Expression of α- and β-globin genes occurs within different nuclear domains in haemopoietic cells
Expression of α- and β-globin genes occurs within different nuclear domains in haemopoietic cells
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DOI：
10.1038/35078577
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发表时间：
2001-06-01
影响因子：
21.3
通讯作者：
Fisher, AG
中科院分区：
文献类型：
--
作者：
Brown, KE;Amoils, S;Fisher, AG
α-和β-珠蛋白基因簇已被广泛研究（1 - 3）。这些基因的调控确保了来自两个基因座的蛋白质以平衡的量产生，并且其表达具有组织局限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-和β-珠蛋白基因座的亚核位置，在这些细胞中基因要么活跃表达要么沉默。在成红细胞中，α-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分离的区域。然而，在不表达珠蛋白基因的循环淋巴细胞中，α-和β-珠蛋白基因的分布明显不同。β-珠蛋白基因座与在此研究的几个不活跃基因（人类c - fms和SOX - 1）以及先前研究的（小鼠λ5、CD4、CD8α、RAGs、TdT和Sox - 1）（4,5）一样，在高比例的循环淋巴细胞中与近中心异染色质相关联。相比之下，在正常人淋巴细胞的细胞核中、在缺乏调控元件HS - 40或α-珠蛋白基因座整个上游区域的α-地中海贫血患者的淋巴细胞中，或者在小鼠成红细胞以及来自人类α-珠蛋白转基因小鼠的淋巴细胞中，α-珠蛋白基因与着丝粒异染色质均无关联。这些数据表明，α-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。
The alpha- and beta -globin gene clusters have been extensively studied(1-3). 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 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, CD8 alpha, RAGs, TdT and Sox-1)(4,5), 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.