title: Expression of alpha- and beta-globin genes occurs within different nuclear domains in haemopoietic cells.
abstract: The alpha- and beta-globin gene clusters have been extensively studied. 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 alpha- and beta-globin loci in primary human cells in which the genes are either actively expressed or silent. In erythroblasts, the alpha- and beta-globin genes are localized in areas of the nucleus that are discrete from alpha-satellite-rich constitutive heterochromatin. However, in cycling lymphocytes, which do not express globin genes, the distribution of alpha- and beta-globin genes was markedly different. beta-globin loci, in common with several inactive genes studied here (human c-fms and SOX-1) and previously (mouse lambda5, CD4, CD8alpha, RAGs, TdT and Sox-1), were associated with pericentric heterochromatin in a high proportion of cycling lymphocytes. In contrast, alpha-globin genes were not associated with centromeric heterochromatin in the nucleus of normal human lymphocytes, in lymphocytes from patients with alpha-thalassaemia lacking the regulatory HS-40 element or entire upstream region of the alpha-globin locus, or in mouse erythroblasts and lymphocytes derived from human alpha-globin transgenic mice. These data show that the normal regulated expression of alpha- and beta-globin gene clusters occurs in different nuclear environments in primary haemopoietic cells.
authors.affiliation: Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
authors.forename: K E
authors.initials: KE
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Amoils
authors.forename: J M
authors.initials: JM
authors.lastname: Horn
authors.forename: V J
authors.initials: VJ
authors.lastname: Buckle
authors.forename: D R
authors.initials: DR
authors.lastname: Higgs
authors.forename: M
authors.initials: M
authors.lastname: Merkenschlager
authors.forename: A G
authors.initials: AG
authors.lastname: Fisher
mesh_terms: D002467:Cell Nucleus / Q000502:physiology*; D002478:Cells, Cultured; D015870:Gene Expression; D005914:Globins / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000502:physiology
chemical_list: D005914:Globins