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.

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

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