POSITION-INDEPENDENT, HIGH-LEVEL EXPRESSION OF THE HUMAN BETA-GLOBIN GENE IN TRANSGENIC MICE
POSITION-INDEPENDENT, HIGH-LEVEL EXPRESSION OF THE HUMAN BETA-GLOBIN GENE IN TRANSGENIC MICE
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DOI：
10.1016/0092-8674(87)90584-8
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发表时间：
1987-12-24
期刊：
影响因子：
64.5
通讯作者：
KOLLIAS, G
中科院分区：
文献类型：
--
作者：
GROSVELD, F;VANASSENDELFT, GB;KOLLIAS, G
我们构建了包含人类β-珠蛋白基因座和β-珠蛋白基因的5''和3''侧翼区域的“小基因座”。这些区域的特征是红细胞特异性DNAase I超超敏位点，并且通常位于β-珠蛋白基因的大约50kb 5''和20kb 3''处。该小位点在转基因小鼠中以组织特异性表达，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是相同的并且与内源性小鼠β-珠蛋白基因的表达一样高。这些结果表明，人β-珠蛋白基因座侧翼的DNA区域含有显性调节序列，其指定位置无关的表达并通常激活完整的人多基因β-珠蛋白基因座。
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.