Luo H Y, Deisseroth A B, Chui D H
Department of Pathology, McMaster University School of Medicine, Hamilton, Ontario, Canada.
Blood. 1995 Aug 1;86(3):1212-7.
The human alpha-globin-like embryonic zeta-globin chains are present in abundance during the first 5 to 6 weeks of gestation. Subsequently, zeta-globin chains are present in fetal blood at a very low level, which is supplanted by the expression of alpha-globin chains. Adult individuals who are carriers of the (--SEA/) alpha-thalassemia deletion, in contrast to normal adults, have low levels of embryonic zeta-globin chains in their circulating erythrocytes. In this investigation, we constructed stable mouse-human hybrid cells with murine erythroleukemia cells bearing human chromosome 16, with either the normal alpha-globin gene cluster (alpha alpha/) or the (--SEA/) type of alpha-thalassemia deletion. The results on the human zeta-globin gene expression in these hybrid cells indicate that murine adult erythroid transcription factors can induce the expression of human embryonic zeta-globin gene is cis to the (--SEA/) deletion, in parallel with the endogenous mouse alpha-globin gene expression. These data also show the importance of the DNA sequences within the (--SEA) deletion in regulating the expression of zeta-globin gene in cis during normal human hemoglobin ontogeny.
人类α-珠蛋白样胚胎ζ-珠蛋白链在妊娠的前5至6周大量存在。随后，ζ-珠蛋白链在胎儿血液中的水平非常低，其被α-珠蛋白链的表达所取代。与正常成年人相比，携带（--SEA/）α-地中海贫血缺失的成年个体，其循环红细胞中的胚胎ζ-珠蛋白链水平较低。在本研究中，我们用携带人类16号染色体的小鼠红白血病细胞构建了稳定的小鼠-人类杂交细胞，该染色体带有正常的α-珠蛋白基因簇（αα/）或（--SEA/）型α-地中海贫血缺失。这些杂交细胞中人类ζ-珠蛋白基因表达的结果表明，小鼠成年红细胞转录因子可诱导人类胚胎ζ-珠蛋白基因在（--SEA/）缺失的顺式作用下表达，与内源性小鼠α-珠蛋白基因表达平行。这些数据还表明了（--SEA）缺失内的DNA序列在正常人类血红蛋白个体发生过程中顺式调节ζ-珠蛋白基因表达的重要性。
