McCune S L, Townes T M
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Alabama at Birmingham 35294.
Nucleic Acids Res. 1994 Oct 25;22(21):4477-81. doi: 10.1093/nar/22.21.4477.
The DNase I hypersensitive site 5' HS2 of the human beta-globin locus control region confers position-independent, high-level expression on the human beta-globin gene in transgenic mice. When a 5' HS2 beta-globin construct is flanked by retroviral vector sequences derived from Moloney Murine Leukemia Virus (MoMLV), expression of the beta-globin gene is severely inhibited. Apparently, one or more elements within the MoMLV genome is capable of repressing transcription of the human beta-globin gene in transgenic mice. A construct lacking the retroviral enhancer also fails to express the beta-globin gene, indicating that this region of the virus is not essential for repression. Further analysis may permit the identification of specific viral sequences that inhibit gene expression; these sequences could then be deleted or mutated to produce improved viral vectors.
人类β-珠蛋白基因座控制区的脱氧核糖核酸酶I高敏位点5' HS2赋予转基因小鼠中人类β-珠蛋白基因位置独立的高水平表达。当一个5' HS2β-珠蛋白构建体两侧是源自莫洛尼鼠白血病病毒（MoMLV）的逆转录病毒载体序列时，β-珠蛋白基因的表达会受到严重抑制。显然，MoMLV基因组中的一个或多个元件能够抑制转基因小鼠中人类β-珠蛋白基因的转录。一个缺少逆转录病毒增强子的构建体也无法表达β-珠蛋白基因，这表明病毒的该区域对于抑制并非必不可少。进一步的分析可能有助于鉴定抑制基因表达的特定病毒序列；然后可以删除或突变这些序列以产生改进的病毒载体。
