Brown K E, Amoils S, Horn J M, Buckle V J, Higgs D R, Merkenschlager M, Fisher A G
Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
Nat Cell Biol. 2001 Jun;3(6):602-6. doi: 10.1038/35078577.
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.
α-珠蛋白基因簇和β-珠蛋白基因簇已得到广泛研究。这些基因的调控确保了来自两个基因座的蛋白质能够以平衡的量产生，并且其表达具有组织限制性且特定于发育阶段。在此，我们比较了原代人类细胞中内源性α-珠蛋白基因座和β-珠蛋白基因座的亚核定位，这些细胞中的基因要么处于活跃表达状态，要么处于沉默状态。在成红细胞中，α-珠蛋白基因和β-珠蛋白基因定位于细胞核中与富含α-卫星的组成型异染色质不同的区域。然而，在不表达珠蛋白基因的循环淋巴细胞中，α-珠蛋白基因和β-珠蛋白基因的分布明显不同。β-珠蛋白基因座与我们在此研究的几个无活性基因（人类c-fms和SOX-1）以及之前研究的基因（小鼠λ5、CD4、CD8α、RAGs、TdT和Sox-1）一样，在高比例的循环淋巴细胞中与着丝粒周围异染色质相关。相比之下，在正常人淋巴细胞的细胞核中、在缺乏α-珠蛋白基因座调控元件HS-40或整个上游区域的α-地中海贫血患者的淋巴细胞中，或者在源自人类α-珠蛋白转基因小鼠的小鼠成红细胞和淋巴细胞中，α-珠蛋白基因均不与着丝粒异染色质相关。这些数据表明，α-珠蛋白基因簇和β-珠蛋白基因簇的正常调控表达发生在原代造血细胞的不同核环境中。
