Grosveld F, van Assendelft G B, Greaves D R, Kollias G
Laboratory of Gene Structure and Expression, National Institute for Medical Research, London, England.
Cell. 1987 Dec 24;51(6):975-85. doi: 10.1016/0092-8674(87)90584-8.
We have constructed a "minilocus" that contains the 5' and 3' flanking regions of the human beta-globin locus and the beta-globin gene. These regions are characterized by erythroid-specific DNAase I-superhypersensitive sites and are normally located approximately 50 kb 5' and 20 kb 3' of the beta-globin gene. This minilocus is expressed tissue-specifically in transgenic mice at a level directly related to its copy number yet independent of its position of integration in the genome. Moreover, the expression per gene copy is the same in each mouse and as high as that of the endogenous mouse beta-globin gene. These results indicate that the DNA regions flanking the human beta-globin locus contain dominant regulatory sequences that specify position-independent expression and normally activate the complete human multigene beta-globin locus.
我们构建了一个“微型基因座”，它包含人类β-珠蛋白基因座的5'和3'侧翼区域以及β-珠蛋白基因。这些区域的特征是具有红系特异性的DNA酶I超敏感位点，通常位于β-珠蛋白基因5'端约50 kb和3'端约20 kb处。这个微型基因座在转基因小鼠中呈组织特异性表达，其表达水平与其拷贝数直接相关，但与其在基因组中的整合位置无关。此外，每个基因拷贝的表达在每只小鼠中都是相同的，并且与内源性小鼠β-珠蛋白基因的表达水平一样高。这些结果表明，人类β-珠蛋白基因座侧翼的DNA区域包含显性调控序列，这些序列决定了位置独立的表达，并通常激活完整的人类多基因β-珠蛋白基因座。
