cell clones in src-infected bone marrow cultures is an indirect or transient effect of the oncogene. Mol Cell Biol. 1986 Mar;6(3):959–963. doi: 10.1128/mcb.6.3.959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Yancopoulos G. D., Alt F. W. Regulation of the assembly and expression of variable-region genes. Annu Rev Immunol. 1986;4:339–368. doi: 10.1146/annurev.iy.04.040186.002011. [DOI] [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