Tuan D, London I M
Proc Natl Acad Sci U S A. 1984 May;81(9):2718-22. doi: 10.1073/pnas.81.9.2718.
We have mapped the DNase I-hypersensitive sites around the epsilon-globin and c-myc genes in two human leukemia cell lines K562 and HL60. In K562 cells in which the epsilon-globin gene is transcribed, six DNase I-hypersensitive sites are found in 6 kilobases (kb) of upstream flanking DNA; in HL60 cells in which the c-myc gene is expressed, two DNase I-hypersensitive sites are observed in 2 kb of upstream DNA. Neither the inactive epsilon-globin gene in HL60 cells nor the inactive c-myc gene in K562 cells displays such upstream DNase I-hypersensitive sites. Our results are consistent with previous studies that have shown DNase I-hypersensitive sites within 1 kb of the 5' end of other expressed genes. In addition, we have found sites displaying even more DNase I sensitivity further upstream of expressed epsilon-globin and c-myc genes. Among the six DNase I-hypersensitive sites of the expressed epsilon-globin gene in K562 cells, the most sensitive site is located about 6 kb upstream of the epsilon-globin gene. When correlated with the DNA sequence upstream of the epsilon-globin gene, this site was found to correspond to a region that contains a stretch of 28 consecutive Ts, three enhancer core-like sequences, and a stretch of consecutive (C-A)15(T-A)6 alternating purine and pyrimidine bases. These findings suggest the possibility that an enhancer element for epsilon-globin gene expression resides within this DNase I-hypersensitive site.
我们已绘制了两个人类白血病细胞系K562和HL60中ε-珠蛋白基因和c-myc基因周围的DNA酶I超敏位点。在转录ε-珠蛋白基因的K562细胞中，在6千碱基（kb）的上游侧翼DNA中发现了6个DNA酶I超敏位点；在表达c-myc基因的HL60细胞中，在2 kb的上游DNA中观察到2个DNA酶I超敏位点。HL60细胞中无活性的ε-珠蛋白基因和K562细胞中无活性的c-myc基因均未显示出此类上游DNA酶I超敏位点。我们的结果与先前的研究一致，这些研究表明在其他表达基因5'端1 kb范围内存在DNA酶I超敏位点。此外，我们在表达的ε-珠蛋白基因和c-myc基因的更上游发现了对DNA酶I敏感性更高的位点。在K562细胞中表达的ε-珠蛋白基因的6个DNA酶I超敏位点中，最敏感的位点位于ε-珠蛋白基因上游约6 kb处。当与ε-珠蛋白基因上游的DNA序列相关联时，发现该位点对应于一个区域，该区域包含一段连续28个T、三个增强子核心样序列以及一段连续的（C-A）15（T-A）6嘌呤和嘧啶交替碱基。这些发现提示ε-珠蛋白基因表达的增强子元件可能位于这个DNA酶I超敏位点内。
