Expression of α- and β-globin genes occurs within different nuclear domains in haemopoietic cells (original) (raw)

Nature Cell Biology volume 3, pages 602–606 (2001)Cite this article

Abstract

The α- and β-globin gene clusters have been extensively studied1,2,3. Regulation of these genes ensures that proteins derived from both loci are produced in balanced amounts, and that expression is tissue-restricted and specific to developmental stages. Here we compare the subnuclear location of the endogenous α- and β-globin loci in primary human cells in which the genes are either actively expressed or silent. In erythroblasts, the α- and β-globin genes are localized in areas of the nucleus that are discrete from α-satellite-rich constitutive heterochromatin. However, in cycling lymphocytes, which do not express globin genes, the distribution of α- and β-globin genes was markedly different. β-globin loci, in common with several inactive genes studied here (human _c_-fms and SOX-1) and previously (mouse λ5, CD4, CD8α, RAGs, TdT and Sox-1)4,5, were associated with pericentric heterochromatin in a high proportion of cycling lymphocytes. In contrast, α-globin genes were not associated with centromeric heterochromatin in the nucleus of normal human lymphocytes, in lymphocytes from patients with α-thalassaemia lacking the regulatory HS-40 element or entire upstream region of the α-globin locus, or in mouse erythroblasts and lymphocytes derived from human α-globin transgenic mice. These data show that the normal regulated expression of α- and β-globin gene clusters occurs in different nuclear environments in primary haemopoietic cells.

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References

  1. Grosveld, F. Curr. Opin. Genet. Dev. 9, 152–157 (1999).
    Article CAS Google Scholar
  2. Bulger, M. & Groudine, M. Genes Dev. 13, 2465–2477 (1999).
    Article CAS Google Scholar
  3. Higgs, D. R., Sharpe, J. A. & Wood W. G. Semin. Hematol. 35, 93–104 (1998).
    CAS PubMed Google Scholar
  4. Brown, K. E., Baxter, J., Graf, D., Merkenschlager, M. & Fisher, A. G. Mol. Cell 3, 207–217 (1999).
    Article CAS Google Scholar
  5. Brown, K. E., Guest, S. S., Smale, S. T., Hahm, K., Merkenschlager, M. & Fisher, A. G. Cell 91, 845–854 (1997).
    Article CAS Google Scholar
  6. Cockell, M. & Gasser, S. M. Curr. Opin. Genet. Dev. 2, 199–205 (1999).
    Article Google Scholar
  7. Craddock C. F. et al. EMBO J. 14, 1718–1726 (1995).
    Article CAS Google Scholar
  8. Flint, J. et al. Nature Genet. 15, 252–257 (1997).
    Article CAS Google Scholar
  9. Bulger, M. et al. Proc. Natl Acad. Sci. USA 96, 5129–5134 (1999).
    Article CAS Google Scholar
  10. Vyas, P. et al. Cell 69, 781–793 (1992).
    Article CAS Google Scholar
  11. Grosveld, F., Blom van Assendelft, G., Greaves, D. & Kolias, G. Cell 51, 975–985 (1987).
    Article CAS Google Scholar
  12. Hardison, R. J. Exp. Biol. 201, 1099–1117 (1998).
    CAS PubMed Google Scholar
  13. Smith Z. E. & Higgs, D. R. Hum. Mol. Genet. 8, 1373–1386 (1999).
    Article CAS Google Scholar
  14. Engel, J. D. & Tanimoto, K. Cell 100, 499–502 (2000).
    Article CAS Google Scholar
  15. Francastel, C., Walters, M. C., Groudine, M. & Martin D. I. K. Cell 99, 259–269 (1999).
    Article CAS Google Scholar
  16. Bender, M. A., Bulger, M., Close, J. & Groudine, M. Mol. Cell 5, 387–393 (2000).
    Article CAS Google Scholar
  17. Schübeler, D. et al. Genes Dev. 14, 940–950 (2000).
    PubMed PubMed Central Google Scholar
  18. Morley, B. J., Abbott, C. A. & Wood W. G. Blood 78, 1355–1363 (1991).
    CAS PubMed Google Scholar
  19. Conkie, D., Kleiman, L., Harrison, P. R. & Paul, J. Exp. Cell Res. 93, 315–324 (1975).
    Article CAS Google Scholar
  20. Ashmun, R. A. et al. Blood 3, 827–837 (1989).
    Google Scholar
  21. Malas, S., Duthie, S. M., Mohri, F., Lovell-Badge, R. & Episkopou, V. Mamm. Genome 8, 866–868 (1997).
    Article CAS Google Scholar
  22. Waye J. S., Creeper, L. A. & Willard, H. F. Chromosoma 95, 182–188 (1987).
    Article CAS Google Scholar
  23. Tufarelli, C., Frischauf, A.-M., Hardison, R., Flint, J. & Higgs, D. R. Genomics 71, 307–314 (2001).
    Article CAS Google Scholar
  24. Higgs, D. R. Cell 95, 299–302 (1998).
    Article CAS Google Scholar
  25. Bulger, M. et al. Proc. Natl Acad. Sci. USA 97, 14560–14565 (2000).
    Article CAS Google Scholar
  26. Barbour, V. M. et al. Blood 96, 800–807 (2000).
    CAS PubMed Google Scholar
  27. Wreggett, K. A. et al. Cytogenet. Cell Genet. 66, 99–103 (1994).
    Article CAS Google Scholar
  28. Ijdo, J. W., Wells, R. A., Baldini, A. & Reeders S. T. Nucleic Acids Res. 19, 4780 (1991).
    Article CAS Google Scholar
  29. Lundgren, M. et al. Cell 103, 733–743 (2000).
    Article CAS Google Scholar
  30. Jimenez, G. Gale, K. B. & Enver, T. Nucleic Acids Res. 20, 5797–5803 (1992).
    Article CAS Google Scholar

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Acknowledgements

We thank B. Wood and J. Sharpe for allowing us to analyse α-PAC transgenic mice, C. Sherr and G. Brown for supplying cosmid a (human _c_-fms), S. Malas for cosmids SxT1 and SxB1 (human Sox-1), P. Fraser for suppling plasmid pB129 (mouse β-globin), D. Graf for advice and G. Reed and R. Newton for photographic assistance. We thank the MRC Tissue Bank at the Hammersmith Hospital for supplying human tissues and I. Devonish for secretarial assistance. The work was supported by the Medical Research Council (UK), and K. Brown is a Dorothy Hodgkin Fellow of the Royal Society.

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Author notes

  1. Karen E. Brown and Shannon Amoils: K. E. Brown and S. Amoils contributed equally to this study.

Authors and Affiliations

  1. Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK
    Karen E. Brown, Shannon Amoils, Jacqueline M. Horn, Matthias Merkenschlager & Amanda G. Fisher
  2. MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital Headington, Oxford, OX3 9DS, UK
    Veronica J. Buckle & Douglas R. Higgs

Authors

  1. Karen E. Brown
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  2. Shannon Amoils
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  3. Jacqueline M. Horn
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  4. Veronica J. Buckle
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  5. Douglas R. Higgs
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  6. Matthias Merkenschlager
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  7. Amanda G. Fisher
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Correspondence toAmanda G. Fisher.

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Brown, K., Amoils, S., Horn, J. et al. Expression of α- and β-globin genes occurs within different nuclear domains in haemopoietic cells.Nat Cell Biol 3, 602–606 (2001). https://doi.org/10.1038/35078577

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