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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Grosveld, F. Curr. Opin. Genet. Dev. 9, 152–157 (1999).
Bulger, M. & Groudine, M. Genes Dev. 13, 2465–2477 (1999).
Higgs, D. R., Sharpe, J. A. & Wood W. G. Semin. Hematol. 35, 93–104 (1998).
Brown, K. E., Baxter, J., Graf, D., Merkenschlager, M. & Fisher, A. G. Mol. Cell 3, 207–217 (1999).
Brown, K. E., Guest, S. S., Smale, S. T., Hahm, K., Merkenschlager, M. & Fisher, A. G. Cell 91, 845–854 (1997).
Cockell, M. & Gasser, S. M. Curr. Opin. Genet. Dev. 2, 199–205 (1999).
Craddock C. F. et al. EMBO J. 14, 1718–1726 (1995).
Flint, J. et al. Nature Genet. 15, 252–257 (1997).
Bulger, M. et al. Proc. Natl Acad. Sci. USA 96, 5129–5134 (1999).
Vyas, P. et al. Cell 69, 781–793 (1992).
Grosveld, F., Blom van Assendelft, G., Greaves, D. & Kolias, G. Cell 51, 975–985 (1987).
Hardison, R. J. Exp. Biol. 201, 1099–1117 (1998).
Smith Z. E. & Higgs, D. R. Hum. Mol. Genet. 8, 1373–1386 (1999).
Engel, J. D. & Tanimoto, K. Cell 100, 499–502 (2000).
Francastel, C., Walters, M. C., Groudine, M. & Martin D. I. K. Cell 99, 259–269 (1999).
Bender, M. A., Bulger, M., Close, J. & Groudine, M. Mol. Cell 5, 387–393 (2000).
Schübeler, D. et al. Genes Dev. 14, 940–950 (2000).
Morley, B. J., Abbott, C. A. & Wood W. G. Blood 78, 1355–1363 (1991).
Conkie, D., Kleiman, L., Harrison, P. R. & Paul, J. Exp. Cell Res. 93, 315–324 (1975).
Ashmun, R. A. et al. Blood 3, 827–837 (1989).
Malas, S., Duthie, S. M., Mohri, F., Lovell-Badge, R. & Episkopou, V. Mamm. Genome 8, 866–868 (1997).
Waye J. S., Creeper, L. A. & Willard, H. F. Chromosoma 95, 182–188 (1987).
Tufarelli, C., Frischauf, A.-M., Hardison, R., Flint, J. & Higgs, D. R. Genomics 71, 307–314 (2001).
Higgs, D. R. Cell 95, 299–302 (1998).
Bulger, M. et al. Proc. Natl Acad. Sci. USA 97, 14560–14565 (2000).
Barbour, V. M. et al. Blood 96, 800–807 (2000).
Wreggett, K. A. et al. Cytogenet. Cell Genet. 66, 99–103 (1994).
Ijdo, J. W., Wells, R. A., Baldini, A. & Reeders S. T. Nucleic Acids Res. 19, 4780 (1991).
Lundgren, M. et al. Cell 103, 733–743 (2000).
Jimenez, G. Gale, K. B. & Enver, T. Nucleic Acids Res. 20, 5797–5803 (1992).
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/35078577
This article is cited by
-
Loss of Tau protein affects the structure, transcription and repair of neuronal pericentromeric heterochromatin
Scientific Reports (2016)
-
Specific positioning of the casein gene cluster in active nuclear domains in luminal mammary epithelial cells
Chromosome Research (2011)
-
Spatial organization of genes as a component of regulated expression
Chromosoma (2010)
-
Changes in chromatin structure during processing of wax-embedded tissue sections
Chromosome Research (2010)
-
Transcriptional competence of the integrated HIV-1 provirus at the nuclear periphery
The EMBO Journal (2009)