Autonomous developmental control of human embryonic globin gene switching in transgenic mice.
Autonomous developmental control of human embryonic globin gene switching in transgenic mice.
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转基因小鼠中人胚胎珠蛋白基因转换的自主发育控制。
DOI：
10.1126/science.2251502
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Stamatoyannopoulos,G
中科院分区：
文献类型：
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作者：
Raich,N;Enver,T;Nakamoto,B;Josephson,B;Papayannopoulou,T;Stamatoyannopoulos,G
β样珠蛋白基因的表达在发育过程中受到调控的机制正在深入研究中。分析了人胚胎(ε)珠蛋白表达的时间调控。将3.7kb全长的人ε-珠蛋白基因片段连接到2.5kb的基因座控制区，并研究了该基因在转基因小鼠中表达的发育时间。人ε-珠蛋白转基因在卵黄囊来源的原始红系细胞中表达，但在胎肝或骨髓来源的特定红系细胞中不表达。ε基因在确定的红系细胞中不表达，这表明ε-珠蛋白基因的发育调控仅依赖于ε-珠蛋白基因本身和LCR的存在(即一种自主的负控机制)。ε-珠蛋白基因发育调控的自主性使其有别于γ和β-珠蛋白基因的竞争性调控机制，因此，提示至少有两种不同的机制在人类血红蛋白转换中起作用。
The mechanisms by which expression of the β-like globin genes are developmentally regulated are under intense investigation. The temporal control of human embryonic (ε) globin expression was analyzed. A 3.7-kilobase (kb) fragment that contained the entire human ε-globin gene was linked to a 2.5-kb cassette of the locus control region (LCR), and the developmental time of expression of this construct was studied in transgenic mice. The human ε-globin transgene was expressed in yolk sac-derived primitive erythroid cells, but not in fetal liver or bone marrow-derived definitive erythroid cells. The absence of ε gene expression in definitive erythroid cells suggests that the developmental regulation of the ε-globin gene depends only on the presence of the LCR and the ε-globin gene itself (that is, an autonomous negative control mechanism). The autonomy of ε-globin gene developmental control distinguishes it from the competitive mechanism of regulation of γ and β-globin genes, and therefore, suggests that at least two distinct mechanisms function in human hemoglobin switching.