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

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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Figure 1: Structure of the human α- and β-globin loci.
Figure 2: Primary cultures of human erythroblasts.
Figure 3: Intranuclear position of human α-globin and β-globin loci in primary T lymphocytes, B-lymphoblastoid cell lines and in lymphocytes from α-PAC transgenic mice.

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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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Correspondence to Amanda 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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